MONOPRIL-HCT

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MONOPRIL-HCT (MONOPRIL-HCT).

How it works

Fosinopril is an angiotensin-converting enzyme (ACE) inhibitor that inhibits the conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone secretion; hydrochlorothiazide is a thiazide diuretic that inhibits sodium and chloride reabsorption in the distal convoluted tubule, increasing electrolyte and water excretion.

What the body does with it

Metabolism	Fosinopril is hydrolyzed by intestinal and hepatic esterases to its active metabolite fosinoprilat; further metabolism by CYP450 is minimal. Hydrochlorothiazide is not metabolized extensively.
Excretion	Fosinopril: renal (44%), biliary (46%); hydrochlorothiazide: renal (>95% as unchanged drug).
Half-life	Fosinoprilat: 11.5-12 h (terminal half-life extended in renal and hepatic impairment); hydrochlorothiazide: 5.6-14.8 h (varies with renal function).
Protein binding	Fosinoprilat: >99% (primarily albumin); hydrochlorothiazide: 40-68% (albumin).
Volume of Distribution	Fosinoprilat: 1.3-2.4 L/kg (extensive tissue distribution); hydrochlorothiazide: 3-5 L/kg (binds to red blood cells).
Bioavailability	Fosinopril: 36% (oral, as active metabolite fosinoprilat); hydrochlorothiazide: 65-75% (oral).
Onset of Action	Fosinopril: 1 h (antihypertensive effect); hydrochlorothiazide: 2 h (diuresis).
Duration of Action	Fosinopril: 24 h (once-daily dosing); hydrochlorothiazide: 6-12 h (diuretic effect).

Classification & Brands

Dosing & administration

1 tablet (10-20 mg fosinopril / 12.5-25 mg hydrochlorothiazide) orally once daily; maximum dose 80 mg fosinopril / 50 mg hydrochlorothiazide per day.

Dosage form	TABLET
Renal impairment	Contraindicated if CrCl <30 mL/min. For CrCl 30-60 mL/min: start with lowest dose (10 mg/12.5 mg) and titrate cautiously; monitor renal function and electrolytes.
Liver impairment	No specific adjustment required for mild to moderate impairment (Child-Pugh A/B); use with caution in severe impairment (Child-Pugh C) due to risk of fosinopril accumulation.
Pediatric use	Safety and efficacy not established; use not recommended.
Geriatric use	Start at lowest dose (10 mg/12.5 mg) to avoid hypotension and electrolyte imbalances; monitor renal function and serum potassium regularly.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for MONOPRIL-HCT (MONOPRIL-HCT).

Breastfeeding	Hydrochlorothiazide is excreted in breast milk in low amounts (M/P ratio ~0.5-0.6); fosinoprilat concentrations unknown. Use with caution in breastfeeding due to potential for neonatal electrolyte disturbances and hypotension; avoid in breastfeeding of preterm or hypotensive infants.
Teratogenic Risk	FDA Pregnancy Category D. First trimester: Potential for fetotoxicity (oligohydramnios, fetal renal dysfunction, skull ossification defects). Second and third trimesters: Fetal hypotension, anuria, irreversible renal injury, oligohydramnios, pulmonary hypoplasia, skeletal deformities, and neonatal death risk. Avoid use in pregnancy, especially during second and third trimesters.

Warnings & precautions

■ 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 pregnancy is detected.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Anuria","Hypersensitivity to fosinopril, hydrochlorothiazide, or sulfonamide-derived drugs","History of angioedema related to prior ACE inhibitor therapy","Hereditary or idiopathic angioedema","Pregnancy (second and third trimesters)","Concomitant use with aliskiren in patients with diabetes or renal impairment (eGFR <60 mL/min)"]

Clinical Precautions

Precautions

["Angioedema: Risk of head, neck, or intestinal angioedema; black patients may have higher risk.","Hypotension: Excessive hypotension may occur, especially in volume-depleted patients.","Renal impairment: Monitor renal function; may cause acute renal failure.","Hyperkalemia: Risk in patients with renal impairment, diabetes, or those taking potassium-sparing diuretics.","Electrolyte imbalance: Hydrochlorothiazide may cause hypokalemia, hyponatremia, and hypomagnesemia.","Hepatic impairment: Rare but potentially fatal hepatotoxicity.","Cough: Persistent nonproductive cough may occur.","Neutropenia/agranulocytosis: Risk with ACE inhibitors, especially in patients with renal impairment or collagen vascular disease."]

Clinical Tips & Counseling

Drug interactions

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MONOPRIL-HCT

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MONOPRIL-HCT (MONOPRIL-HCT).

How it works

What the body does with it

Metabolism	Fosinopril is hydrolyzed by intestinal and hepatic esterases to its active metabolite fosinoprilat; further metabolism by CYP450 is minimal. Hydrochlorothiazide is not metabolized extensively.
Excretion	Fosinopril: renal (44%), biliary (46%); hydrochlorothiazide: renal (>95% as unchanged drug).
Half-life	Fosinoprilat: 11.5-12 h (terminal half-life extended in renal and hepatic impairment); hydrochlorothiazide: 5.6-14.8 h (varies with renal function).
Protein binding	Fosinoprilat: >99% (primarily albumin); hydrochlorothiazide: 40-68% (albumin).
Volume of Distribution	Fosinoprilat: 1.3-2.4 L/kg (extensive tissue distribution); hydrochlorothiazide: 3-5 L/kg (binds to red blood cells).
Bioavailability	Fosinopril: 36% (oral, as active metabolite fosinoprilat); hydrochlorothiazide: 65-75% (oral).
Onset of Action	Fosinopril: 1 h (antihypertensive effect); hydrochlorothiazide: 2 h (diuresis).
Duration of Action	Fosinopril: 24 h (once-daily dosing); hydrochlorothiazide: 6-12 h (diuretic effect).

Classification & Brands

Dosing & administration

1 tablet (10-20 mg fosinopril / 12.5-25 mg hydrochlorothiazide) orally once daily; maximum dose 80 mg fosinopril / 50 mg hydrochlorothiazide per day.

Dosage form	TABLET
Renal impairment	Contraindicated if CrCl <30 mL/min. For CrCl 30-60 mL/min: start with lowest dose (10 mg/12.5 mg) and titrate cautiously; monitor renal function and electrolytes.
Liver impairment	No specific adjustment required for mild to moderate impairment (Child-Pugh A/B); use with caution in severe impairment (Child-Pugh C) due to risk of fosinopril accumulation.
Pediatric use	Safety and efficacy not established; use not recommended.
Geriatric use	Start at lowest dose (10 mg/12.5 mg) to avoid hypotension and electrolyte imbalances; monitor renal function and serum potassium regularly.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for MONOPRIL-HCT (MONOPRIL-HCT).

Breastfeeding	Hydrochlorothiazide is excreted in breast milk in low amounts (M/P ratio ~0.5-0.6); fosinoprilat concentrations unknown. Use with caution in breastfeeding due to potential for neonatal electrolyte disturbances and hypotension; avoid in breastfeeding of preterm or hypotensive infants.
Teratogenic Risk	FDA Pregnancy Category D. First trimester: Potential for fetotoxicity (oligohydramnios, fetal renal dysfunction, skull ossification defects). Second and third trimesters: Fetal hypotension, anuria, irreversible renal injury, oligohydramnios, pulmonary hypoplasia, skeletal deformities, and neonatal death risk. Avoid use in pregnancy, especially during second and third trimesters.

Warnings & precautions

■ 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 pregnancy is detected.