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Captopril

Pronunciation

Pronunciation: KAP-toe-pril
Class: ACE inhibitor

Trade Names

Captopril
- Tablets, oral 12.5 mg
- Tablets, oral 25 mg
- Tablets, oral 50 mg
- Tablets, oral 100 mg

APO-Capto (Canada)
Gen-Captopril (Canada)
PMS-Captopril (Canada)

Pharmacology

Competitively inhibits angiotensin I–converting enzyme, preventing conversion of angiotensin I to angiotensin II, a potent vasoconstrictor that also stimulates aldosterone secretion. Results in decreased BP, potassium retention, and reduced sodium reabsorption.

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Pharmacokinetics

Absorption

T max is about 1 h. Food reduces absorption 30% to 40%.

Distribution

Approximately 25% to 30% protein bound.

Elimination

More than 90% of a dose is eliminated in the urine; 40% to 50% is unchanged drug. The half-life is less than 3 h.

Peak

60 to 90 min.

Special Populations

Renal Function Impairment

Excretion is reduced. Dosage reduction may be needed.

Indications and Usage

Treatment of diabetic nephropathy (proteinuria more than 500 mg/day) in patients with type 1 insulin-dependent diabetes mellitus and retinopathy; treatment of CHF, usually in combination with diuretics and digitalis; treatment of hypertension; to improve survival following MI in clinically stable patients with left ventricular dysfunction manifested as an ejection fraction of 40% or less and to reduce the incidence of overt heart failure and subsequent hospitalizations for CHF in these patients.

Unlabeled Uses

Hypertensive emergencies/urgencies; pediatric hypertension; Raynaud phenomenon.

Contraindications

Hypersensitivity to any component of this product or any other ACE inhibitor.

Dosage and Administration

Diabetic Nephropathy
Adults

PO 25 mg 3 times daily.

Heart Failure
Adults

PO 25 mg (6.25 or 12.5 mg in patients with low or normal BP who have been treated vigorously with diuretics and may be hyponatremic and/or hypovolemic) 3 times daily initially. Titrate over the next several days to 50 mg 3 times daily. Further increases in dosage should be delayed, when possible, for at least 2 wk to determine if a satisfactory response occurs (usual dosage, 50 or 100 mg 3 times daily; max, 450 mg/day).

Hypertension
Adults

PO 25 mg 2 or 3 times daily initially. Increase to 50 mg 2 or 3 times daily if satisfactory reduction of BP is not achieved in 1 or 2 weeks; if satisfactory response is not seen at this dose, a modest dose of thiazide-type diuretic should be added. If further BP reduction is still required, increase to captopril 100 mg 2 or 3 times daily, and then, if necessary, to captopril 150 mg 2 or 3 times daily (usual dosage, 25 to 150 mg 2 or 3 times daily; max, 450 mg/day). When necessitated by the patient's clinical condition, the daily dose of captopril may be increased every 24 h or less under continuous medical supervision until a satisfactory BP response is obtained or the maximum captopril dose is reached.

Left Ventricular Dysfunction after Myocardial Infarction
Adults

PO Initiate therapy as early as 3 days after myocardial infarction with a single dose of captopril 6.25 mg, then start captopril 12.5 mg 3 times daily. Increase to captopril 25 mg 3 times daily after several days, and then to the target dosage of captopril 50 mg 3 times daily over the next several weeks as tolerated.

Renal function impairment

Reduce the initial daily dosage and use smaller increments for titration, which should be slow (eg, 1 to 2 wk intervals), in patients with significant renal impairment. After desired therapeutic effect is achieved, back-titrate to the minimal effective dose.

General Advice

Dose should be taken 1 h before meals.

Storage/Stability

Store between 68° and 77°F.

Drug Interactions

Adrenergic neuron blocking agents (eg, reserpine), ganglionic blocking agents (eg, mecamylamine)

An additive or synergistic decrease in BP may occur. Use with caution and closely monitor BP.

Aliskiren

The risk of hyperkalemia may be increased. Close monitoring of potassium concentrations is warranted.

Angiotensin II receptor antagonists (eg, candesartan, telmisartan)

The risk of hyperkalemia and renal dysfunction may be increased as a result of additive renal toxicity. If coadministration cannot be avoided, closely monitor renal function and potassium plasma concentrations.

Beta-adrenergic blocking agents (eg, propranolol)

The antihypertensive response may be increased. However, the overall response is less than additive. Use with caution and closely monitor BP.

Capsaicin

The risk of coughing may be increased. If cough is severe, discontinue one or both drugs.

Digoxin

Findings are conflicting. Increased, decreased, and no change in digoxin concentrations have been reported. Monitor digoxin concentrations and adjust the digoxin dose as needed.

Eplerenone

Serious hyperkalemia, possibly with cardiac arrhythmias or arrest, may occur as result of additive potassium-sparing effects. Periodic monitoring of serum potassium concentrations is recommended until the effect of combined therapy is established. Eplerenone dose reduction may be necessary to decrease potassium concentrations.

Everolimus, sirolimus

The risk of angioedema may be increased. If an interaction is suspected, stop one or both drugs.

Gold salts (eg, sodium aurothiomalate)

The risk of gold-induced nitritoid reactions may be increased. Closely monitor patients for signs and symptoms of nitritoid reactions (facial flushing, nausea, hypotension, syncope).

Lithium

Increased lithium levels and symptoms of lithium toxicity may occur. Coadminister with caution and perform frequent monitoring of serum lithium concentrations. It may be necessary to adjust the lithium dose or discontinue captopril. If a diuretic is also used, the risk of lithium toxicity may be increased.

Loop diuretics (eg, furosemide)

The effects of loop diuretics may be decreased. Closely monitor fluid status and body weight in patients receiving loop diuretics when captopril is started or stopped.

NSAIDs (eg, indomethacin), salicylates (eg, aspirin)

Hypotensive effects may be reduced, especially in low-renin or volume-dependent hypertensive patients. Also, nephrotoxicity associated with captopril or NSAIDs may be increased. Closely monitor BP. If BP control deteriorates, consider stopping the NSAID. Periodic measurement of renal function is warranted. It may be necessary to reduce the aspirin dosage to less than 100 mg daily or select alternative therapy.

Potassium-containing salt substitutes, potassium preparations, potassium-sparing diuretics (eg, amiloride, spironolactone, triamterene)

Hyperkalemia, possibly with cardiac arrhythmias or arrest, may occur. Use with caution. Closely monitor serum potassium concentrations.

Sulfonylureas (eg, glyburide)

The risk of hypoglycemia may be increased. Close clinical and laboratory monitoring is warranted.

Thiazide diuretics (eg, chlorothiazide)

BP-lowering effects of captopril and thiazide diuretics are approximately additive. In addition, coadministration may increase the risk of acute renal dysfunction. Monitor BP and renal function when using captopril with a thiazide diuretic, especially in elderly patients and in patients with impaired renal function. If an adverse interaction is suspected, stop one or both agents.

Tizanidine

The risk of severe hypotension may be increased. Coadminister with caution and closely monitor BP.

Trimethoprim

The risk of hyperkalemia may be increased because of additive or synergistic inhibition of renal potassium excretion. If coadministration cannot be avoided, closely monitor potassium plasma concentrations and the clinical response.

Vasodilators (eg, nitroglycerin)

Data on the effect of concomitant use are not available; therefore, nitroglycerin, other nitrates (as used for management of angina), or other drugs having vasodilator activity should, if possible, be discontinued before starting captopril. If vasodilator therapy is resumed during captopril therapy, administer such agents with caution and consider lower dosages.

Laboratory Test Interactions

False-positive urine acetone test may occur.

Adverse Reactions

Cardiovascular

Chest pain, palpitations, tachycardia (1%); hypotension; cardiac arrest, cerebrovascular accident/insufficiency, rhythm disturbances, orthostatic hypotension, syncope (postmarketing).

CNS

Dizziness, fatigue, headache, insomnia, paresthesia (up to 2%); asthenia, ataxia, confusion, depression, nervousness, somnolence (postmarketing).

Dermatologic

Rash, often with pruritus, and sometimes with fever, arthralgia, and eosinophilia (4% to 7%); pruritus (2%); alopecia (up to 2%); bullous pemphigus, erythema multiforme (including Stevens-Johnson syndrome), exfoliative dermatitis (postmarketing).

EENT

Blurred vision (postmarketing).

GI

Dysgeusia (2% to 4%); abdominal pain, anorexia, aphthous ulcers, constipation, diarrhea, dry mouth, gastric irritation, nausea, peptic ulcer, vomiting (up to 2%); dyspepsia, glossitis, pancreatitis (postmarketing).

Genitourinary

Proteinuria (1%); nephrotic syndrome; oliguria; renal failure; renal insufficiency; gynecomastia, impotence (postmarketing).

Hepatic

Elevations of liver transaminases, alkaline phosphatase, serum bilirubin; cholestasis, jaundice, hepatic necrosis, hepatitis (postmarketing).

Hematologic

Agranulocytosis; anemia; neutropenia; pancytopenia; thrombocytopenia; aplastic anemia, hemolytic anemia (postmarketing).

Lab Tests

Increases in BUN, serum creatinine, and serum potassium; positive antinuclear antibody.

Metabolic

Symptomatic hyponatremia (postmarketing).

Musculoskeletal

Myalgia, myasthenia (postmarketing).

Respiratory

Cough, dyspnea (up to 2%); bronchospasm, eosinophilic pneumonitis, rhinitis (postmarketing).

Miscellaneous

Syndrome that may include fever, myalgia, arthralgia, interstitial nephritis, vasculitis, rash, eosinophilia, elevated erythrocyte sedimentation rate (postmarketing).

Precautions

Warnings

Pregnancy

When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, discontinue therapy as soon as possible.


Monitor

BP

Monitor and record BP and pulse. If symptomatic hypotension occurs, hold medication.

CBC

Ensure that CBC with differential is evaluated prior to starting therapy, at 2 wk intervals for 3 mo, and periodically thereafter in patients with renal impairment. Also assess WBC count in patients with suspected infection.

Heart failure patients

Assess heart failure patients for evidence of worsening failure (eg, daily weights, evaluation of peripheral edema, shortness of breath). Patients should inform health care provider of rapid weight gain (eg, 2 lb in 1 day or 5 lb in 1 wk) or worsening edema or other symptoms of heart failure (eg, worsening shortness of breath).


Pregnancy

Category D (second and third trimester); Category C (first trimester).

Lactation

Excreted in breast milk. The American Academy of Pediatrics classifies captopril as compatible with breast-feeding.

Children

Safety and efficacy not established.

Hypersensitivity

Anaphylactoid reactions have occurred in patients taking ACE inhibitors undergoing desensitization, and in patients being dialyzed with high-flux membranes or undergoing LDL apheresis with dextran sulfate absorption.

Renal Function

Because captopril is excreted primarily by the kidneys, patients with renal impairment may require smaller or less frequent doses.

Special Risk Patients

Patients with aortic stenosis may be at increased risk of decreased coronary perfusion when treated with vasodilators.

Angioedema

Angioedema involving the extremities, face, lips, mucous membranes, tongue, glottis, or larynx may occur. Intestinal angioedema has also been reported. Use with extreme caution in patients with hereditary angioedema.

Cough

Persistent nonproductive cough may occur, presumably because of the inhibition of the degradation of endogenous bradykinin.

Hepatic failure

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and sometimes death.

Hyperkalemia

Elevations in serum potassium have been observed; risk factors include renal insufficiency, diabetes, and concomitant use of potassium supplements or drugs known to increase serum potassium.

Hypotension/First-dose effect

Significant decreases in BP may occur after first dose, especially in patients with severe salt or volume depletion or with CHF.

Neutropenia and agranulocytosis

Neutropenia with myeloid hypoplasia has occurred; about half of the patients developed systemic or oral cavity infections or other features of the syndrome of agranulocytosis.

Proteinuria

May occur, especially in patients with prior renal disease or those receiving high captopril dosages (more than 150 mg/day); generally resolves within 6 mo.

Renal effects

Patients, especially those with preexisting renal disease, may develop increases in BUN and serum creatinine.

Surgery/Anesthesia

Risk of hypotension may be increased; if hypotension occurs, it can be corrected by volume expansion.

Overdosage

Symptoms

Hypotension.

Patient Information

  • Advise patients to take prescribed dose 1 h before meals because food can reduce absorption and benefits of medication.
  • Advise patients to try to take each dose at about the same time each day.
  • Inform hypertensive patients that drug controls, but does not cure, hypertension and to continue taking drug as prescribed even when BP is not elevated.
  • Caution patients not to change the dose or stop taking unless advised by health care provider.
  • Instruct patients to continue taking other medications for the condition as prescribed by health care provider.
  • Instruct patients in BP and pulse measurement skills.
  • Advise patients to monitor and record BP and pulse at home and to inform health care provider if abnormal measurements are noted. Also advise patients to take a record of BP and pulse to each follow-up visit.
  • Caution patients to avoid sudden position changes to prevent orthostatic hypotension.
  • Instruct patients to lie or sit down if experiencing dizziness or light-headedness when standing.
  • Emphasize to hypertensive patients the importance of other modalities on BP control: weight control, regular exercise, smoking cessation, and moderate intake of alcohol and salt.
  • Emphasize to heart failure patients the importance of other modalities that can help control heart failure symptoms: weight control, progressive exercise program, smoking cessation, and moderate intake of alcohol and salt.
  • Advise heart failure patients to weigh themselves daily, keep a record of daily weights, and notify health care provider if rapid weight gain (eg, 5 lb in 1 wk) is noted or if edema or shortness of breath worsen.
  • Caution patients that inadequate fluid intake or excessive perspiration, diarrhea, or vomiting can lead to excessive fall in BP, resulting in light-headedness or fainting.
  • Advise patients that medication may cause dizziness or light-headedness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
  • Caution patients to avoid unnecessary exposure to UV light (sunlight, tanning booths) and to use sunscreen and wear protective clothing when exposed to UV light to avoid a photosensitivity reaction.
  • Instruct patients to stop taking drug and immediately report any of the following symptoms to health care provider: sore throat, fever, irregular heartbeat, chest pains, fainting, progressive edema, signs or symptoms of angioedema (eg, swelling of the hands, feet, face, lips, eyelids, or tongue, hoarseness, difficulty swallowing or breathing).
  • Instruct patients to inform health care provider if a persistent cough or changes in taste develop while taking this medication.
  • Caution patients not to take any prescription or OTC medications, potassium-containing salt substitutes, potassium supplements, or dietary supplements unless advised by health care provider.

Copyright © 2009 Wolters Kluwer Health.

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