CAPOZIDE 50/15
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CAPOZIDE 50/15 (CAPOZIDE 50/15).
CAPOZIDE 50/15 combines captopril (angiotensin-converting enzyme inhibitor) and hydrochlorothiazide (thiazide diuretic). Captopril inhibits ACE, reducing angiotensin II formation, decreasing aldosterone secretion, and lowering blood pressure. Hydrochlorothiazide increases sodium and water excretion by inhibiting the Na+/Cl- cotransporter in distal convoluted tubules.
| Metabolism | Captopril undergoes partial hepatic metabolism to disulfide dimers and mixed disulfides; approximately 50% eliminated renally as unchanged drug. Hydrochlorothiazide is not metabolized and is excreted unchanged in urine. |
| Excretion | Captopril: renal excretion of unchanged drug and metabolites, primarily in urine (60-75%), with ~20% as unchanged captopril; small amount in feces (5-10%). Hydrochlorothiazide: renal excretion (95% unchanged), <5% via biliary/fecal. |
| Half-life | Captopril: terminal half-life ~2 hours (in patients with normal renal function; prolonged in renal impairment to 21-36 hours). Hydrochlorothiazide: half-life 6-15 hours (mean ~9 hours; prolonged in renal impairment). Clinical context: dosing interval affected by renal function. |
| Protein binding | Captopril: 25-30% bound (primarily albumin). Hydrochlorothiazide: 40-68% bound (albumin). |
| Volume of Distribution | Captopril: Vd ~0.7 L/kg (0.2-2 L/kg), distributes extensively into tissues including kidneys, heart, and lungs. Hydrochlorothiazide: Vd ~0.8-3 L/kg (mean ~1.5 L/kg), crosses placenta, minimal CNS penetration. |
| Bioavailability | Captopril: oral bioavailability ~60-75% (reduced by food, dose-dependent). Hydrochlorothiazide: oral bioavailability ~65-75% (affected by food). |
| Onset of Action | Captopril: onset 15-30 minutes oral; peak effect 1-1.5 hours. Hydrochlorothiazide: onset ~2 hours oral; peak diuretic effect 4-6 hours. |
| Duration of Action | Captopril: duration ~6-12 hours (dose-dependent). Hydrochlorothiazide: duration 6-12 hours (diuretic effect); antihypertensive effect persists up to 24 hours with chronic dosing. |
| Molecular Weight | Captopril: 217.29 Da; Hydrochlorothiazide: 297.74 Da |
Oral, 1 tablet (captopril 50 mg / hydrochlorothiazide 15 mg) once daily. May increase to 2 tablets daily in divided doses if needed.
| Dosage form | TABLET |
| Renal impairment | GFR 30-60 mL/min: start with captopril 25 mg / HCTZ 12.5 mg once daily; GFR <30 mL/min: avoid HCTZ, use captopril alone. Maximum daily dose of HCTZ is 50 mg. |
| Liver impairment | Child-Pugh A: no dose adjustment; Child-Pugh B: initiate at half dose and titrate slowly; Child-Pugh C: avoid HCTZ due to risk of electrolyte imbalance and encephalopathy. |
| Pediatric use | Not recommended for pediatric use; safety and efficacy not established. Off-label use: captopril initial 0.3 mg/kg/dose q8h, titrate; HCTZ 1-2 mg/kg/day divided q12-24h. |
| Geriatric use | Initiate at half dose (captopril 25 mg / HCTZ 12.5 mg) once daily, titrate slowly. Monitor renal function, electrolytes, and volume status. Avoid in elderly with advanced renal impairment or recurrent falls. |
| 1st trimester | Contraindicated: associated with fetal renal dysplasia, oligohydramnios, and skull ossification defects. |
| 2nd trimester | Contraindicated: may cause fetal hypotension, hyperkalemia, and decreased renal function. |
| 3rd trimester | Contraindicated: risk of fetal and neonatal morbidity including renal failure, hypotension, and hyperkalemia. |
Clinical note
Comprehensive clinical and safety monograph for CAPOZIDE 50/15 (CAPOZIDE 50/15).
| Placental transfer | Both captopril and hydrochlorothiazide cross the placenta. Captopril has been detected in cord blood at concentrations equivalent to maternal levels. |
| Breastfeeding | Captopril is excreted into breast milk in very low concentrations; however, due to potential for neonatal adverse effects (hypotension, hyperkalemia, renal impairment), caution is advised. Hydrochlorothiazide is also excreted and may suppress lactation. Use only if benefits outweigh risks. |
■ FDA Black Box Warning
Fetal toxicity: Drugs acting directly on the renin-angiotensin system (including ACE inhibitors) can cause injury and death to the developing fetus. Discontinue as soon as pregnancy is detected.
| Serious Effects |
Hypersensitivity to captopril, hydrochlorothiazide, or sulfonamide-derived drugsHistory of angioedema related to previous ACE inhibitor therapyAnuriaSevere renal impairment (eGFR <30 mL/min/1.73m²)Pregnancy (second and third trimesters)
| Precautions | Angioedema, Hypotension (especially in volume-depleted patients), Neutropenia/agranulocytosis (increased risk with renal impairment and collagen vascular disease), Renal impairment (monitor renal function), Electrolyte disturbances (hypokalemia, hyponatremia, hypercalcemia), Hyperuricemia/gout, Sulfonamide allergy (related to HCTZ), Cough (common with ACE inhibitors) |
| Food/Dietary | Avoid high-potassium foods (e.g., bananas, oranges, spinach) unless potassium levels are monitored. Grapefruit juice may increase captopril absorption; limit consumption. Sodium restriction is recommended to enhance antihypertensive effect. Alcohol may exacerbate orthostatic hypotension. |
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| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | First trimester: Increased risk of congenital malformations (cardiac, CNS) due to captopril (ACE inhibitor). Second and third trimesters: Fetal oligohydramnios, renal dysfunction, skull ossification defects, hypotension, and anuria; captopril is contraindicated after first trimester. Hydrochlorothiazide (HCTZ) may cause fetal/neonatal jaundice, electrolyte disturbances, and thrombocytopenia. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function (serum creatinine, BUN, electrolytes), and urinalysis for proteinuria. Fetal monitoring includes ultrasound for growth, amniotic fluid volume, and fetal anatomy; periodic fetal heart rate monitoring. |
| Fertility Effects | Captopril may interfere with renin-angiotensin system and could theoretically affect spermatogenesis or ovulation, but no consistent data. HCTZ has no known significant effect on fertility. |
| Clinical Pearls | CAPOZIDE 50/15 combines captopril 50 mg (ACE inhibitor) and hydrochlorothiazide 15 mg (thiazide diuretic). Monitor serum potassium and creatinine within 2 weeks of initiation due to risk of hyperkalemia from captopril and hypokalemia from HCTZ. First-dose hypotension can occur, especially in volume-depleted patients; consider starting with a lower captopril dose. Avoid use in pregnancy (category D). Contraindicated in bilateral renal artery stenosis. Ensure patient is well-hydrated before starting therapy. HCTZ may exacerbate gout; monitor uric acid. |
| Patient Advice | Take exactly as prescribed, usually once daily. Do not skip doses or double up. · This medication controls blood pressure but does not cure it; continue even if you feel well. · Avoid potassium supplements or salt substitutes containing potassium unless directed by your doctor. · May cause dizziness, especially when standing up quickly; rise slowly. If severe, report to your doctor. · Avoid alcohol as it can increase dizziness and blood pressure lowering effects. · Notify your doctor if you develop severe diarrhea, vomiting, or excessive sweating which can cause dehydration. · Women: Inform your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. Do not use if pregnant. · Report symptoms like swelling of face/lips/tongue, difficulty breathing (angioedema), or decreased urination. · May increase sensitivity to sunlight; use sunscreen and protective clothing. |