PMBs explained 2021

GROWING PMB-X ANTIDEPRESSANT Vol. 5

Prescribed Minimum Benefits eXplained

SSRI’s

NEW SNRI’s

PORTFOLIO. 1

CUSTOMER CARE LINE 0860 PHARMA (742 762) / +27 21 707 7000 www.pharmadynamics.co.za DULTA 30, 60 mg. Each tablet contains 30, 60 mg duloxetine respectively. S5 A46/1.2/0889, 890. NAM NS3 18/1.2/0126, 0127.

DYNA SERTRALINE 50, 100. Each tablet contains 50, 100 mg sertraline respectively. S5 A43/1.2/0339, 0340. NAM NS3 14/1.2/0627, 0628.

EXLOV XR 50, 100 mg. Each extended release tablet contains desvenlafaxine benzoate equivalent to 50, 100 mg desvenlafaxine respectively.

S5 A51/1.2/0009, 0010. SERRAPRESS 20 mg. Each tablet contains 20 mg paroxetine. S5 A38/1.2/0069. NAM NS3 08/1.2/0101.

ZYTOMIL 10, 20 mg. Each film coated tablet contains 10, 20 mg escitalopram respectively. S5 A42/1.2/0912, 0914. NAM NS3 10/1.2/0479, 0481.

For full prescribing information, refer to the professional information approved by SAHPRA. 1) Data on file. NSCA639/01/2021

GROWING ANTIDEPRESS PMB-X ANT PORTFOLIO. Vol. 5

NEW SNRI’s

1

Prescribed Minim um Benefits eXpla ined

PMB-X

SSRI’s

Prescribed Minimum Benefits eXplained

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DULTA 30, namics .co.za 7000 DYNA SERTRALI 60 mg. Each tablet contains 30, NE EXLOV XR 50, 100 50, 100. Each tablet contains 60 mg duloxetine respectively.

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by SAHPRA. 1) 12, 0914. NAM NS3 10/1.2/047 Data on file. NSCA639/ 9, 0481.

01/2021

PMBs often cause confusion among patients and medical practitioners.

This PMB Guide deals firstly with the new Covid-19 definition and then lists the 25 chronic conditions. Prescribed Minimum Benefits are a set of defined benefits to ensure that all medical scheme members have access to certain minimum health services, regardless of the benefit option they have selected. The aim is to provide people with continuous care to improve their health and wellbeing and to make healthcare more affordable. PMBs are a feature of the Medical Schemes Act, in terms of which medical schemes have to cover the costs related to the diagnosis, treatment and care of: • Any emergency medical condition • A limited set of 270 medical conditions (defined in the Diagnosis Treatment Pairs) • 25 chronic conditions (defined in the Chronic Disease List).

When deciding whether a condition is a PMB, only look at the symptoms and not at any other factors, such as how the injury or condition was contracted. This approach is called diagnosis-based.

Once the diagnosis has been made, the appropriate treatment and care is decided upon as well as where the patient should receive the treatment (at a hospital, as an outpatient or at a doctor’s rooms). An emergency medical condition means the sudden and, at the time, unexpected onset of a health condition that requires immediate medical treatment and/or an operation.

If the treatment is not available, the emergency could result in weakened bodily functions, serious and lasting damage to organs, limbs or other body parts, or even death.

In an emergency it is not always possible to diagnose the condition before admitting the patient for treatment. However, if doctors suspect that the patient suffers from a condition that is covered by PMBs, the medical scheme has to approve treatment.

Schemes may request that the diagnosis be confirmed with supporting evidence within a reasonable period of time. Schemes must fund the diagnostic investigations up to the point where the diagnosis is confirmed. If a PMB is confirmed, the scheme must fund the treatment.

PMB review

The current PMB package is currently being reviewed. There have been complaints that it does not prioritise the needs of

2 PMB-X GUIDELINES 2021

the country and the design doesn’t prioritise primary healthcare services. There are inconsistencies and flaws in the current regulations. The current package covers only emergency medical conditions, CDLs and a limited set of diagnosis and treatment pairs for certain medical conditions. There also needs to be consistency with developments in health policy.

Focus areas will be to document the relationship between the PMBs and the public healthcare system, specify a comprehensive set of essential healthcare benefits, and coding of the package to include clear diagnosis and procedure codes.

There are different interpretations of how the PMBs are to be used, by patients, service providers, medical schemes and administrators. This creates disputes and serious problems of members not accessing the benefits that they are entitled to.

The following applies to all 25 chronic conditions Medical management reasonably necessary for the delivery of treatment described in this algorithm is included within this benefit, subject to the application of managed health care interventions by the relevant medical scheme.

1

2

To the extent that a medical scheme applies managed health care interventions in respect of this benefit, for example clinical protocols for diagnostics procedures or medical management, such interventions must – a. not be inconsistent with this algorithm; b. b e developed on the basis of evidence-based medicine, taking into account considerations of cost-effectiveness and affordability; and c. comply with all other applicable regulations made in terms of the Medical Scheme Act, 131 of 1998

3

This algorithm may not necessarily always be clinically appropriate for the treatment of children. If this is the case, alternative paediatric clinical management is included within this benefit if it is supported by evidence-based medicine, taking into account considerations of cost-effectiveness and affordability.

*All chronic disease algorithyms are as per the Medical Schemes Act, 131 of 1998.

EDITORIAL

CONTENTS PMB-X GUIDELINES 2021

13- Addison’s disease 14 - Asthma

16 - Bipolar Mood Disorder 19 - Bronchiectasis 20 - Cardiac failure

23 - Cardiomyopathy 25 - COPD

27 - Chronic renal disease

30 - Coronary artery disease 33 - Crohn’s disease

36 - Diabetes insipidus

37 - Diabetes mellitus types 1 & 2 45 - Dysrhythmia

EDITOR: Claire Rush McMillan Claire.Rush@newmedia.co.za LAYOUT & DESIGN: Naresh Budraj

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48 - Epilepsy

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54 - Haemophilia

Unless previously agreed in writing, Medical Chronicle owns all rights to all contributions, whether image or text.

51 - Glaucoma

58 - Hyperlipidaemia 61 - Hypertension

68 - Hypothyroidism

69 - Multiple sclerosis

70 - Parkinson’s disease

72 - Rheumataoid arthritis 76 - Schizophrenia

79 - Systemic lupus

SOURCES: Shutterstock, supplied images, editorial staff. While precautions have been taken to ensure the accuracy of its contents and information given to readers, neither the editor, publisher, or its agents can accept responsibility for damages or injury which arise therefrom. All rights reserved. © PMBX. No part of this publication be reproduced, stored in a retrieval system or transmitted in any form or by any means, photocopying, electronic, mechanical or otherwise without the prior written permission of the copyright owners. Attention African readers: Please note that some products might not be available in your region and product names could vary. Please contact your local distributors, agents or pharmaceutical companies concerned for any discrepancies.

erythematosus

80 - Ulcerative colitis PMB-X GUIDELINES 2021 3

Covid-19

COVID-19

PMB definition guideline v7.5 The Council for Medical Schemes (CMS) released this guideline to clarify PMB entitlements of medical scheme beneficiaries within the context of the pandemic, ensuring that there is uniform interpretation among all stakeholders. It sets out recommendations for the vaccination, screening, diagnosis, treatment, and care of individuals with suspected, and confirmed COVID-19 as per WHO case definitions.

Thursday, May 27, 2021 at 16:17:06 South Africa Standard Time

Disclaimer: This document may change as guidance from the Subject: Re: Naresh Budraj shared "PMBX Booklet 2021 Final" with you.

National Institute of Communicable Diseases (NICD), World Date: Thursday, 27 May 2021 at 16:16:20 South Africa Standard Time Health Organisation (WHO) and Department of Health (NDOH) From: Claire Rush evolves.

The contents are up to date as at the time of publishing.

To: Naresh Budraj ABachments: image001.png, image002.png, image003.png, image005.png, Please always check for updates on the image004.png, National Institute for image008.png, image009.png Communicable Diseases (NICD) and the National Department of Thanks! (DOH) websites.

Health

Just one small change then done. This table (Table 1, pg 4) had text that’s a different font. Please use this:

(Calibri) 1: Possible ICD-10 codes for identifying Covid-19 Table PMB code

Diagnosis

Treatment

ICD-10 code

177D

COVID-19

Vaccina]on, Screening, Tes]ng, Medical management including Ven]la]on, Rehabilita]on.

U07.1

Kind regards

U07.2

ICD-10 DescripHon COVID-19, virus iden]fied COVID-19, virus not iden]fied

• All persons living in the same household as a Covid-19 case, and people working closely in the same environment as a case.

• Healthcare workers or other people providing direct care for a Covid-19 case while not wearing recommended personal protective equipment (PPE) (e.g., gowns, gloves, N95 respirator, eye protection).

• A contact in an any mode of transportation where passenger details are captured sitting within two seats (in any direction) of the case, travel companions or persons providing care, and crew members serving in the section where the case was seated.

• NICD had previously defined high-risk persons separately to the suspected case definition.

CMS has noted that high-risk persons are now included in the new definition with the exception of people who are admitted with pneumonia.

2.11. The purpose of the document is to provide detailed clarification in respect of benefit and entitlements to members and beneficiaries of medical schemes.

2. SCOPE AND PURPOSE 2.1.

The WHO has published ICD-10 codes to be used for the Claire Rush COVID-19 and CMS recommends that correct coding be used to Subject to the managed care protocols, PMB level of care benefits Editor: Medical Chronicle enable correct identification and reporting thereof. must be paid in full of the risk benefit irrespective of member’s plan T +27 (0)11 877 6111 2.2. A new DTP has been assigned to ICD-10 codes to ensure the type or benefit option. correct PMB classification of COVID-19.

2.3. The surveillance for COVID-19 is essential to permit early 3. EPIDEMIOLOGY recognition of suspected cases, early diagnosis, containment, and 3.1. Coronaviruses are a large family of viruses that are common prevention of onward transmission. in many different species of animals, including camels, cattle, cats, 2.4. It is also important to note that COVID-19 is a Category 1 and bats. These viruses cause illness ranging from the common Notifiable Medical Condition that requires immediate reporting by cold to more severe diseases such as bronchitis, pneumonia, LinkedIn • Twitter available • Facebook upon diagnosis followed by a written the most• Instagram rapid means and respiratory and multi-organ failure. Coronaviruses are also or electronic notification to the Department of Health within 24 responsible for previous epidemics including severe acute hours of diagnosis by health care providers, private or public health respiratory syndrome (SARS) and middle east respiratory laboratories. syndrome (MERS).

From: Naresh Budraj <naresh.budraj@newmedia.co.za> Date: Thursday 27 May 2021 at 4:08 PM 2.5.

Medical schemes are also required to notify and submit 3.2. These viruses were originally transmitted between animals and To: Claire Rush <Claire.Rush@newmedia.co.za> COVID-19 information theFinal" CMS, with Circular people. In the case of SARS, viruses were transmitted from civet Subject: Nareshrelated Budraj shared "PMBX Bookletto 2021 with consistent you.

29 of 2020. cats to humans while in MERS, the infection travelled to humans 2.6. The ICD-10 code U07.2 includes the following: from a type of camel.

Page 1 of 2 • Clinically-epidemiologically diagnosed Covid-19.

3.3. In the case of Covid-19, scientists have pointed to infected • Probable Covid-19 animal species, including pangolins and bats as the original source • Suspected Covid-19 of the virus. While it is suspected that the initial Covid-19 epidemic 2.7. At the time of publishing this guideline, the NICD guidelines for started through animal-to-human transmission, the current “case-finding, diagnosis, management and public health response” epidemic is being fuelled by human-to-human transmission and were in the process of being updated and hence not available on the virus has spread to more than 208 countries and territories, NICD website. including South Africa.

2.8. Given the antigen testing national guidelines published on 11 3.4. Most countries have experienced or are currently experiencing December 2020, and the updated WHO case definitions, the CMS a second wave of Covid-19 infections. Several new variants of has adjusted the current case definition to be aligned with both SARS-CoV-2 have been identified from September 2020. guidelines. Upon publishing of national guidelines by the NICD, the CMS will also ensure that the PMB definition guidelines are aligned The main variants are: with these guidelines.

• 20I/501Y.V1, VOC 202012/01, or B.1.1.7 first identified in the 2.9. The table 2 summarises the case definition for Covid-19.

United Kingdom.

2.10. A person having had face-to-face contact (≤1 metre) or • 20H/501Y.V2 or B.1.351 first identified in South Africa. having been in a closed space with a confirmed COVID19 case for • P.1 first identified in four travellers from Brazil. at least 15 minutes. This includes, amongst others: 3.5. Although these new variants are now circulating globally, there

4 PMB-X GUIDELINES 2021

Covid-19 Table 2: Case definition of SARS-CoV-2 infection

3.6. As of the 22 January, there were 98,135,997 confirmed cases globally with 2,101,562 deaths.

3.7. Data from the 22 January 2021 showed that South Africa had a total of 1 380 807 positive cases with 86% recovery rate which is 14% higher than the global recovery rate.

3.8. Additionally, the mortality rate in South Africa is currently at 2,9%, which is slightly higher than the global mortality of 2,1%.

4. ROUTE OF TRANSMISSION FROM COVID-19 PATIENTS 4.1. New evidence on the transmission has been evolving and there is evidence on the following modes of transmission.

• Symptomatic: Data from published epidemiology and virologic studies provides evidence that Covid-19 is primarily transmitted from symptomatic people to others who are in close contact through respiratory droplets, by direct contact with infected persons, or by contact with contaminated objects and surfaces.

• Pre- symptomatic: The incubation period for Covid-19, which is the time between exposure to the virus (becoming infected) and symptom onset, is on average 5-6 days, however, this period can take up to 14 days. During this period, also known as the “presymptomatic” period, some infected persons can be contagious.

Therefore, transmission from a pre-symptomatic case can occur before symptom onset.

• Asymptomatic: There are few reports of laboratory-confirmed cases who are truly asymptomatic. This does not exclude the possibility that it may occur. Asymptomatic cases have been reported as part of contact tracing efforts in some countries. The proportion of asymptomatic carriers is currently unknown.

4.2. South Africa has developed a Covid-19 exposure notification application called COVID Alert SA to help South Africans know when they have been in close contact with someone who has tested positive for Covid-19. Additional information on the app can be found here.

4.3. The World Health Organization (WHO) has acknowledged that there is “evidence emerging” of the airborne spread of the novel coronavirus, after a group of scientists urged for an update to its guidance on how the respiratory disease passes between people especially in closed, poorly ventilated spaces.

4.4. A PHIRST-C study is being conducted in South Africa to gain a better understanding of the transmission dynamics of SARSCoV-2, asymptomatic infection prevalence, and the extent of transmission from asymptomatic infection.

4.5. According to the WHO, the reproductive number (R) for the virus is approximately 2.2 (meaning that on average each person spreads the infection to two others).

4.6. In South Africa, the reproductive number was 1.33 at the start of the pandemic and rose to its highest in April 2020, to 1.5. The NICD reported an R of 1.1. on 26 August 2020, indicating a decline in the number of new cases and the slowing down of Covid-19 transmissions. The average R was 0.99 between 21 September and 27 October 2020. There is currently no data for the reproductive rate during the second wave, however given the rate of transmission prior to the current lockdown, it can be assumed that there has been an increase in the average R rate.

is currently ongoing research to establish their impact on disease severity, mortality and vaccine efficacy.

5. RISK FACTORS 5.1. Risk factors for acquiring the infection include: • Individuals with a recent travel history to high-risk countries • History of exposure to individuals infected with Covid-19.

5.2. Risk factors for severe disease once infected include: • Individuals 60 years and older: Among more than 44 000 confirmed cases of Covid-19 in China, the case fatality rate was highest among older persons: o ≥80 years: 14.8% o 70–79 years: 8.0% o 60–69 years: 3.6% PMB-X GUIDELINES 2021 5

Covid-19 o 50–59 years: 1.3% o 40–49 years: 0.4% o <40 years: 0.2%.

• Individuals who live in a nursing home or long-term care facility • People with severe obesity (body mass index [BMI] of 40 or higher) • Individuals at any age with underlying comorbidities, particularly if not well controlled. Patients with no reported underlying medical conditions have had an overall case fatality of 0.9%, but case fatality was higher for patients with comorbidities. o Cardiovascular disease o Diabetes mellitus o Hypertension o Chronic respiratory disease o I mmunosuppression: this could be due to cancer treatment, smoking, bone marrow or organ transplantation, immune deficiencies, poorly controlled HIV or AIDS, and prolonged use of corticosteroids and other immune weakening medications o People with chronic kidney disease undergoing dialysis. o People with liver disease.

5.3. Disease in children appears to be relatively rare and mild with approximately 2.4% of the total reported cases reported amongst individuals aged under 19 years. A very small proportion, that is 2.5% of those aged under 19 years have developed severe disease while only 0.2% became critical.

6. SIGNS AND SYMPTOMS 6.1. Eighty percent of symptomatic patients develop mild disease, an estimated 15% develop severe disease (with hypoxaemia, dyspnoea and tachypnoea) while 5% become critically ill (with respiratory failure, septic shock and/or multiorgan dysfunction).

6.2. The most common presenting symptoms have been: • Fever (~90%, but only present in 44% on admission).

• Dry cough (68%) • Anosmia and ageusia (30%) • Fatigue (38%), • Sputum production (34%) • Shortness of breath (19%), • Myalgia or arthralgia (15%), • Sore throat (14%), • Headache (13.6%) • Chills (12%) 6.3. Gastrointestinal symptoms such as nausea or vomiting (5.0%) and diarrhoea (3.8%) appear to be uncommon.

6.4. In addition to the above symptoms, it has been observed that children between the ages of 2 – 15 years are at risk of developing Paediatric Inflammatory Multisystem Syndrome (PIMS) associated with Covid-19, which may include some of the following symptoms: • abdominal pain • skin rash • red, cracked lips.

• red eyes • swelling of the hands or feet • reddish, swollen toes (‘COVID toes’) • swollen glands on one or both sides of the neck • vision problems • paleness 7. DIAGNOSTIC WORKUP 7.1. Consultations 7.1.1. Given the modes of transmission discussed earlier, surveillance for Covid-19 is essential to permit early recognition of suspected cases, early diagnosis, containment, and prevention of further spread.

7.1.2. Screening is questionnaire based and may be part of virtual or face to face consultation. The consultation for screening by a healthcare worker (nurses or doctors) for Covid-19 is PMB level of care. The healthcare worker will establish the clinical, epidemiological criteria, and any other criteria that may warrant subsequent laboratory investigation.

6 PMB-X GUIDELINES 2021

7.1.3. To further reduce the person to person risk of transmission and reduce the number of patients at doctors rooms, telehealth delivered through online platforms must be reimbursed as PMB level of care in line with the latest Health Professions Council of South Africa (HPCSA) communication as published on their website.

7.1.4. In accordance with the HPCSA recommendations, “Telehealth should preferably be practiced in circumstances where there is an already established practitioner-patient relationship.

Where such a relationship does not exist, practitioners may still consult using Telehealth provided such consultations are done in the best clinical interest of patients.”

7.1.5. In addition, HPCSA, emphasise that “Although practitioners may charge fees for consultations undertaken through Telehealth platforms, the Council [HPCSA] strongly cautions against practices that may amount to over-servicing, perverse incentives and supersession.”

7.1.6. In the out of hospital setting, no prior authorisation is required for telehealth consultations with a general practitioner, however, specialist consultations may require pre-authorisation.

7.1.7. Schemes may use designated service providers (DSPs), and managed care protocols may apply.

7.2 LABORATORY WORKUP 7.2.1 South African Health Products Regulatory Authority (SAHPRA) has approved three different types of in-vitro tests for Covid-19 namely molecular tests, and serological tests, and antigen tests.

7.2.2 Molecular tests detect the presence of the SARS-CoV-2 virus’ genetic material (nucleic acid) and are performed on material obtained by means of nasopharyngeal and/or oropharyngeal swabs. Such tests are good at detecting the virus early in the infection and can detect the virus in a person before they become symptomatic.

7.2.3 Serological tests are tests that detect antibodies to the SARS-CoV-2 virus and are conducted on samples likely to have antibodies, such as finger-pick blood samples. Serological tests are conducted at the point-of-care and detect the presence of immunoglobulin M (IgM) and/or immunoglobulin G (IgG) antibodies to SARS-CoV-2.

7.2.4 Antigen tests directly detect SARSCoV-2 proteins produced by replicating virus in respiratory secretions and have been developed as both laboratory-based tests and point of care tests which are referred to as rapid diagnostic tests (RDTs). RDTs provide diagnostic information faster than molecular tests and hence clinical decision making can be quicker when compared to molecular testing.

7.2.5 On 11 December 2020, the NDoH published a guideline on the role of the rapid antigen testing as an alternative for the diagnosis of SARS-COV-2. The accuracy and interpretation of the rapid antigen tests is dependent on symptoms, prevalence and exposure to the SARS-COV-2 virus. Understanding the application of these variables is important in avoiding inaccurate conclusions due to false positive or false negative results.

7.2.6 SAHPRA has provided a list of serological, molecular and antigen tests that are registered in South Africa and this is available on their website. Role and funding of antigen testing for SARS-COV-2 7.2.7. The guidance on the use of antigen testing has been specified in the NDoH guideline and antigen tests which meet the minimum performance requirements of more than 97% specificity and more than 80% sensitivity may be used for diagnosing infection with SARS-CoV-2, where no RT-PCR is available or have prolonged turnaround times.

7.2.8. Based on the algorithm provided by the NDoH, the CMS recommends antigen testing to be funded as PMB level of care for those individuals where the pre-test probability of Covid-19 disease (the likelihood that the patient has Covid-19 before their results are known, based on epidemiologic and clinical factors) is relatively high, and positive test results have a high positive predictive value.

Covid-19 7.2.9. The figure below is adapted from the NDoH guidelines, and the CMS recommends antigen testing only within five days of symptom onset for cases where there is a high probability of a high positive predictive value (PPV) and a low negative predictive value (NPV). It is only under these conditions that high accuracy of the antigen test can be predicted.

Figure 1: Antigen testing recommendation: Adapted from the NDoH guidelines.

FUNDING OF ANTIGEN TEST WITHIN THE HIGH PRETEST PROBABILITY POPULATION Pre-test probability Low 1. Asymptomatic OR 2. No known exposure OR 3. Low community prevalence Negative Ag - RDT

High NPV Manage as a true negative

Positive Ag - RDT

Low PPV

Request confirmatory PCR as soon as possible, isolate while awaiting results

High 1. Symptomatic OR 2. Known exposure OR 3. High community prevalence Negative Ag - RDT

Low NPV

Request confirmatory PCR as soon as possible, isolate while awaiting results

Positive Ag - RDT

High PPV

Manage as true positive result according to prevailing guidelines

7.2.10. The probability of a true positive test is high in a population with high community prevalence or symptomatic individuals or individuals with known exposure. The sensitivity of the test is higher within the first 5 days of symptom onset; hence the timing of the test is also important.

7.2.11. If an antigen test is positive in the high pre-test probability population, the antigen result is considered a true positive result and hence there is no role of a confirmatory RT-PCR test. The antigen test is PMB level of care in these individuals.

7.2.12. If an antigen test is negative in the high pre-test probability population, a confirmatory RT-PCR test is required and if the PCR test is positive, both the antigen and the PCR test constitute PMB level of care.

7.2.13. If an antigen test is negative in the high pre-test probability population, a confirmatory RT-PCR test is required and if the PCR test is negative, both the antigen and the PCR test constitute PMB level of care.

Funding of antigen test within the low pre-test probability population.

7.2.14. If the patient is asymptomatic or no known exposure or there is low community prevalence, there is a low probability of getting a true positive result and hence the use of an antigen test in this population is not recommended.

7.2.15. A negative antigen test is not PMB level of care.

7.2.16. If the patient in 7.2.14 then proceeds to have an RT-PCR test and the RT-PCR is positive, then both the RT-PCR and the positive antigen test will be PMB level of care.

7.2.17. If the patient in 7.2.14 then proceeds to have an RT-PCR test and the RT-PCR is negative, then both the RT- PCR and the positive antigen test will not constitute PMB level of care.

7.2.18. The CMS will ensure that the antigen testing criteria, including any documented thresholds for prevalence, is always aligned with the NDoH recommendations.

FUNDING OF RT-PCR TEST 7.2.19. RT-PCR testing for Covid-19 is PMB level of care upon referral from a health care worker (doctor or nurse)

who has screened a patient. Patients to be tested are individuals who meet the criteria for a suspected case definition and the RTPCR test must be funded from the risk benefit irrespective of the RT-PCR result.

7.2.20. RT-PCR test after a positive antigen result for patients who have a high pre-test probability is not PMB level of care. This is because a positive antigen result in that population is already considered a true positive and there is no need for a confirmatory RT-PCR test.

7.2.21. Routine RT-PCR testing of asymptomatic, unscreened and unreferred patients which turns out positive is PMB level of care.

7.2.22. Routine RT-PCR testing of asymptomatic, unscreened and unreferred patients which turns out negative is funded at the discretion of the scheme, based on scheme rules.

7.2.23. A single positive RT-PCR test is sufficient proof of Covid-19 infection, and there is no role of repeat confirmatory test. A repeat confirmatory RT-PCR test is not PMB level of care.

7.2.24. An RT-PCR test can however be falsely negative due to factors such as sampling technique or timing of the test. If alternative diagnosis has been explored and there is still clinical suspicion of Covid-19, a motivation should be submitted to the scheme for a repeat test.

7.2.25. According to the WHO, as of 24 April 2020, no study has evaluated whether the presence of antibodies to SARS-CoV-2 confers immunity to subsequent infection by this virus in humans.

There is currently no evidence that people who have recovered from Covid-19, and have antibodies are protected from reinfection.

As such the number of RT-PCR tests per member should not be capped for a member who presents with Covid-19 symptoms and meets the case definition.

7.2.26.The table below summarises the role and PMB recommendations of the different molecular, antibody, and antigen tests for diagnosis of SARS-CoV-2.

7.2.27. In addition to a RT- PCR and/ or antigen testing, and where clinically indicated, the following laboratory investigations are also PMB level of care for confirmed cases depending on the severity of symptoms: • Full blood count including differential count.

• Nasopharyngeal swabs or aspirates and oropharyngeal swabs for detection of viral and atypical pathogens • Sputum for MCS and Mycobacterium tuberculosis detection (GeneXpert MTB/RIF Ultra) • Other adjunct investigations that may be clinically appropriate or indicated may require motivation e.g. liver function tests, renal function tests, CRP, glucose, D-dimer levels, prothrombin, blood gas, and urine for lipoarabinomannan (LAM) test if HIV positive.

7.3 IMAGING RADIOLOGY 7.3.1 Imaging modalities are not PMB level of care for screening or diagnosis of COVID – 19, as the definitive test for SARS-CoV-2 is the RT-PCR or the antigen test.

7.3.2 Chest X-ray is PMB level of care for patients with confirmed Covid-19.

7.3.3 CT scan is PMB level of care in patients presenting with features indicating worsening respiratory function. CT scan is also recommended in Covid-19 patients with functional impairment and/or hypoxemia after recovery from Covid-19.

8. MANAGEMENT OF SUSPECTED AND CONFIRMED CASES WITH MILD TO MODERATE DISEASE. 8.1. The clinical management of a suspected or a confirmed Covid-19 case depends on the severity and the presenting symptoms and not the risk of deterioration. High risks patients who present with mild symptoms should therefore be managed based on their symptoms.

8.2. Suspected and confirmed cases who are medically well, or who have mild disease may be managed at home, based on the treating provider’s guidance.

8.3. Although antibiotics do not treat viral infections, empiric treatment for secondary bacterial and fungal infections might be PMB-X GUIDELINES 2021 7

Covid-19 Table 3: Role and PMB recommendations of the different molecular, antibody, and antigen tests for diagnosis of SARS-CoV-2.

required. Where evidence suggests bacterial or fungal infections this should be paid for as PMB level of care 8.4. Pre-existing PMB chronic conditions such as diabetes mellitus, HIV, asthma etc, should be managed as per the corresponding Diagnostic Treatment Pair (DTP) and/ or Chronic Disease List (CDL), and are deemed PMB level of care.

8.5. Treatment and care for the management of mild to moderate disease is PMB level of care. 8.6. Given that the scheme is notified of all positive cases of Covid-19, irrespective of the severity, medication prescribed by the doctor for managing Covid-19 symptoms must be funded as PMB level of care. The provider should include the correct ICD 10 code (U07.1) on the prescription.

To reduce the administrative burden, and given that this is not a chronic condition, no prior authorisation is required. Generic substitution is permissible, unless the provider instructs otherwise.

9. MANAGEMENT OF SEVERE CASES 9.1. Patients with severe disease are closely monitored, and any signs of clinical deterioration (e.g. respiratory failure and sepsis) are managed appropriately.

9.2. Based on clinical diagnosis, treatment of co-infections with empiric antibiotics is recommended and this may include treatment of pneumocystis pneumonia (PCP), influenza, and atypical bacterial pathogens.

9.3. Supportive treatment includes oxygen therapy in patients who are short of breath. The target oxygen saturation (SpO2) rates are ≥90% in non-pregnant adults and SpO2 ≥92-95 % in pregnant patients.

9.4. Funding of oxygen therapy for Covid-19 is based on the oxygen saturation results. Given the pandemic and limited health resources, blood gases are not a pre-requisite for oxygen funding.

Hence the only criterion is for a patient to meet the oxygen

8 PMB-X GUIDELINES 2021

saturation required.

9.5. Ambulatory oxygen and pulse oximeter are PMB level of care subject to provider motivation and oxygen saturation results.

9.6. Patients with severe disease are generally hospitalised and the cost of their management must be funded according to the PMB Regulations.

9.7. Patients might be admitted to the intensive care unit (ICU) and the use of mechanical ventilators where indicated is PMB level of care.

9.8. If clinical setting is appropriate and there is provider preference, non- invasive ventilation is PMB level of care in line with the NICD guidelines. In the absence of an indication for endotracheal intubation, a trial of high-flow nasal oxygen (HFNO), continuous positive airway pressure (CPAP), synchronised inspiratory positive airway pressure (SiPEP) or other non-invasive ventilation (NIV) technique may be considered for adults with Covid-19, and acute hypoxaemic respiratory failure failing standard oxygen therapy.

10. PHARMACOLOGICAL MANAGEMENT 10.1. All pharmacological management recommendations are based on the guidance issued in the NDoH/ NICD version 5 guidance on the clinical management of suspected or confirmed Covid-19 cases and the NEMLC subcommittee medicine reviews which are available here.

10.2. The use of a short duration of low-dose systemic corticosteroids in hospitalised severe Covid-19 patients receiving respiratory support (as either invasive mechanical ventilation or non‐invasive oxygen supplementation) and for Covid-19 patients with septic shock is PMB level of care.

10.3. Hospitalised patients not on respiratory support should not routinely be administered systemic corticosteroids, unless indicated for another reason such as an acute exacerbation of asthma or chronic obstructive pulmonary disease.

10.4. Prophylactic doses of either unfractionated or low molecular weight heparin is PMB level of care for all hospitalised patients. In line with the NEMLC recommendations, there is insufficient evidence for the use of therapeutic doses of either unfractionated or low molecular weight heparin as thromboprophylaxis for patients with severe Covid-19. Therapeutic doses are PMB level of care for patients with a hypercoagulable state as clinically indicated.

10.5. Low molecular weight heparin is PMB level of care at discharge subject to motivation by treating provider.

10.6. Routine use of oseltamivir for all patients with influenza is not PMB level of care. Oseltamivir is PMB level of care for severely ill patients when administered within 72 hours of symptom onset when prevalence of influenza is moderate to high.

10.7. Off label medication and investigational medicine is not PMB level of care. In line with the NEMLC recommendations, the following are not currently PMB level of care for the treatment of Covid-19 and the funding is based on scheme rules: - Convalescent plasma - Interferon beta - Intravenous immunoglobulin Tocilizumab - Azithromycin - Convalescent plasma - Favipiravir - Ivermectin - Remdesivir - Hydroxychloroquine/chloroquine Lopinavir/ritonavir - Colchicine - Bromhexine 11. PALLIATIVE CARE FOR COVID-19 11.1. Palliative care is a multifaceted, integrated approach to improving the quality of life of adults and paediatric patients, and their families facing the problems associated with lifethreatening illness such as Covid-19. CMS is cognisant of the WHO definition of palliative care. However, palliative care for confirmed Covid-19 cases is PMB level of care.

11.2. Palliative care includes but not limited to: - complex symptom management - advance care planning or goals of care conversations - complex discussions with patient, and more often with family: o diagnoses and current/future care plans, o when a patient’s condition deteriorates, or withdrawal of treatment decisions needs to be made.

Covid-19 o family’s own (mental) health.

- i ntegration of psychosocial support especially for families on the outside: o i solation causing mayor distress and mental health issues with patients and families. op rimary physicians do not have capacity to always keep loved ones updated or discuss when difficult decisions need to be made quickly.

- bereavement support to families 11.3. Palliative care includes a multi-disciplinary team approach.

The team may consist of doctors (GPs and specialists), psychologists, social workers, palliative care home nurses. Palliative care can be provided in different settings including: - in the home (even if severe and patient so wishes e.g. frail elderly or people with dementia), - long term care facilities, - hospices, - and in hospital including general ward, ICU and high care.

11.4. CMS recommends the funding of palliative care. Where a multi-disciplinary team is involved in the treatment and care of Covid-19 patients, the primary provider must submit an initial treatment plan to the scheme for pre-authorisation and weekly updates to allow the scheme to make informed continued funding decisions.

12. Management of Covid-19 in special populations – children, newborns, pregnant and breastfeeding women and people living with HIV.

12.1. MANAGEMENT OF CHILDREN 12.1.1. Although the understanding of Covid-19 related symptoms continues to evolve, the current guidance from NICD states that the clinical presentation and case definition of adults and children are the same.

12.1.2. All suspected children with an acute respiratory infection should be tested for Covid-19.

12.2. MANAGEMENT OF NEWBORNS 12.2.1. The case definition is the same as adults and children, although atypical presentation is expected in neonates.

12.2.2. Covid-19 should be included in differential diagnosis of any neonate presenting with acute respiratory symptoms and such neonates should be tested for Covid-19.

12.2.3. Babies in good health, who are born from a Covid-19 infected mother do not need a Covid-19 test, and such testing is therefore not PMB level of care.

12.2.4. Unwell or symptomatic babies should have a Covid-19 test on day 3 of life if the case definition is met, or at another time if clinically indicated.

12.2.5. According to the NICD guidelines, tests done before 72 hours may give a false negative result and should be repeated on day 5 of life if the first test is negative.

12.3. MANAGEMENT OF PREGNANT AND BREASTFEEDING 12.3.1. According to the NICD guidelines, there is currently

PMB-X GUIDELINES 2021 9

Covid-19

no indication that pregnant women are at higher risk of either contracting Covid-19 or of worse maternal outcomes with Covid-19.

12.3.2. Pregnant women with Covid-19 can have a vaginal delivery.

Covid-19 is not an indication of caesarean section.

13. FUNDING OF COVID-19 VACCINE 13.1. On the 24 December 2020, the Minister of Health approved the inclusion of Covid-19 vaccine as a PMB level of care.

13.2. Medical Schemes must ensure that the identification and prioritisation of the scheme members and beneficiaries to be vaccinated must be aligned with the NDoH guidelines.

13.3. All SAHPRA approved vaccinations for Covid-19 must be funded for beneficiaries identified and prioritised as guided by the NDoH. 13.4. All Covid-19 vaccinations which are administered outside South Africa, will be funded at the discretion of the scheme, based on scheme rules.

13.5. The management of all side effects and complications which may result from administration of the COVID19 vaccine must be reimbursed by the medical scheme when claimed with the relevant ICD-10 coding.

13.6. All appropriate and related vaccine inoculation costs must be reimbursed.

13.7. Given the national reporting requirements, schemes and providers must ensure that relevant information related to the administration of the Covid-19 vaccine, including adverse events, is collected and shared with the relevant authorities.

14. Funding of PPE The department of Labour has issued guidance on workplace preparedness for Covid-19 and all employers (public or private sectors) are obligated to provide their workers with personal protective equipment (PPE) needed to keep them safe while performing their duties. The types of PPE required during a Covid-19 outbreak will be based on the risk of being infected with SARS-CoV-2 while working and tasks that may lead to exposure.

PPE for non-healthcare workers is currently not PMB level of care irrespective of the level of risk and these costs cannot be transferred to members or schemes. PPE for health workers who are treating and managing suspected and confirmed Covid-19 patients is PMB level of care. Claims should be backdated to 7 May 2020, when the PMB regulations for Covid-19 were promulgated.

15. Off label medication There is consensus in literature as reported by the WHO and SAHPRA, that currently there are no pharmaceutical products that have shown to be safe and effective for the treatment of Covid-19. CMS recommends discretionary funding of offlabel use of medications that show clinical benefit.

The NDoH acknowledges that investigational medicines should be used in the realm of a clinical trial, but given the nature of the pandemic, a pragmatic approach might be required, and such medicines should be used under the Monitored Emergency Use of Unregistered Interventions (MEURI) framework. Any medicines, including vaccines that become available for Covid-19 and listed on the national essential medicines list are PMB level of care.

16. Follow up care. Patients may continue to be PCR positive after clinical resolution, although for how long such virus is viable (and thus infectious) remains to be determined. A repeat RT-PCR test to ensure that the patient is no longer positive will be funded at the discretion of the scheme based on the scheme rules. A patient can de-isolate after the recommended period without further testing.

Health minister Dr Zweli Mkhize, announced on 17 July 2020 that the isolation period had been reduced to 10 days from 14 days on condition that the patient does not have a fever and the symptoms are improving.

10 PMB-X GUIDELINES 2021

On referral by the treating provider, chest physiotherapy and other rehabilitative modalities such as psychotherapy are also PMB level of care for confirmed Covid-19 cases.

Asymptomatic patient

De-isolate 10 days after testing

Mild disease

De-isolate 10 days after symptom onset

Severe disease

De-isolate 10 days after clinical stability achieved

Covid-19

Table 4: Applicable codes in relation to COVID-19 funding

17. What is not PMB level of care for Covid-19 The following is not PMB level of care: • Follow-up treatment and care for any person who tests negative for Covid-19 (RT-PCR test).

• A repeat RT-PCR test to ensure that the patient is no longer positive will be funded at the discretion of the scheme based on the scheme rules.

• Routine RT-PCR testing of asymptomatic, unscreened and unreferred patients which turns out negative is based on scheme rules. This includes people returning to work, school or those intending to travel.

• Routine preadmission (including elective admissions) RT-PCR testing for asymptomatic patients which turns out negative is based on scheme rules.

• Routine antigen testing of patients who are unscreened, asymptomatic, no known exposure or if there is low community prevalence is not PMB level of care irrespective of the result. This is based on the high possibility of a false positive result in this population as shown on figure 1 and stated earlier (section 7.2.14).

• Serum antibody testing is not currently PMB level of care. Only exception is the diagnosis of Covid-19 in patients who are admitted with suspected SARSCoV2 infection and test negative for RT-PCR including children with suspected multi system inflammatory syndrome.

• Off label medication and investigational medicine is not PMB level of care PPE for non-healthcare workers is not PMB level of care.

PMB-X GUIDELINES 2021 11

PMBs: CHRONIC CONDITIONS

Addison’s disease

Addison’s disease Addison’s disease is a rare endocrine disorder, occurring in all age groups and affecting men and women equally. The disease is characterised by weight loss, muscle weakness, fatigue, low blood pressure, and sometimes darkening of the skin in both exposed and non-exposed parts of the body. Addison’s disease occurs when the adrenal glands do not produce enough cortisol and in some cases, aldosterone. For this reason, it is sometimes called chronic adrenal insufficiency, or hypocortisolism.

Diagnosis

Oral corticosteroid replacement in divided doses Adjust to individual needs

Disease identification card or disc recommended

Instressed ill patients dose must be increased

Defective aldosterone secretion and/or still insufficient mineral corticoid effect

Add fludrocortisone 50-100pg daily Adjust to patients needs

Monitor BP, weight, as well as electrolytes during therapy

Glossary: • BP – Blood pressure Applicable ICD 10 Coding • E27.1 Primary adrenocortical insuffiency

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Asthma

Asthma

Asthma affects more than 25 million people worldwide and continues to grow in prevalence.

According to Center for Disease Control and Prevention report, the total annual cost of asthma in the US between 2008 and 2013, including medical care, absenteeism, and mortality, was $81.9 billion.

The condition is often poorly controlled.

Diagnosis

Made on symptoms and signs Object measurement: FEV1 improvement possible > 15% [& 200ml increase after short actingh β2 agonist (400μg MDI and spacer)]

Aims of Management: Control symptoms and prevent exacerbations Achieve best possible peak flow Minimise adverse effects

Stepwise Approach: Start treatment at step most apprpiate to intial severity Acheive early control Maintain stepping up or stepping down therapy

CLASSIFICATION OF SEVERITY Management of Chronic Asthma in Adults Classify Severity at Presentation

Intermittent

Mild Catgegory

1

11

Daytime symptoms

≤ 2/week

2-4/week

PEF (predicted)

≥ 80%

≥ 80%

Night-time symptoms

≤ 1/month

2-4/month

Persistent Moderate

Severe

> 4/week

Continous

111

> 4/week 60-80%

START TREATMENT AT MOST APPROPIATE STEP Step 1: Mild Intermittent Asthma Inhaled short acting β2 agonist as required

14 PMB-X GUIDELINES 2021

1V

Frequent < 60%

Step 2: Mild Persistent Asthma Reliever: β2 agonist as required: Preventer: Add inhaled corticosteroid 400-800μg/day (Equivalent to beclomethasone MDI & spacer)

Step Up

Step Down

Asthma

Step 3: Moderate Persistent Asthma

1. Short-acting β2 agonist as required 2. I ncrease dose of inhaled corticosteroid to 1200μg/day (beclomethasone or equivalent) if not controlled 3. Add inhaled long-acting β2 agonist (LAβA) to 1200μg/day inhaled corticosteroid (beclomethasone or equivalent) 4. Reassess control: • If adequate: continue LAβA • If no response: stop LAβA; consider SR theophylline

Step 4: Severe Persistent Asthma

Step Up

Step Down

1. Short β2 agonist as required 2. Increase inhaled steriod to 2000 g/day (beclomethasone or equivalent); plus LAβA or SR theophylline

Step5: Very Severe Persistent Asthma

1. Therapy as in Step 4 2. Review for oral steriods

Glossary • FEVI – Forced expiratory volume in 1 second • β2 – Beta-2 receptor • MDI – Metered dosage inhaler • PEF – Peak expiratory flow • LAβA – Long acting beta-2 receptor agonist • SR – Slow release Applicable ICD 10 Coding: • J45 Asthma • J45.0 Predominantly allergic asthma • J45.1 Nonallergic asthma • J45.8 Mixed asthma • J45.9 Asthma, unspecified • J45 Status asthmaticus

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Bipolar

Bipolar Bipolar disorder can best be conceptualised as a multiplex dysregulation syndrome involving a broad spectrum of basic mental qualities besides mood. The presence of depressive symptomatology during acute mania has been recognised for centuries.

DSM- IV diagnosis Acute phase

Manic episode • Mania or hypomania with euphoric mood • Rapid cycling • Mixed or dysphoric mood • Mania with psychosis • Lithium and/or Valproate and/or Typical or atypical antipsychotic as required • If IMI Olanzapine is given, no Benzodiazepine must be used within 2 hours a • Benzodiazepine for use only in acute phase

Remission

Depressive episode • Mild to moderate • Severe • Depression with psychosis Cyclothymia • Lithium and/or Valproate and/or Lam otrigine and/or antidepressants and/or mood stabilisers as required • Do not give antidepressants without mood stabilisers

Response

Poor response within 4 to 6 weeks

16 PMB-X GUIDELINES 2021 *Treatment *Treatment algorithm algorithm not not to to be be associated associated with with advertisement advertisement

Bipolar

CUSTOMER CARE LINE 0860 PHARMA (742 762) / +27 21 707 7000 www.pharmadynamics.co.za DYNA-LAMOTRIGINE 25, 50, 100, 200 mg. Each tablet contains 25, 50, 100, 200 mg lamotrigine respectively. S3 A40/2.5/0173, 0169, 0166, 0167. NAM NS2 08/2.5/0177, 0178, 0179, 0180. For full prescribing information, refer to the professional information approved by SAHPRA, January 2006. DLAC612/12/2020.

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Bipolar

Continuation phase Remission

Check adherence and/ or optimise medication

Remission

Utilise all three mood stabilisers in combination Incomplete response

Consider ECT

Remission Maintenance phase To maintain the patient optimally eliminate treatment

Add atypical antipsychotic and/or another mood stabiliser Incomplete response

Review management and diagnosis in accordance with public sector practice

Continue maintenance

Relapse

Glossary: • DSM-iV: Diagnostic and Statistical manual of Menta Disorders- Fourth Edition • ECT: Electroconvulsive therapy Applicable ICD10 Coding • F31 Bipolar Affective Disorder • F31.0 Bipolar affective disorder, current episode hypomanic • F31.1 Bipolar affective disorder, current episode manic without psychotic symptoms • F31.2 Bipolar affective disorder, current episode manic with psychotic symptoms • F31.3 Bipolar affective disorder, current episode mild or moderate depression • F31.4 Bipolar affective disorder, current episode severe depression without psychotic symtoms • F31.5 Bipolar affective disorder, current episodes severe depression with psychotic symptoms • F31.6 Bipolar affective disorder, current episode mixed • F31.7 Bipolar affective disorder, currently in remission • F31.8 Other bipolar affective disorder • F31.9 Bipolar affective disorder, unspecified

18 PMB-X GUIDELINES 2021

Bronchiectasis

Bronchiectasis

Some of the signs and symptoms of a bronchiectasis exacerbation overlap with those of acute bronchitis.

Bronchiectasis is divided into two categories: cystic fibrosis (CF)-bronchiectasis and non-CF bronchiectasis.

Diagnosis Treat underlying cause if possible e.g. COPD Life style modifications No smoking and avoid other irritants Postural drainage Treat airways obstruction and complications e.g. haemoptysis and cor pulmonale Treat infection Empiric therapy:

Stable with mild bronchiectasis: E.g.

Amoxycillin 500mg 8 hourly for 14 days Or Doxycycline 100mg twice daily for 14 days May need prolonged therapy in some cases up to 3 weeks Further antibiotic therapy should be based on sputum microscopic culture and sensitivity investigations Glossary: • COPD – Chronic obstructive pulmonary disease Applicable ICD 10 Coding: • J47 Bronchiectasis • Q33.4 Congenital bronchiectasis

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Cardiac Failure

Cardiac Failure

The prevalence and incidence of cardiac failure are increasing. This is likely due to improved survival rates of people with coronary heart disease but also increasing elderly people in the population, with disproportionally more elderly women.

CARDIAC FAILURE

Diagnosis

All patients should have once only pneumococcal immunisation and annual influenza immunisation

o Patients should avoid salt rich food; o Exercise as per individualised programme; o Consume only 1-2 units of alcohol per day (except if alcohol induced); o Stop smoking and lose weight

Consider ACE inhibitor in all patients

Add β-blocker in patients with ongoing symptoms who have NYHA class II – III symptoms

Continued symptoms?

Add diuretic if patient is fluid overloaded Use thiazide if normal renal function or Loop diuretic if impaired renal function and volume overloaded Monitor serum K+, consider replacement therapy if necessary

Consider loop diuretic if impaired renal function and volume overloaded and NYHA class III/IV

Add spironolactone low dose if NYHA class III/IV Monitor serum K+

Consider digoxin in patients with NYHA class III/IV with persisting symptoms, very poor LV function or persisting cardiomegaly

Start with low dose digoxin in elderly 0.125mg/day

If systolic failure refractory to treatment, review NOTE: If patient truly intolerant to ACE inhibitor, consider hydralazine & isosorbide dinitrate combination therapy

Copyright: Council for Medical Schemes

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BISOPROLOL: • HIGHLY SELECTIVE ß-BLOCKER • 24 HOUR BP REDUCTION • DOSING FLEXIBILITY

CUSTOMER CARE LINE 0860 PHARMA (742 762) / +27 21 707 7000 www.pharmadynamics.co.za BILOCOR 5, 10. Each tablet contains 5, 10 mg bisoprolol fumarate respectively. S3 A38/5.2/0053, 0051. NAM NS2 06/5.2/0061, 0062. For full prescribing information, refer to the professional information approved by SAHPRA, 23 July 2010. BILOCOR CO 2,5/6,25, 5/6,25, 10/6,25. Each tablet contains 2,5, 5, 10 mg bisoprolol fumarate respectively and 6,25 mg hydrochlorothiazide. S3 A44/7.1.3/1010, 1011, 1012. NAM NS2 13/7.1.3/0260, 0261, 0262. For full prescribing information, refer to the professional information approved by SAHPRA, 6 May 2019. BRI731/05/2021.

Cardiac Failure

Glossary: • ACE inhibitor – Angiotensin converting enzyme inhibitor • Serum K+ – Serum potassium • β-blocker – Beta-receptor blocker • NYHA – New York Heart Association • LV – Left ventricular Applicable ICD 10 Coding: • I50 Heart failure o I50.0 Congestive heart failure o I50.1 Left ventricular failure o I50.9 Heart failure, unspecified • • •

I11.0 Hypertensive heart disease with (congestive) heart failure I13.0 Hypertensive heart and renal disease with (congestive) heart failure I13.2 Hypertensive heart and renal disease with both (congestive) heart failure and renal failure

Note: 1. Medical management reasonably necessary for the delivery of treatment described in this algorithm is included within this benefit, subject to the application of managed health care interventions by the relevant medical scheme.

22 PMB-X GUIDELINES 2021

2. To the extent that a medical scheme applies managed health care

Cardiomyopathy

Cardiomyopathy Cardiomyopathy refers to diseases of the heart muscle. In most cases, cardiomyopathy causes the heart muscle to become enlarged, thick or rigid. In rare instances, diseased heart muscle tissue is replaced with scar tissue.

Diagnosis

All patients should have once only pneumococcal immunisation and annual influenza immunisation

o Patients should avoid salt rich food; o Exercise as per individualised programme; o Consume only 1-2 units of alcohol per day (except if alcohol induced); o Stop smoking and lose weight o Adequate contraception is essential in patients with previous peripartum cardiomyopathy Add warfarin if atrial fibrillation or history of an embolic event

Consider ACE inhibitor in all patients

Add β-blocker in patients with ongoing symptoms who have NYHA class || – ||| symptoms and are euvolaemic Continued symptoms?

Add spironolactone low dose if NYHA class |||/|V Monitor serum K+ Consider digoxin in patients with NYHA class |||/|V with persisting symptoms, atrial fibrillation, very poor LV function or persisting cardiomegaly

Add diuretic if patient is fluid overloaded Use thiazide if normal renal function or Loop diuretic if impaired renal function and volume overloaded

Consider loop diuretic if impaired renal function and volume overloaded and NYHA class |||/|V Monitor serum K+, consider replacement if necessary

Start with low dose digoxin in elderly 0,125mg/day

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Cardiomyopathy

If systolic failure refractory to treatment, review Glossary: • ACE inhibitor – Angiotensin converting enzyme inhibitor • Serum K+ – Serum potassium • β-blocker – Beta-receptor blocker • NYHA – New York Heart Association • LV – Left ventricular Applicable ICD 10 Coding: o I42 Cardiomyopathy o I42.0 Dilated cardiomyopathy o I42.1 Obstructive hypertrophic cardiomyopathy o I42.2 Other hypertrophic cardiomyopathy o I42.3 Endomyocardial (eosinophilic) disease o I42.4 Endocardial fibroelastosis o I42.5 Other restrictive cardiomyopathy o I42.6 Alcoholic cardiomyopathy o I42.7 Cardiomyopathy due to drugs and other external agents o I42.8 Other cardiomyopathies o I42.9 Cardiomyopathy, unspecified o I25.5 Ischaemic cardiomyopathy

24 PMB-X GUIDELINES 2021

COPD

COPD

Chronic obstructive pulmonary disease (COPD) is a severe lung disease that affects millions of people, many of whom don’t know that they have it. Symptoms include constant coughing, wheezing, or chest tightness. COPD is an umbrella term used to describe progressive lung diseases including emphysema, chronic bronchitis, and refractory (non-reversible) asthma.

CHRONIC OBSTRUCTIVE PULMONARY DISEASE Diagnosis All patients should stop smoking, avoid irritants and have an annual influenza vaccination Early effective treatment of exacerbations

Stage I FEV1 at least 50% of predicted Mild effort-related dyspnoea

Stage II FEV1 35-49% of predicted Continuous dyspnoea

Bronchodilators: relieve symptoms, do not alter decline in FEV1 β2 agonist inhaler: 2 puffs 6 hourly as needed or Ipratropium bromide inhaler: 2 puffs 6 hourly as needed or Combination of above: 6 hourly as needed and Oral theophylline 6-8mg/kg/day in divided doses adjusted to plasma trough levels

No improvement?

Consider oral corticosteroid trial: prednisone 40mg/day for 14 days

Bronchodilators: relieve symptoms, do not alter decline in FEV1 β2 agonist inhaler: 2 puffs 6 hourly as needed or Ipratropium bromide inhaler: 2 puffs 6 hourly as needed or Combination of above: 6 hourly as needed and Oral theophylline 6-8mg/kg/day in divided doses adjusted to plasma trough levels & Oral corticosteroid trial: prednisone 40mg/day for 14 days

Improvement of FEV1 < 10 % and significant symptomatic improvement

Objective improvement in FEV1 of >12% and >200ml to more than 80% predicted

Consider the risk-benefit of low dose prednisone 10mg alternate days or 5mg daily and optimise bronchodilator therapy

Treat as for Asthma

Stage III FEV1 < 35% of predicted Respiratory failure Cor Pulmonale

No objective response: Stop corticosteroids Optimise bronchodilator therapy and other supportive therapy

Severe advanced disease

Consider long term domiciliary oxygen Treat complications Prevent weight loss Copyright: Council for Medical Schemes

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COPD

Glossary: • FEV1 – Forced expiratory volume in 1 second • β2 – Beta-2 receptor Applicable ICD 10 Coding: • J43 Emphysema o J43.0 MacLeod's syndrome o J43.1 Panlobular emphysema o J43.2 Centrilobular emphysema o J43.8 Other emphysema o J43.9 Emphysema, unspecified •

J44 Other chronic obstructive pulmonary disease o J44.0 Chronic obstructive pulmonary disease with acute lower respiratory infection o J44.1 Chronic obstructive pulmonary disease with acute exacerbation, unspecified o J44.8 Other specified chronic obstructive pulmonary disease o J44.9 Chronic obstructive pulmonary disease, unspecified

Note: 26 PMB-X GUIDELINES 1. Medical2021 management reasonably necessary for the delivery of treatment described in this algorithm is included within this benefit, subject to the

Renal Disease

Chronic Renal Disease Increasing evidence, acquired over decades, indicates that the adverse outcomes of chronic kidney disease, such as kidney failure, cardiovascular disease, and premature death, can be prevented or delayed. Earlier stages of chronic kidney disease can be detected through laboratory testing. Treatment of earlier stages of chronic kidney disease is effective in slowing the progression toward kidney failure.

Diagnosis

Mild Chronic Renal failure Cr 100-200 μmol/l

CHRONIC RENAL DISEASE

Moderate Chronic Renal failure Diagnosis Cr 200-400 μmol/l

Severe Chronic Renal failure Cr >400 μmol/l

Renal Failure (Crfailure 100-200 μmol/l) Mild Chronic Renal failureMild Chronic Moderate Chronic Renal Severe Chronic Renal failure Cr 100-200 µmol/l Cr 200-400 µmol/l Cr >400 µmol/l Treat hypertension vigorously i.e. BP < 130/85 mmHg Mild Chronic Renal Failure (Cr 100-200µmol/l)

Treat hypertension vigorously i.e. BP < 130/85 mmHg

Avoid diuretics unless volume overloaded Usually 3 agents required especially when Cr ≥150 μmol/l Avoid diuretics unless volume overloaded Target BP < 130/85mmHg Usually 3 agents required especially when Cr ≥150 µmol/l Target BP < 130/85mmHg

Use ACE inhibitors: retard decline and are anti-proteinuric; more effective if Na+ Use ACE inhibitors: retard decline depleted and are anti-proteinuric; more effective if Na+ or Calcium antagonist: have proven reno-protective effects, but not anti-proteinuric depleted or Calcium antagonist: have proven reno-protective effects, but not anti-proteinuric

Add thiazide diuretic to augment ACE inhibitor or add β-blocker as combination therapy Add thiazide diuretic to augment ACE inhibitor or add β-blocker as combination therapy

Continue monitoring renal function and blood pressure Continue monitoring renal function and blood pressure

Moderate Chronic Renal Failure (Cr 200-400μmol/l) Moderate Chronic Renal Failure (Cr 200-400µmol/l)

Treat hypertension vigorously i.e. BP < 130/85 mmHg Treat hypertension vigorously i.e. BP < 130/85 mmHg

Avoid diuretics unless volume overloaded Usually 3 agents required, target BP < 130/85mmHg Use ACE inhibitors: retard decline and are anti-proteinuric; more effective if Na+ depleted or Calcium antagonist: have proven reno-protective effects, but not anti-proteinuric

Add thiazide diuretic to augment ACE inhibitor or add β-blocker as combination therapy Continue monitoring renal function and blood pressure Copyright: Council for Medical Schemes

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Avoid diuretics unless volume overloaded Usually 3 agents required, target BP < 130/85mmHg

Renal Disease Use ACE inhibitors: retard decline and are anti-proteinuric; more effective if Na+ depleted or Calcium antagonist: have proven reno-protective effects, but not anti-proteinuric

Add thiazide diuretic to augment ACE inhibitor or add β-blocker as combination therapy Continue monitoring renal function and blood pressure Copyright: Council for Medical Schemes

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Prevent Osteodystrophy Prevent Osteodystrophy

Give phosphate binder with meals Give phosphate binder with meals (Calcium carbonate) (Calcium carbonate)

Reserve 1α-hydroxy cholecalciferol for Reserve 1α-hydroxy cholecalciferol for hypocalcaemia or progressive hypocalcaemia or progressive hyperparathyroidism hyperparathyroidism 4 Monitor serum Ca++ and/or for levels high levels Monitor serum Ca++ and/or PO4 PO for high

Prevent Anaemia Prevent Anaemia

Treatiron irondeficiency deficiency 2-3 Treat 2-3 mg/kg/day orally mg/kg/dayelemental elementaliron iron orally Treat if if Treatwith withIVIViron irontherapy therapy necessary necessary

Treat folate deficiency Treat folate deficiency 2,5-5mg/day folic folic acid acid 2,5-5mg/day

Iron Irontherapy therapyfailure: failure: Erythropoietin 8 gm/dl Erythropoietinwhen whenHb Hb< < 8 gm/dl Severe Chronic Renal Failure (Cr> 400µmol/l) Severe Chronic Renal Failure (Cr> 400µmol/l) Patients require early nephrological referral for Patients require early nephrological referral for management and assessment for dialysis and transplant management and assessment for dialysis and transplant Glossary: Glossary: • ACE inhibitor – Angiotensin converting enzyme inhibitor ACE inhibitor – Angiotensin •• Serum Na+ – Serum sodium converting enzyme inhibitor Serum Na+ – Serum sodium •• β-blocker – Beta-receptor blocker β-blocker Beta-receptor blocker •• BP – Blood –pressure BP- – Blood pressure •• Hb Haemoglobin Hb - Haemoglobin •• Cr/Serum Cr – Serum creatinine Cr/Serum – Serum creatinine •• Serum Ca++Cr- Serum calcium Serum Ca++ - Serum calcium •• 1α-hydroxy – 1-alpha-hydroxy 4 – Phosphate •• PO 1α-hydroxy – 1-alpha-hydroxy • PO4 – Phosphate Applicable ICD 10 Coding: • N03 Chronic nephritic syndrome Applicable ICD 10 Coding: N03.0 Chronic nephritic syndrome, minor glomerular abnormality • oN03 Chronic nephritic syndrome oo N03.1 nephritic syndrome, focal and segmental N03.0Chronic Chronic nephritic syndrome, minor glomerularglomerular abnormality o lesions N03.1 Chronic nephritic syndrome, focal and segmental glomerular o N03.2 Chronic nephritic syndrome, diffuse membranous lesions o glomerulonephritis N03.2 Chronic nephritic syndrome, diffuse membranous glomerulonephritis Copyright: Council for Medical Schemes

Copyright: Council for Medical Schemes

Page 2 of 3

Page 2 of 3

28 PMB-X GUIDELINES 2021 *Treatment algorithm not to be associated with advertisement

On guard

24 30 Telmisartan offers: sustained

24

hour BP control1

protection against the early morning BP surge1

cardiovascular protection1 conveniently packed in

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40 mg 80 mg

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CUSTOMER CARE LINE 0860 PHARMA (742 762) / +27 21 707 7000 www.pharmadynamics.co.za TESAR 40, 80 mg. Each tablet contains 40, 80 mg telmisartan respectively. S3 A45/7.1.3/0978, 0979. NAM NS2 17/7.1.3/0023, 0024. For full prescribing information, refer to the professional information approved by SAHPRA, 30 August 2019. 1) Grassi G, et al. Cardioprotective effects of telmisartan in uncomplicated and complicated hypertension. Journal of Renin-Angiotensin-Aldosterone System 2008;9(2):66-74. TRH708/01/2021.

Coronary Artery Disease

Coronary Artery Disease

Coronary artery disease develops when the major blood vessels that supply the heart with blood, oxygen and nutrients (coronary arteries) become damaged or diseased. Plaque in the arteries and inflammation are usually to blame for coronary artery disease. When plaque builds up, it decreases blood flow to the heart. Eventually, the decreased blood flow may cause angina, shortness of breath, or other coronary artery disease signs and symptoms.

A complete blockage can cause a heart attack.

CORONARY ARTERY DISEASE Diagnosis

Address and manage risk factors: 1. Lifestyle modification: Stop smoking, modify diet, increase aerobic exercise and limit alcohol consumption to 2 units/day 2. Hyperlipidaemia 3. Diabetes mellitus Manage as per disease–specific algorithm 4. Hypertension

All patients should receive aspirin 75-325 mg/day (unless contraindicated)

Sublingual nitrates for short term control of angina symptoms Regular symptomatic treatment required?

YES

NO Continue sublingual nitrates

Treat with a β-receptor antagonist (unless contraindicated)

If symptoms uncontrolled: Add long acting nitrate or a long acting dihydropyridine

Review

If β-receptor antagonist contraindicated or not tolerated Treat with rate limiting calcium channel antagonist: a long acting dihydropyridine or a “long” acting nitrate If symptoms uncontrolled add one of the other alternatives

Review if: uncontrolled symptoms; symptoms limit patient’s desired activities; patients at high risk Copyright: Council for Medical Schemes

30 PMB-X GUIDELINES 2021 *Treatment algorithm not to be associated with advertisement

Page 1 of 2

WHEN ALL THE PARTS FIT...

PERFECTLY. EFFICACY 2 SAFETY 2 PROVEN OUTCOMES 3

CUSTOMER CARE LINE 0860 PHARMA (742 762) / +27 21 707 7000 www.pharmadynamics.co.za AMLOC 5, 10 mg. Each tablet contains amlodipine maleate equivalent to 5, 10 mg amlodipine respectively. S3 A38/7.1/0183, 0147. NAM NS2 06/7.1/0011, 0012. BOT S2 BOT 0801198, 0801199. For full prescribing information, refer to the professional information approved by SAHPRA, 29 September 2017. 1) IQVIA MAT Units, Aug 2020. 2) Dahlof B, Sever PS, Poulter NR, et al. for the Ascot investigators. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial - Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005;366:895-906. 3) Nissen SE, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure. The CAMELOT study: A randomised controlled trial. JAMA 2004;292:2217-2226. ACJ706/01/2021.

Coronary Artery Disease

Glossary: • β-receptor antagonist – Beta-receptor antagonist Applicable ICD 10 Coding: • I20 Angina pectoris o I20.0 Unstable angina o I20.1 Angina pectoris with documented spasm o I20.8 Other forms of angina pectoris o I20.9 Angina pectoris, unspecified • I25 Chronic ischaemic heart disease o I25.0 Atherosclerotic cardiovascular disease, so described o I25.1 Atherosclerotic heart disease o I25.2 Old myocardial infarction o I25.3 Aneurysm of heart o I25.4 Coronary artery aneurysm o I25.5 Ischaemic cardiomyopathy o I25.6 Silent myocardial ischaemia o I25.8 Other forms of chronic ischaemic heart disease o I25.9 Chronic ischaemic heart disease, unspecified

Note: 32 PMB-X GUIDELINES 2021 *Treatment algorithm not to be associated with advertisement 1. Medical management reasonably necessary for the delivery of treatment described in this algorithm is included within this benefit, subject to the

Crohn’s Disease

Crohn’s Disease Crohn’s disease is an idiopathic inflammatory disorder of unknown aetiology with genetic, immunologic, and environmental influences. The incidence of Crohn’s disease has steadily increased over the past several decades.

It is, in most cases, a progressive, destructive disease.

CROHN’S DISEASE Diagnosis

Perianal Disease

Severe disease and or abscess

YES Refer for surgical intervention

NO Consider antibiotics e.g. quinolone or metronidazole

In remission

Colonic disease: Any 5-ASA or azathioprine or methotrexate if indicated

Small Bowel disease: Azathioprine or methotrexate if indicated

Recurrent flares azathioprine or methotrexate with corticosteroid

Post-operative recurrence azathioprine or methotrexate with corticosteroid

Mild-mo

Oral c Possibly e.g. me q

Patie

YES Taper corticoster graduall Consider 5prophylax colonic

*Treatment algorithm not to be associated with advertisement PMB-X GUIDELINES 2021 33 Copyright: Council for Medical Schemes

Page 1 of 2

! ! ee

BREAK fr

from gut health issues

A MULTIVITAMIN FOR YOUR GUT

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1 > TRANSPARENT LABELING.

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34 PMB-X GUIDELINES 2021

3 No artificial additives, colourants or flavourants.

Free from lactose, gluten, sugar, tartrazine & soya.

progast.global

This unregistered medicine has not been evaluated by the SAHPRA for its quality, safety or intended use.

Crohn’s Disease

CROHN’S DISEASE Diagnosis

Active disease

In remission

ase: or e or te if d

Small Bowel disease: Azathioprine or methotrexate if indicated

ares e or with oid

Post-operative recurrence azathioprine or methotrexate with corticosteroid

Mild-moderate disease

Severe disease

Oral corticosteroids Possibly oral antibiotics e.g. metronidazole or a quinolone

IV corticosteroids with or without antibiotics

Review

Patient improved?

YES Taper corticosteroid gradually Consider 5-ASA prophylaxis if colonic

NO Review

Glossary: • 5-ASA – 5-Aminosalicylic acid • IV – Intravenous Page 1 of 2

Applicable ICD 10 Coding: • K50 Crohn's disease [regional enteritis] o K50.0 Crohn's disease of small intestine o K50.1 Crohn's disease of large intestine o K50.8 Other Crohn's disease o K50.9 Crohn's disease, unspecified Note: 1. Medical management reasonably necessary for the delivery of treatment described in this algorithm is included within this benefit, subject to the application of managed health care interventions by the relevant medical scheme.

2. To the extent that a medical scheme applies managed health care interventions in respect of this benefit, for example clinical protocols for *Treatment algorithm not toor bemedical associated with advertisement PMB-X GUIDELINES diagnostic procedures management, such interventions must – 2021 35 a. not be inconsistent with this algorithm;

Diabetes Insipidus

Diabetes Insipidus DIABETES INSIPIDUS

Diabetes insipidus is rare, and is caused by a problem with the production, or action, of the hormone Diagnosis of central diabetes vasopressin. The kidneys are unable to retain water.

This leads to the production of large volumes of insipidus usually via water Disease identification card urine and, in turn, greatly increased thirst.

It can occur mostly found deprivation test at any age, but is or disc recommended in adults.

DIABETES INSIPIDUS Rule out and treat any underlying cause Diagnosis of central diabetes insipidusTreat usually via waterare if symptoms deprivation test debilitating

Disease identification card or disc recommended

Treat with desmopressin Rule out and treat any underlying cause Dosage form appropriate for patient Oral or nasal spray/solution 4 times daily depending on response!

Treat if symptoms are debilitating Use lowest dose possible to control symptoms Treat with desmopressin Avoid unplanned treatment withdrawal Dosage form appropriate for patient Patient education essential regarding adherence

Oral or nasal spray/solution 4 times daily depending on response!

Monitor serum sodium

Monitor serum sodium

Use lowest dose possible to control symptoms Avoid unplanned treatment withdrawal Patient education essential regarding adherence

Applicable ICD 10 Coding: • E 23.2 Diabetes insipidus

Copyright: Council for Medical Schemes

Applicable ICD 10 Coding: 36 PMB-X GUIDELINES 2021 insipidus • E 23.2 Diabetes

Page 1 of 2

Diabetes Mellitus 1

Diabetes Mellitus 1 In Type 1 diabetes, the immune system attacks the insulin-producing beta cells in the pancreas.

This usually happens in younger people, but it can happen at any age. When this happens, the pancreas no longer produces insulin.

DIABETES MELLITUS TYPE 1 Diagnosis of Type 1

Life style modification Home glucose monitoring essential

Disease identification card or disc recommended

Monitor HbA1c at 3-6 monthly intervals Insulin for all Individualisation essential HbA1c target of ≤7.0 % achieved within 3 months?

YES Continue management

NO If conventional regimen, an intensive insulin regimen may be indicated Review by specialist physician if necessary

Glossary: • HbA1c – Glycosylated hemoglobin Applicable ICD 10 Coding: • E10 Insulin-dependent diabetes mellitus o E10.0 Insulin-dependent diabetes mellitus with coma o E10.1 Insulin-dependent diabetes mellitus with ketoacidosis o E10.2 Insulin-dependent diabetes mellitus with renal complications o E10.3 Insulin-dependent diabetes mellitus with *Treatment algorithm not to be associated with ophthalmic advertisement PMB-X GUIDELINES 2021 37 complications

YES Continue management

Diabetes Mellitus 1

NO If conventional regimen, an intensive insulin regimen may be indicated Review by specialist physician if necessary

Glossary: • HbA1c – Glycosylated hemoglobin Applicable ICD 10 Coding: • E10 Insulin-dependent diabetes mellitus o E10.0 Insulin-dependent diabetes mellitus with coma o E10.1 Insulin-dependent diabetes mellitus with ketoacidosis o E10.2 Insulin-dependent diabetes mellitus with renal complications o E10.3 Insulin-dependent diabetes mellitus with ophthalmic complications o E10.4 Insulin-dependent diabetes mellitus with neurological complications o E10.5 Insulin-dependent diabetes mellitus with peripheral circulatory complications o E10.6 Insulin-dependent diabetes mellitus with other specified complications o E10.7 Insulin-dependent diabetes mellitus with multiple complications o E10.8 Insulin-dependent diabetes mellitus with unspecified complications o E10.9 Insulin-dependent diabetes mellitus without complications Applicable ICD 10 Coding: (continued) • E12 Malnutrition-related diabetes mellitus Copyright: Council for Schemes Page 1 of 2 o Medical E12.0 Malnutrition-related diabetes mellitus with coma o E12.1 Malnutrition-related diabetes mellitus with ketoacidosis o E12.2 Malnutrition-related diabetes mellitus with renal complications o E12.3 Malnutrition-related diabetes mellitus with ophthalmic complications o E12.4 Malnutrition-related diabetes mellitus with neurological complications o E12.5 Malnutrition-related diabetes mellitus with peripheral circulatory complications o E12.6 Malnutrition-related diabetes mellitus with other specified complications o E12.7 Malnutrition-related diabetes mellitus with multiple complications o E12.8 Malnutrition-related diabetes mellitus with unspecified complications o E12.9 Malnutrition-related diabetes mellitus without complications •

O24 Diabetes mellitus in pregnancy o O24.0 Pre-existing diabetes mellitus, insulin-dependent o O24.2 Pre-existing malnutrition-related diabetes mellitus o O24.3 Pre-existing diabetes mellitus, unspecified

Note: 1. Medical management reasonably necessary for the delivery of treatment described in this algorithm is included within this benefit, subject to the application of managed health care interventions by the relevant medical scheme.

2. To the extent that a medical scheme applies managed health care interventions in respect of this benefit, for example clinical protocols for diagnostic procedures or medical management, such interventions must – a. not be inconsistent with this algorithm; b. be developed on the basis of evidence-based medicine, taking into account considerations of cost-effectiveness and affordability; and 38 PMB-X GUIDELINES 2021 *Treatment *Treatment algorithm algorithm not not to to be be associated associated with with advertisement advertisement c. comply with all other applicable regulations made in terms of the Medical Schemes Act, 131 of 1998

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30 G x 8 mm 32 G x 4 mm

References: 1. NovoRapid® approved package insert March 2015. 2. Heise T, et al. Insulin degludec: four times lower pharmacodynamic variability than insulin glargine under steady-state conditions in type 1 diabetes. Diabetes, Obesity and Metabolism 2012;14:859 -864. 3. HeiseT, et al. Day-to-Day and Within-Day Variability in Glucose-Lowering Effect Between Insulin Degludec and Insulin Glargine (100 U/mL and 300 U/mL): A Comparison Across Studies. Journal of Diabetes Science and Technology 2018;12(2):356-363.

S3 Proprietary Name: Tresiba® 100 U/ml. Composition: Insulin degludec 100 units/ml. Indications: Treatment of adult and children older than 1 year diabetes mellitus patients, as basal add-on co-medication in patients who are inadequately controlled: a) In type 1 diabetes mellitus, Tresiba® should be used with short-acting soluble insulin at the meal times. b) In type 2 diabetes mellitus, Tresiba® should be used as an add-on to oral antidiabetic medicines with or without the use of short acting insulin at meal times. Contra-indications: Hypersensitivity to the active substance or to any of the excipients & pregnancy. Warnings and Special precautions: Hypoglycaemia, Immune system disorder, Hyperglycaemia, Injection site reaction, Lipodystrophy, Combination of thiazolidinediones (TZDs) and Tresiba®, Insulin initiation and glucose control intensification: Intensification or rapid improvement in glucose control has been associated with transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy. Long-term glycaemic control decreases the risk of diabetic retinopathy and neuropathy. Interactions: Combination with thiazolidinediones (TZDs), the following substances may reduce the insulin requirement: Oral antidiabetic medicinal products, Glucagon-like peptide-1 (GLP-1) receptor agonists, monoamine oxidase inhibitors (MAOI), beta-blockers, angiotensin converting enzyme (ACE) inhibitors, salicylates, anabolic steroids and sulphonamides. The following substances may increase the insulin requirement: Oral contraceptive, thiazides, glucocorticoids, thyroid hormones, sympathomimetics, growth hormones and danazol. Beta-blocking agents may mask the symptoms of hypoglycaemia. Octreotide and lanreotide may either increase or decrease the insulin requirement. Alcohol may intensify or reduce the hypoglycaemic effect of insulin.

Pregnancy & Lactation: Safety has not been established and Tresiba® should not be recommended for use during pregnancy. Lactation: There is no clinical experience with Tresiba® during breast-feeding. It is unknown whether insulin degludec is excreted in human milk.

Dosage & Directions for use: Tresiba® is to be dosed in accordance with the individual patient’s needs. It is recommended to optimise glycaemic control via dose adjustment based on fasting plasma glucose. In patients with type 2 diabetes mellitus, Tresiba® can be administered alone or in any combination with oral antidiabetic medicines, GLP-1 receptor agonists and bolus insulin. In type 1 diabetes mellitus, Tresiba® must be combined with short/rapid-acting insulin to cover mealtime insulin requirements. Initiation of Tresiba®: For patients with type 2 diabetes mellitus, the recommended daily starting dose of Tresiba® is 10 units, followed by individual dosage adjustments. For patients with type 1 diabetes mellitus, Tresiba® is to be used once-daily with mealtime insulin and requires subsequent individual dosage adjustments.

Tresiba® can be used in adolescents and children from the age of 1 year, when changing basal insulin to Tresiba®, dose reduction of basal and bolus insulin needs to be considered on an individual basis. When adding Tresiba® to GLP-1 receptor agonist, the recommended daily starting dose is 10 units followed by individual dosage adjustments. When adding GLP-1 receptor agonists to Tresiba®, it is recommended to reduce the dose of Tresiba® by 20 % to minimise the risk of hypoglycaemia. Tresiba® is for subcutaneous administration only. Tresiba® must not be administered intravenously as it may result in severe hypoglycaemia. Tresiba® must not be administered intramuscularly as it may change the absorption. Tresiba® is not to be used with insulin infusion pumps. Side-effects: Common: Injection site reactions, Uncommon: Peripheral oedema, Rare: Hypersensitivity, Rare: Urticaria, Very common: Hypoglycaemia, Uncommon: Lipodystrophy. Known symptoms of overdosage and particulars of its treatment: Mild hypoglycaemic episodes can be treated by oral administration of glucose or other products containing sugar. It is therefore recommended that the patient always carries glucose-containing products. Severe hypoglycaemic episodes, where the patient is not able to treat himself, can be treated with glucagon (0,5 to 1 mg) given intramuscularly or subcutaneously by a trained person or with glucose given intravenously by a health care professional. Reg. No: Tresiba® 100 U/ml: 47/21.1/0108. For full prescribing information, please refer to the Professional Information approved by the Medicines Regulatory Authority.

Proprietary Name: NovoRapid®. Scheduling Status: S3 Composition: 100 units /ml Insulin Aspart. Indications: Treatment of patients with diabetes mellitus who require insulin. Contra-Indications: Hypoglycaemia. Hypersensitivity to insulin aspart or to any of the excipients. Warnings & Special Precautions: When using insulin in combination with pioglitazone, patients should be observed for signs and symptoms of heart failure, weight gain and oedema. Pioglitazone should be discontinued if any signs of cardiac function deterioration occur. Insulin antibodies-Insulin administration may cause insulin antibodies to form. In rare cases, the presence of such insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to hyperglycaemia or hypoglycaemia. Patients whose blood glucose control is greatly improved, e.g. by intensified insulin therapy, may experience a change including a less pronounced intensity of their usual warning symptoms of hypoglycaemia and should be advised accordingly.

Inadequate dosing or discontinuation of treatment, especially in Type 1 diabetes (insulin-dependent diabetes mellitus) may lead to hyperglycaemia and diabetic ketoacidosis. Transferring a patient to a new type or brand of insulin should be done under strict medical supervision. Hypoglycaemia may constitute a risk when driving or operating machinery. Pregnancy and lactation: NovoRapid® can be used in pregnancy. No restrictions on use during breast-feeding. Dosage and Directions for Use: Due to the fast onset of action NovoRapid® should generally be given immediately before a meal. When necessary, NovoRapid® may be given immediately after the meal. Dosage of NovoRapid® is individual and determined on the basis of the physician’s advice in accordance with the needs of the patient. It should normally be used in combination with intermediate-acting or long-acting insulin given at least once a day. The individual insulin requirement is usually between 0.5 and 1.0 Units/kg/day in adults and children from 2 years.

NovoRapid® can be used in pregnancy. NovoRapid® may be used for Continuous Subcutaneous Insulin Infusion (CSII) in the pump systems. NovoRapid® is administered subcutaneously by injection in the abdominal wall, the thigh or the deltoid region, or the gluteal region or by infusion in the abdominal wall. NovoRapid® may also be administered intravenously. Side Effects: Hypoglycaemia is the most commonly reported adverse reaction during treatment. Uncommon – oedema, injection site reactions (pain, redness, swelling, bruising and itching at the injection site), refraction anomalies may occur during treatment with NovoRapid® and is usually of transitory nature. Lipodystrophy may occur at the injection site as a consequence of failure to rotate injection site within an area. Rare - peripheral neuropathy: Fast improvement in blood glucose control may be associated with acute painful neuropathy, which is usually reversible. Very rare - anaphylactic reactions: generalised hypersensitivity reactions are potentially life-threatening.

Reg. No.: 34/21.1/0160. (ver. 2). For full prescribing information, please refer to the Professional Information approved by the Medicines Regulatory Authority.

Novo Nordisk (Pty) Ltd. Reg. No.: 1959/000833/07. 150 Rivonia Road, 10 Marion Street Office Park, Building C1, Sandton, Johannesburg, 2196. Tel: (011) 202 0500 Fax: (011) 807 7989. www.novonordisk.za.com. Fax: (011) 807 7989. www.novonordisk.com. ZA21TSM00001.

RLC 0121/6658

Diabetes Mellitus 2

Diabetes Mellitus 2 Type 2 diabetes is the most common type of diabetes. Of all people with diabetes, 90% have type 2 diabetes. Some ethnic groups, like the South African Indian population, are more prone to developing diabetes, and in these groups, the percentage is even higher. Type 2 diabetes usually occurs in older people, but recently, more and more younger people, and sometimes even children, develop type 2 diabetes.

DIABETES MELLITUS TYPE 2 Diagnosis of Type 2

Address other risk factors Disease identification card or disc recommended

Lifestyle modification as part of initial management

Measure HbA1c every 3 months depending on control and changes in therapy Target HbA1c should be ≤ 7.0%

Have lifestyle modifications been successful?

NO

YES

Consider oral hypoglycaemic agents Is there renal and/or cardiac dysfunction

YES

Continue to monitor HbA1c every 6 months

NO

Is Patient’s BMI > 25?

YES Consider sulphonylurea

Use metformin

NO

Consider either metformin or a sulphonylurea depending on plasma glucose

40 PMB-X GUIDELINES 2021 *Treatment algorithm not to be associated with advertisement Adequate control?

for

SUSTAINED CONTROL

Once daily formulation Improved compliance

Packed in

1

Sustained 24 hour glycaemic control

2

60’s

Within reference at major medical schemes.*

CUSTOMER CARE LINE 0860 PHARMA (742 762) / +27 21 707 7000 www.pharmadynamics.co.za DYNA GLICLAZIDE SR 30 mg. Each tablet contains 30 mg gliclazide. S3 A42/21.2/0249. NAM NS2 12/21.2/0110. For full prescribing information, refer to the professional information approved by SAHPRA, 28 July 2017. 1) Crepaldi G and Fioretto P. Gliclazide modified release: Its place in the therapeutic armamentarium. Metabolism 2000;49(10) supplement 2:21-25. 2) McGavin JK, et al. Gliclazide modified release. Drugs 2002;62(9):1357-1364. *Conditions apply. DGLL732/05/2021.

PMB-X GUIDELINES 2018 41

NO

Diabetes Mellitus 2

YES

Consider oral hypoglycaemic agents Is there renal and/or cardiac dysfunction

YES

Continue to monitor HbA1c every 6 months

NO

Is Patient’s BMI > 25?

YES Consider sulphonylurea

NO

Use metformin

Consider either metformin or a sulphonylurea depending on plasma glucose

Adequate control?

NO

YES

Continue to monitor blood glucose and HbA1c 3-6 monthly Copyright: Council for Medical Schemes Optimise dose of oral

hypoglycaemic agent

Page 1 of 3

Adequate control?

NO

If patient on metformin consider adding a sulphonylurea

YES

If patient on sulphonylurea and has normal renal function and has no cardiac dysfunction add metformin If poor renal function: Consider adding a thiazolidinedione or insulin

Continue to monitor blood glucose and HbA1c 3-6 monthly

Is control adequate?

YES

NO

Monitor HbA1c every 3 to 6 months

Consider adding / enhancing insulin therapy

Glossary: • HbA1c – Glycosylated hemoglobin • BMI – Body mass index Applicable ICD 10 Coding: • E11 Non-insulin-dependent diabetes mellitus o E11.0 Non-insulin-dependent diabetes mellitus with coma o E11.1 Non-insulin-dependent diabetes mellitus with ketoacidosis o E11.2 Non-insulin-dependent diabetes mellitus with renal complicationsalgorithm not to be associated with advertisement 42 PMB-X GUIDELINES 2021 *Treatment o E11.3 Non-insulin-dependent diabetes mellitus with ophthalmic complications

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6x more Xultophy patients achieved HbA1c < 7 % without weight gain or hypoglycaemia vs basal-bolus4 ®

Make Xultophy® your intensification option of choice T2D = type 2 diabetes. Composite endpoint in a randomised phase 3 clinical trial comparing Xultophy® (n=252) and IGlar U100 + IAsp (n=254).4 Images shown are models, not real patients.

References: 1. Polonsky W et al. J Diabetes Complications. 2015;29(8):1171–6. 2. Celano C et al. Curr Diab Rep. 2013;13(6):917–929. 3. Moore Beckerle C and Lavin MA. Diabetes Spectrum. 2013;26(3):172–178.

4. Billings L et al. Diabetes Care. 2018;41(5):1009–1016.

Scheduling status: S4 Proprietary name and dosage form: Xultophy® (solution for injection). Composition: Each mℓ of solution contains 100 units insulin degludec and 3,6 mg liraglutide in a pre-filled pen. Indications: Xultophy® is indicated for the treatment of adults with type 2 diabetes mellitus to improve glycaemic control added to one or more oral hypoglycaemic medicines. Contraindications: Hypersensitivity to either or both active substances, i.e. insulin degludec and liraglutide or to any of the excipients, Type 1 diabetes mellitus, diabetic ketoacidosis, pancreatitis, pregnancy and lactation. Warnings and special precautions: Xultophy® should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. Too high dose, omission of a meal, or unplanned strenuous physical exercise may lead to hypoglycaemia. In combination with sulphonylurea, the risk of hypoglycaemia may be lowered by a reduction in the dose of sulphonylurea. Patients must be advised to take precautions to avoid hypoglycaemia while driving. Inadequate dosing and/or discontinuation of anti-diabetic treatment may lead to hyperglycaemia and potentially to hyperosmolar coma. When using Xultophy® in combination with pioglitazone, patients should be observed for signs and symptoms of heart failure, weight gain, and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms occurs. Acute pancreatitis has been observed with the use of GLP-1 receptor agonists, including liraglutide. Patients should be informed of the characteristic symptoms of acute pancreatitis. If pancreatitis is suspected, Xultophy® should be discontinued; if acute pancreatitis is confirmed, Xultophy® should not be restarted. Thyroid adverse events, such as goitre have been reported in clinical trials with GLP-1 receptor agonists including liraglutide, and in patients with pre-existing thyroid disease. Xultophy® should therefore be used with caution in these patients. There is no experience with Xultophy® in patients with inflammatory bowel disease and diabetic gastroparesis. Xultophy® is not recommended in these patients. Signs and symptoms of dehydration, including renal impairment and acute renal failure, have been reported in clinical trials with GLP-1 receptor agonists including liraglutide. Patients must always check the pen label to avoid accidental mix-ups with other injectable diabetes medicinal products. Transfer to Xultophy® from doses of basal insulin <20 and >50 units has not been studied. There is no therapeutic experience in patients with congestive heart failure New York Heart Association (NYHA) class IV and Xultophy® is therefore not recommended for use in these patients. Interactions: Substances that may reduce the Xultophy® requirement: Anti-diabetic products, monoamine oxidase inhibitors (MAOI), beta-blockers, angiotensin converting enzyme (ACE) inhibitors, salicylates, anabolic steroids and sulphonamides. Substances that may increase the Xultophy® requirement: Oral contraceptives, thiazides, glucocorticoids, thyroid hormones, sympathomimetics, growth hormones and danazol.

Beta-blockers may mask the symptoms of hypoglycaemia. Octreotide/lanreotide may either increase or decrease the Xultophy® requirement. Alcohol may intensify or reduce the hypoglycaemic effect of Xultophy®. Pregnancy and lactation: Xultophy® should not be used during pregnancy. If a patient becomes pregnant, treatment with Xultophy® should be discontinued. Xultophy® should not be used during breast-feeding. Dosage and directions for use: Xultophy® is given once daily by subcutaneous administration and can be administered at any time of the day, preferably at the same time of the day. A minimum of 8 hours between injections should always be ensured.

Xultophy® is to be dosed in accordance with the individual patient’s needs. It is recommended to optimise glycaemic control via dose adjustment based on fasting plasma glucose. Xultophy® is administered as dose steps. The pre-filled pen can provide from 1 up to 50 dose steps in one injection in increments of one dose step. The maximum daily dose is 50 dose steps. The starting dose of Xultophy® as add-on to oral antidiabetes drugs (OADs) is 10 dose steps, and 16 dose steps when transferring from GLP-1 receptor agonist or basal insulin therapy. Close glucose monitoring is recommended during the transfer and in the following weeks when transferring from either GLP-1 receptor agonist or basal insulin. In elderly patients, in patients with mild, moderate or severe renal impairment and in patients with mild or moderate hepatic impairment, glucose monitoring should be intensified. Xultophy® is not recommended in patients with end-stage renal disease or severe hepatic impairment. Xultophy® is not to be used in children/adolescents. Side effects: Hypoglycaemia, decreased appetite, nausea, diarrhoea, vomiting, constipation, dyspepsia, gastritis, abdominal pain, gastroesophageal reflux disease, abdominal distension, injection site reaction, urticaria, hypersensitivity, dehydration, eructation, flatulence, rash, pruritus, lipodystrophy and increased heart rate, anaphylactic reaction, pancreatitis, and peripheral oedema. Known symptoms of overdosage and particulars of its treatment: Hypoglycaemia may develop if a patient is dosed with more Xultophy® than required: Mild hypoglycaemic episodes can be treated by oral administration of glucose or other products containing sugar. Severe hypoglycaemic episodes, where the patient is not able to treat himself, can be treated with glucagon (0,5 to 1 mg) given intramuscularly or subcutaneously. Registration number: 50/21.13/0985 For full prescribing information, refer to the Professional Information approved by the medicine regulatory authority.

Novo Nordisk (Pty) Ltd. Reg. No.: 1959/000833/07. 150 Rivonia Road, 10 Marion Street Office Park, Building C1, Sandton, Johannesburg, 2196.

Tel: (011) 202 0500 Fax: (011) 807 7989. www.novonordisk.com. 15277T. ZA20XUM00026 October 2020.

*Treatment algorithm not to be associated with advertisement PMB-X GUIDELINES 2021 43

Diabetes Mellitus 2

Is control adequate?

YES

NO

Monitor HbA1c every 3 to 6 months

Consider adding / enhancing insulin therapy

Glossary: • HbA1c – Glycosylated hemoglobin • BMI – Body mass index Applicable ICD 10 Coding: • E11 Non-insulin-dependent diabetes mellitus o E11.0 Non-insulin-dependent diabetes mellitus with coma o E11.1 Non-insulin-dependent diabetes mellitus with ketoacidosis o E11.2 Non-insulin-dependent diabetes mellitus with renal complications o E11.3 Non-insulin-dependent diabetes mellitus with ophthalmic complications o E11.4 Non-insulin-dependent diabetes mellitus with neurological complications o E11.5 Non-insulin-dependent diabetes mellitus with peripheral circulatory complications o E11.6 Non-insulin-dependent diabetes mellitus with other specified complications o E11.7 Non-insulin-dependent diabetes mellitus with multiple complications o E11.8 Non-insulin-dependent diabetes mellitus with unspecified complications o E11.9 Non-insulin-dependent diabetes mellitus without complications Applicable ICD 10 Coding: (continued)

•

E12 Malnutrition-related diabetes mellitus Page 2 of 3 diabetes mellitus with coma o E12.1 Malnutrition-related diabetes mellitus with ketoacidosis o E12.2 Malnutrition-related diabetes mellitus with renal complications o E12.3 Malnutrition-related diabetes mellitus with ophthalmic complications o E12.4 Malnutrition-related diabetes mellitus with neurological complications o E12.5 Malnutrition-related diabetes mellitus with peripheral circulatory complications o E12.6 Malnutrition-related diabetes mellitus with other specified complications o E12.7 Malnutrition-related diabetes mellitus with multiple complications o E12.8 Malnutrition-related diabetes mellitus with unspecified complications o E12.9 Malnutrition-related diabetes mellitus without complications

•

O24 Diabetes mellitus in pregnancy o O24.1 Pre-existing diabetes mellitus, non-insulin-dependent o O24.2 Pre-existing malnutrition-related diabetes mellitus o O24.3 Pre-existing diabetes mellitus, unspecified

Copyright: Council for Schemes o Medical E12.0 Malnutrition-related

Note: 1. Medical management reasonably necessary for the delivery of treatment described in this algorithm is included within this benefit, subject to the application of managed health care interventions by the relevant medical scheme.

2. To the extent that a medical scheme applies managed health care interventions in respect of this benefit, for example clinical protocols for diagnostic procedures or medical management, such interventions must – a. not be inconsistent with this algorithm; b. be developed on the basis of evidence-based medicine, taking into account considerations of cost-effectiveness and affordability; and c. comply with all other applicable regulations made in terms of the Medical Schemes Act, 131 of 1998

44 PMB-X GUIDELINES 2021 3.

This algorithm may not necessarily always be clinically appropriate for the treatment of children. If this is the case, alternative paediatric clinical

Dysrhythmia

Dysrhythmia Cardiac dysrhythmia (or arrhythmia) is a disturbance in the rate of cardiac muscle contractions, or any variation from the normal rhythm or rate of heart beat. It encompasses abnormal regular and irregular rhythms as well as loss of rhythm. Cardiac dysrhythmias are found in a vast range of conditions and may be defined in a number of ways, including by site of origin (supraventricular, ventricular, atrial), mechanism of disturbance (fibrillation, automaticity, re-entry or triggered activity), rate of disturbance (tachycardia, bradycardia) and electrocardiogram appearance (long QT syndrome).

DYSRHYTHMIAS Chronic Atrial Fibrillation Diagnosis

Anticoagulate: warfarin (maintain INR: 2-3,5) If warfarin not tolerated, consider aspirin alone

Monitor heart rate Control: at rest ≤ 80 beats/min exercise (6 min walk test) ≤ 110 beats/min

Heart rate controlled:

Bradycardia < 60 beats/min

No treatment needed

Review for permanent pacemaker

Heart rate: > 80 beats/min at rest > 110 beats/min at exercise Treat with: 1. β-blockers e.g. Atenolol 25-50mg bd or, 2. Digoxin 0,125-0,25mg daily or, 3. Verapamil or if treatment fails or not tolerated, 4. Amiodarone, If treatment fails or not tolerated: Review for AV node ablation and permanent pacemaker

PMB-X GUIDELINES 2021 45

Dysrhythmia

Chronic Atrial Flutter Diagnosis

Anticoagulate: warfarin (maintain INR: 2-3.5) If warfarin not tolerated, consider aspirin alone

Review for cardioversion

Patient in sinus rhythm?

YES

NO

Recurrence?

No treatment needed Typical flutter?

Review for flutter ablation

Not ablatable flutter?

Assess ventricular rate: Clinically and/or Holter monitor Control: at rest ≤ 80 beats/min exercise (6 min walk test) ≤ 110 beats/min Heart rate inadequate?

Consider trial of therapy: β-blockers (7 days) or amiodarone (14 days)

If treatment fails or not tolerated Review for AV node ablation and permanent pacemaker

Copyright: Council for Medical Schemes

46 PMB-X GUIDELINES 2021

Page 2 of 4

Dysrhythmia

Ventricular Tachycardia Diagnosis

Review for cardioversion

Early recurrence post-conversion

NO

Exclude, assess and manage the following: • Acute myocardial infarct • Electrolyte imbalance • Left ventricular dysfunction

YES

Cardioversion

Ventricular tachycardia persists

β-blockers e.g. atenolol 50mg bd if tolerated, or if LV function decreased or patient in heart failure, commence amiodarone

Poor response?

Review for electrophysiological studies

Glossary: • INR – International normalized ratio • β-blocker – Beta-receptor blocker • AV node – Atrioventricular node • LV – Left ventricular Applicable ICD 10 Coding: • I47.2 Ventricular tachycardia • I48 Atrial fibrillation and flutter

Copyright: Council for Medical Schemes

Page 3 of 4

PMB-X GUIDELINES 2021 47

Epilepsy

Epilepsy Epilepsy is a brain disorder that causes repeated seizures. There are many different types of epilepsy and many different kinds of seizures. A person having a seizure may seem confused, stare into space, wander, make unusual movements, or not be able to talk. Traumatic brain injuries, stroke, certain infections (such as cysticercosis, which is the leading cause of epilepsy worldwide), and pregnancy complications are some causes of epilepsy.

EPILEPSY

Diagnosis

Primary partial seizures

Disease identification card or disc recommended

Start with phenytoin or carbamazepine or sodium valproate or valproic acid or phenobarbitone

Primary generalised seizures Start with sodium valproate or valproic acid

Not tolerated or controlled?

Not tolerated or controlled?

Alternatives: Phenytoin or carbamazepine or sodium valproate or valproic acid or lamotrigine or topiramate or oxcarbazepine

Alternatives and/or addition: For absent seizures: ethosuximide For myoclonic seizures: clonazepam For tonic-clonic seizures: carbamazepine or phenytoin or lamotrigine or topiramate or oxcarbazepine

Ongoing seizures?

Ongoing seizures?

Add second drug Suggested combinations: Carbamazepine and sodium valproate or valproic acid, Phenytoin and sodium valproate or valproic acid, Sodium valproate or valproic acid and lamotrigine, Anticonvulsant and topiramate

Uncontrolled seizures Review for further management

Copyright: Council for Medical Schemes

Add second drug: If taking sodium valproate or valproic acid for absent seizures add ethosuximide, If taking sodium valproate or valproic acid for myoclonic seizures add clonazepam If taking sodium valproate or valproic acid for tonic-clonic seizures add lamotrigine

Uncontrolled seizures Review for further management

Page 1 of 2

48 PMB-X GUIDELINES 2021 *Treatment algorithm not to be associated with advertisement

Epilepsy

DYNA LEVETIRACETAM NOW AVAILABLE ON THE 2021 DISCOVERY PMB CDL MEDICINE 1 LIST UNDER “EPILEPSY”

CUSTOMER CARE LINE 0860 PHARMA (742 762) / +27 21 707 7000 www.pharmadynamics.co.za DYNA LEVETIRACETAM 250, 500, 750 mg. Each tablet contains 250, 500, 750 mg levetiracetam respectively. S3 A44/2.5/0368, 0369, 0370. NAM NS2 13/2.5./0178, 0179, 0180. For full prescribing information, refer to the professional information approved by SAHPRA, 18 October 2012. 1) Data on file. DLEB616/10/2020.

*Treatment algorithm not to be associated with advertisement PMB-X GUIDELINES 2021 49

Epilepsy

Applicable ICD 10 Coding: • G40 Epilepsy o G40.0 Localization-related (focal)(partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset o G40.1 Localization-related (focal)(partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures o G40.2 Localization-related (focal)(partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures o G40.3 Generalized idiopathic epilepsy and epileptic syndromes o G40.4 Other generalized epilepsy and epileptic syndromes o G40.5 Special epileptic syndromes o G40.6 Grand mal seizures, unspecified (with or without petit mal) o G40.7 Petit mal, unspecified, without grand mal seizures o G40.8 Other epilepsy o G40.9 Epilepsy, unspecified • G41 Status epilepticus o G41.0 Grand mal status epilepticus o G41.1 Petit mal status epilepticus o G41.2 Complex partial status epilepticus o G41.8 Other status epilepticus o G41.9 Status epilepticus, unspecified

Note: 50 PMB-X GUIDELINES 2021 1. Medical management reasonably necessary for the delivery of treatment

Glaucoma

Glaucoma

The second leading cause of blindness worldwide, glaucoma is a group of diseases that damages the eye’s optic nerve. Since there are often no early symptoms, 50% of people don’t know that they have the disease. Although there is currently no cure for glaucoma, if it’s caught early, patients can prevent vision loss.

GLAUCOMA Diagnosis

Closed angle

Open angle

Start with βblocker eye drops

Advanced and highrisk glaucoma Review for surgery

Contraindications?

Alternative first-line topical monotherapies: α2-agonist, carbonic anhydrase inhibitor, prostaglandin analogue

Intolerance?

Poor response?

Decrease dose or switch to alternative first line agent

Check adherence Increase dose if possible Switch to alternative first line agent

Inadequate response to monotherapy?

Check adherence Try combination therapy, using the first line agents

Intolerance?

Decrease dose or switch to alternative combination

Inadequate response to combination first line agents?

Check adherence Review for further medication or surgery

Copyright: Council for Medical Schemes

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PMB-X GUIDELINES 2021 51

Glaucoma

Glossary: • β-blocker – Beta-receptor blocker • α2-agonist – Alpha-2 receptor agonist Applicable ICD 10 Coding: • H40 Glaucoma o H40.0 Glaucoma suspect o H40.1 Primary open-angle glaucoma o H40.2 Primary angle-closure glaucoma o H40.3 Glaucoma secondary to eye trauma o H40.4 Glaucoma secondary to eye inflammation o H40.5 Glaucoma secondary to other eye disorders o H40.6 Glaucoma secondary to drugs o H40.8 Other glaucoma o H40.9 Glaucoma, unspecified • Q15.0 Congenital glaucoma

Note: 52 PMB-X GUIDELINES 2021 *Treatment algorithm not to be associated with advertisement 1. Medical management reasonably necessary for the delivery of treatment

When

GLAUCOMA

works on the nerves

causing tunnel vision, it’s time to reduce IOP

TEST • TREAT • PRESERVE

1,2

sight

Novartis South Africa (Pty) Ltd. Magwa Crescent West, Waterfall City, Jukskei View 2090. Tel. +27 11 347 6600. Co. Reg. No. 1946/020671/07. ZA2104080511. Exp. 30/03/2023

41339/04/21

References: 1. Weinreb RN, Khaw PT. Primary open-angle glaucoma. Lancet 2004; 363:1711-20. 2. Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review. JAMA. 2014; 311(18):1901-1911.

S4 TRAVATAN® Eye Drops, solution (0,004 %). Reg. No. 36/15.4/0333. Composition: 40 μ g of travoprost per ml in a sterile ophthalmic solution, preserved with polyquaternium-1 (POLYQUAD) 0,001 % (m/v). S4 DUOTRAV® eye drops, solution.

Reg. No. A40/15.4/0511. Composition: 1 ml of solution contains 40 μg travoprost and 6,83 mg timolol maleate equivalent to 5 mg timolol, preserved with 0,001 % (m/v) polyquaternium-1 (POLYQUAD®). S3 AZOPTIC® Eye Drops, suspension.

Reg. No. 34/15.4/0382. Composition: A sterile, aqueous suspension containing 10 mg brinzolamide per ml with benzalkonium chloride 0,01 % (m/v) as preservative. S4 AZARGA® eye drops, suspension. Reg. No. 44/15.4/0046. Composition: 1 ml of suspension contains 10 mg brinzolamide and 5 mg timolol (as timolol maleate). Preservative: benzalkonium chloride 0,01 % (w/v). Note: Before prescribing, consult full prescribing information.

Haemophilia

Haemophilia

Haemophilia is a bleeding disorder, usually inherited with an X-linked recessive inheritance pattern, which results from the deficiency of a coagulation factor. Haemophilia A results from the deficiency of clotting factor VIII. Haemophilia B results from the deficiency of clotting factor IX. Acquired haemophilia is a separate non-inherited HAEMOPHILIA condition. It is much rarer than congenital haemophilia and has an autoimmune-related aetiology with no genetic inheritance pattern.

Haemophilia A Diagnosis

Mild Disease Factor VIII 5-40% of the normal value

Moderate Disease Factor VIII 1-5% of the normal value

Desmopressin response study

Ineffective

Desmopressin prophylaxis before surgery and dental procedures

Factor VIII prophylaxis before surgery and dental procedures

Not NSAIDs or aspirin

Severe Disease Factor VIII < 1% of the normal value

All require bleeding charts Home-based action plan Factor VIII available for self initiated therapy

Effective

Pain: Use appropriate analgesics e.g. paracetamol and opiods

Disease identification card or disc recommended

If patient bleeds - initiate home-based action plan

Non-drug measures e.g. ice packs; bed rest; no weight bearing if possible; elevation; splint and staged mobilisation

Home-based initiation of Factor VIII

Mucous membrane only: use tranexamic acid

Episode aborted?

YES

Fill in bleeding chart Review patient at next opportunity Copyright: Council for Medical Schemes

NO

Admit for Factor VIII

Page 1 of 3

54 PMB-X GUIDELINES 2021 *Treatment algorithm not to be associated with advertisement

Human coagulation factor VIII

Need More INFO ?

www.octapharma.com | 011 465 4269 S4 octanate® 250, octanate® 500, octanate® 1 000. Powder for solution for injection. Registration Numbers: 36/30.3/0344/5/6. octanate® 250 IU contains 250 IU human coagulation factor VIII per vial. octanate® 500 contains 500 IU human coagulation factor VIII per vial. octanate® 1 000 contains 1 000 IU human coagulation factor VIII per vial. For full prescribing information refer to the professionaI information leaflet approved by SAHPRA. Pharmacological Classification: A 30.3 Biologicals (Blood fractions).

HCR: Octapharma SA (Pty) Ltd., Reg. No: 2011/003640/07, Building #3, Design Quarter Complex, Cnr. William Nicol Drive and Leslie Ave East, Fourways, 2191.

Tel: 011 465 4269. Fax: 011 465 4301. 08.NATE.NINE.DP.03/21

Haemophilia

Haemophilia B Diagnosis Disease identification card or disc recommended

Mild Disease Factor IX 5-25% of the normal value

Moderate Disease Factor IX 1-5% of the normal value

Will require Factor IX prophylaxis before surgery and dental procedures

Severe Disease Factor IX < 1% of the normal value

All require bleeding charts Home-based action plan Factor IX available for self initiated therapy

If patient bleeds - initiate home-based action plan

Pain: Use appropriate analgesics e.g. paracetamol and opiods Not NSAID’s or aspirin

Non-drug measures e.g. ice packs; bed rest; no weight bearing if possible; elevation; splint and staged mobilisation

Home-based initiation of Factor IX

Mucous membrane only: use tranexamic acid

Episode aborted?

YES

NO

Fill in bleeding chart Review patient at next opportunity

Admit for Factor IX

Glossary: • Factor VIII – Factor eight • Factor IX – Factor nine • NSAID’s – Non-steroidal anti-inflammatory agents Applicable ICD 10 Coding: • D66 Hereditary factor VIII deficiency • D67 Hereditary factor IX deficiency

Copyright: Council for Medical Schemes

Page 2 of 3

56 PMB-X GUIDELINES 2018 *Treatment algorithm not to be associated with advertisement

Hyperlipidaemia

Human coagulation factor IX

www.octapharma.com | 011 465 4269 S4 octanine® F 500, octanine® F 1 000. Powder for solution for injection. Registration Numbers: 37/30.3/0646/7. octanine® F 500: contains 500 IU human coagulation factor IX per vial. octanine® F 1 000: contains 1 000 IU human coagulation factor IX per vial. For full prescribing information refer to the professionaI information leaflet approved by SAHPRA. Pharmacological Classification: A 30.3 Biologicals (Blood fractions).

HCR: Octapharma SA (Pty) Ltd., Reg. No: 2011/003640/07, Building #3, Design Quarter Complex, Cnr. William Nicol Drive and Leslie Ave East, Fourways, 2191.

Tel: 011 465 4269. Fax: 011 465 4301. 08.NATE.NINE.DP.03/21

*Treatment algorithm not to be associated with advertisement PMB-X GUIDELINES 2021 57

Hyperlipidaemia

Hyperlipidaemia Hyperlipidaemia, or high cholesterol, refers to high levels of fat proteins in the blood. The condition can affect one fat protein or several. Most people will have no symptoms, but having hyperlipidaemia increases the risk of developing heart disease. Genetic predisposition, cigarette smoking, obesity, poor diet, and an inactive lifestyle can all lead to hyperlipidaemia.

HYPERLIPIDAEMIA Fasting plasma TC > 5mmol/l

YES

NO Manifest coronary heart disease?

Other risk factors?

E.g. diabetes, smoking, hypertension

YES

NO

Characterise hyperlipidaemia Full risk assessment, Fasting TG, TC, HDLC, LDLC Screen for secondary causes e.g. diabetes, hypothyroidism

Primary hyperlipidaemia

• •

Lifestyle modification Follow-up in 5 years

Secondary hyperlipidaemia Treat cause of secondary hyperlipidaemia Lifestyle modification Modify other risk factors Follow up

Does the patient have: Genetic dyslipidaemia with LDLC > 3mmol/l? or Established vascular disease?

Persistent hyperlipidaemia YES

NO

10 year MI risk > 20% 60 years age risk >30% Utilise Framingham Risk Score

YES

Consider drug therapy Life style & risk-factor modification

Copyright: Council for Medical Schemes

Resolved hyperlipidaemia

NO

Lifestyle modification Modify other risk factors Follow up

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58 PMB-X GUIDELINES 2021 *Treatment algorithm not to be associated with advertisement

hyperlipidaemia YES

NO

hyperlipidaemia

10 year MI risk > 20% 60 years age risk >30% Utilise Framingham Risk Score

YES

NO

Consider drug therapy Life style & risk-factor modification

Lifestyle modification Modify other risk factors Follow up

HYPERLIPIDAEMIA Copyright: Council for Medical Schemes Fasting

Page 1 of 3

plasma TC > 5mmol/l

YES

NO Manifest coronary heart disease?

Other risk factors?

E.g. diabetes, smoking, hypertension

YES

NO

Characterise hyperlipidaemia Full risk assessment, Fasting TG, TC, HDLC, LDLC Screen for secondary causes e.g. diabetes, hypothyroidism

Primary hyperlipidaemia

• •

Lifestyle modification Follow-up in 5 years

Secondary hyperlipidaemia Treat cause of secondary hyperlipidaemia Lifestyle modification Modify other risk factors Follow up

Does the patient have: Genetic dyslipidaemia with LDLC > 3mmol/l? or Established vascular disease?

Persistent hyperlipidaemia YES

NO

10 year MI risk > 20% 60 years age risk >30% Utilise Framingham Risk Score

YES

Consider drug therapy Life style & risk-factor modification

Copyright: Council for Medical Schemes

Resolved hyperlipidaemia

NO

Lifestyle modification Modify other risk factors Follow up

Page 1 of 3

*Treatment algorithm not to be associated with advertisement PMB-X GUIDELINES 2021 59

Predominant Predominant hypercholesterolaemia hypercholesterolaemia

Predominant Predominant hypertriglyceridaemia hypertriglyceridaemia (triglycerides (triglycerides >> 5mmol/l) 5mmol/l)

Consider the the use use of of aa statin statin Consider Use the the lowest lowest dose dose Use possible to to achieve achieve target target possible response response

Target achieved? achieved?

Target LDLC ≤≤ 3mmol/l 3mmol/l or or aa reduction reduction of of LDLC 45% 45% Is target target reached reached in in patients patients with with Is severe hypercholesterolaemia? hypercholesterolaemia? severe

NO NO

YES YES

Review Review management management

Follow up 6-12 Follow up 6-12 monthly monthly

Consider Consider fibrate fibrate therapy therapy Poor Poor response response Review Review

Glossary: Glossary: • TC – Total cholesterol •• TC cholesterol TG–– Total Triglycerides •• TG – Triglycerides HDLC – High density lipoproteins cholesterol •• HDLC Highdensity densitylipoproteins lipoproteinscholesterol cholesterol LDLC – – Low •• LDLC – Low density lipoproteins cholesterol MI – Myocardial infarct • MI – Myocardial infarct Applicable ICD 10 Coding: Applicable ICDPure 10 Coding: • E78.0 hypercholesterolaemia •• E78.0 E78.1 Pure Pure hypercholesterolaemia hyperglyceridaemia •• E78.1 E78.2 Pure Mixedhyperglyceridaemia hyperlipidaemia •• E78.2 hyperlipidaemia E78.3 Mixed Hyperchylomicronaemia •• E78.3 E78.4 Hyperchylomicronaemia Other hyperlipidaemia •• E78.4 hyperlipidaemia E78.5 Other Hyperlipidaemia, unspecified • E78.5 Hyperlipidaemia, unspecified

Copyright: Council for Medical Schemes Copyright: Council for Medical Schemes

60 PMB-X GUIDELINES 2021

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Hypertension

Hypertension Hypertension is the most important cardiovascular risk factor worldwide. Treatment of hypertension can reduce the risk to develop myocardial infarction, stroke, heart failure and death. Worldwide, the control of blood pressure remains inadequate. There may be multiple reasons for this poor control rate. One possible strategy to get more effective and more long-lasting blood pressure reductions could be to start early therapy and aim for early blood pressure control before there is irreversible damage to blood vessels and other target organs.

PMB-X GUIDELINES 2021 61

Hypertension

HYPERTENSION Measure BP in sitting position Systolic<130mmHg and diastolic< 85 mmHg

YES

Recheck in 1 year

NO

Diabetes?

CCF?

YES

Start drug treatment

NO

Systolic 140-159mmHg or diastolic 90-99mmHg Recheck within 2 months

Systolic>160mmHg and diastolic >100mmHg

Systolic >140mmHg or diastolic > 90mmHg

YES

Target organ disease

NO

Start drug treatment

Initial drug choices (unless contraindicated)

Systolic >140mmHg or diastolic > 90mmHg

Lifestyle modifications Review in 6 months

For uncomplicated hypertension Start with diuretic

Compelling Indications

Copyright: Council for Medical Schemes

62 PMB-X GUIDELINES 2018 *Treatment algorithm not to be associated with advertisement

Page 1 of 4

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NEW

Lower the blood pressure, not the adventure TRUST

24 years of Novartis Valsartan Legacy*1 REAL-WORLD EVIDENCE

Proven efficacy in global studies5,6

R172,76**4

EFFICACY IN HIGH RISK GROUPS

R200,76**4

BP reductions in the elderly, obese and patients with diabetes or isolated systolic hypertension6 ONE THIRD OF PATIENTS WILL NEED ≥ 3 ANTIHYPERTENSIVE AGENTS7

Clone of the Novartis originator Co-Exforge8,9

15973

**Prices include 15 % VAT; *24 years of valsartan monotherapy; BP = blood pressure; HCTZ = hydrochlorothiazide. Also available in: 5/160/25 mg and 10/160/25 mg.

References: 1. NOVARTIS. HOW A LEADER IN HEALTHCARE WAS CREATED OUT OF CIBA, GEIGY AND SANDOZ. Chapter 8 From life sciences to focus on healthcare | 1996-2013;160. 2. Novartis HTN Portfolio – BPA MIS 2018 Data Dosage Forms and Countries. 3. Novartis HTN Portfolio – Patients Treated Since Launch. 4. Novartis SA Co-Copalia 20200916_021 New Medicine. 5. Sison J, Assaad-Khalil SH, Najem R, et al. Real-world clinical experience of amlodipine/valsartan and amlodipine/valsartan/hydrochlorothiazide in hypertension: the EXCITE study. Curr Med Res Opin 2014:30(10);1937-1945. 6. Assaad-Khalil SH, Najem R, Sison J, et al. Real-world effectiveness of amlodipine/valsartan and amlodipine/valsartan/hydrochlorothiazide in high-risk patients and other subgroups. Vasc Health Risk Man 2015:11;71-78. 7. Düsing R. Optimizing blood pressure control through the use of fixed combinations. Vasc Health and Risk Man 2010:6:321-325. 8. Co-Copalia® Professional Information, February 2020. 9. Co-Exforge® Professional Information, July 2012.

CO COPALIA: 5 mg/160 mg/12.5 mg tablets: Each film-coated tablet contains 6,94 mg amlodipine besylate (equivalent to 5 mg amlodipine base), 160 mg valsartan and 12.5 mg hydrochlorothiazide. CO COPALIA: 10 mg/160 mg/12.5 mg tablets: Each film-coated tablet contains 13,87 mg amlodipine besylate (equivalent to 10 mg amlodipine base), 160 mg valsartan and 12.5 mg hydrochlorothiazide. CO COPALIA: 5 mg/160 mg/25 mg tablets: Each film-coated tablet contains 6,94 mg amlodipine besylate (equivalent to 5 mg amlodipine base), 160 mg valsartan and 25 mg hydrochlorothiazide. CO COPALIA: 10 mg/160 mg/25 mg tablets: Each film-coated tablet contains 13,87 mg amlodipine besylate (equivalent to 10 mg amlodipine base), 160 mg valsartan and 25 mg hydrochlorothiazide CO COPALIA™: 10 mg/320 mg/25 mg tablets: Each film-coated tablet contains 13,87 mg amlodipine besylate (equivalent to 10 mg amlodipine base), 320 mg valsartan and 25 mg hydrochlorothiazide. Pharmacological Classification: A 7.1.3 Vascular Medicines – other hypotensives. Indications: The treatment of essential hypertension in patients stabilised on individual components given at the same doses. CO COPALIA is not indicated for the initial therapy of hypertension. Contraindications: • Hypersensitivity to amlodipine, valsartan, hydrochlorothiazide and other sulfonamides or to any of the excipients of CO COPALIA •The use of CO COPALIA during pregnancy and lactation is contra-indicated. • CO COPALIA should be discontinued as soon as possible when pregnancy is suspected.

• A history of angioedema related to previous therapy with angiotensin receptor blockers (ARBs): These patients must never again be given these medicines. • Hereditary or idiopathic angioedema. • Severe hepatic impairment. • CO COPALIA should not be given to patients with Addison’s disease. • Anuria, severe renal impairment (creatinine clearance less than 30 ml/min). • Lithium therapy: Concomitant administration with CO COPALIA may lead to toxic blood concentrations of lithium. • Refractory hypokalaemia, hyponatraemia, hypercalcaemia and symptomatic hyperuricaemia. • Safety and efficacy have not been established in children. • Safety has not been established in porphyria. • Hypertrophic obstructive cardiomyopathy (HOCM). • Bilateral renal artery stenosis. Renal artery stenosis in patients with a single kidney. • Aortic stenosis. • Concomitant therapy with potassium sparing diuretics such as spironolactone, triamterene, amiloride.. Warnings/Precautions: • Risk of hypotension in sodium- and/or volume-depleted patients. • Caution is advised when administering CO COPALIA to patients with renal impairment or systemic lupus erythematosus. • Like other thiazide diuretics, HCTZ can cause hypokalemia, which may favor the onset of digitalis-induced cardiac arrhythmias. • Caution in patients with hypokalaemia, hyponatraemia, hypercalcaemia or symptomatic hyperuricaemia. • Disturbance of serum electrolyte balance (monitoring recommended), glucose tolerance and serum levels of cholesterol, tryglicerides and uric acid. • Not recommended in patients below 18 years of age. • Caution in patients with hepatic impairment or biliary obstructive disorders. 26/08/2020. Dosage: One tablet of CO COPALIA 5/160/12.5 mg or 10/160/12.5 mg or 5/160/25 mg or 10/160/25 mg or 10/320/25 mg daily. Interactions: • Monitoring when used concomitantly with lithium. • Caution when used concomitantly with medicines that may increase potassium levels. • Monitoring of serum potassium levels with skeletal muscle relaxants (e.g. curare derivatives). • Caution with medicines causing hypokalaemia (e.g. corticosteroids, ACTH, amphotericin, penicillin G, carbenoxolone, antiarrhythmics). • Concomitant treatment with NSAIDs may decrease antihypertensive effects. • Electrolyte imbalance with digitalis glycosides. • Caution with insulin and oral antidiabetic agents. • Caution with anionic exchange resins, allopurinol, amantadine, diazoxide, cytotoxic medicines, anticholinergic agents, vitamin D, calcium salts, ciclosporin and methyldopa. Adverse reactions: Amlodipine. Very common: Vomiting. Common and uncommon adverse reactions: • Headache, somnolence, dizziness, palpitations, flushing, abdominal pain, nausea, edema, fatigue, insomnia, mood changes including anxiety, tremor, hypoaesthesia, dysgeusia, paresthesia, syncope, visual impairment, diplopia, tinnitus, hypotension, dyspnea, rhinitis, dyspepsia, dry mouth, constipation, diarrhoea, alopecia, hyperhidrosis, pruritus, rash, purpura, skin discolouration, photosensitivity, back pain, muscle spasm, myalgia, arthralgia, micturion disorders, nocturia, pollakiura, gynecomastia, erectile dysfunction, asthenia, pain, malaise, chest pain, weight decreased, weight increased. • Very rare adverse reactions: hyperglycaemia, hypertonia, ventricular tachycardia, cough, gastritis, gingival hyperplasia, jaundice, urticaria, Thrombocytopenia, leucocytopenia, allergic reactions, peripheral neuropathy, arrhythmia, bradycardia, atrial fibrillation, myocardial infarction, vasculitis, pancreatic, hepatitis, angioedema, erythema multiforme, Steven- Johnson-Syndrome, Hepatic enzyme increased (mostly consistent with cholestasis). Valsartan. Less frequent reactions: • Vertigo, cough, abdominal pain, fatigue. Frequency not known: • viral infections, upper respiratory tract infection, sinusitis, pharyngitis, rhinitis, rash, pruritus, decrease in hemoglobin, decrease in hematocrit, increase of serum potassium, elevation of liver function values including increase of serum bilirubin, myalgia, elevation of serum creatinine, increased blood urea, hypersensitivity including serum sickness, vasculitis, angioedema, renal failure and impairment, thrombocytopenia, neutropenia, insomnia, decrease libido.

Hydrochlorothiazide. Frequent reactions: • Hypokalaemia and rise in blood lipids, hypomagnesemia, hyperuricaemia, hyponatraemia, urticaria and other forms of rash, decreased appetite, mild nausea and vomiting, orthostatic hypotension , impotence. • Less frequent: Jaundice or cholestasis, abdominal discomfort, photosensitivity reaction, hyperglycemia, glycosuria and worsening of diabetic metabolic state, sleep disorders, depression, visual impairment, pyrexia, dysrhythmias, , vasculitis, lupus erythematosus, toxic epidermal necrolysis, erythema multiforme, pancreatitis, pneumonitis, pulmonary edema, (hypersensitivity reactions), hypochloremic alkalosis, hypercalcaemia, diarrhoea, thrombocytopenia with or without purpura, agranulocytosis, leucopenia, pancytopenia, bone marrow depression, hemolytic or aplastic anemia, renal failure, acute angle-closure glaucoma. Pack Size: CO COPALIA 5/160/12.5 mg, 10/160/12.5 mg, 5/160/25 mg, 10/160/25 mg, and 10/320/25 mg contain 28 tablets per pack 26/08/2020. Registration No: CO-COPALIA: 5 mg/160 mg /12,5 mg tablets: 48/7.1.3/0872. COCOPALIA: 5 mg/160 mg/25 mg tablets: 48/7.1.3/0873. CO-COPALIA: 10 mg/160 mg/12,5 mg tablets: 48/7.1.3/0874. CO-COPALIA: 10 mg/160 mg/25 mg tablets: 48/7.1.3/0875. CO-COPALIA: 10 mg/320 mg/25 mg tablets: 48/7.1.3/0876. Before prescribing, consult full Professional Information, approved 19 February 2020.

CO-EXFORGE 5 mg/160 mg/12,5 mg: 44/7.1.3/0075; CO-EXFORGE 5 mg/160 mg/25 mg: 44/7.1.3/0076; CO-EXFORGE 10mg/160 mg/12,5 mg: 44/7.1.3/0077; CO-EXFORGE 10 mg/160 mg/25 mg: 44/7.1.3/0078; CO-EXFORGE 10 mg/320 mg/25 mg: 44/7.1.3/0079. Composition: CO-EXFORGE 5 mg/160 mg/12,5 mg: Each film-coated tablet contains 6,94 mg amlodipinebesylate (equivalent to 5 mg of amlodipine base), 160 mg of valsartan and 12,5 mg hydrochlorothiazide; CO-EXFORGE 5 mg/160 mg/25 mg: Each film-coated tablet contains 6,94 mg amlodipine besylate (equivalent to 5 mg of amlodipine base), 160 mg of valsartan and 25 mg hydrochlorothiazide; CO-EXFORGE 10 mg/160 mg/12,5 mg: Each film-coated tablet contains 13,87 mg amlodipine besylate (equivalent to 10 mg of amlodipine base), 160 mg of valsartan and 12,5 mg hydrochlorothiazide; CO-EXFORGE 10 mg/160 mg/25 mg: Each film-coated tablet contains 13,87 mg amlodipine besylate (equivalent to 10 mg of amlodipine base), 160 mg of valsartan and 25 mg hydrochlorothiazide; CO-EXFORGE 10 mg/320 mg/25 mg: Each filmcoated tablet contains 13,87 mg amlodipine besylate (equivalent to 10 mg of amlodipine base), 320 mg of valsartan and 25 mg hydrochlorothiazide. Before prescribing, consult full Professional Information, approved 27 July 2012.

Novartis South Africa (Pty) Ltd. Magwa Crescent West, Waterfall City, Jukskei View, 2090. Tel: +27 11 347 6600.

Company Reg. No.: 1946/020671/07. Kindly report all adverse events and quality complaints occurring with Novartis product within 24 hours • Email: patientsafety.sacg@novartis.com • Tel: 0861 929 929 Fax: +27 11 929 2262 • Or report adverse events directly through our website: https://psi.novartis.com/.

To report Quality Complaints email: qa.phzais@novartis.com. ZA2012078025 Exp. 12/2022.

Hypertension

• • • • • • • • • • • •

Angina: β-blocker, CCB Prior myocardial infarct or CAD: β-blocker and ACE inhibitor Post MI: β-blocker or ACE inhibitor (in patients with systolic dysfunction) Heart Failure: ACE inhibitor, β-blocker, diuretics (furosemide or spironolactone) Left ventricular hypertrophy: ACE inhibitor Stroke: Low dose diuretic, ACE inhibitor Type 1 Diabetes with proteinuria: ACE inhibitor, usually in combination with diuretic Type 2 Diabetes with microalbuminuria: ACE inhibitor or ARB, usually in combination with diuretic Type 2 Diabetes without proteinuria: ACE inhibitor, usually in combination with a diuretic Type 2 Diabetes with proteinuria: ACE inhibitor or ARB usually in combination with diuretic Isolated systolic hypertension (elderly): diuretic preferred (low dose thiazides), long-acting CCB Prostatism: α-blocker (this should not be used as monotherapy)

Start with low dose and titrate if necessary Goal BP not achieved: <140/90 mmHg in uncomplicated cases, <135/85mmHg in diabetes

No response or adverse event

Inadequate response but drug tolerated

Substitute another drug from different class

Add second agent from different class (especially diuretic if not already used)

Goal BP not achieved Add agent from different class or review

Copyright: Council for Medical Schemes

64 PMB-X GUIDELINES 2018 *Treatment algorithm not to be associated with advertisement

Page 2 of 4

R186.764

R158.764

COPALIA

®

Amlodipine besylate / Valsartan

Lower the blood pressure, not the adventure • Most affordable ARB/CCB in SA market at the time of print4 • Copalia® has a wealth of RWE from patients around the globe5-10 • 24 years of Novartis Valsartan Legacy*1

15508

*24 Years is of valsartan monotherapy; ARB – angiotensin II receptor blocker; CCB – calcium channel blocker; RWE – real-world evidence References: 1. NOVARTIS. HOW A LEADER IN HEALTHCARE WAS CREATED OUT OF CIBA, GEIGY AND SANDOZ. Chapter 8 From life sciences to focus on healthcare | 1996-2013;160. 2. Novartis HTN Portfolio - BPA MIS 2018 Data Dosage Forms and Countries. 3. Novartis HTN Portfolio - Patients Treated Since Launch. 4. South African Medicine Price Registry. Database of Medicine Prices. Price comparison: last accessed April 2020. Copalia new price: sent by DOH 12 June 2020. 5. Sison J, Assaad-Khalil SH, Najem R, et al. Real-world clinical experience of amlodipine/valsartan and amlodipine/valsartan/hydrochlorothiazide in hypertension: the EXCITE study. Curr Med Res Opin 2014:30(10);1937-1945. 6. Assaad-Khalil SH, Najem R, Sison J, et al. Real-world effectiveness of amlodipine/valsartan and amlodipine/valsartan/ hydrochlorothiazide in high-risk patients and other subgroups. Vasc Health Risk Man 2015:11;71-78. 7. Hu D, Liu L, Li W. Efficacy and Safety of Valsartan/Amlodipine Single-Pill Combination in 11,422 Chinese Patients with Hypertension: an Observational Study. Adv Ther 2014;31:762-775. 8. Xu R, Hu D, Liu L, et al. EFFICACY AND SAFETY OF VALSARTAN/AMLODIPINE SINGLE-PILL COMBINATION IN VERY ELDERLY OR ELDERLY CHINESE HYPERTENSIVE PATIENTS: SUB-GROUP ANALYSIS OF A PROSPECTIVE OBSERVATIONAL STUDY. J Hypertens 2014;32(1):e293. 9. Kizilirmak P, Berktas M, Yalçin MR, et al. Efficacy and safety of valsartan and amlodipine single-pill combination in hypertensive patients (PEAK study). Arch Turk Soc Cardiol 2013;41(5):406-417. 10. Kizilirmak P, Ar İdilhan, B İlerigelen. Efficacy and safety of valsartan/ amlodipine single-pill combination in patients with essential hypertension (PEAK LOW). Arch Turk Soc Cardiol 2014;42(4):339-348.

COPALIA® 5/160 mg tablet. COPALIA® 10/160 mg tablet. COPALIA® 5/320 mg tablet. COPALIA® 10/320 mg tablet. Pharmacological classification: A 7.1.3 Vascular medicines-other hypotensives.

Indications: Treatment of mild to moderate essential hypertension in patients whose blood pressure is normalized with the individual components in the same doses as the proposed fixed dose combination of COPALIA. Contraindications: • Sensitivity to any of the components of COPALIA. • A history of angioedema related to previous therapy with ACE inhibitors or angiotensin receptor blockers (ARBs): These patients must never again be given these medicines. • Hereditary or idiopathic angioedema. • Hypertrophic obstructive cardiomyopathy (HOCM. • Aortic stenosis. • Severe renal function impairment (creatinine clearance less than 30 ml/min). • Bilateral renal artery stenosis. • Renal artery stenosis in patients with a single kidney. • Concomitant therapy with potassium sparing diuretics such as spironolactone, triamterene, amiloride.

• Porphyria. • Lithium therapy: Concomitant administration with COPALIA may lead to toxic blood concentrations of lithium. • Pregnancy and lactation. Warnings/Precautions: Risk of hypotension in sodium- and/or volume-depleted patients. • Severe renal impairment (creatinine clearance < 30 ml/min) and dialysis. • Caution in patients with hepatic impairment or biliary obstructive disorders. Caution in use with potassium supplements, potassium sparing diuretics or other medicines that may increase potassium levels. • Caution when driving or operating machines. • Not recommended in patients below 18 years of age. Interactions: • Caution and monitoring of serum potassium levels when used concomitantly with potassium supplements, potassium sparing diuretics, salt substitutes containing potassium, or other drugs that may increase potassium level. Adverse reactions: • The most common and uncommon adverse reactions are: Nasopharyngitis, influenza, headache, oedema, peripheral oedema, pitting oedema, facial oedema, hot flush, fatigue, flushing, asthenia, dizziness, somnolence, dizziness postural, paraesthesia, vertigo, tachycardia, palpitations, orthostatic hypotension, cough, pharyngolaryngeal pain, diarrhoea, nausea, abdominal pain, constipation, dry mouth, rash, erythema, joint swelling, back pain, arthralgia. Rare adverse reactions are: visual disturbance, anxiety, tinnitus, syncope, hypotension, hyperhidrosis, exanthema, pruritus, muscle spasm, sensation of heaviness, pollakiuria, polyuria, erectile dysfunction • Rare adverse reactions but potentially serious are: Hypersensitivity. • Additional potentially serious adverse experiences reported with amlodipine monotherapy are: Thrombocytopenia, leucopenia, allergic reactions, peripheral neuropathy, arrhythmia, bradycardia, atrial fibrillation, myocardial infarction, vasculitis, pancreatic, hepatitis, angioedema, erythema multiforme, Steven-Johnson-Syndrome, Hepatic enzyme increased (mostly consistent with cholestasis). • Additional potentially serious adverse experiences reported in clinical trials with valsartan monotherapy are: Neutropenia, thrombocytopenia, hypersensitivity including serum sickness, vasculitis, angioedema, renal failure and impairment.

Registration numbers: COPALIA® 5/160 mg tablet: 45/7.1.3/0850. COPALIA® 10/160 mg tablet: 45/7.1.3/0851. COPALIA® 5/320 mg tablet: 45/7.1.3/1013.* COPALIA® 10/320 mg tablet: 45/7.1.3/1014.* Before EXFORGE® 5/160 mg; EXFORGE® 10/160 mg; EXFORGE® 5/320 mg; EXFORGE® 10/320 mg. Composition: EXFORGE 5/160 prescribing, consult full Professional Information approved 11 June 2015. mg: Each film-coated tablet contains 6,94 mg amlodipine besylate (equivalent to 5 mg amlodipine base) and 160 mg valsartan. EXFORGE 10/160 mg: Each film-coated tablet contains 13,87 mg amlodipine besylate (equivalent to 10 mg amlodipine base) and 160 mg valsartan. EXFORGE 5/320 mg: Each film-coated tablet contains 6,94 mg amlodipine besylate (equivalent to 5 mg amlodipine base and 320 mg valsartan. EXFORGE 10/320 mg: Each film-coated tablet contains 13,87 mg amlodipine besylate (equivalent to 10 mg amlodipine base) and 320 mg valsartan. Registration Numbers: EXFORGE 5/160 mg: 41/7.1.3/0291. EXFORGE 10/160 mg: 41/7.1.3/0292. EXFORGE 5/320 mg: 41/7.1.3/0770. EXFORGE 10/320 mg: 41/7.1.3/0771. Before prescribing, consult full Professional Information approved 26 October 2012. *Copalia® 5/160 mg and 10/160 mg available Novartis South Africa (Pty) Ltd. Magwa Crescent West, Waterfall City, Jukskei View, 2090. Tel: +27 11 347 6600. Company Reg. No.: 1946/020671/07.

Kindly report all adverse events and quality complaints occurring with Novartis product within 24 hours • Email: patientsafety.sacg@novartis.com • Tel: 0861 929 929 • Fax: +27 11 929 2262 • Or report adverse events directly through our website: https://psi.novartis.com/ To report Quality Complaints email: qa.phzais@novartis.com. ZA2008123866. Exp. 08/2022

INTRODUCING OUR

NEW VALSARTAN RANGE

REDUCE THE RIPPLE EFFECT ELEVATED BP IS A RISK FACTOR FOR:1

• myocardial infarction • heart failure • stroke and renal disease VALSARTAN HAS:2

• proven efficacy in a broad range of patients • a placebo-like side effect profile for common adverse events CONVENIENTLY PACKED IN 30 TABLETS.

CUSTOMER CARE LINE 0860 PHARMA (742 762) / +27 21 707 7000 www.pharmadynamics.co.za REGOVAL 80, 160 mg. Each tablet contains 80, 160 mg valsartan respectively. S3 A43/7.1.3/0548, 0549. For full prescribing information, refer to the professional information approved by SAHPRA, October 2019. REGOVAL CO 80/12,5, 160/12,5, 160/25 mg. Each tablet contains 80, 160, 160 mg valsartan respectively and 12,5, 12,5, 25 mg hydrochlorothiazide respectively. S3 A44/7.1.3/0018, 0019, 0020. For full prescribing information, refer to the professional information approved by SAHPRA, September 2019.

1) Williams B, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Journal of Hypertension 2018;36:1953-2041. 2) Black HR, et al. Valsartan, more than a decade of experience. Drugs 2009;69(17):2393-2414. RGLB703/01/2021.

66 PMB-X GUIDELINES 2021 *Treatment algorithm not to be associated with advertisement

Hypertension

Glossary: • α-blocker – Alpha-receptor blocker • ACE inhibitor – Angiotensin converting enzyme inhibitor • ARB – Angiotensin receptor blocker • BP – Blood pressure • β-blocker – Beta-receptor blocker • CCB – Calcium channel blocker • CCF – Chronic / Congestive cardiac failure • CAD – Coronary artery disease • LV – Left ventricular • MI – Myocardial infarct Applicable ICD 10 Coding: • I10 Essential (primary) hypertension • I11 Hypertensive heart disease o I11.0 Hypertensive heart disease with (congestive) heart failure o I11.9 Hypertensive heart disease without (congestive) heart failure • I12 Hypertensive renal disease o I12.0 Hypertensive renal disease with renal failure o I12.9 Hypertensive renal disease without renal failure • I13 Hypertensive heart and renal disease o I13.0 Hypertensive heart and renal disease with (congestive) heart failure o I13.1 Hypertensive heart and renal disease with renal failure o I13.2 Hypertensive heart and renal disease with both (congestive) heart failure and renal failure o I13.9 Hypertensive heart and renal disease, unspecified • I15 Secondary hypertension o I15.0 Renovascular hypertension o I15.1 Hypertension secondary to other renal disorders o I15.2 Hypertension secondary to endocrine disorders o I15.8 Other secondary hypertension o I15.9 Secondary hypertension, unspecified • O10 Pre-existing hypertension complicating pregnancy, childbirth and the puerperium o O10.0 Pre-existing essential hypertension complicating pregnancy, childbirth and the puerperium o O10.1 Pre-existing hypertensive heart disease complicating pregnancy, childbirth and the puerperium o O10.2 Pre-existing hypertensive renal disease complicating pregnancy, childbirth and the puerperium o O10.3 Pre-existing hypertensive heart and renal disease complicating pregnancy, childbirth and the puerperium o O10.4 Pre-existing secondary hypertension complicating pregnancy, childbirth and the puerperium o O10.9 Unspecified pre-existing hypertension complicating pregnancy, childbirth and the puerperium • O11 Pre-existing hypertensive disorder with superimposed proteinuria

Copyright: Council for Medical Schemes

Page 3 of 4

*Treatment algorithm not to be associated with advertisement PMB-X GUIDELINES 2018 67

Hypothyroidism

Hypothyroidism Hypothyroidism is a condition in which the thyroid gland is not able to produce enough thyroid hormone. Since the main purpose of thyroid hormone is to drive the body’s metabolism, patients will have symptoms associated with a slowHYPOTHYROIDISM metabolism.

Clinical symptoms suggestive of hypothyroidism Serum TSH

Normal

Elevated TSH

No further testing

Do FT4

Decreased FT4

Normal But TSH > 10

Overt hypothyroidism

Consider sub-clinical hypothyroidism Repeat FT4 and TSH

If TSH persistently elevated and patient symptomatic consider treating as for hypothyroidism

Start thyroxine 50µg/day for 2 weeks Then 100µg/day In elderly and patients with cardiac disease use low dose thyroxine

Monitor TSH and FT4 every 3 months for first year, then annually

Applicable ICD 10 Coding: (continued) Glossary: Glossary: • E03 Other hypothyroidism • TSH – Thyroid stimulating hormone o E03.0 Congenital hypothyroidism with diffuse goitre • TSH – Thyroid stimulating hormone • FT4 – Free thyroxine o E03.1 Congenital hypothyroidism without goitre

•

FT4 – Free thyroxine

o E03.2 Hypothyroidism due to medicaments and other Applicable ICD 10 Coding: exogenous substances • E01.8 Other iodine-deficiency-related o E30.3 Postinfectious hypothyroidism Applicable ICD 10 Coding: thyroid disorders and allied conditions o E03.4 Atrophy thyroid (acquired) • iodine-deficiency E01.8 Other iodine-deficiency-related thyroid of disorders and allied conditions • E02 Subclinical o E03.5 Myxoedema coma • E02 Subclinical iodine-deficiency hypothyroidism hypothyroidism o E03.8 Other specified hypothyroidism

Copyright: Council for Medical Schemes

o E03.9 Hypothyroidism, unspecified • E89.0 Postprecedural hypothyroidism

68 PMB-X GUIDELINES 2021 *Treatment algorithm not to be associated with advertisement

Page 1 of 2

Multiple Sclerosis

Multiple Sclerosis Multiple sclerosis (MS) occurs when there is a breakdown of myelin, a fatty white substance wrapped around axons, which are long strands that carry messages from and between brain cells. When myelin starts to break down, communication between brain cells slows, leading to muscle weakness and problems with movement, balance, sensation and vision. MS can be relapsing-remitting, in which symptoms occur then disappear for weeks or months and then may reappear, or progressive, which is marked by a gradual decline in function.

Diagnosis

Chronic progressive

Relapsing-remitting

Benign

Active disease

Reassure Continued observation

Frequent relapse Secondary progressive

Consider Betainterferon

Symptomatic treatment: Spasticity Consider: baclofen Hyperreflexic bladder Consider: oxybutinin or imipramine or amitriptyline Pain Consider: amitriptyline or carbamazepine or opioid analgesic

Supportive therapy

Acute relapse

IV methylprednisolone For 5 days (500mg to 1g daily)

Response?

NO Review

YES Continue therapy

Glossary:

• IV – Intravenous Applicable ICD 10 Coding:

• G35 Multiple sclerosis

PMB-X GUIDELINES 2021 69

Parkinson’s Disease

Parkinson’s Disease Parkinson’s disease is a neurodegenerative disorder in which dopamine-producing brain cells die off, resulting in tremors, muscle stiffness, loss of balance and slow movement. Additional symptoms may include emotional changes and disrupted sleep.

PARKINSON’S DISEASE Diagnosis

Cognition intact

YES

NO

Consider selegiline or dopamine agonist

Functionally disabled

Functionally disabled Review

Levodopa with carbidopa in combination and/or dopamine agonist

Age < 60 Failed therapy: Review YES

Tremor predominant Consider amantadine or anticholinergics

NO

Levodopa with carbidopa in combination Consider addition of dopamine agonist

Levodopa with carbidopa in combination Consider addition of amantadine Advancing disease

Add dopamine agonist

70 PMB-X GUIDELINES 2021 Applicable ICD 10 Coding:

•

G20 Parkinson's disease

PARKINSON’S DISEASE

Parkinson’s Disease

Diagnosis

Cognition intact

YES

NO

Consider selegiline or dopamine agonist

Functionally disabled

Functionally disabled Review

Levodopa with carbidopa in combination and/or dopamine agonist

Age < 60 Failed therapy: Review YES

Tremor predominant Consider amantadine or anticholinergics

NO

Levodopa with carbidopa in combination Consider addition of dopamine agonist

Levodopa with carbidopa in combination Consider addition of amantadine Advancing disease

Add dopamine agonist

Applicable ICD 10 Coding: • G20 Parkinson's disease • G21 Secondary parkinsonism o G21.0 Malignant neuroleptic syndrome o G21.1 Other drug-induced secondary parkinsonism o G21.2 Secondary parkinsonism due to other external agents o G21.3 Postencephalitic parkinsonism o G21.8 Other secondary parkinsonism o G21.9 Secondary parkinsonism, unspecified

Copyright: Council for Medical Schemes

Page 1 of 2

PMB-X GUIDELINES 2021 71

Rheumatoid Arthritis

Rheumatoid Arthritis Rheumatoid arthritis is an autoimmune disease in which the body’s immune system mistakenly attacks the joints. This creates inflammation that causes the synovium to thicken, resulting in swelling and pain, in and around the joints.

RHEUMATOID ARTHRITIS Diagnosis Active erosive disease?

NO

YES

Non drug measures (rest, range-of-motion exercises) and add NSAID

Non drug measures (rest, range-of-motion exercises) and add NSAID

Adequate response?

YES

NO

Continue therapy

Therapy fails

NO

YES

Add a DMARD e.g. methotrexate or sulphasalazine Corticosteroids may be necessary at all of these levels, to enable patient to be more functional while waiting for the DMARD to be effective

Adequate response?

Continue therapy YES

Continue therapy

NO

Review

72 PMB-X GUIDELINES 2021 *Treatment algorithm not to be associated with other advertisement Consider DMARD therapies:

e.g.

FULL DOSE RANGE – ONLY 30 mg GENERIC 1

For further product information contact PHARMA DYNAMICS P O Box 30958 Tokai Cape Town 7966 Fax +27 21 701 5898 Email info@pharmadynamics.co.za CUSTOMER CARE LINE 0860 PHARMA (742 762) / +27 21 707 7000 www.pharmadynamics.co.za EXTRIB 30, 60, 90, 120 mg. Each film coated tablet contains 30, 60, 90, 120 mg etoricoxib respectively. S3 A50/3.1/0234/0235/0236/0237.

For full prescribing information, refer to the package insert approved by SAHPRA, 15 June 2020. 1) IQVIA MAT Units, February 2021. EBA1/05/2021.

*Treatment algorithm not to be associated with advertisement PMB-X GUIDELINES 2021 73

YES

NO

Rheumatoid Arthritis

Continue therapy

Therapy fails

NO

YES

Add a DMARD e.g. methotrexate or sulphasalazine Corticosteroids may be necessary at all of these levels, to enable patient to be more functional while waiting for the DMARD to be effective

Adequate response?

Continue therapy YES

Continue therapy

NO

Review Consider other DMARD therapies: e.g. penicillamine, azathioprine, cyclophosphamide, leflunamide

Glossary: • DMARD – Disease modifying antirheumatic drugs • NSAID – Non-steroidal anti-inflammatory agents Copyright: Council for Medical Schemes

Applicable ICD 10 Coding: • M05 Seropositive rheumatoid arthritis o M05.0 Felty's syndrome o M05.1 Rheumatoid lung disease (J99.0*) o M05.2 Rheumatoid vasculitis o M05.3 Rheumatoid arthritis with involvement of other organs and systems o M05.8 Other seropositive rheumatoid arthritis o M05.9 Seropositive rheumatoid arthritis, unspecified • M06 Other rheumatoid arthritis o M06.0 Seronegative rheumatoid arthritis o M06.1 Adult-onset Still's disease o M06.2 Rheumatoid bursitis o M06.3 Rheumatoid nodule o M06.4 Inflammatory polyarthropathy o M06.8 Other specified rheumatoid arthritis o M06.9 Rheumatoid arthritis, unspecified • M08.0 Juvenile rheumatoid arthritis

Page 1 of 2

Note: 1. Medical management reasonably necessary for the delivery of treatment described in this algorithm is included within this benefit, subject to the application of managed health care interventions by the relevant medical scheme.

2. To the extent that a medical scheme applies managed health care interventions in respect of this benefit, for example clinical protocols for diagnostic procedures or medical management, such interventions must – 74 PMB-X GUIDELINES 2021 *Treatment algorithm not to be associated with advertisement a. not be inconsistent with this algorithm; b. be developed on the basis of evidence-based medicine, taking into

CONSIDER THESE MULTIPLE BENEFITS… …FOR YOUR PATIENTS WITH

OSTEOARTHRITIS

30 mg strength provides a lower dose option in this indication 1,2 The convenience of once-daily dosing 1,2

Choice of the original or the clone

EXINEF 30 mg tablets are now only 3

May be taken with or without food 1,2

INDICATED FOR PATIENTS WITH OSTEOARTHRITIS 1,2

1,2

R81.37 SINGLE EXIT PRICE INCLUDING VAT

RECOMMENDED DOSE

In some patients with insufficient relief from symptoms, the dose may be increased to

30 mg ONCE DAILY

60 mg ONCE DAILY

®

®

REFERENCES: 1. Approved ARCOXIA® package insert, March 2020. 2. Approved EXINEF® package insert, May 2020. 3. SA Medicine Price Registry: Database of Medicine Prices, December 2020.

Available at: http://mpr.gov.za.

INDICATIONS: ARCOXIA®/EXINEF® is indicated for: symptomatic relief of osteoarthritis (OA) and rheumatoid arthritis (RA); treatment of ankylosing spondylitis (AS); treatment of acute gouty arthritis; short term relief of acute pain, treatment limited to a maximum period of 8 days; treatment of primary dysmenorrhoea; treatment of moderate to severe acute post-operative pain associated with dental surgery.

SELECTED SAFETY INFORMATION: CONTRAINDICATIONS: Known hypersensitivity to etoricoxib or to any of the excipients of ARCOXIA®/EXINEF®, patients who have developed signs of asthma, acute rhinitis, nasal polyps, angioedema or urticaria following the administration of aspirin or other non-steroidal anti-inammatory drugs (NSAIDs) including ARCOXIA®/EXINEF®. Active peptic ulceration or active gastrointestinal (GI) bleeding, severe hepatic dysfunction (Child-Pugh score greater than 9 or serum albumin less than 25 g/L), severe renal impairment (eCrCl less than 30 mL/min), uncontrolled hypertension, pregnancy and lactation, children and adolescents under 16 years of age, inammatory bowel disease, congestive heart failure (NYHA II – IV), established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease, perioperative analgesia in the setting of coronary artery bypass surgery (CABG), concomitant administration with ARCOXIA®/EXINEF® may lead to toxic blood concentrations of lithium and digoxin (approximate increase of 33 % in digoxin Cmax in healthy volunteers). WARNINGS AND SPECIAL PRECAUTIONS: ARCOXIA®/EXINEF® may predispose patients to cardiovascular events, gastrointestinal events or cutaneous reactions which may be fatal. Long-term administration of NSAIDs such as ARCOXIA®/EXINEF®, has resulted in renal papillary necrosis and other renal injury. Selective COX-2 inhibitor class of medicines, such as ARCOXIA®/EXINEF®, are associated with an increased risk of arterial thrombotic events (especially myocardial infarction (MI) and stroke). As the cardiovascular risks may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used. Caution should be used when initiating treatment with ARCOXIA®/EXINEF® in patients with dehydration. It is advisable to rehydrate patients prior to starting therapy with ARCOXIA®/EXINEF®. Caution should be exercised in patients with history of cardiac failure, left ventricular dysfunction or hypertension, and in patients with pre-existing oedema from any other reason. ARCOXIA®/EXINEF® is not a substitute for aspirin for cardiovascular prophylaxis because of its lack of effect on platelets. Because ARCOXIA®/EXINEF® does not inhibit platelet aggregation, antiplatelet therapies should not be discontinued. Concomitant administration of low-dose aspirin with ARCOXIA®/EXINEF® increases the rate of gastrointestinal adverse effects. Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported in association with the use of selective COX-2 inhibitors such as ARCOXIA®/EXINEF®. When using ARCOXIA®/EXINEF® in the elderly and in patients with renal, hepatic or cardiac dysfunction, medically appropriate supervision should be intensified. Upper gastrointestinal complications: perforations, ulcers or bleedings (PUBs), some of them resulting in a fatal outcome, have occurred in patients treated with ARCOXIA®/EXINEF® Elevations of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) have been reported in approximately 1% of patients in clinical trials treated for up to 1 year with ARCOXIA®/EXINEF® 60 mg and 90 mg daily. Contains lactose. Patients with the rare hereditary conditions of galactose intolerance e.g. galactosaemia, Lapp lactase deficiency, glucose-galactose malabsorption or fructose intolerance should not take ARCOXIA®/EXINEF®. SIDE EFFECTS: Very common (≥ 1/10) and common (≥ 1/100, < 1/10) side effects: Post-dental extraction alveolar osteitis (dry socket), oedema/uid retention, dizziness, headache, palpitations, hypertension, gastrointestinal disorders (e.g. abdominal pain, atulence, heartburn), diarrhoea, dyspepsia, epigastric discomfort, nausea, ecchymosis, asthenia/fatigue, u-like disease, increased ALT and AST.

MSD (Pty) Ltd (Reg. No. 1996/003791/07), Private Bag 3, Halfway House, 1685. Tel: 011 655 3000. www.msd.co.za

For full prescribing information refer to the package insert approved by the Medicines Regulatory Authority.

S3 ARCOXIA® – Reg. No’s: 30 mg – 44/3.1/0063, 60 mg – 37/3.1/0399, 90 mg – 37/3.1/0400, 120 mg – 37/3.1/0401. Each ARCOXIA tablet contains 30 mg, 60 mg, 90 mg or 120 mg of etoricoxib.

S3 EXINEF® – Reg. No’s: 30 mg – 44/3.1/0898, 60 mg – 44/3.1/0899, 90 mg – 44/3.1/0900, 120 mg – 44/3.1/0901. Each EXINEF tablet contains 30 mg, 60 mg, 90 mg or 120 mg of etoricoxib.

Copyright © 2021 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.to All rights 04/23 *Treatment algorithm not be reserved. associated with advertisement PMB-X GUIDELINESZA-CXB-110002 2021 2018

75

Schizophrenia

Schizophrenia Schizophrenia represents a heterogeneous group of disorders that may differentially affect presentation, course, treatment response, and outcome. A common element is psychosis, which is integral to the diagnosis. Antipsychotic medications play a central role in recommendations related to pharmacotherapy.

Over the course of schizophrenia, psychotic symptoms can come and go, and decision making regarding use of antipsychotics is influenced by treatment response and side effects, as well as phase of illness (acute vs stable).

SCHIZOPHRENIA Make Diagnosis

Typical antipsychotic or atypical antipsychotic agent most appropriate and cost effective to suit patient’s need

No response to one?

Check adherence Use another typical antipsychotic or atypical antipsychotic

Adherent but no response?

Non-adherence?

Use depot formulation

Use another typical antipsychotic or atypical antipsychotic

No response?

No response?

Use another depot formulation No response?

Clozapine

If partial response try adding augmentation agent e.g. mood stabiliser, antidepressant or ECT

No response or refusal to use clozapine?

76 PMB-X GUIDELINES 2021 *Treatment algorithm not to be associated with advertisement

• Parity priced to Zoxadon

(market leading risperidone)1

• Spontaneous disintegration2 • Pleasant Peppermint flavour

CUSTOMER CARE LINE 0860 PHARMA (742 762) / +27 21 707 7000 www.pharmadynamics.co.za ZOXADON ODT 0,5 mg, 1 mg, 2 mg. Each orodispersible tablet contains 0,5 mg, 1 mg, 2 mg risperidone respectively. S5 A46/2.6.5/0362, 0363, 0364.

For full prescribing information, refer to the professional information approved by SAHPRA, May 2019. 1) IQVEA MAT Units November 2020. 2) Data on file.

ZNODT647/03/2021.

cost effective to suit patient’s need

Schizophrenia

No response to one?

Check adherence Use another typical antipsychotic or atypical antipsychotic

Adherent but no response?

Non-adherence?

Use depot formulation

Use another typical antipsychotic or atypical antipsychotic

No response?

No response?

Use another depot formulation No response?

Clozapine

If partial response try adding augmentation agent e.g. mood stabiliser, antidepressant or ECT

No response or refusal to use clozapine?

Review for combination therapy of atypical antipsychotic as well as typical antipsychotic agents and ECT

Glossary: • ECT – Electroconvulsive therapy Copyright: Council for Medical Schemes

Applicable ICD 10 Coding: • F20 Schizophrenia o F20.0 Paranoid schizophrenia o F20.1 Hebephrenic schizophrenia o F20.2 Catatonic schizophrenia o F20.3 Undifferentiated schizophrenia o F20.4 Post-schizophrenic depression o F20.5 Residual schizophrenia o F20.6 Simple schizophrenia o F20.8 Other schizophrenia o F20.9 Schizophrenia, unspecified

Page 1 of 2

Note: 1. Medical management reasonably necessary for the delivery of treatment described in this algorithm is included within this benefit, subject to the application of managed health care interventions by the relevant medical scheme.

78 PMB-X GUIDELINES 2021 2. To the extent that a medical scheme applies managed health care interventions in respect of this benefit, for example clinical protocols for

Systemic Lupus Erythematosus

Systemic Lupus Erythematosus Lupus is an autoimmune disease that can damage any part of the body (skin, joints, and/or organs). This disease can be severe and potentially life-threatening. It can cause permanent organ damage. However, many people with lupus experience a mild version of it. Currently, there’s no known cure for lupus.

Education and appropriate lifestyle modification, no smoking

Diagnosis

NO

Symptomatic SLE? YES Mild to moderate disease, non-organ threatening

Severe life-threatening or organ-threatening disease

Photosensitivity?

NO

Consider: NSAID’s for symptomatic musculoskeletal manifestations Topical corticosteroids for skin disease Low dose corticosteroids e.g. prednisone 5mg/day

YES Consider: High dose corticosteroids orally or pulse IV or cytotoxic drugs e.g. cyclophosphamide or methotrexate

Sunscreen

Antiphospholid antibodies?

YES

NO

Consider low dose aspirin Disease controlled and in remission?

YES Consider the need for continued therapy

NO Review for alternative therapy

Glossary: Glossary: IV – Intravenous • IV•– Intravenous • NSAID’s – Non-steroidal anti-inflammatory agents • NSAID’s – Non-steroidal anti-inflammatory agents • –SLE – Systemic erythematosus • SLE Systemic lupus lupus erythematosus

Applicable ICD 10 Coding: Applicable ICD 10 Coding: • M32 Systemic lupus erythematosus • M32 Systemic lupus erythematosus o M32.0 systemic lupus erythematosus o Drug-induced M32.0 Drug-induced systemic lupus erythematosus o M32.1 lupus erythematosus with organ or system involvement o Systemic M32.1 Systemic lupus erythematosus with organ or system involvement o M32.8 systemic lupus erythematosus o Other M32.8forms Otherof forms of systemic lupus erythematosus o M32.9 lupus erythematosus, unspecified o Systemic M32.9 Systemic lupus erythematosus, unspecified • L93 erythematosus • Lupus L93 Lupus erythematosus o Discoid L93.0 Discoid lupus erythematosus o L93.0 lupus erythematosus o Subacute L93.1 Subacute cutaneous lupus erythematosus o L93.1 cutaneous lupus erythematosus o Other L93.2local Other localerythematosus lupus erythematosus o L93.2 lupus

Note:

PMB-X GUIDELINES 2021 79

1. Medical management reasonably necessary for the delivery of treatment

Ulcerative Colitis

Ulcerative Colitis Ulcerative colitis is a chronic inflammatory bowel disease (IBD) distinguished by inflammation of the large intestine (rectum and colon). The innermost lining of the large intestine becomes inflamed, and ulcers may form on the surface. The condition can also affect eyes, skin and joints.

80 PMB-X GUIDELINES 2021 *Treatment algorithm not to be associated with advertisement

! ! e re

BREAK f

from gut health issues

A MULTIVITAMIN FOR YOUR GUT

ANTI-INFLAMMATORY

PROBIOTIC BOTANICAL

GENTLE NATURAL

BOTANICAL LAXATIVE

1 > TRANSPARENT LABELING.

2

> PRODUCED IN A GMP FACILITY. > SCIENTIFICALLY FORMULATED. > ETHICALLY CHOSEN SUPPLIERS.

3 No artificial additives, colourants or flavourants.

Free from lactose, gluten, sugar, tartrazine & soya.

progast.global PMB-X GUIDELINES 2021 81

This unregistered medicine has not been evaluated by the SAHPRA for its quality, safety or intended use.

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