Azilsartan Medoxomil
Contraindicated
Textbook
Potentially excessive hypotension, increased risk of adverse effects.
Do not use in conjunction with other ARBs.
Source: G&G 14e · p602
Drug reference
Sacubitril-Valsartan
Angiotensin receptor-neprilysin inhibitor (ARNI) · Antihypertensive
Also known as Entresto, ARNI, sacubitril/valsartan
START
Stop ACE inhibitor ≥36 hours before. Verify BP >100 mmHg systolic, K+ <5.0 mmol/L, eGFR >30. Check no history of angioedema.
TYPICAL MAX
US ENTRESTO label: Adult target: sacubitril/valsartan 97/103 mg twice daily, as tolerated; do not use with an ACE inhibitor or within 36 hours of one.
STOP IF
Angioedema, SBP <90 mmHg, K+ >6.0 mmol/L, eGFR drop >30% from baseline, acute kidney injury, pregnancy.
WATCH
Potassium and creatinine at 1-2 weeks after start and each dose increase. Risk of angioedema higher in Black patients and those with prior ACEI angioedema.
CDSCO approvedSchedule HATC C09DX04
KDIGO 2024 + manufacturer label
- ONSET
- 1h · Onset ~1 hour
- PEAK
- 2h · Tmax ~1-4 hours
- t½
- 11h · t½ LBQ657 ~11h
- DURATION
- 12h · 12 hours (BID)
EXCRETION
Fecal (valsartan), urine+fecal (LBQ657)
route + CYP
INTERACTIONS
12 major
incl. contraindicated
PREGNANCY
Contraindicated in pregnancy—causes fetal harm, oligohydramnios, fetal lung hypoplasia, skeletal malformations, neonatal death. Discontinue immediately if pregnancy detected.
FDA category + note
Top interactionssee all 12 →
- Azilsartan MedoxomilContraindicatedTextbookG&G 14e · p602
- AzilsartanContraindicatedTextbookG&G 14e · p602
- BenazeprilContraindicatedTextbookG&G 14e · p602
- CandesartanContraindicatedTextbookG&G 14e · p602
Available in India
72 branded formulations and 73 fixed-dose combinations. Look up specific brands in the Drugs workspace.
Mechanism
Dual mechanism: sacubitril inhibits neprilysin (increasing natriuretic peptides, bradykinin, and adrenomedullin), promoting vasodilation and natriuresis; valsartan blocks AT1 receptors, inhibiting angiotensin II effects on vasoconstriction, aldosterone release, and cardiac remodeling
Indications
Chronic heart failure with reduced ejection fraction (HFrEF, NYHA II-IV)Chronic heart failure with mildly reduced or preserved ejection fraction (HFpEF, LVEF below normal)
Dosing
- Adult
- US ENTRESTO tablets: usual adult start 49/51 mg twice daily; start at half this dose (24/26 mg twice daily) if not taking an ACE inhibitor/ARB or previously taking a low dose. Separate ACE inhibitors by at least 36 hours. Double every 2–4 weeks as tolerated to 97/103 mg twice daily. Correct volume/salt depletion and individualize management of hypotension.
- Pediatric
- US ENTRESTO, symptomatic heart failure with systemic left ventricular systolic dysfunction, age ≥1 year: for the tablet/oral-suspension schedule at weight <40 kg, use combined sacubitril/valsartan 1.6 mg/kg twice daily, then 2.3 and 3.1 mg/kg twice daily at two-week intervals as tolerated. Use the label’s weight-band tablet doses at ≥40 kg and its separate SPRINKLE schedule when using oral pellets. No/low prior ACEI/ARB, moderate hepatic impairment or severe renal impairment requires a reduced start; patients weighing 40–50 kg meeting these criteria start 0.8 mg/kg twice daily using suspension or pellets. Do not halve or substitute tablet strengths without the label-specific instructions.
- Renal adjustment
- eGFR ≥30: no adjustment. eGFR 15-29: start 24/26mg BID. eGFR <15: limited data.
- Hepatic adjustment
- US ENTRESTO label: Child-Pugh A: no starting-dose adjustment. Child-Pugh B: start at half the usual dose and titrate as tolerated. Child-Pugh C: not recommended.
- Geriatric
- No specific adjustment; monitor renal function and potassium.
- Max dose
- 97mg sacubitril / 103mg valsartan BID
Pharmacokinetics
Onset
Blood pressure reduction within 2-4 hours; clinical benefit over weeks to months
Peak effect
Steady-state in ~3 days; Tmax sacubitril ~1h, Tmax valsartan ~2-4h
Duration
24 hours (BID dosing)
Half-life
Sacubitril (prodrug) ~1.4h; LBQ657 (active metabolite) ~11h; valsartan ~9.9h
Bioavailability
US ENTRESTO label: Sacubitril absolute oral bioavailability is at least 60%. Valsartan in ENTRESTO is more bioavailable than other marketed valsartan tablets. Food has no clinically significant effect; ENTRESTO may be taken with or without food.
Protein binding
US ENTRESTO label: Sacubitril, LBQ657 and valsartan are 94–97% bound to plasma proteins.
Metabolism
US ENTRESTO label: Sacubitril is converted by esterases to LBQ657; valsartan undergoes limited metabolism, with about 20% recovered as metabolites. CYP-mediated metabolism is minimal.
Excretion
US ENTRESTO label: After oral dosing, 52–68% of sacubitril (mainly LBQ657) and about 13% of valsartan and metabolites are recovered in urine; 37–48% of sacubitril (mainly LBQ657) and 86% of valsartan and metabolites are recovered in feces.
Contraindications
- Concomitant ACE inhibitor use (within 36 hours)
- History of angioedema with ACE inhibitors or ARBs
- Concomitant aliskiren use in diabetes
- Severe hepatic impairment (Child-Pugh C)
- Bilateral renal artery stenosis
- US ENTRESTO label: Discontinue ENTRESTO as soon as pregnancy is detected because of fetal toxicity.
Side effects
Common
HypotensionHyperkalemiaCoughDizzinessRenal impairmentAngioedema (rare but serious)
Serious
- Angioedema (potentially life-threatening)
- Severe hypotension
- Acute kidney injury
- Hyperkalemia (>6.0 mmol/L)
- Fetal toxicity in pregnancy
Pregnancy & lactation
Pregnancy
Contraindicated in pregnancy—causes fetal harm, oligohydramnios, fetal lung hypoplasia, skeletal malformations, neonatal death. Discontinue immediately if pregnancy detected.
Lactation
Not recommended during breastfeeding—insufficient data; valsartan excreted in rat milk.
Drug interactions
Azilsartan
Contraindicated
Textbook
Potentially excessive hypotension, increased risk of adverse effects.
Do not use in conjunction with other ARBs.
Source: G&G 14e · p602
Benazepril
Contraindicated
Textbook
Increased risk of angioedema.
Do not use in conjunction with ACEIs.
Source: G&G 14e · p602
Candesartan
Contraindicated
Textbook
Potentially excessive hypotension, increased risk of adverse effects.
Do not use in conjunction with other ARBs.
Source: G&G 14e · p602
Captopril
Contraindicated
Textbook
Increased risk of angioedema.
Do not use in conjunction with ACEIs.
Source: G&G 14e · p602
Enalapril
Contraindicated
Textbook
Increased risk of angioedema.
Do not use in conjunction with ACEIs.
Source: G&G 14e · p602
Eprosartan
Contraindicated
Textbook
Potentially excessive hypotension, increased risk of adverse effects.
Do not use in conjunction with other ARBs.
Source: G&G 14e · p602
Fosinopril
Contraindicated
Textbook
Increased risk of angioedema.
Do not use in conjunction with ACEIs.
Source: G&G 14e · p602
Irbesartan
Contraindicated
Textbook
Potentially excessive hypotension, increased risk of adverse effects.
Do not use in conjunction with other ARBs.
Source: G&G 14e · p602
Losartan + Hydrochlorothiazide
Contraindicated
Textbook
Potentially excessive hypotension, increased risk of adverse effects.
Do not use in conjunction with other ARBs.
Source: G&G 14e · p602
Losartan
Contraindicated
Textbook
Potentially excessive hypotension, increased risk of adverse effects.
Do not use in conjunction with other ARBs.
Source: G&G 14e · p602
Moexipril
Contraindicated
Textbook
Increased risk of angioedema.
Do not use in conjunction with ACEIs.
Source: G&G 14e · p602
Related guidelines
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Partially reviewed; remaining content unreviewed·Updated: 2026-09-11