captopril/hydrochlorothiazide (Rx)

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Brand and Other Names:Capozide

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

captopril/hydrochlorothiazide

tablet

  • 25mg/15mg
  • 25mg/25mg
  • 50mg/15mg
  • 50mg/25mg
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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

<18 years: Safety and efficacy not established

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Interactions

Interaction Checker

and captopril/hydrochlorothiazide

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    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

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            Adverse 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
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            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)

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            Pregnancy & 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.

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            Pharmacology

            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
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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
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            Code Definition
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