Understanding Heart Failure in India
Guidlines defined for the treatment of Heart Failure
Quick Review- Role of ARNI in Heart Failure final
Decoding the clinical Evidence for Sacubitril Valsartan in Heart Failure
The Drug Review Sacubitril Valsartan
John McMurray
BHF Cardiovascular Research Centre, University of Glasgow & Queen Elizabeth University Hospital, Glasgow, Scotland, UK
Dr. Partho P Chowdhury
MD (DELHI UNIVERSITY), DM (IPGMER,KOL) Consultant Interventional Cardiologist Specialist in Radial Angioplasty, Complex Angioplasty, Pacemaker, ICD, CRT Implantation, Device Closure Meditrina Hospital, Jharkhand
Professor Dr. J.C Mohan
MBBS, MD (General Medicine) DM (Cardiology) M.NAMS FACC (Fellow American College of Cardiology) FASE (Honorary Fellow of American Society of Echocardiography) FESC (Fellow of European Society of Cardiology) Jaipur Golden Hospital, Delhi
Dr. Armendra Kumar Pandey
MBBS, DNB (Medicine) FNIC, DNB (Cardilogy) Consultant-Cardiology Dharamshila Narayana Superspeciality Hospital
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Watch Video At: https://youtu.be/sceEr6m2QnQ
Dr. Dilip Kumar
MBBS, MD, DM (Card) FRCP (GLASG), FHRS, FSCAI, FESC, IBHRE, CCDS Chief Academic Co-ordinator Medica Institute of Cardiac Sciences Kolkata
Watch Video At: https://youtu be/5rOxlgEIXaY
Dr. Animesh Agarwal
MD, DM (Cardiology), AFESC International Associate American College of Cardiology
Senior Consultant & HOD Department of Cardiology Jindal Institute of Medical Sciences, Haryana
Watch Video At: https://youtu.be/7x2WKKUV1rA
DM, FESC Director Cardiology
Sri Guru Harkrishan Sahib (C) Eye Hospital Trust, Sohan (Sohana Hospital)
4/17
Dr. Harpreet Singh Gilhotra
Watch Video At: https://youtu be/ovMzlsB4o3M
Dr. Amit Handa
Consultant- Cardiologist MD (Med.), DM (Cardiology) Ivy Multi Speciality Hospital Punjab
Watch Video At: https://youtu.be/YzWI1O20RCk
5/17
Dr. Niroj Kumar Mishra
M.D. (Medicine) Clinical Director
(AN ISO:9001:2008 CERTIFIED HOSPITAL) KAR CLINIC & HOSPITAL PVT.LTD., Bhubaneswar
Watch Video At: https://youtu.be/0xvq7sAwrUA
Dr. Nitin Tiwari
M.B.B.S (Gold Medallist) D.M.(Card), D.N.B.(Card), M.D. (Card), D.N.B (Med.), M.N.A.M.S., M.A.P.S.I.C., F.I.A.M.S. FIC (France), FIC (Germany), FESC (Europe), FACC (USA) Interventional Cardiologist WOCKHARDT HEART HOSPITAL, Nagpur
6/17
Watch Video At: https://youtu be/YbckiC1zSP8
Dr. Idris Ahmed Khan
MD, DM (Card, PGI Chandigarh)
Consultant Interventional Cardiologist BOMBAY HOSPITAL, INDORE
Watch Video At: https://youtu.be/vc9lm8gWjbg
7/17
Dr. Johann Christopher
MD, DNB (Cardiology)
Consultant Cardilogist Division of Cardiac Imaging CARE HOSPITALS, CARE OUTPATIENT CENTRE Hyderabad
Watch Video At: https://youtu.be/Kx0B93PygOw
Dr. C.K. Ponde
Consultant Cardiologist M.D. (Gen.Med), D.M (Card), D.N.B. (Card) FACC (USA), FSCAI (USA) FCSI, FISE, FICC, FIAE
8/17
Watch Video At: https://youtu be/vTx4E4Y3tZs
Prof Dr Satyanarayan Routray
MBBS, MD (MEDICINE), DM (CARDIOLOGY), FICC,FCSI Professor and HOD SCB Medical College & Hospital Cuttack
Watch Video At: https://youtu.be/lnBKczf D0
9/17
DM (Cardiology), DNB (Cardiology) Fellow of American College of Cardiology Director: Cath Lab, Ruby Hall Clinic Chief Cardiologist, Hearty Transplant Department, Ruby Hall Clinic, Pune
About Azmarda
Azmarda contains Sacubitril/Valsartan, the first agent to be approved in a new class of drugs called angiotensin receptor neprilysin inhibitor (ARNI) . 3
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How Azmarda Works?
Sacubitril acts as a neprilysin inhibitor by preventing the breakdown of natriuretic peptides. This leads to a prolonged duration of the favorable effects of these peptides. Valsartan is an angiotensin receptor blocker, and it works by blocking the reninangiotensin-aldosterone system .
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Absorption
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Composition Pharmacokinetics of Azmarda
Following oral administration, Azmarda dissociates into sacubitril, which is further metabolized to sacubitrilat, and valsartan, which reach peak plasma concentrations in 0.5 hours, 2 hours, and 1.5 hours, respectively.
The oral absolute bioavailability of sacubitril and valsartan is estimated to be ≥ 60% and 23%, respectively. Azmarda can be administered with or without food.
Distribution
Azmarda is highly bound to plasma proteins (94% - 97%). Based on the comparison of plasma and CSF exposures, sacubitrilat does cross the blood brain barrier to a limited extent (0.28%).
Azmarda has an apparent volume of distribution ranging from 75L to 103L.
Biotransformation
Sacubitril is readily converted to sacubitrilat by esterases; sacubitrilat is not further metabolized to a significant extent.
Valsartan is minimally metabolized, as only about 20% of the dose is recovered as metabolites.
Elimination
Following oral administration, 52 to 68% of sacubitril (primarily as sacubitrilat) and ~13% of valsartan and its metabolites are excreted in urine; 37 to 48% of sacubitril (primarily as sacubitrilat), and 86% of valsartan and its metabolites are excreted in feces. Sacubitril, sacubitrilat, and valsartan are eliminated from plasma with a mean elimination half-life (T1/2) of approximately 1.43 hours, 11.48 hours, and 9.90 hours, respectively.
Clinical Evidences
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Dosage
The recommended starting dose of AZMARDA is 100 mg twice daily. A starting dose of 50 mg twice daily is recommended for patients not currently taking an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB), and should be considered for patients previously taking low doses of these agents. The dose of AZMARDA should be doubled every 2-4 weeks to the target dose of 200 mg twice daily, as tolerated by the patient.
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Questions and Answers
1. What is Azmarda (Sacubitril Valsartan)?
2. What is Azmarda (Sacubitril Valsartan) indicated for?
3. How does Azmarda (Sacubitril Valsartan) work?
4. What are the dosage forms and strengths of Azmarda (Sacubitril Valsartan)?
5. What are the dosage and administration of Azmarda (Sacubitril Valsartan)?
6. What is the clinical pharmacodynamics of Azmarda (Sacubitril Valsartan)?
7. What are the clinical pharmacokinetics of Azmarda (Sacubitril Valsartan)?
8. What benefits of Azmarda (Sacubitril Valsartan) have been shown in studies?
9. What are the risks associated with Azmarda (Sacubitril Valsartan)? What are the precautions to be taken while using Azmarda (Sacubitril Valsartan)?
10. What are the contraindications of Azmarda (Sacubitril Valsartan)?
11. What are the adverse reactions of Azmarda (Sacubitril Valsartan)?
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12. What are the precautions to be taken for special populations groups while using Azmarda?
13. What is the safety profile of Azmarda (Sacubitril Valsartan) in females of childbearing potential, pregnancy, breastfeeding, and fertility?
14. What happens to the overdosage of Azmarda (Sacubitril Valsartan)?
15. What measures are being taken to ensure the safe and effective use of Azmarda (Sacubitril Valsartan)?
References
1. Chaturvedi V, Parakh N, Seth S, et al. Heart failure in India: The INDUS (INDiaUkieri Study) study. J PractCardiovascSci2016;2:28-35 2. Murphy SP, Ibrahim NE, Januzzi JL Jr. Heart Failure With Reduced Ejection Fraction: A Review. JAMA. 2020 Aug 4;324(5):488-504 3. Nicolas D, Kerndt CC, Reed M. Sacubitril/Valsartan. [Updated 2021 Jul 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 4. Ayalasomayajula, S., Langenickel, T., Pal, P., et.al (2017). Clinical Pharmacokinetics of Sacubitril/Valsartan (LCZ696): A Novel Angiotensin Receptor-Neprilysin Inhibitor. Clinical pharmacokinetics, 56(12), 1461–1478.
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