23 minute read
Cannabis and Mental Illness
Written by Professor Brendan Kelly, Professor of Psychiatry, Trinity College Dublin
Cannabis is the most common illegal drug that I come across in clinical practice, but public discussion about cannabis is often very confused. The problem is that two questions about the drug get mixed up together. First, is cannabis bad for mental health? Second, if cannabis is bad for mental health, what should we do about it? These two questions are linked, but are also separate in several important respects. With regard to the first question, overwhelming evidence now confirms that cannabis is bad for mental health. In 2017, the US National Academies of Sciences, Engineering and Medicine reviewed all of the evidence (positive and negative) pertaining to likely links between cannabis and psychosis, and concluded that the higher the cannabis use, the greater the risk of schizophrenia and other psychoses. Looking at the effects of cannabis more broadly, the College of Psychiatrists of Ireland summarised the evidence in 2021 in a (freely available) paper titled “Cannabis and Your Mental Health.” The College points out that “cannabis can make existing mental illness get worse. Cannabis use can trigger new mental illness, that is, sometimes people become mentally ill for the first time very soon after using cannabis. The number of people admitted to psychiatric hospitals in Ireland with a cannabis related diagnosis has trebled since 2002.” The College adds that “cannabis is linked with psychosis. Cannabis users are three to four times more likely to develop psychosis than those who never use it”. In addition, “cannabis can make depression worse. It can also bring on depression.” Early use is especially troubling, because “the younger a person begins using cannabis, the more at risk they are of developing a major depressive disorder. Cannabis use disorder has been associated with a greater risk of developing bipolar affective disorder and having more frequent relapses. Cannabis can make anxiety disorders worse. Adolescent cannabis users are at higher risk of developing anxiety disorders, particularly those people who use high-potency cannabis.” Finally, “cannabis use is also associated with self-harm and suicidal behaviour” because “young people who smoke cannabis regularly are three times more likely to attempt suicide than people who never use cannabis. Long-term cannabis users are more likely to report thoughts of suicide than non-users. In 2018, cannabis was the most common street drug used among men aged 15-24 who had self-harmed in Ireland.”
I can confirm all of this from clinical practice: cannabis presents a systematic risk to mental health. The situation improves if the person stops smoking cannabis, but sometimes symptoms return. If this happens, is their ongoing illness due to cannabis alone or would it have happened anyway, with cannabis acting as a trigger? Was schizophrenia precipitated or caused by cannabis? These are difficult questions in individual cases, but the overall research is clear: cannabis is strongly associated with psychosis and other mental illnesses. Cannabis is bad for mental health.
The second question about cannabis is a little different: Given that cannabis is bad for mental health, what should we do in order to reduce the harm caused by cannabis in society? Should cannabis be illegal, decriminalised or legalised? This is a topic of continual public debate and there are many issues to be balanced: medical evidence, the need to protect the vulnerable, and the value of civil liberties.
In the end, we should do whatever reduces cannabis use and minimises the harm from cannabis that I see every week in my clinical work. The first priority must be public education. Regardless of whether it is legal or illegal, cannabis is bad for mental health. If you smoke cannabis, please seek assistance stopping. Your mental health will thank you.
Brendan Kelly is Professor of Psychiatry at Trinity College Dublin and author of “In Search of Madness: A Psychiatrist’s Travels Through the History of Mental Illness” (Gill Books, 2022).
BRING PROTECTION TO LIFE
BY REDUCING THE RISK OF THE COMPOSITE OF DECLINING KIDNEY FUNCTION, ESKD, AND RENAL OR CV DEATH*1
FORXIGA is now approved for adult patients with CKD.2
GFR
treatment
FORXIGA 10 mg
Once daily. No titration required
*In DAPA-CKD, the primary endpoint showed that FORXIGA in conjunction with other CKD therapies reduced the relative risk of the composite endpoint of ≥50% sustained decline in eGFR, reaching ESKD, and renal or CV death by 39% (5.3% ARR) vs placebo with other CKD therapies in 4304 adult patients with CKD with an eGFR of 75 to 25 mL/ min/1.73m2 (median follow-up of 2.4 years; p<0.001).1 DAPA-CKD was stopped early due to efficacy benefit, because of the unplanned early stop, this secondary endpoint is considered nominally significant; Secondary endpoints showed that FORXIGA in conjunction with other CKD therapies reduced the relative risk of the composite of CV death or hHF by 29% (1.8% ARR: nominal p=0.009) and also reduced the relative risk of all-cause mortality by 31% (2.1% ARR; nominal p=0.004) vs placebo with other CKD therapies. There were comparable rates of the individual component of CV death, FORXIGA vs placebo (3.0% vs 3.7%; HR 0.81; 95% CI, 0.58, 1.12)1 ©AstraZeneca 2022. All Rights Reserved.
ABRIDGED PRESCRIBING INFORMATION FORXIGA® (dapagliflozin) 5MG & 10MG FILM-COATED TABLETS.
Consult Summary of Product Characteristics (SmPC) before prescribing. Indications: Adults and children aged 10 years and above:
Type 2 diabetes mellitus: For the treatment of insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise, as monotherapy when metformin is considered inappropriate due to intolerance, or in addition to other medicinal products for the treatment of type 2 diabetes. Adults: Heart Failure: Indicated in adults for the treatment of symptomatic chronic heart failure with reduced ejection fraction. Chronic kidney disease: Indicated in adults for the treatment of chronic kidney disease. Presentation: Film-coated tablets. 5mg or 10mg of dapagliflozin (as propanediol monohydrate). Each 5mg tablet contains 25mg of lactose. Each 10mg tablet contains 50mg of lactose.
Dosage and Administration: Adults: Type 2 diabetes
mellitus: The recommended dose is 10mg once daily. Consider a lower dose of insulin or insulin secretagogue such as a sulphonylurea when used in combination with dapagliflozin to reduce the risk of hypoglycaemia. Children and adolescents: No dose adjustment in children aged 10 years and above. No safety and efficacy data available for children below 10 years of age. Heart Failure: The recommended dose is 10mg once daily. Chronic kidney disease: The recommended dose is 10 mg once daily. Children and adolescents: <18 years: Safety and efficacy not yet established. Elderly: ≥65 years: No dose adjustment is recommended based on age. Renal impairment: No dose adjustment is required based on renal function. Due to limited experience, it is not recommended to initiate treatment with dapagliflozin in patients with GFR < 25 mL/min. If GFR falls below 45 mL/min, additional glucose lowering treatment should be considered in patients with diabetes mellitus if further glycaemic control is needed. Mild or moderate hepatic impairment: No dose adjustment. Severe hepatic impairment: Starting dose of 5mg is recommended, if well tolerated, dose may be increased to 10mg. Method of administration: Forxiga can be taken orally at any time of day with or without food. Tablets should be swallowed whole. Contraindications: Hypersensitivity to dapagliflozin, or excipients. Warnings and Precautions: Renal impairment: Due to limited experience, it is not recommended to initiate treatment with dapagliflozin in patients with GFR < 25 mL/min. The glucose lowering efficacy of dapagliflozin is dependent on renal function, and is reduced in patients with GFR < 45 mL/min and is likely absent in patients with severe renal impairment. Hepatic impairment: Exposure is increased in patients with severe hepatic impairment. Use in patients at risk of volume depletion and/or hypotension: Dapagliflozin increases diuresis which may lead to a modest decrease in blood pressure, it may be more pronounced in patients with very high blood glucose concentrations. Exercise caution in patients for whom a dapagliflozin induced drop in blood pressure could pose a risk, such as patients on anti hypertensive therapy with a history of hypotension or elderly patients. Careful monitoring of volume status and electrolytes is recommended in conditions leading to volume depletion, such as acute gastrointestinal illness. In volume depleted patients temporary interruption of dapagliflozin is recommended until volume depletion is corrected. Diabetic ketoacidosis (DKA): Rare cases of DKA, including life-threatening and fatal cases, have been reported in patients treated with SGLT2 inhibitors, including dapagliflozin. In a number of cases, the presentation of the condition was atypical with only moderately increased blood glucose values, below 14mmol/L (250mg/dL). The risk of DKA must be considered in the event of non-specific symptoms such as nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue or sleepiness. Patients should be assessed for ketoacidosis immediately if these symptoms occur, regardless of blood glucose level. In patients where DKA is suspected or diagnosed, dapagliflozin treatment should be stopped immediately. Treatment should be interrupted in patients who are hospitalised for major surgical procedures or acute serious medical illnesses. Monitoring of ketones is recommended in these patients. Measurement of blood ketone levels is preferred to urine. Treatment with dapagliflozin may be restarted when the ketone values are normal and the patient’s condition has stabilised. Before initiating dapagliflozin, factors in patient history that may predispose to ketoacidosis should be considered. Patients who may be at higher risk of DKA include patients with a low beta cell function reserve (e.g. patients with low C peptide or latent autoimmune diabetes in adults (LADA) or patients with a history of pancreatitis), patients with conditions that lead to restricted food intake or severe dehydration, patients for whom insulin doses are reduced and patients with increased insulin requirements due to acute medical illness, surgery or alcohol abuse. SGLT2 inhibitors should be used with caution in these patients. Restarting SGLT2 inhibitor treatment in patients experiencing a DKA while on SGLT2 inhibitor treatment is not recommended, unless another clear precipitating factor is identified and resolved. Dapagliflozin should not be used for treatment of patients with type 1 diabetes. Necrotising fasciitis of the perineum (Fournier’s gangrene): Postmarketing cases have been reported in female and male patients taking SGLT2 inhibitors. Urgent surgical intervention and antibiotic treatment is required. Advise patients to seek medical attention if they experience a combination of pain, tenderness, erythema, or swelling in the genital or perineal area, with fever or malaise. Either uro-genital infection or perineal abscess may precede necrotising fasciitis. If suspected, discontinue Forxiga and institute prompt treatment (including antibiotics and surgical debridement). Urinary tract infections: Temporary interruption of dapagliflozin should be considered when treating pyelonephritis or urosepsis. Elderly (≥65 years): Elderly patients are more likely to have impaired renal function, be treated with medicines such as anti-hypertensives or diuretics, and be at a greater risk of volume depletion. Cardiac failure: Experience with dapagliflozin in NYHA class IV is limited. Chronic kidney disease: There is no experience with dapagliflozin for the treatment of chronic kidney disease in patients without diabetes who do not have albuminuria. Patients with albuminuria may benefit more from treatment with dapagliflozin. Lower limb amputations: Counsel patients with diabetes on routine preventative foot care as an increase in cases of lower limb amputation (primarily of the toe) has been observed in long term, clinical studies in type 2 diabetes mellitus with SGLT2 inhibitors. Urine laboratory assessments: Patients will test positive for glucose in the urine due to mechanism of action. Lactose: Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take Forxiga. Drug Interactions: Diuretics: Dapagliflozin may add to the diuretic effect of thiazide and loop diuretics and may increase the risk of dehydration and hypotension. Insulin and insulin secretagogues: Consider a lower dose of insulin or insulin secretagogue when used in combination with dapagliflozin to reduce the risk of hypoglycaemia. Interference with 1,5 AG assay: Monitoring glycaemic control with 1,5-AG assay is not recommended as measurements of 1,5 AG are unreliable in assessing glycaemic control in patients taking SGLT2 inhibitors. Alternative methods should be used. Pregnancy and Lactation: Not recommended during the second and third trimesters of pregnancy. Treatment should be discontinued when pregnancy is detected. Do not use whilst breast-feeding. Ability to Drive and Use Machines: Alert patients on the risk of hypoglycaemia when dapagliflozin is used in combination with a sulphonylurea or insulin. Undesirable Events: Consult SmPC for full list of side effects. Very common (≥1/10): Hypoglycaemia (when used with SU or insulin). Common (≥1/100 to <1/10): Vulvovaginitis, balanitis and related genital infections, urinary tract infection, dizziness, rash, back pain, dysuria, polyuria, haematocrit increased, creatinine renal clearance decreased during initial treatment, dyslipidaemia. Uncommon (≥1/1,000 to < 1/100): Fungal infection, volume depletion, thirst, constipation, dry mouth, nocturia, vulvovaginal pruritus, pruritus genital, blood creatinine increased during initial treatment, blood urea increased, weight decreased. Rare (≥ 1/10,000 to < 1/1,000): Diabetic ketoacidosis (when used in type 2 diabetes mellitus). Very Rare (< 1/10,000): Angioedema, necrotising fasciitis of the perineum (Fournier’s gangrene). Legal Category: Product subject to prescription which may be renewed (B). Marketing Authorisation Number: EU/1/12/795/002; EU/1/12/795/007. Marketing Authorisation Holder: AstraZeneca AB, SE-151 85 Södertälje, Sweden.
Further product information available on request from:
AstraZeneca Pharmaceuticals (Ireland) DAC, Block B, Liffey Valley Office Campus, Dublin 22. Tel: +353 1 609 71 00. FORXIGA is a trademark of the AstraZeneca group of companies. Date of API preparation: 11/2021 Veeva ID: IE-3322
Adverse events should be reported directly to: HPRA Pharmacovigilance, Website: www.hpra.ie Adverse events should also be reported to AstraZeneca Patient Safety on Freephone 1800 800 899
References:
1. Heerspink HJL et al. N Engl J Med. 2020;383(15):1436–1446. 2. FORXIGA 10 mg film-coated tablets. Summary of product characteristics. November 2021. CKD = chronic kidney disease; CV = cardiovascular; DAPACKD = Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease; ESKD = end-stage kidney disease; hHF = hospitalisation for heart failure; HR = hazard ratio.
For a DEEP & DURABLE response
when multiple myeloma relapses choose KYPROLIS®
In the phase 3 ASPIRE trial, Kyprolis (carfi lzomib), lenalidomide and dexamethasone (KRd) delivered: 32% of KRd patients achieved a CR or better vs 9% in the Rd arm3,4
DURABLE RESPONSE
Median PFS1
(Primary Endpoint n=792)
26.3
DEEP RESPONSE
ORR1,2 (Secondary Endpoint)
87.1%
Extended Survival OS3
(Secondary endpoint)
48.3
KRd was generally well tolerated. For full details of the Kyprolis safety pro le, please refer to the Summary of Product Characteristics (SPC) available online at www.medicines.ie/medicines/kyprolis-32623/spc.
months
vs Rd 17.6 months
(HR 0.69,95% CI:0.57-0.83; 1-sided p<0.0001) Median follow-up 32 months
vs Rd 66.7%
(OR 3.47, 95% CI: 2.41-5.00; 1 sided p<0.0001) Median follow-up 32 months
months
vs Rd 40.4 months
(HR 0.79, 95% CI: 0.67-0.95; 1 sided p<0.0045) Median follow-up 67 months
Results are from ITT population (1-3 prior lines of treatment).
KRd
KYPROLIS® in combination with lenalidomide and dexamethasone (KRd) is indicated for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.4
Kyprolis® (car lzomib) Brief Prescribing Information
Please refer to the Summary of Product Characteristics (SmPC) before prescribing Kyprolis. Pharmaceutical Form: Powder for solution for infusion presented as a single use vial. Indication: Kyprolis in combination with daratumumab and dexamethasone, with lenalidomide and dexamethasone or with dexamethasone alone is indicated for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. Dosage and Administration: Intravenous (iv) infusion on two consecutive days each week for 3 weeks (days 1, 2, 8, 9, 15 and 16), followed by a 12 day rest period. Each 28-day period is considered one treatment cycle. Kyprolis in combination with lenalidomide and dexamethasone (KRd): Infuse over 10 minutes at a starting dose of 20mg/m2 (max dose 44mg) on days 1 & 2 of cycle 1. If tolerated, increase dose to 27mg/m2 (max dose 60mg) on day 8 of cycle 1. From cycle 13, omit doses on day 8 & 9 of each cycle. In combination with Kyprolis, lenalidomide is administered as 25 mg orally on days 1–21 and dexamethasone is administered as 40 mg orally or iv on days 1, 8, 15, and 22 of the 28 day cycles. Continue treatment until disease progression or until unacceptable toxicity occurs; treatment beyond 18 cycles should be based on an individual bene t:risk assessment as data are limited. Consider appropriate dose reduction for lenalidomide according to the current lenalidomide SmPC. Kyprolis in combination with dexamethasone (Kd): Infuse over 30 minutes at a starting dose of 20 mg/m2 (max dose 44 mg) on days 1 and 2 of cycle 1. If tolerated, increase dose to 56 mg/m2 (max dose 123 mg) on day 8 of cycle 1. Dexamethasone is administered as 20 mg orally or iv on days 1, 2, 8, 9, 15, 16, 22, and 23 of the 28 day cycles. Continue treatment until disease progression or until unacceptable toxicity occurs. Kyprolis in combination with daratumumab and dexamethasone (KdD): Infuse over 30 minutes at a starting dose of 20mg/m2 (max dose 44mg) on days 1 & 2 of cycle 1. If tolerated, increase dose to 56mg/m2 (max dose 123mg) on day 8 of cycle 1. In combination with Kyprolis, daratumumab is administered at 8mg/kg on days 1 & 2 of cycle 1, then 16mg/kg on day 8 and weekly thereafter. Administer preinfusion medication to reduce risk of infusion-related reactions with daratumumab. Dexamethasone is administered as 20 mg orally or iv on days 1, 2, 8, 9, 15, & 16, then 40mg on day 22 of each cycle. For patients > 75 years of age, dexamethasone is administered as 20 mg orally or intravenously weekly after the rst week. Order of administration on days when more than one medicine is administered: dexamethasone, preinfusion medication for daratumumab, car lzomib, daratumumab, post infusion medication for daratumumab. Continue treatment until disease progression or until unacceptable toxicity occurs. Refer to the current daratumumab SmPC for additional detail regarding concomitant medication and appropriate dose reduction for daratumumab. All regimens: Modify dosing based on haematologic, renal and other non-haematologic toxicity as de ned in the SmPC. Consider antiviral prophylaxis in patients treated with Kyprolis to decrease the risk of herpes zoster reactivation. Monitor platelet counts frequently. Thromboprophylaxis is recommended based on an individual bene t:risk assessment. Adequate hydration is required before Kyprolis administration in cycle 1, especially in patients at high risk of tumour lysis syndrome or renal toxicity, give additional uids after Kyprolis administration in cycle 1 as needed. Monitor all patients for evidence of volume overload and tailor uid requirements to individual patient needs. Oral and/or intravenous hydration is not required on days when intravenous daratumumab is dosed in the KdD regimen. Monitor serum potassium monthly or more frequently as clinically indicated. Assess renal function at treatment initiation and monitor at least monthly, particularly in patients with lower baseline creatinine clearance (CrCL < 30 mL/min) for whom there are limited ef cacy and safety data. Assess liver enzymes and bilirubin at treatment initiation and monitor monthly during treatment, regardless of baseline values; pay special attention to patients with moderate and severe hepatic impairment for whom there are very limited ef cacy and safety data. Contraindications: Hypersensitivity to the active substance or to any of the excipients; women who are breast-feeding. Refer to relevant SmPC for contraindications, special warnings and precautions for products used in combination with Kyprolis. Special Warnings and Precautions: For patients who experience grade 3 or 4 cardiac events or dyspnoea, or pulmonary toxicities/hypertension or hypertensive crisis, stop Kyprolis until recovery and consider whether to restart Kyprolis at 1 dose level reduction based on a bene t/risk assessment. Cardiac disorders: New or worsening cardiac failure, myocardial ischaemia and infarction have occurred, including fatal outcomes. The risk of cardiac failure is increased in elderly (≥ 75 years) and Asian patients. A thorough assessment for cardiovascular risk factors prior to starting treatment is recommended. Patients with signs or symptoms of NYHA Class III or IV cardiac failure, recent history of myocardial infarction (in the last 4 months), and in patients with uncontrolled angina or arrhythmias should have a comprehensive cardiological assessment prior to starting treatment. Electrocardiographic changes: Cases of QT interval prolongation and of ventricular tachycardia have been reported. Pulmonary toxicity: Acute respiratory distress syndrome (ARDS), acute respiratory failure, and acute diffuse in ltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred, some events have been fatal. Pulmonary hypertension: Pulmonary hypertension has been reported, some events have been fatal. Dyspnoea: Evaluate dyspnoea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes. Hypertension: Hypertension, including hypertensive crisis and hypertensive emergency, has been observed, some events have been fatal. Control hypertension prior to starting and during treatment. Evaluate all patients for hypertension during treatment. If hypertension cannot be controlled, reduce dose. Acute renal failure: Cases of acute renal failure have been reported, some of these events have been fatal. Tumour lysis syndrome (TLS): Cases of TLS, including with fatal outcome, have been reported. Consider patients with a high tumour burden at greater risk. Ensure patients are well hydrated before Kyprolis administration in cycle 1 and subsequent cycles as needed. Consider uric acid lowering medicinal products in patients at high risk for TLS. Monitor for evidence of TLS during treatment. Stop Kyprolis until TLS is resolved. Infusion reactions: Infusion reactions, including life-threatening reactions, have been reported in patients who received Kyprolis. Reactions can occur immediately following or up to 24 hours after administration of Kyprolis. Dexamethasone should be administered prior to Kyprolis to reduce the incidence and severity of reactions. Haemorrhage and thrombocytopenia: Haemorrhage, often associated with thrombocytopenia has been reported; some events have been fatal. Venous thromboembolic events: Events, including deep vein thrombosis and pulmonary embolism with fatal outcomes, have been reported. Closely monitor patients with known risk factors for thromboembolism, minimise all modi able risk factors (e.g. smoking, hypertension and hyperlipidaemia), and administer other agents that may increase the risk of thrombosis with caution (e.g. erythropoietic agents or hormone replacement therapy). Hepatic toxicity: Cases of hepatic failure, including fatal cases, have been reported. Thrombotic microangiopathy: Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome (TTP/HUS) have been reported, some events have been fatal. Monitor for signs and symptoms of TTP/HUS and stop treatment if suspected. Once excluded, Kyprolis can be restarted. The safety of reinitiating Kyprolis in patients previously experiencing TTP/HUS is unknown. Posterior reversible encephalopathy syndrome (PRES): Cases of PRES have been reported. Kyprolis should be discontinued if PRES is suspected. The safety of reinitiating Kyprolis therapy in patients previously experiencing PRES is not known. Hepatitis B Virus (HBV) reactivation: Cases of HBV reactivation have been reported. Patients should be screened for HBV before initiation of treatment. For patients with positive HBV serology, consider prophylaxis with antivirals. Monitor for clinical and laboratory signs of HBV reactivation during and after the end of treatment. The safety of resuming car lzomib after HBV is adequately controlled is not known. Resumption of therapy should be discussed with experts in managing HBV. Progressive Multifocal Leukoencephalopathy (PML): Cases of PML have been reported in patients receiving car lzomib who have had prior or concurrent immunosuppressive therapy. Patients should be monitored for any new of worsening neurological, cognitive or behavioural signs and symptoms that may be suggestive of PML. If PML is suspected, further administration must be suspended until PML has been excluded by a specialist with appropriate diagnostic testing. If PML is con rmed, car lzomib must be discontinued. Contraception: Female patients of child bearing potential (and/or their partners) must use effective contraception measures during and for one month following treatment. Kyprolis may decrease the ef cacy or oral contraceptives. Patients using oral contraceptives or hormonal contraception associated with a risk of thrombosis should switch to an alternative method. Male patients must use effective contraception measures during and for 3 months following treatment if their partner is pregnant or of childbearing potential not using effective contraception. Sodium content: Each 10mg, 30mg and 60mg vial contains 37, 109 and 216 mg sodium, respectively. Cyclodextrin content: Each 10mg, 30mg and 60mg contains 500, 1500 and 3000 mg of cyclodextrin (betadex sulfobutyl ether sodium), respectively. Interactions: Caution should be observed when car lzomib is combined with medicinal products that are substrates of CYP1A2, 2C8, 2C9, 2C19 and 2B6 (e.g. oral contraceptives), or with substrates of P-gp (e.g. digoxin, colchicine). Fertility, pregnancy and lactation: No available data on use of Kyprolis in pregnant women; should not be used during pregnancy unless the potential bene t outweighs the potential risk to the foetus. Breast-feeding is contra-indicated during and for at least 2 days after treatment with Kyprolis. No fertility studies have been performed. Undesirable Effects: Adverse reactions in patients receiving Kyprolis: very common (≥ 1/10) pneumonia, respiratory tract infection, thrombocytopenia, neutropenia, anaemia, lymphopenia, leukopenia, hypokalaemia, decreased appetite, insomnia, dizziness, peripheral neuropathy, headache, hypertension, dyspnoea, cough, vomiting, diarrhoea, constipation, abdominal pain, nausea, back pain, arthralgia, pain in extremity, muscle spasms, increased blood creatinine, pyrexia, peripheral oedema, asthenia, fatigue, chills; common (≥ 1/100 to < 1/10) sepsis, lung infection, in uenza, herpes zoster, urinary tract infection, bronchitis, gastroenteritis, viral infection, nasopharyngitis, rhinitis, febrile neutropenia, dehydration, hyperkalaemia, hypomagnesaemia, hyponatraemia, hypercalcaemia, hypocalcaemia, hypophosphataemia, hyperuricaemia, hypoalbuminaemia, hyperglycaemia, anxiety, confusional state, paraesthesia, hypoaesthesia, cataract, blurred vision, tinnitus, cardiac failure, myocardial infarction, atrial brillation, tachycardia, ejection fraction decreased, palpitations, deep vein thrombosis, hypotension, ushing, pulmonary embolism, pulmonary oedema, epistaxis, oropharyngeal pain, dysphonia, wheezing, pulmonary hypertension, gastrointestinal haemorrhage, dyspepsia, toothache, increased alanine aminotransferase, increased aspartate aminotransferase, increased gammaglutamyltransferase, hyperbilirubinaemia, rash, pruritus, erythema, hyperhidrosis, musculoskeletal pain, musculoskeletal chest pain, bone pain, myalgia, muscular weakness, acute kidney injury, renal failure, renal impairment, decreased creatinine renal clearance, chest pain, pain, infusion site reactions, in uenza-like illness, malaise, increased c-reactive protein, increased blood uric acid, infusion related reaction; uncommon (≥ 1/1,000 to < 1/100) clostridium dif cile colitis, cytomegalovirus infection, hepatitis B virus reactivation, drug hypersensitivity, HUS, TTP, tumour lysis syndrome, intracranial haemorrhage, cerebrovascular accident, PRES, cardiac arrest, cardiomyopathy, myocardial ischaemia, pericarditis, pericardial effusion, ventricular tachycardia, hypertensive crisis, haemorrhage, ARDS, acute respiratory failure, pulmonary haemorrhage, interstitial lung disease, pneumonitis, gastrointestinal perforation, acute pancreatitis, hepatic failure, cholestasis, multiorgan dysfunction syndrome. In a phase III study comparing KdD with Kd, secondary primary malignancies were reported (1.9% in KdD; 1.3% in Kd arm). Please consult the Summary of Product Characteristics for a full description of adverse reactions. Pharmaceutical Precautions: Do not mix or administer as an infusion with other medicinal products. Store at 2°C to 8°C (in a refrigerator). Do not freeze. Store in original carton to protect from light. Reconstitute with sterile water for injections. Reconstituted solutions in the vial, syringe, or intravenous bag may be stored at 2°C – 8°C for up to 24 hours or at 25°C for up to 4 hours. Inspect visually before administration; do not administer if any discoloration or particulate matter is observed. Legal Category: POM. Presentation, Basic Costs and Marketing Authorisation Number: Kyprolis 60 mg, pack of 1: EU/1/15/1060/001. Kyprolis 30 mg, pack of 1: EU/1/15/1060/003. Kyprolis 10 mg, pack of 1: EU/1/15/1060/002. Price in Republic of Ireland is available on request. Marketing Authorisation Holder: Amgen Europe B.V., Minervum 7061, NL-4817 ZK Breda, The Netherlands. Further information is available from Amgen Ireland Limited, 21 Northwood Court, Santry, Dublin D09 TX31. Kyprolis is a registered trademark owned or licensed by Amgen Inc., its subsidiaries, or af liates. Date of PI preparation: April 2021 (Ref: IE-KYP-0321-00001)
