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). |
| Molecular Weight | Fosinopril: 563.7 Da; Hydrochlorothiazide: 297.7 Da |
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 | Contraindicated due to risk of fetal renal impairment, oligohydramnios, and skull ossification defects from fosinopril (ACE inhibitor) action on renin-angiotensin system; hydrochlorothiazide may cause electrolyte disturbances and volume depletion, potentially reducing placental perfusion. |
| 2nd trimester | Contraindicated; ACE inhibitors are associated with fetal hypotension, renal dysplasia, anuria, oligohydramnios, and growth restriction, particularly in the second and third trimesters. Hydrochlorothiazide may contribute to maternal hypovolemia and placental hypoperfusion. |
| 3rd trimester | Contraindicated; neonatal risks include persistent anuria, hypotension, hyperkalemia, and pulmonary hypoplasia from ACE inhibitor exposure; hydrochlorothiazide can cause fetal electrolyte imbalances, jaundice, and thrombocytopenia. |
Clinical note
Other antihypertensive drugs can have additive effects Lithium levels may be increased Can cause hypokalemia and hyponatremia.
| FDA category | Animal |
| Placental transfer |
■ 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 |
History of angioedema related to previous ACE inhibitor therapyHereditary or idiopathic angioedemaPregnancy (second and third trimesters)Anuria or severe renal impairment (CrCl <30 mL/min)Hypersensitivity to fosinopril, hydrochlorothiazide, or sulfonamide-derived drugsConcomitant use with aliskiren in patients with diabetes
| 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 |
| Food/Dietary |
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| Fosinopril undergoes placental transfer; animal studies show fetal exposure, and human data confirm crossing. Hydrochlorothiazide crosses the placenta, detectable in umbilical cord blood. |
| Breastfeeding | Fosinopril is excreted in low concentrations into breast milk; hydrochlorothiazide also appears in breast milk, potentially reducing milk production and causing infant electrolyte disturbances. Use is generally discouraged; if necessary, monitor infant for hypotension and electrolyte imbalances. |
| Lactation Rating | L3 (Moderately safe) – limited data but potential for adverse effects; alternative agents preferred. |
| Teratogenic Risk | 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. |
| Avoid potassium-rich foods (bananas, oranges, spinach, avocados) in large amounts without monitoring; potassium-sparing effects of ACE inhibitor combined with HCTZ can cause hyperkalemia. Avoid high-sodium foods to optimize antihypertensive effect. Grapefruit juice does not significantly interact with this combination. Limit alcohol intake as it may potentiate hypotension. Maintain adequate fluid intake; excessive fluid loss (e.g., from diarrhea, vomiting) may increase risk of hypotension and electrolyte imbalance. |
| Clinical Pearls | Fosinopril/HCTZ combines an ACE inhibitor with a thiazide diuretic; monitor renal function and electrolytes (especially potassium, sodium, and magnesium) within 2 weeks of initiation and periodically thereafter. Fosinopril is hepatically and renally eliminated; no dose adjustment needed in renal impairment but caution if severe. HCTZ may cause hyperglycemia, hyperuricemia, and dyslipidemia. Synergistic antihypertensive effect; orthostatic hypotension may occur, especially volume-depleted patients. Avoid use in pregnancy (ACE inhibitor risk). Assess for cough and angioedema. HCTZ may increase sensitivity to sunlight. |
| Patient Advice | Take this medication exactly as prescribed, usually once daily. · Avoid salt substitutes containing potassium unless approved by your doctor. · May cause dizziness or lightheadedness; rise slowly from sitting or lying down. · Report persistent dry cough, swelling of face/lips/tongue, difficulty breathing, or severe diarrhea/vomiting immediately. · Use sun protection (sunscreen, protective clothing) as hydrochlorothiazide increases sun sensitivity. · Do not use if pregnant or planning to become pregnant; use effective contraception. · Maintain adequate fluid intake to prevent dehydration, especially during hot weather or exercise. · Monitor blood pressure regularly and keep follow-up appointments for blood tests. · Avoid alcohol as it may enhance blood pressure-lowering effects and increase dizziness. |