RAMIPRIL

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

Ramipril is a prodrug that is hydrolyzed in the liver to its active metabolite ramiprilat, which inhibits angiotensin-converting enzyme (ACE), thereby decreasing angiotensin II production, reducing vasoconstriction, aldosterone secretion, and sodium retention.

What the body does with it

Metabolism	Ramipril is extensively metabolized in the liver (ester hydrolysis) to its active metabolite ramiprilat; further metabolism may involve glucuronidation.
Excretion	Primarily renal (60% as unchanged drug and metabolites) and fecal (40% via biliary elimination).
Half-life	Terminal half-life of ramiprilat is 13–17 hours (prolonged to 50 hours in renal impairment). Accumulation half-life is 110 hours after multiple doses.
Protein binding	Ramipril: ~73% bound to serum proteins; ramiprilat: ~56% bound.
Volume of Distribution	Ramipril: ~90 L; ramiprilat: ~500 L (approx 7 L/kg), indicating extensive tissue distribution.
Bioavailability	Oral: ~50–60% (ramipril is a prodrug; ramiprilat bioavailability is 28–44%).
Onset of Action	Oral: 1–2 hours for peak plasma concentration of ramiprilat; antihypertensive effect begins within 1–2 hours.
Duration of Action	24 hours for blood pressure reduction; hemodynamic effects persist for 24 hours allowing once-daily dosing.

Classification & Brands

Dosing & administration

Initial: 2.5 mg orally once daily; Maintenance: 2.5-20 mg/day in 1-2 divided doses; Maximum: 20 mg/day.

Dosage form	TABLET
Renal impairment	GFR 30-60 mL/min: initial 1.25 mg once daily, max 5 mg/day. GFR 10-30 mL/min: initial 1.25 mg once daily, max 2.5 mg/day. GFR <10 mL/min: not recommended.
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh Class B: initial 1.25 mg once daily. Child-Pugh Class C: use not recommended due to risk of severe hypotension.
Pediatric use	Hypertension: Children ≥6 years: initial 2.5 mg once daily; titrate up to 6.25 mg/m²/day up to 10 mg/day. Not established for other indications.
Geriatric use	Initial dose: 1.25 mg once daily; titrate cautiously due to age-related renal impairment and risk of hypotension.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Risk of angioedema can occur at any time discontinue immediately.

Breastfeeding

Excreted into human milk in very low concentrations; M/P ratio not determined. No adverse effects in breastfeeding infants are reported, but caution is advised in preterm or hypotensive infants. American Academy of Pediatrics considers use compatible with breastfeeding.

Teratogenic Risk

First trimester: Exposure associated with potential risk of congenital malformations, particularly cardiovascular and central nervous system defects, though absolute risk is low. Second and third trimesters: Contraindicated due to fetal renal dysfunction, oligohydramnios, skull ossification defects, and neonatal hypotension, hyperkalemia, and renal failure. Use is not recommended at any stage of pregnancy.

Warnings & precautions

■ FDA Black Box Warning

USE IN PREGNANCY: Drugs that act directly on the renin-angiotensin system can cause fetal injury and death; discontinue as soon as pregnancy is detected.

Side Effect Profile

Common Effects	Dry cough Headache Fatigue
Serious Effects

Absolute Contraindications

["History of angioedema related to previous ACE inhibitor therapy","Hypersensitivity to ramipril or any ACE inhibitor","Concomitant use with aliskiren in patients with diabetes or renal impairment (GFR < 60 mL/min)"]

Clinical Precautions

Precautions

["Angioedema (black patients at higher risk)","Hypotension (especially in volume-depleted patients)","Renal impairment (monitor serum creatinine)","Hyperkalemia (monitor potassium levels)","Cough (nonproductive, persistent)"]

Clinical Tips & Counseling

Drug interactions

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