ALTACE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ALTACE (ALTACE).
Angiotensin-converting enzyme inhibitor; inhibits ACE, preventing conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone secretion.
| Metabolism | Hepatic metabolism via ester hydrolysis to active metabolite ramiprilat; further glucuronidation. |
| Excretion | Renal: 60% (30% as ramiprilat, 30% as metabolites); Fecal: 40% (unabsorbed drug and biliary metabolites) |
| Half-life | Ramiprilat: 13–17 hours (prolonged in renal impairment, up to 50 hours in severe renal insufficiency; multiple doses: 45–60 hours effective half-life due to tissue binding) |
| Protein binding | Ramipril: 73%; Ramiprilat: 56% (primarily to albumin) |
| Volume of Distribution | Ramipril: ~90 L (1.3 L/kg for 70 kg); Ramiprilat: ~500 L (7.1 L/kg); High Vd indicates extensive tissue binding (especially ACE in vascular endothelium) |
| Bioavailability | Oral: 50–60% (ramipril); Reduced by food (not clinically significant); Absolute bioavailability of ramiprilat: 28% after oral ramipril |
| Onset of Action | Oral: 1–2 hours (peak effect on ACE inhibition); Peak hypotensive effect: 3–6 hours |
| Duration of Action | Oral: 24 hours (blood pressure reduction persists throughout once-daily dosing due to tissue ACE binding; clinical effect may last up to 48 hours) |
2.5-5 mg orally once daily initially, titrated to 10-20 mg once daily; maximum 20 mg/day
| Dosage form | TABLET |
| Renal impairment | GFR 30-60 mL/min: initial dose 2.5 mg/day; GFR <30 mL/min: initial dose 2.5 mg/day; not recommended in dialysis |
| Liver impairment | Child-Pugh A-B: initiate at 2.5 mg once daily; Child-Pugh C: not recommended |
| Pediatric use | Children ≥6 years: initial 2.5 mg orally once daily; titrate to maximum 10 mg/day; weight-based: 0.08-0.3 mg/kg once daily |
| Geriatric use | Geriatric patients (≥65 years): initiate at 2.5 mg once daily; titrate cautiously; monitor renal function and electrolytes |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ALTACE (ALTACE).
| Breastfeeding | Minimal excretion into breast milk; M/P ratio unknown but likely low due to high protein binding. Considered compatible with breastfeeding by most authorities; monitor infant for hypotension and renal effects if used while nursing. |
| Teratogenic Risk | First trimester exposure associated with potential increased risk of congenital malformations (cardiac, CNS) based on retrospective data; second and third trimester exposure causes fetal oligohydramnios, renal dysplasia, pulmonary hypoplasia, and neonatal hypotension, anuria, hyperkalemia, and skull ossification defects (fetotoxic profile consistent with ACE inhibitors). Contraindicated in pregnancy. |
■ FDA Black Box Warning
Fetal toxicity: Drugs acting directly on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.
| Serious Effects |
["History of angioedema with previous ACE inhibitor","Hypersensitivity to ramipril or any ACE inhibitor","Concomitant use with aliskiren in patients with diabetes or renal impairment (GFR <60 mL/min)","Pregnancy"]
| Precautions | ["Angioedema","Hyperkalemia","Renal impairment","Hepatic impairment","Cough","Symptomatic hypotension","Neutropenia/agranulocytosis"] |
| Food/Dietary | Avoid potassium-rich foods in large quantities (bananas, oranges, tomatoes, spinach, avocados, salt substitutes containing potassium chloride). Use of alcohol may potentiate hypotensive effects. No specific restrictions required, but a consistent dietary sodium level is recommended for blood pressure control. |
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| Fetal Monitoring | Maternal: Blood pressure, renal function (serum creatinine, BUN), serum electrolytes (potassium), liver enzymes, CBC with differential, and urinalysis for proteinuria. Fetal: Serial ultrasound for fetal growth, amniotic fluid volume (oligohydramnios), and renal structure if exposed in 2nd/3rd trimester; neonatal monitoring for hypotension, anuria, hyperkalemia after delivery. |
| Fertility Effects | No direct adverse effects on human fertility documented; ACE inhibitors may be associated with erectile dysfunction in males but impact on spermatogenesis or oocyte quality is not established. Animal studies show no impairment of fertility. |
| Clinical Pearls | Initiate at 2.5 mg daily in patients with renal impairment (CrCl <30 mL/min), volume depletion, or concomitant diuretic therapy. Monitor BP and renal function within 2 weeks of initiation or dose increase. Dual blockade of the renin-angiotensin system (e.g., with an ARB or aliskiren) is not recommended due to increased risk of hypotension, hyperkalemia, and renal impairment. For heart failure, titrate as tolerated from 1.25 mg daily to target 10 mg daily. Contraindicated in pregnancy; discontinue as soon as pregnancy is detected. |
| Patient Advice | Take exactly as prescribed, usually once daily. Swallow capsule whole with plenty of water; do not crush or chew. · May cause dizziness, lightheadedness, or fainting, especially when first starting or increasing the dose. Avoid driving or operating machinery until you know how the medication affects you. · Avoid salt substitutes containing potassium; seek medical attention for signs of high potassium (muscle weakness, slow/irregular heartbeat, tingling). · Report swelling of face, lips, tongue, or difficulty breathing immediately as these may indicate angioedema. · Do not take if pregnant or planning pregnancy; use effective contraception. Stop the drug and notify your doctor immediately if you become pregnant. · Inform all healthcare providers you are taking ramipril. Avoid NSAIDs (ibuprofen, naproxen) without consulting your doctor. · Maintain adequate fluid intake but do not take extra salt without discussing with your doctor. |