MONOPRIL-HCT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MONOPRIL-HCT (MONOPRIL-HCT).
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.
| 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). |
| Molecular Weight | Fosinopril: 563.7 Da; Hydrochlorothiazide: 297.7 Da |
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. |
| 1st trimester | Contraindicated. Fetal toxicity including oligohydramnios and renal dysfunction. Risk of fetopathy. |
| 2nd trimester | Contraindicated. Use linked to oligohydramnios, fetal renal failure, skull ossification defects. |
| 3rd trimester | Contraindicated. High risk of neonatal hypotension, renal failure, hyperkalemia, and death. |
Clinical note
Comprehensive clinical and safety monograph for MONOPRIL-HCT (MONOPRIL-HCT).
| Placental transfer | Both fosinopril and hydrochlorothiazide cross the placenta. Animal studies show fetal abnormalities. Human data limited but adverse effects documented. |
| Breastfeeding | Fosinopril and hydrochlorothiazide are excreted in breast milk. Hydrochlorothiazide may suppress lactation. Use with caution or avoid. |
■ 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.
| Serious Effects |
AnuriaHistory of angioedema with ACE inhibitorsHypersensitivity to sulfonamide-derived drugs (hydrochlorothiazide)Pregnancy
| 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. |
| Food/Dietary | Avoid salt substitutes containing potassium chloride; limit high-potassium foods (bananas, oranges, leafy greens) if used with potassium-sparing diuretics or in renal impairment. Do not consume alcohol excessively as it may increase hypotensive effects. |
Loading safety data…
| Lactation Rating |
| L4 |
| 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. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function (serum creatinine, BUN), electrolytes (sodium, potassium), and urine output throughout pregnancy. Fetal monitoring includes ultrasound for amniotic fluid volume (oligohydramnios) and fetal growth; consider fetal renal assessment if exposed after first trimester. |
| Fertility Effects | No specific studies on fertility. ACE inhibitors may cause reversible oligospermia in men; hydrochorothiazide has no known significant fertility impact. Use with caution in couples planning pregnancy. |
| Clinical Pearls | First-dose hypotension is common; start at evening or bedtime and titrate slowly. Monitor serum potassium, creatinine, and BUN at baseline and periodically. Avoid use in bilateral renal artery stenosis or severe aortic stenosis. Contraindicated in pregnancy (ACE inhibitors cause fetal harm). |
| Patient Advice | Take this medication exactly as prescribed, usually once daily. · Avoid potassium supplements or salt substitutes containing potassium without consulting your doctor. · Report any signs of infection (fever, sore throat), swelling of face/tongue (angioedema), or difficulty breathing immediately. · Do not stop taking this medication abruptly without consulting your physician. · Drink plenty of fluids to prevent dehydration; avoid excessive sweating or diarrhea without medical advice. |