ACCUPRIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ACCUPRIL (ACCUPRIL).
Angiotensin-converting enzyme (ACE) inhibitor; inhibits ACE, thereby blocking conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone secretion, leading to decreased blood pressure.
| Metabolism | Primarily hepatic ester hydrolysis to active metabolite quinaprilat; minor additional metabolism. |
| Excretion | Primarily renal (about 60% as unchanged drug and 40% as metabolites, mainly quinaprilat), with biliary/fecal elimination accounting for less than 10%. |
| Half-life | Quinaprilat terminal elimination half-life is approximately 3 hours. In patients with renal impairment (CrCl <30 mL/min), half-life can be prolonged up to 10-25 hours, requiring dose adjustment. |
| Protein binding | Quinaprilat is approximately 97% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Quinaprilat Vd is about 0.7 L/kg (range 0.6-0.8). This indicates distribution into total body water and some tissue binding. |
| Bioavailability | Oral bioavailability of quinapril is at least 60% (mean ~60-70%), with extensive first-pass metabolism to the active metabolite quinaprilat. |
| Onset of Action | Oral: 1-2 hours for peak effect on blood pressure reduction. |
| Duration of Action | 24 hours. Clinical effect persists for at least 24 hours with once-daily dosing, though some patients may require twice-daily dosing for optimal BP control. |
| Molecular Weight | 395.9 |
10-40 mg orally once daily; initial dose 10 mg, titrate to target dose based on blood pressure response; maximum 80 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-60 mL/min: initial dose 5 mg daily; maximum 20 mg/day. GFR <30 mL/min: initial dose 2.5 mg daily; maximum 10 mg/day. |
| Liver impairment | Child-Pugh Class A or B: initial dose 5 mg daily; titrate cautiously. Child-Pugh Class C: avoid use or use with extreme caution; no established dosing. |
| Pediatric use | Not recommended for pediatric patients due to lack of safety and efficacy data; alternative agents preferred. |
| Geriatric use | Initial dose 5 mg daily; titrate slowly; monitor for hypotension and renal function; consider lower maximum dose. |
| 1st trimester | Contraindicated: associated with fetal renal impairment, oligohydramnios, skull ossification defects, and potential teratogenic effects based on human data and animal studies. |
| 2nd trimester | Contraindicated: exposure during second and third trimesters can cause fetal hypotension, renal failure, oligohydramnios, and skull hypoplasia; risk of neonatal renal dysfunction and death. |
| 3rd trimester | Contraindicated: as for t2, with additional risk of neonatal hypotension, hyperkalemia, and irreversible renal damage. |
Clinical note
Comprehensive clinical and safety monograph for ACCUPRIL (ACCUPRIL).
| Placental transfer | Crosses placenta extensively; detectable in fetal tissues and amniotic fluid; associated with fetotoxic effects. |
| Breastfeeding | Excreted into breast milk in low concentrations; due to potential risk of infant renal dysfunction and hypotension, alternative agents are preferred, especially when nursing preterm or jaundiced infants. |
■ FDA Black Box Warning
Fetal toxicity: Use during pregnancy causes oligohydramnios, fetal renal dysfunction, skull hypoplasia, and death. Discontinue once pregnancy is detected.
| Serious Effects |
History of angioedema related to previous ACE inhibitor therapyHereditary or idiopathic angioedemaPregnancy (second and third trimesters)Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (GFR <60 mL/min/1.73 m²)
| Precautions | Angioedema: Risk of angioedema, especially in black patients and those with prior ACE inhibitor-related angioedema., Hyperkalemia: Risk factors include renal impairment, diabetes, concomitant potassium-sparing diuretics or potassium supplements., Hypotension: Symptomatic hypotension can occur, particularly in volume- or salt-depleted patients., Renal impairment: Monitor renal function; may cause acute renal failure in patients with bilateral renal artery stenosis or those with severe heart failure., Cough: Persistent dry cough is common. |
| Food/Dietary | Avoid high-potassium foods (e.g., bananas, oranges, potatoes, spinach, salt substitutes) unless monitored. Grapefruit juice may decrease absorption; separate intake by at least 2 hours. Alcohol may potentiate hypotensive effects. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) - limited data suggests minimal risk with caution; however, many sources advise avoidance. |
| Teratogenic Risk | First trimester: Potential risk of congenital malformations (cardiac, renal). Second and third trimesters: Fetal renal impairment, oligohydramnios, skull ossification defects, hypotension, hyperkalemia, and death. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, electrolytes. Fetal ultrasound for oligohydramnios and fetal growth restriction. |
| Fertility Effects | No known adverse effects on human fertility; animal studies show no impairment. |
| Clinical Pearls | ACCUPRIL (quinapril) is an ACE inhibitor. Peak effect on blood pressure occurs 2-4 hours after dosing. It is a prodrug; its active metabolite is quinaprilat. Dosing should be adjusted in patients with renal impairment (CrCl <30 mL/min). Monitor serum potassium and renal function, especially in patients on diuretics or NSAIDs. First-dose hypotension is possible; start low and go slow. For hypertension, effects may take 1-2 weeks to fully manifest. Dry cough is common and not dose-related. Avoid in pregnancy (category D). |
| Patient Advice | Take this medication exactly as prescribed, usually once or twice daily with or without food. · Avoid salt substitutes containing potassium unless directed by your doctor. · If you miss a dose, take it as soon as you remember; if near next dose, skip the missed one. Do not double the dose. · Report any persistent dry cough, dizziness, or swelling of the face, lips, or throat immediately. · Stay hydrated, but avoid excessive fluid intake if you have heart failure. · This medication can cause dizziness, especially after the first dose. Avoid driving until you know how it affects you. · Notify your doctor if you experience signs of infection (fever, sore throat) or easy bruising/bleeding. · Women of childbearing age should use effective contraception; stop taking and inform your doctor if you become pregnant. |