MONOPRIL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MONOPRIL (MONOPRIL).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for MONOPRIL (MONOPRIL).

Breastfeeding	Not recommended during breastfeeding due to potential for adverse effects in the infant; M/P ratio not established.
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

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

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

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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MONOPRIL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MONOPRIL (MONOPRIL).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for MONOPRIL (MONOPRIL).

Breastfeeding	Not recommended during breastfeeding due to potential for adverse effects in the infant; M/P ratio not established.
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

Warnings & precautions

■ 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.