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
97/103mg BID. Do not use with ACEI. Max benefit seen at target dose from PARADIGM-HF trial.
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
- Replace ACE inhibitor/ARB: stop ACEI 36h prior. Start 49/51mg (sacubitril/valsartan) BID if not on ACEI or low-dose ACEI; start 24/26mg BID if on moderate-high ACEI dose. Double every 2-4 weeks to target 97/103mg BID. Reduce to 24/26mg BID if SBP <100 mmHg.
- Pediatric
- ≥1 year: weight-based dosing starting at 1.6mg/kg BID (sacubitril component), titrate to 3.1mg/kg BID.
- Renal adjustment
- eGFR ≥30: no adjustment. eGFR 15-29: start 24/26mg BID. eGFR <15: limited data.
- Hepatic adjustment
- Mild (Child-Pugh A): no adjustment. Moderate (Child-Pugh B): use caution, consider lower start. Severe: contraindicated.
- 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
Sacubitril ~60%; valsartan ~23% (food decreases valsartan AUC by 40%)
Protein binding
LBQ657 ~53%; valsartan ~95%
Metabolism
Sacubitril converted to active LBQ657 via esterases; valsartan minimally metabolized (CYP2C9 ~20%)
Excretion
Primarily fecal/biliary (valsartan ~83% unchanged in feces); LBQ657 ~50% urine, 40% 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
- Pregnancy
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
Ask House about Sacubitril-Valsartan
Continue into a citation-backed clinical answer with the drug context already attached.
Sources: Goodman & Gilman 14e·Verified: 2026-05-19 · House clinical team·Cockpit curated: 2026-05-19