FOSINOPRIL SODIUM AND HYDROCHLOROTHIAZIDE
Clinical safety rating: safe
Other antihypertensive drugs can have additive effects Lithium levels may be increased Can cause hypokalemia and hyponatremia.
Fosinopril is an ACE inhibitor that inhibits the conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone secretion. Hydrochlorothiazide is a thiazide diuretic that inhibits the sodium-chloride symporter in the distal convoluted tubule, increasing excretion of sodium and water.
| Metabolism | Fosinopril is hydrolyzed by esterases to its active metabolite, fosinoprilat, which is primarily excreted via hepatic (biliary) and renal routes. Hydrochlorothiazide is not extensively metabolized and is excreted unchanged by the kidneys. |
| Excretion | Fosinopril: 45% renal, 55% biliary/fecal; Hydrochlorothiazide: >95% renal (unchanged). |
| Half-life | Fosinoprilat: 11.5 h (terminal); Hydrochlorothiazide: 6-15 h (biphasic, terminal phase 10-15 h). |
| Protein binding | Fosinoprilat: >99% (primarily albumin); Hydrochlorothiazide: 40-68% (albumin). |
| Volume of Distribution | Fosinoprilat: 1.3-2.0 L/kg (extensive tissue binding); Hydrochlorothiazide: 0.8-3 L/kg (wide distribution). |
| Bioavailability | Fosinopril: 36% (oral, not affected by food); Hydrochlorothiazide: 65-75% (oral). |
| Onset of Action | Fosinopril: antihypertensive effect within 1 h; Hydrochlorothiazide: diuresis within 2 h. |
| Duration of Action | Fosinopril: 24 h; Hydrochlorothiazide: 6-12 h (antihypertensive effect up to 24 h). |
1 tablet (fosinopril 10 mg/hydrochlorothiazide 12.5 mg or fosinopril 20 mg/hydrochlorothiazide 12.5 mg) orally once daily. Maximum dose: fosinopril 80 mg/hydrochlorothiazide 50 mg per day.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if GFR <30 mL/min or anuria. For GFR 30-60 mL/min, use with caution and consider dose reduction. No adjustment required for GFR >60 mL/min. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Fosinopril at reduced dose (e.g., 5 mg) with hydrochlorothiazide at 12.5 mg; monitor closely. Child-Pugh C: Avoid use due to risk of electrolyte disturbances and altered metabolism. |
| Pediatric use | Not recommended for use in pediatric patients due to lack of safety and efficacy data. |
| Geriatric use | Initiate at lowest available dose (fosinopril 10 mg/hydrochlorothiazide 12.5 mg orally once daily) due to increased sensitivity to blood pressure reduction and electrolyte imbalances. Monitor renal function and electrolytes frequently. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other antihypertensive drugs can have additive effects Lithium levels may be increased Can cause hypokalemia and hyponatremia.
| FDA category | Animal |
| Breastfeeding | Fosinopril: Undetectable or low levels in breast milk; M/P ratio not established. Hydrochlorothiazide: Excreted in breast milk at low concentrations; M/P ratio ~0.5. Considered compatible with breastfeeding but monitor infant for electrolyte imbalance, dehydration, and diuretic effects. |
| Teratogenic Risk |
■ 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 possible once pregnancy is detected.
| Common Effects | edema |
| Serious Effects |
["Hypersensitivity to fosinopril, hydrochlorothiazide, or any component","History of ACE inhibitor-induced angioedema or hereditary/idiopathic angioedema","Anuria","Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (GFR <60 mL/min/1.73 m²)","Pregnancy"]
| Precautions | ["Angioedema","Hyperkalemia","Hypotension","Renal impairment","Hepatic impairment","Electrolyte disturbances (hypokalemia, hyponatremia)","Acute angle-closure glaucoma","Sulfonamide allergy cross-sensitivity","Exacerbation of autoimmune disease","Cough"] |
Loading safety data…
| First trimester: Potential association with congenital malformations (neural tube defects, renal anomalies) based on ACE inhibitor class effects. Second and third trimesters: Fetal hypotension, anuria, oligohydramnios, pulmonary hypoplasia, skull ossification defects, and neonatal renal failure. Hydrochlorothiazide: Crosses placenta; fetal/neonatal electrolyte disturbances, thrombocytopenia, and jaundice reported. |
| Fetal Monitoring | Serial fetal ultrasound for amniotic fluid volume and fetal growth; maternal blood pressure, serum creatinine, electrolytes, liver function tests, and uric acid. Monitor for oligohydramnios and fetal renal function in second/third trimesters. |
| Fertility Effects | Limited data. ACE inhibitors may theoretically affect male fertility via renin-angiotensin system in reproductive tissues; no clinical studies confirm impairment. Hydrochlorothiazide has no known significant effect on fertility. |