CAPOZIDE 25/15
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CAPOZIDE 25/15 (CAPOZIDE 25/15).
Combination of captopril (ACE inhibitor) and hydrochlorothiazide (thiazide diuretic). Captopril inhibits angiotensin-converting enzyme, reducing angiotensin II formation, decreasing vasoconstriction and aldosterone secretion. Hydrochlorothiazide inhibits sodium reabsorption in the distal convoluted tubule, increasing diuresis and reducing plasma volume.
| Metabolism | Captopril: partially metabolized via oxidation to disulfide dimers and mixed disulfides with other thiols. Hydrochlorothiazide: not metabolized, excreted unchanged in urine. |
| Excretion | Captopril: 95% renally excreted, primarily as unchanged drug and metabolites (disulfide dimers). Hydrochlorothiazide: at least 95% renally excreted as unchanged drug. |
| Half-life | Captopril: ~2 hours (terminal) in normal renal function; increases to 20-60 hours in severe renal impairment. Hydrochlorothiazide: 6-15 hours (terminal), prolonged in renal impairment. |
| Protein binding | Captopril: 25-30% bound to albumin. Hydrochlorothiazide: 40-68% bound, primarily to albumin and α1-acid glycoprotein. |
| Volume of Distribution | Captopril: ~0.7 L/kg (distributes extensively into tissues; small Vd reflects limited tissue binding). Hydrochlorothiazide: 0.2-0.8 L/kg (Vd correlates with degree of tissue accumulation; larger in obesity). |
| Bioavailability | Captopril: 60-70% (oral; food reduces absorption by 30%). Hydrochlorothiazide: 65-70% (oral; slight variability with formulation). |
| Onset of Action | Captopril: 15-30 min (oral) for blood pressure reduction. Hydrochlorothiazide: 2 hours (oral) for diuresis; antihypertensive effect may take 1-2 weeks. |
| Duration of Action | Captopril: 6-12 hours (dose-dependent; antihypertensive effect). Hydrochlorothiazide: 6-12 hours (diuresis); antihypertensive effect persists for 24 hours with chronic dosing. |
| Molecular Weight | Captopril: 217.29 Da; Hydrochlorothiazide: 297.74 Da (combination product: not a single compound) |
Oral: 1 tablet (captopril 25 mg / hydrochlorothiazide 15 mg) once daily initially; titrate to a maximum of 2 tablets twice daily based on blood pressure response.
| Dosage form | TABLET |
| Renal impairment | GFR 30-60 mL/min: reduce dose or increase dosing interval; use with caution, maximum captopril 75 mg/day. GFR <30 mL/min: not recommended; loop diuretics preferred over thiazides. |
| Liver impairment | Child-Pugh Class A or B: no adjustment needed. Child-Pugh Class C: use with caution; monitor electrolytes and renal function due to potential fluid and electrolyte disturbances. |
| Pediatric use | Not established; safety and efficacy in pediatric patients not confirmed. |
| Geriatric use | Initiate at lowest possible dose (e.g., captopril 12.5 mg / hydrochlorothiazide 12.5 mg) and titrate slowly; monitor renal function, electrolytes, and blood pressure closely due to increased risk of hypotension and electrolyte imbalance. |
| 1st trimester | Risk of fetal harm: captopril crosses placenta; associated with increased risk of congenital malformations (e.g., renal dysplasia, oligohydramnios) when used in first trimester. Use only if no alternative. |
| 2nd trimester | Avoid during second and third trimesters due to risk of fetal hypotension, oligohydramnios, and neonatal renal failure. Use only if no alternative. |
| 3rd trimester | Contraindicated in third trimester due to risk of oligohydramnios, fetal/neonatal renal impairment, and hypotension. |
Clinical note
Comprehensive clinical and safety monograph for CAPOZIDE 25/15 (CAPOZIDE 25/15).
| Placental transfer | Both components cross the placenta: captopril transfers readily; hydrochlorothiazide also crosses. Degree: significant (captopril ~100% of maternal plasma levels in fetal cord blood). |
| Breastfeeding | Captopril is excreted into breast milk in low concentrations; hydrochlorothiazide is also excreted. Risk of neonatal electrolyte disturbances (hypokalemia, hyponatremia) and potential for renal impairment. Avoid or use with caution; monitor infant for adverse effects. |
■ FDA Black Box Warning
USE IN PREGNANCY: Drugs that act 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 inhibitorsPregnancy (especially second and third trimesters)Hypersensitivity to captopril, hydrochlorothiazide, or sulfonamide-derived drugsConcomitant aliskiren use in patients with diabetes mellitus
| Precautions | Fetal/neonatal morbidity and mortality, Hypotension, Neutropenia/agranulocytosis, Proteinuria, Angioedema, Impaired renal function, Hyperkalemia, Cough, Hepatic failure, Electrolyte disturbances (hypokalemia, hyponatremia, hypomagnesemia), Hyperuricemia, Sulfonamide sensitivity (hydrochlorothiazide), Acute angle-closure glaucoma, Systemic lupus erythematosus exacerbation |
| Food/Dietary | Avoid high-potassium foods (e.g., bananas, oranges, spinach) if potassium levels are elevated. Avoid salt substitutes containing potassium. Maintain adequate fluid intake; dehydration may potentiate hypotension. Grapefruit juice may alter captopril absorption; limit intake. Alcohol may enhance hypotensive effects. |
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| Lactation Rating | L3 (Moderately Safe) - avoid if possible |
| Teratogenic Risk | First trimester: Not associated with increased risk of major congenital malformations based on retrospective data, but angiotensin II receptor antagonists (ARBs) class effect includes risk of fetal renal dysfunction, oligohydramnios, and skull ossification defects when used in the second and third trimesters. Second and third trimesters: Known to cause fetal renal hypoperfusion, oligohydramnios, anuria, renal failure, skull hypoplasia, limb contractures, craniofacial deformation, and potentially neonatal hypotension, hyperkalemia, and death. Pregnancy category D for second/third trimesters. |
| Fetal Monitoring | Serial fetal ultrasound to monitor amniotic fluid volume and fetal renal function; fetal echocardiography if oligohydramnios occurs; neonatal monitoring for hypotension, hyperkalemia, and renal function after delivery. |
| Fertility Effects | Animal studies with captopril (component) show decreased fertility; no human data available for combination. Possible adverse effects on sperm parameters and libido has been reported with ACE inhibitors. |
| Clinical Pearls | CAPOZIDE 25/15 combines captopril 25 mg and hydrochlorothiazide 15 mg. Use with caution in renal impairment; monitor serum creatinine and potassium. Avoid in pregnancy. First-dose hypotension (orthostatic) common; start at bedtime. Hypokalemia from thiazide may be offset by captopril's potassium-sparing effect, but monitor electrolytes. Contraindicated in bilateral renal artery stenosis. May cause acute gout attacks in predisposed patients. Reduce dose in hepatic impairment. |
| Patient Advice | Take this medication exactly as prescribed, usually once or twice daily. · Avoid sudden standing to prevent dizziness; rise slowly. · Do not use potassium supplements or salt substitutes without consulting your doctor. · Report any signs of infection (fever, sore throat), swelling of the face or extremities, or difficulty breathing. · This drug may cause a persistent dry cough; inform your doctor if bothersome. · Avoid alcohol, as it may increase dizziness or orthostatic hypotension. · Use sun protection; this drug may increase sensitivity to sunlight. · Do not stop taking this medication abruptly without medical advice. · If you are pregnant, planning to become pregnant, or breastfeeding, discuss with your doctor immediately. |