CAPTOPRIL AND HYDROCHLOROTHIAZIDE
Clinical safety rating: safe
Other antihypertensive drugs can have additive effects Lithium levels may be increased Can cause hypokalemia and hyponatremia.
Captopril is an angiotensin-converting enzyme (ACE) inhibitor that inhibits the conversion of angiotensin I to angiotensin II, resulting in vasodilation and decreased aldosterone secretion. Hydrochlorothiazide is a thiazide diuretic that inhibits the Na+/Cl- cotransporter in the distal convoluted tubule, increasing excretion of sodium and water.
| Metabolism | Captopril undergoes oxidation and glucuronidation; active metabolite is captopril-cysteine disulfide. Hydrochlorothiazide is not extensively metabolized; eliminated unchanged by the kidneys. |
| Excretion | Captopril: renal (95%), primarily as unchanged drug and disulfide metabolites. Hydrochlorothiazide: renal (≥95%) as unchanged drug via tubular secretion. |
| Half-life | Captopril: ~2 hours (prolonged to 6-8 hours in heart failure or renal impairment). Hydrochlorothiazide: 5.6-14.8 hours (mean ~9.6 hours; prolonged in renal impairment). |
| Protein binding | Captopril: 25-30% (albumin). Hydrochlorothiazide: 40-68% (albumin). |
| Volume of Distribution | Captopril: 0.7 L/kg (distributes into most tissues except CNS). Hydrochlorothiazide: 3-4 L/kg (extensively distributed, crosses placenta). |
| Bioavailability | Captopril: 60-75% (oral, reduced by food). Hydrochlorothiazide: 65-75% (oral). |
| Onset of Action | Captopril: 15-60 minutes (oral); HCTZ: 2 hours (oral). Antihypertensive effect: 1-2 hours for both. |
| Duration of Action | Captopril: dose-dependent, 6-12 hours; HCTZ: 6-12 hours (antihypertensive effect up to 24 hours). |
1 tablet (captopril 25 mg / hydrochlorothiazide 15 mg) orally once daily, titrated up to a maximum of 1 tablet (captopril 50 mg / hydrochlorothiazide 25 mg) twice daily.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if GFR <30 mL/min. For GFR 30-60 mL/min: reduce dose or use loop diuretic; avoid if possible due to thiazide inefficacy. For GFR >60 mL/min: no adjustment. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce captopril dose by 25%; caution with hydrochlorothiazide. Child-Pugh C: avoid due to risk of electrolyte disturbances and hepatic encephalopathy. |
| Pediatric use | Not recommended for children <18 years due to insufficient safety and efficacy data. |
| Geriatric use | Initiate at lowest dose (e.g., captopril 12.5 mg / hydrochlorothiazide 6.25 mg) once daily; monitor renal function, electrolytes, and blood pressure closely due to increased sensitivity and risk of hypovolemia. |
| 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 | Captopril: excreted in breast milk in low amounts (M/P ratio approximately 0.01); monitor infant for hypotension and renal effects. Hydrochlorothiazide: excreted in breast milk (M/P ratio approximately 0.5); may suppress lactation and cause neonatal electrolyte disturbances. Combination not recommended during breastfeeding. |
| 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 |
["History of angioedema related to previous ACE inhibitor therapy","Concomitant use with aliskiren in patients with diabetes","Anuria","Sulfonamide allergy (hydrochlorothiazide)"]
| Precautions | ["Hypotension","Hyperkalemia","Renal impairment","Angioedema","Electrolyte imbalances (hypokalemia, hyponatremia) due to hydrochlorothiazide","Exacerbation of gout","Sulfonamide allergy cross-reactivity (hydrochlorothiazide)"] |
| Food/Dietary | Avoid high-potassium foods in excess (e.g., bananas, oranges, spinach, potatoes) due to ACE inhibitor effect; limit sodium intake; avoid salt substitutes containing potassium chloride; alcohol may enhance hypotensive effect. |
Loading safety data…
| First trimester: Increased risk of congenital malformations (cardiac, CNS) associated with ACE inhibitors. Second and third trimesters: Fetal oligohydramnios, renal dysplasia, skull hypoplasia, hypotension, and anuria. Hydrochlorothiazide may cause neonatal electrolyte disturbances and thrombocytopenia. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, electrolytes, and urine output. Perform fetal ultrasound for oligohydramnios and serial assessments of fetal growth and amniotic fluid volume. Monitor neonatal renal function and blood pressure if exposed in utero. |
| Fertility Effects | No known direct effects on fertility. Captopril may theoretically affect angiotensin II-mediated reproductive functions; hydrochlorothiazide may cause electrolyte imbalances that could impact overall health and fertility. |
| Clinical Pearls | Monitor serum potassium and renal function at baseline and periodically; risk of first-dose hypotension, especially in volume-depleted patients; may cause dry cough due to ACE inhibition; thiazide component may exacerbate gout or hyperuricemia; avoid use in pregnancy (ACE inhibitor risk). |
| Patient Advice | Take exactly as prescribed; do not stop without consulting your doctor. · Avoid potassium supplements or salt substitutes containing potassium unless approved. · Report persistent dry cough, dizziness, or signs of infection. · Take medication at the same time each day; if a dose is missed, take it as soon as remembered unless close to next dose. · Do not use during pregnancy; use effective contraception. · May cause dizziness, especially when starting therapy; avoid driving if affected. · Limit alcohol intake to prevent dizziness and blood pressure drop. · Stay hydrated but avoid excessive fluid intake that may affect electrolytes. |