Dosing and uses of Capozide (captopril/hydrochlorothiazide)
Adult dosage forms and strengths
captopril/hydrochlorothiazide
tablet
- 25mg/15mg
- 25mg/25mg
- 50mg/15mg
- 50mg/25mg
Hypertension
Initial: 25 mg captopril/15 mg hydrochlorothiazide PO qDay; not to exceed 150 mg captopril/50 mg chlorothiazide
Increase either or both components based on clinical response q6weeks
To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy
Renal Impairment
CrCl ≥30mL/min: No dosage adjustment required
CrCl <30mL/min: Not recommended
Hepatic Impairment
Dose adjustment not necessary
Administration
Dosage adjustment may be required in geriatrics
Less effective in African-Americans
Food decreases absorption; manufacturer recommends dosing 1 hr before meaL
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Capozide (captopril/hydrochlorothiazide) adverse (side) effects
Captopril
1-10%
- Chest pain (1%)
- Cough (1-2%)
- Dysgeusia (2-4%)
- Hypersensitivity reactions
- Hyperkalemia (1-11%)
- Hypotension (1-3%)
- Palpitations (1%)
- Pruritis rash (2%)
- Tachycardia (1%)
<1%
- Angioedema
- ARF if renal artery stenosis
- Impotence
- Neutropenia
- Photosensitivity
Frequency not defined
- Orthostatic hypotension, ataxia, angioedema, cardiac arrest, CHF, rhythm disturbances, somnolence, confusion, nervousness, depression, Stevens-Johnson syndrome, exfoliative dermatitis, bullous pemphigus, increased billirubin, gynecomastia, increased alkaline phosphatase, dyspepsia, pancreatitis, glossitis, impotence, urinary frequency, agranulocytosis anemia, thrombocytopenia, anemia, pancytopenia, blurred vision, bronchospasm, eosinophilic pneumonitis, rhinitis, cholestasis, hyponatremia
Hydrochlorothiazide
<1%
- Anaphylaxis, anemia, confusion, erythema multiforme skin reactions including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis, hypomagnesemia, hyponatremia, hypochloremia, dizziness, fatigue, headache, hypercalcemia, hyperuricemia, hyperglycemia, hyperlipidemia, hypercholesterolemia, muscle weakness or cramps, nausea, purpura, rash, vertigo, vomiting
Frequency not defined
- Anorexia
- Epigastric distress
- Hypotension
- Orthostatic hypotension
- Photosensitivity
Warnings
Black box warnings
Captopril: Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system causing oligohydramnios, which may result in fetal injury and/or death
Contraindications
Hypersensitivity to either component or sulfonamides
History of hereditary or idiopathic angioedema
Bilateral renal artery stenosis or anuria
Do not coadminister with aliskiren in patients with diabetes
Pregnancy (2nd and 3rd trimesters): significant risk of fetal and neonatal morbidity and mortality
Cautions
Excessive hypotension if concomitant diuretics, hypovolemia, hyponatremia
Risk of hyperkalemia, especially in patients with renal impairment, DM or those taking concomitant K+-elevating drugs
Dual blockade of the renin angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for hypotension, hyperkalemia, and renal function changes (including acute renal failure) compared to monotherapy
DM, fluid or electrolyte imbalance, hyperuricemia or gout, SLE, liver disease, renal disease
May aggravate digitalis toxicity
Sensitivity reactions may occur with or without history of allergy or asthma
Aortic stenosis/ hypertrophic cardiomyopathy
Biliary cirrhosis or biliary obstruction
Myelosuppression
Blood levels do not correlate with BP response
Causes false positive urine acetone
Risk of male sexual dysfunction
Avoid concomitant use with lithium
Acute transient myopia and acute angle-closure glaucoma has been reported, particularly with history of sulfonamide or penicillin allergy (hydrochlorothiazide is a sulfonamide)
Pregnancy and lactation
Pregnancy category: C (1st trimester); D (2nd and 3rd trimester)
Lactation: excreted in breast milk, use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Capozide (captopril/hydrochlorothiazide)
Mechanism of action
Captopril/hydrochlorothiazide is a fixed-combination tablet that combines an angiotensin-converting enzyme (ACE) inhibitor, captopril, and a thiazide diuretic, hydrochlorothiazide
Captopril prevents the conversion of angiotensin I to angiotensin II (a potent vasoconstrictor) through inhibition of ACE by competing with physiologic substrate (angiotensin I) for active site of ACE; inhibition of ACE initially results in decreased plasma angiotensin II concentrations & consequently, blood pressure may be reduced in part through decreased vasoconstriction, increased renin activity, and decreased aldosterone secretion
Hydrochlorothiazide is a thiazide diuretic that inhibits Na reabsorption in distal renal tubules resulting in increased excretion of Na+ and water, also K+ and H+ ions
Pharmacokinetics
CaptopriL
- Half-life: 1.9 hr
- Bioavailability: 60-75%
- Onset: 1-1.5 hr (peak effect blood pressure reduction)
- Duration: 8-12 hr
- Vd: 0.7 L/kg
- Peak plasma time: 1-1.5 hr
- Protein bound: 25-30%
- Metabolism: Liver (50%)
- Metabolites: captopril-cysteine disulfide (inactive)
- Clearance: 0.8 L/kg/hr
- Dialyzable: Yes
- Excretion: Urine (95%)
Hydrochlorothiazide
- Half-life: 6-15 hr
- Bioavailability: 70%
- Onset: 2 hr (diuresis); 4-6 hr (peak effect)
- Duration: 6-12 hr (diuresis); 1 wk (HTN)
- Vd: 3.6-7.8 L/kg
- Peak plasma:1.5-2.5 hr
- Protein bound: 68%
- Metabolism: Minimally metabolized
- Clearance: 335 mL/min
- Excretion: Urine 50-70%
- Dialyzable: No
