captopril
Capoten

Pharmacologic classification: ACE inhibitor
Therapeutic classification: antihypertensive, adjunctive treatment of heart failure
Pregnancy risk category C (D second and third trimesters)


Available forms
Available by prescription only
Tablets: 12.5 mg, 25 mg, 50 mg, 100 mg

Indications and dosages
 Mild to severe hypertension, idiopathic edema ◇, Raynaud’s phenomenon ◇. Adults: Initially, 25 mg P.O. b.i.d. or t.i.d.; if needed, dosage may be increased to 50 mg b.i.d. or t.i.d. after 1 to 2 weeks. If control is still inadequate after 1 to 2 weeks more, a diuretic may be added. Dosage may be increased to a maximum of 150 mg t.i.d. (450 mg daily) while continuing the diuretic. Daily dose may be given b.i.d.
 Heart failure. Adults: 25 mg P.O. t.i.d. If patient takes a diuretic or is hyponatremic or hypovolemic, give an initial dosage of 6.25 to 12.5 mg t.i.d. Maintenance dosage is 50 to 100 mg t.i.d.
 Prevention of diabetic nephropathy. Adults: 25 mg P.O. t.i.d.
 Left ventricular dysfunction after MI. Adults: 6.25 mg P.O. as a single dose 3 days after an MI; then 12.5 mg t.i.d., increasing dosage to 25 mg t.i.d. Target dosage is 50 mg t.i.d.
≡ Dosage adjustment. For elderly patients and those with renal failure, use lower initial daily doses and smaller increments for adjustment. Adjust at 1- to 2-week intervals.

Pharmacodynamics
Antihypertensive action: Captopril inhibits ACE, preventing conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. Reduced formation of angiotensin II decreases peripheral arterial resistance, which results in decreased aldosterone secretion, thus reducing sodium and water retention and lowering blood pressure.
Cardiac load-reducing action: Captopril decreases systemic vascular resistance (afterload) and pulmonary capillary wedge pressure (preload), thus increasing cardiac output in patients with heart failure.

Pharmacokinetics
Absorption: 60% to 75% of an oral dose is absorbed through the GI tract; food may reduce absorption by up to 40%. Antihypertensive effect begins in 15 minutes. Maximum therapeutic effect may take several weeks.
Distribution: Distributed into most body tissues except CNS; drug is about 25% to 30% protein-bound.
Metabolism: About 50% is metabolized in the liver.
Excretion: Excreted primarily in urine; small amounts are excreted in feces. Duration of effect is usually 2 to 6 hours, increasing with higher doses. Elimination half-life is less than 3 hours. Duration of action may be increased in patients with renal dysfunction.

Route Onset Peak Duration
P.O. 1/2-1 hr 1-1 1/2 hr 6-12 hr


Contraindications and precautions
Contraindicated in patients hypersensitive to drug or other ACE inhibitors. Use cautiously in patients with impaired renal function, renal artery stenosis, or serious autoimmune diseases (especially lupus erythematosus) and in those taking drugs that affect WBC counts or immune response.

Interactions
Drug-drug. Antacids: Decreases effects of captopril. Separate administration times.
Digoxin: May increase serum digoxin level by 15% to 30%. Monitor patient closely.
Diuretics, other antihypertensives: Causes risk of excessive hypotension. Diuretics may need to be discontinued or captopril dosage lowered.
Insulin, oral antidiabetics: Causes risk of hypoglycemia when captopril therapy starts. Monitor patient closely.
Lithium: Increases lithium levels; toxicity may occur. Monitor patient closely.
NSAIDs: May decrease antihypertensive effect of captopril. Monitor patient closely.
Potassium-sparing diuretics, potassium supplements: Increases risk of hyperkalemia. Avoid these drugs unless hypokalemic blood levels are confirmed.
Drug-herb. Black catechu: May cause additional hypotensive effects. Discourage use together.
Capsaicin: Increases risk of cough. Discourage use together.

Adverse reactions
CNS: dizziness, fainting, headache, malaise, fatigue, fever.
CV: tachycardia, hypotension, angina pectoris.
GI: anorexia, dysgeusia, nausea, vomiting, abdominal pain, constipation, dry mouth.
Hematologic: leukopenia, agranulocytosis, pancytopenia, anemia, thrombocytopenia.
Metabolic: hyperkalemia.
Respiratory: dry, persistent, tickling, nonproductive cough; dyspnea.
Skin: urticarial rash, maculopapular rash, pruritus, alopecia.
Other: angioedema.

Effects on lab test results
• May increase alkaline phosphatase, bilirubin, and potassium levels.
• May decrease hemoglobin, hematocrit, and WBC, granulocyte, RBC, and platelet counts.

Overdose and treatment
Overdose may cause severe hypotension.
 After acute ingestion, stomach must be emptied by induced emesis or gastric lavage. Follow with activated charcoal to reduce absorption. Subsequent treatment is usually symptomatic and supportive. In severe cases, hemodialysis may be used.

Special considerations
• Diuretic therapy is usually discontinued 2 to 3 days before starting ACE inhibitor therapy to reduce the risk of hypotension; if drug doesn’t adequately control blood pressure, diuretics may be reinstated.
• Captopril may cause false-positive results for urinary acetone.
• Lower dosage or reduced dosing frequency is necessary in patients with impaired renal function. Adjust drug to effective levels over a 1- to 2-week interval, then reduce dosage to lowest effective level.
• Several weeks of therapy may be required before the beneficial effects of captopril are seen.
• Proteinuria and nephrotic syndrome may occur, especially in patients with renal disease or those treated with high doses of drug.
• Obtain WBC and differential counts before treatment, every 2 weeks for 3 months, and periodically thereafter; serum potassium levels must be checked because of potassium retention.
Pregnant patients
• Because ACE inhibitors can cause fetal harm or death, discontinue drug use as soon as pregnancy is detected.
Breast-feeding patients
• Captopril appears in breast milk, but its effect on infants is unknown; use drug with caution in breast-feeding women.
Pediatric patients
• Safety and efficacy in children haven’t been established; use only if potential benefit outweighs risk.
Geriatric patients
• Elderly patients may need lower doses because of impaired drug clearance. They also may be more sensitive to the hypotensive effects of captopril.

Patient education
• Instruct patient to call immediately if she becomes pregnant.
• Tell patient to report light-headedness, especially in first few days, so dosage can be adjusted; signs of infection, such as sore throat or fever, because drug may decrease WBC count; facial swelling or difficulty breathing, because drug may cause angioedema; and loss of taste, which may necessitate discontinuing drug.
• Instruct patient to take captopril 1 hour before meals to prevent decreased absorption.
• Advise patient to avoid sudden position changes to minimize orthostatic hypotension.
• Warn patient to seek medical approval before taking OTC cold preparations.
• Tell patient that a persistent, dry cough may occur and usually doesn’t subside until medication is stopped. Advise patient to call if this effect becomes bothersome.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use