Azmarda:Indication, Composition, Dosage.

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Overview, Indications, Clinical Evidence Dosage
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il-valsartan
Heart Failure - Overview Heart failure is a
progressive chronic syndrome characterized by
decrease in functional status and quality of
life1. The burden of heart failure has increased
to an estimated 23 million people, worldwide. In
India, the prevalence was estimated to be around
1.2/1000 people in the INDUS study. As prevalence
rates of heart failure are high and expected to
rise in the near future because of improved
survival from acute cardiac events and the aging
of the general population, thus HF management
has come to the front-stage of non-communicable
disease management programmes. Once developed,
heart failure has a 1-year mortality rate of 7.2
and a 1-year hospitalization rate of 31.9 in
patients with chronic heart failure, and in
patients hospitalized for acute heart failure,
these rates increase to 17.4 and 43.92. The
pathophysiology of heart failure involves a
maladaptive response during which the
renin-angiotensin-aldosterone system (RAAS) is
activated3. RAAS activation leads to
vasoconstriction, hypertension, increased
aldosterone levels, increased sympathetic tone,
and eventually, cardiac remodeling, all of which
are detrimental to the progression of the
disease3.
Indication
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Heart Failure To reduce the risk of
cardiovascular death and hospitalization for
heart failure in patients with chronic heart
failure (NYHA Class II-IV) and reduced ejection
fraction.
Important update
Understanding ARNI in Hypertension 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
3
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
Watch Video At https//youtu.be/sceEr6m2QnQ Dr.
Dilip Kumar
4
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
5
Watch Video At https//youtu.be/7x2WKKUV1rA Dr.
Harpreet Singh Gilhotra DM, FESC Director
Cardiology Sri Guru Harkrishan Sahib (C) Eye
Hospital Trust, Sohan (Sohana Hospital)
Watch Video At https//youtu.be/ovMzlsB4o3M
6
Dr. Amit Handa Consultant- Cardiologist MD
(Med.), DM (Cardiology) Ivy Multi Speciality
Hospital Punjab
Watch Video At https//youtu.be/YzWI1O20RCk Dr.
Niroj Kumar Mishra M.D. (Medicine) Clinical
Director (AN ISO90012008 CERTIFIED HOSPITAL)
KAR CLINIC HOSPITAL PVT.LTD., Bhubaneswar
7
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
8
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 Dr.
Johann Christopher MD, DNB (Cardiology) Consultan
t Cardilogist Division of Cardiac Imaging CARE
HOSPITALS, CARE OUTPATIENT CENTRE Hyderabad
9
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
Watch Video At https//youtu.be/vTx4E4Y3tZs
10
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 Dr
J.S Hiremath 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.
10/17
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How Azmarda Works?
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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 renin-
angiotensin-aldosterone system3.
Composition
Pharmacokinetics of Azmarda4 Absorption 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.
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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.

• Questions and Answers
• What is Azmarda (Sacubitril Valsartan)?
• What is Azmarda (Sacubitril Valsartan) indicated
  for? 3. How does Azmarda (Sacubitril Valsartan)
  work?

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• 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)?
• What are the clinical pharmacokinetics of Azmarda
  (Sacubitril Valsartan)?
• What benefits of Azmarda (Sacubitril Valsartan)
  have been shown in studies?
• What are the risks associated with Azmarda
  (Sacubitril Valsartan)? What are the precautions
  to be taken while using Azmarda (Sacubitril
  Valsartan)?
• What are the contraindications of Azmarda
  (Sacubitril Valsartan)? 11. What are the adverse
  reactions of Azmarda (Sacubitril Valsartan)?
• What are the precautions to be taken for special
  populations groups while using Azmarda?
• What is the safety profile of Azmarda (Sacubitril
  Valsartan) in females of childbearing potential,
  pregnancy, breastfeeding, and fertility?
• What happens to the overdosage of Azmarda
  (Sacubitril Valsartan)?
• 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 PractCardiovascSci2016228-35 2. Murphy
  SP, Ibrahim NE, Januzzi JL Jr. Heart Failure
  With Reduced Ejection Fraction A Review. JAMA.
  2020 Aug
• 4324(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), 14611478.
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