Sacubitril Valsartan
Contraindicated
Textbook
Increased risk of angioedema.
Do not use in conjunction with ACEIs.
Source: G&G 14e · p602
Drug reference
Ramipril
ACE Inhibitor · Antihypertensive
Also known as Ramiprilat, Cardace, Ramistar, Zaram, Acovil
START
1.25-2.5 mg PO once daily (or BID for HF)
TYPICAL MAX
10 mg/day (HTN) · 10 mg/d (post-MI/HF)
STOP IF
Pregnancy · bilateral RAS · angioedema · hyperkalemia
WATCH
K⁺ · creatinine (1-2 wks) · cough · angioedema (rare)
CDSCO approvedSchedule HJan AushadhiATC C09AA05
KDIGO 2024 + manufacturer label
- ONSET
- 1h · BP effect onset
- PEAK
- 3h · ramiprilat active metabolite Cmax
- t½
- 17h · ramiprilat t½ (effective)
- DURATION
- 1d · once-daily dosing window
EXCRETION
Hepatic prodrug → ramiprilat · renal excretion
route + CYP
INTERACTIONS
12 major
incl. contraindicated
PREGNANCY
Category D — fetal renal injury, oligohydramnios
FDA category + note
Top interactionssee all 12 →
- Sacubitril ValsartanContraindicatedTextbookG&G 14e · p602
- Dual Raas Blockade (e.g., With Arbs Like Losartan, Valsartan, Or Direct Renin Inhibitors Like Aliskiren)ContraindicatedDatabase
- SacubitrilContraindicatedDatabase
- Sacubitril/valsartan (entresto)ContraindicatedDatabase
Available in India
400 branded formulations and 107 fixed-dose combinations. Look up specific brands in the Drugs workspace.
Jan Aushadhi — generic available at GoI pharmacies
Mechanism
Ramipril is a prodrug that is hydrolyzed in the liver to its active metabolite, ramiprilat. Ramiprilat competitively inhibits angiotensin-converting enzyme (ACE), thereby preventing the conversion of angiotensin I to the potent vasoconstrictor angiotensin II. This inhibition leads to decreased systemic vascular resistance, reduced aldosterone secretion, and increased bradykinin levels, resulting in vasodilation, natriuresis, and reduced cardiac remodeling.
Indications
HypertensionCongestive heart failureReduction of cardiovascular risk in patients with established cardiovascular disease or diabetes with at least one additional cardiovascular risk factorTreatment of stable patients who have clinical signs of congestive heart failure within the first few days after an acute myocardial infarctionDiabetic nephropathyNon-diabetic proteinuric renal disease (off-label)cardiovascular diseaseheart failureacute myocardial infarctionhigh risk of cardiovascular eventscoronary artery disease (without heart failure)Congestive heart failure (CHF)Myocardial infarction (MI)Prophylaxis in high cardiovascular risk subjects (reduced cardiac death, MI, or stroke by 22% over 4.5 years)Nondiabetic nephropathyScleroderma crisis
Dosing
- Adult
- Hypertension: Initial 2.5 mg orally once daily. Maintenance 2.5-20 mg once daily. Titrate according to response at intervals of 1-2 weeks. Heart Failure Post-MI: Initial 2.5 mg orally twice daily, titrated upwards as tolerated to a target of 5 mg twice daily. Cardiovascular Risk Reduction: Initial 2.5 mg orally once daily, titrated as tolerated to 10 mg once daily.…
- Pediatric
- Not generally recommended for children < 18 years due to limited data. If used for hypertension in children > 6 years, initial 0.05 mg/kg orally once daily (max 2.5 mg), titrate up to 0.2 mg/kg/day (max 5 mg).
- Renal adjustment
- eGFR 30-60 mL/min/1.73 m²: Initial 1.25 mg once daily; max 5 mg once daily. eGFR < 30 mL/min/1.73 m²: Initial 1.25 mg once daily; max 2.5 mg once daily. Dialysis: Not dialyzable; administer after dialysis on dialysis days.
- Hepatic adjustment
- Initiate with 1.25 mg once daily and titrate carefully. Max 2.5 mg/day in patients with severe hepatic impairment.
- Geriatric
- Start with lower initial doses (e.g., 1.25 mg once daily) and titrate carefully due to potential for decreased renal function and increased sensitivity.
- Max dose
- 10 mg/day
Pharmacokinetics
Onset
1-2 hours
Peak effect
Ramiprilat: 3-6 hours
Duration
24 hours
Half-life
Ramipril: 1-2 hours; Ramiprilat: 13-17 hours (effective half-life with multiple doses)
Bioavailability
Approximately 28% for ramipril; food may delay absorption but not significantly affect extent.
Protein binding
Ramipril ~73%; Ramiprilat ~56%
Metabolism
Prodrug converted to active metabolite ramiprilat by hepatic esterases.
Excretion
Predominantly renal (approx. 60% as ramiprilat and its metabolites); remaining 40% via bile/feces.
Contraindications
- History of angioedema related to previous ACE inhibitor therapy
- Hereditary or idiopathic angioedema
- Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (eGFR < 60 mL/min/1.73 m²)
- Pregnancy (especially 2nd and 3rd trimesters)
- Bilateral renal artery stenosis (or unilateral in a solitary kidney)
- Hypersensitivity to ramipril or any other ACE inhibitor
- Do not use in combination with ARB
- Contraindicated in pregnancy
Side effects
Common
Cough (dry, persistent)DizzinessHeadacheFatigueNauseaVomitingDiarrheaHyperkalemiaHypotension (especially initial dose)coughhypotensionskin rashcough (5%-10%)increase in serum creatinine (<25% normal)Hyperkalemia in CKDAcute kidney failure in severe bilateral renal artery stenosisAngioedema
Serious
- Angioedema (face, limbs, lips, glottis/larynx)
- Acute renal failure
- Symptomatic hypotension
- Severe hyperkalemia
- Agranulocytosis
- Neutropenia
- Hepatic failure
- angioedema
- fetopathic syndrome
- glycosuria
- anemia
- hepatotoxicity
- dysgeusia
- hepatic failure (rare)
- agranulocytosis (rare)
Pregnancy & lactation
Pregnancy
Category D — fetal renal injury, oligohydramnios
Lactation
Excreted into breast milk. Not recommended during breastfeeding due to potential adverse effects on the infant (e.g., hypotension, hyperkalemia).
Drug interactions
Dual Raas Blockade (e.g., With Arbs Like Losartan, Valsartan, Or Direct Renin Inhibitors Like Aliskiren)
Contraindicated
Database
Increased risk of hypotension, hyperkalemia, and renal impairment (including acute renal failure) compared to monotherapy, with no proven additional benefit.
Contraindicated. Avoid concomitant use, especially in patients with diabetes or renal impairment.
Sacubitril
Contraindicated
Database
Fatal angioedema
Wait 36 hours after stopping ACEi before starting ARNI.
Sacubitril/valsartan (entresto)
Contraindicated
Database
Significantly increased risk of angioedema, a potentially life-threatening swelling of the face, lips, tongue, and throat.
Contraindicated. A washout period of at least 36 hours is required between discontinuing ramipril and initiating sacubitril/valsartan, and vice versa.
Aminoglycosides
Severe
Textbook
Increased risk and severity of renal impairment and nephrotoxicity.
Not explicitly stated, but implies careful monitoring of renal function and cautious co-administration.
Source: G&G 14e
Angiotensin Receptor Blockers
Severe
Textbook
Greater incidence of acute kidney injury (AKI) and adverse cardiac events.
The combination of these two classes should be avoided.
Source: Harrison 22e · p2396
Azilsartan
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Candesartan
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Dipeptidyl Peptidase Iv Inhibitor
Severe
Textbook
Increased risk of angioedema.
Avoid combination.
Source: G&G 14e · p600
Losartan + Hydrochlorothiazide
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Olmesartan + Amlodipine
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Olmesartan + Hydrochlorothiazide
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Related guidelines
Other ACE Inhibitor drugs
Ask House about Ramipril
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Sources: KD Tripathi 7e, Goodman & Gilman 14e, Harrison 22e, Katzung·Verified: 2026-05-17 · House clinical team·Cockpit curated: 2026-05-16