MONOPRIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MONOPRIL (MONOPRIL).
Fosinopril is an angiotensin-converting enzyme (ACE) inhibitor. It inhibits ACE, which converts angiotensin I to angiotensin II, a potent vasoconstrictor. Decreased angiotensin II leads to vasodilation, reduced aldosterone secretion, and decreased sodium and water retention.
| Metabolism | Primarily metabolized by hydrolysis to its active metabolite, fosinoprilat. Fosinoprilat is further metabolized by conjugation. Hepatic and renal pathways contribute; elimination is balanced between hepatic and renal routes. |
| Excretion | Renal (44% as fosinoprilat; 46% as fosinoprilat glucuronide); biliary/fecal (48% as fosinoprilat and glucuronide). Total clearance involves both renal and hepatic pathways. |
| Half-life | Terminal elimination half-life of fosinoprilat is 11.5 hours (range 10-14 hours). Accumulation half-life ~26 hours. Clinically, steady state reached in 3-4 days. |
| Protein binding | Fosinoprilat: 99.4% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Apparent Vd of fosinoprilat: 2.3 L/kg. Distribution mainly to plasma and extracellular fluid; minimal tissue binding. |
| Bioavailability | Oral bioavailability of fosinoprilat is 36% (range 25-50%). Food reduces rate but not extent. Prodrug fosinopril is fully absorbed, then hydrolyzed to active fosinoprilat. |
| Onset of Action | Oral: Peak plasma concentrations within 3 hours; antihypertensive effect begins within 1 hour, maximal effect at 2-6 hours. |
| Duration of Action | Antihypertensive effect lasts 24 hours with once-daily dosing. Dose-dependent; higher doses may sustain effect longer. |
| Molecular Weight | 563.65 |
10-40 mg orally once daily; initial dose for hypertension 10 mg once daily; for heart failure, starting dose 5-10 mg orally once daily, target 40 mg once daily.
| Dosage form | TABLET |
| Renal impairment | CrCl <30 mL/min: reduce initial dose to 5 mg once daily; titrate slowly. Not recommended for CrCl <10 mL/min. |
| Liver impairment | No specific Child-Pugh based guidelines; use with caution in severe hepatic impairment due to decreased clearance. |
| Pediatric use | Children ≥6 years: initial 0.1-0.3 mg/kg orally once daily, max 40 mg/day. Safety and efficacy not established in children <6 years. |
| Geriatric use | Initiate at 5 mg orally once daily; titrate slowly due to potential renal impairment and hypotension risk. |
| 1st trimester | Associated with increased risk of fetal renal dysfunction, oligohydramnios, and skull ossification defects. Avoid unless no alternative. |
| 2nd trimester | Can cause fetal renal impairment, oligohydramnios, and neonatal hypotension. Avoid use. |
| 3rd trimester | High risk of fetal and neonatal morbidity including renal failure, hyperkalemia, and hypotension. Contraindicated. |
Clinical note
Comprehensive clinical and safety monograph for MONOPRIL (MONOPRIL).
| Placental transfer | Crosses placenta; fosinoprilat detected in fetal circulation and amniotic fluid. |
| Breastfeeding | Fosinoprilat, the active metabolite, is excreted into breast milk in low concentrations; effects on nursing infant are unknown. Consider risk versus benefit; monitor infant for hypotension and renal impairment. |
■ FDA Black Box Warning
Fetal toxicity: Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible when pregnancy is detected.
| Serious Effects |
History of angioedema related to previous ACE inhibitor therapyHereditary or idiopathic angioedemaHypersensitivity to fosinopril or any componentConcomitant use with aliskiren in patients with diabetesPregnancy (especially 2nd and 3rd trimesters)
| Precautions | Angioedema: Increased risk in patients with history of angioedema unrelated to ACE inhibitors, Hypotension: Excessive hypotension may occur, especially in volume-depleted patients, Hyperkalemia: Monitor serum potassium, especially in patients with renal impairment, diabetes, or those using K+ supplements or K+-sparing diuretics, Renal impairment: Monitor renal function; may increase risk of renal failure, Cough: Persistent, dry cough common |
| Food/Dietary | Avoid high-potassium foods (bananas, oranges, potatoes, spinach, salt substitutes) if at risk for hyperkalemia. Take fosinopril without regard to meals, but consistency in timing is advised. Alcohol may potentiate hypotensive effects; limit intake. |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: No definitive teratogenic risk, but caution advised due to potential fetal renal effects. Second and third trimesters: Increased risk of fetal oligohydramnios, renal dysfunction, skull ossification defects, hypotension, and anuria when used in second and third trimesters; consider discontinuation if pregnancy is detected. |
| Fetal Monitoring | Monitor fetal ultrasound for amniotic fluid volume and renal function; assess maternal blood pressure and renal function regularly; if oligohydramnios occurs, discontinue drug. |
| Fertility Effects | No evidence of significant adverse effects on fertility in animal studies; human data limited. |
| Clinical Pearls | Monopril (fosinopril) is a prodrug activated by hydrolysis; its dual hepatic and renal elimination reduces accumulation in renal impairment. Monitor potassium and renal function. Do not use in pregnancy. First-dose hypotension risk in volume-depleted patients. |
| Patient Advice | Take exactly as prescribed, usually once daily. Swallow tablets whole. · Inform your doctor if you become pregnant or plan to become pregnant. · Avoid salt substitutes containing potassium unless approved by your doctor. · Report any signs of angioedema: swelling of face, lips, tongue, or difficulty breathing. · You may experience dizziness, especially after the first dose; rise slowly from sitting or lying. · Stay hydrated but do not overhydrate; maintain regular fluid intake unless fluid restricted. · Do not stop taking this medication abruptly; consult your doctor first. · Keep appointments for blood pressure and lab tests to monitor kidney function and electrolytes. |