captopril

Angiotensin-converting enzyme (ACE) inhibitors block the conversion of angiotensin I to the vasoconstrictor angiotensin II. ACE inhibitors also prevent the degradation of bradykinin and other vasodilatory prostaglandins. ACE inhibitors also ↑ plasma renin levels and ↓ aldosterone levels. Net result is systemic vasodilation.

Therapeutic effects:

Lowering of BP in patients with hypertension.
Improved survival and reduced symptoms in patients with HF.
Improved survival and reduced development of overt HF after MI.
Decreased progression of diabetic nephropathy with decreased need for transplantation or dialysis.

Pharmacokinetics ⬆ ⬇

Absorption: 60–75% absorbed following oral administration (↓ by food).

Distribution: Well distributed to tissues.

Metabolism/Excretion: 50% metabolized by the liver to inactive compounds; 50% excreted unchanged in urine.

Half-Life: Infants with HF: 3.3 hr (range 1.2–12.4 hr); Children: 1.5 hr (range 0.98–2.3 hr); Adults: 1.9 hr (↑ to 20–40 hr in renal impairment); Adults with HF: 2.1 hr.

Time/Action Profile ⬆ ⬇

(effect on BP—single dose‡)

ROUTE	ONSET	PEAK	DURATION
PO	15–60 min	60–90 min	6–12 hr

‡Full effects may not be noted for several wk.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
History of angioedema with previous use of ACE inhibitors;
Concurrent use with aliskiren in patients with diabetes or moderate to severe renal impairment (CCr <60 mL/min);
Concurrent use with sacubitril/valsartan; must be a 36-hr washout period after switching to/from sacubitril/valsartan;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Patients with collagen vascular disease, renal impairment, hypovolemia, hyponatremia, and concurrent diuretic therapy;
Surgery/anesthesia (hypotension may be exaggerated);
Black patients (monotherapy for hypertension less effective, may require additional therapy; higher risk of angioedema);
Rep: Women of reproductive potential;
Geri: Initial dose ↓ recommended in older adults.

Exercise Extreme Caution in:

History of angioedema.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension, chest pain, palpitations, tachycardia

Derm: rash, pruritus

F and E: hyperkalemia

GI: taste disturbances, abdominal pain, anorexia, constipation, diarrhea, nausea, vomiting

GU: proteinuria, renal impairment

Hemat: AGRANULOCYTOSIS, neutropenia

Neuro: dizziness, fatigue, headache, insomnia

Resp: cough

Misc: ANGIOEDEMA, fever

Interactions ⬆ ⬇

Drug-drug:

Sacubitril↑ risk of angioedema; concurrent use contraindicated; do not administer within 36 hr of switching to/from sacubitril/valsartan.
Excessive hypotension may occur with concurrent use of diuretics.
Additive hypotension with other antihypertensives.
↑risk of hyperkalemia with concurrent use ofpotassium supplements, potassium-sparing diuretics, or potassium-containing salt substitutes.
↑risk of hyperkalemia, renal dysfunction, hypotension, and syncope with concurrent use of angiotensin II receptor blockers or aliskiren; avoid concurrent use with aliskiren in patients with diabetes or CCr <60 mL/min; avoid concurrent use with angiotensin II receptor blockers.
NSAIDs and selective COX-2 inhibitors may blunt the antihypertensive effect and ↑ the risk of renal impairment.
May ↑ levels and the risk of toxicity of lithium .
↑risk of angioedema with temsirolimus, sirolimus, or everolimus.

Drug-Natural Products:

Avoid natural licorice (causes sodium and water retention and ↑ potassium loss).

Drug-Food:

Food significantly ↓ absorption. Administer captopril 1 hr before meals.

Route/Dosage ⬆ ⬇

Note: Use lower doses (½ of those listed) in patients who are sodium and water depleted due to diuretics.

Hypertension

PO (Adults and Adolescents): 12.5–25 mg 2–3 times daily; may be ↑ at 1–2 wk intervals up to 150 mg 3 times daily (initiate therapy with 6.25–12.5 mg 2–3 times daily in patients receiving diuretics).

Heart Failure

PO (Adults ): 25 mg 3 times daily (6.25–12.5 mg 3 times daily in patients who have been vigorously diuresed); titrated up to target dose of 50 mg 3 times daily (max dose = 450 mg/day).
PO (Children ): 0.3–0.5 mg/kg 3 times daily; titrate up to a maximum of 6 mg/kg/day in 2–4 divided doses; Older Children:6.25–12.5 mg every 12–24 hr; titrate up to a maximum of 6 mg/kg/day in 2–4 divided doses.
PO (Infants ): 0.15–0.3 mg/kg; titrate up to a maximum of 6 mg/kg/day in 1–4 divided doses.
PO (Neonates ): 0.05–0.1 mg/kg every 8–24 hr;, may ↑ as needed up to 0.5 mg/kg every 6–24 hr; Premature neonates: 0.01 mg/kg/dose every 8–12 hr.

Left Ventricular Dysfunction Post–Myocardial Infarction

PO (Adults ): 6.25-mg test dose, followed by 12.5 mg 3 times daily; may be ↑ up to 50 mg 3 times daily.

Diabetic Nephropathy

PO (Adults ): 25 mg 3 times daily.

Renal Impairment

PO (Adults ): CCr 10–50 mL/min: Administer 75% of dose; CCr <10 mL/min: Administer 50% of dose.

Availability ⬆ ⬇

(Generic available)

Tablets: 12.5 mg; 25 mg; 50 mg; 100 mg
In combination with: hydrochlorothiazide..

Assessment ⬆ ⬇

Hypertension: Monitor BP and pulse frequently during initial dose adjustment and periodically during therapy. Notify health care professional of significant changes.
- Assess patient for signs of angioedema (swelling of face, extremities, eyes, lips, tongue; difficulty in swallowing or breathing); may occur at any time during therapy. Discontinue medication and provide supportive care.
HF: Monitor weight and assess patient routinely for resolution of fluid overload (peripheral edema, rales/crackles, dyspnea, weight gain, jugular venous distention).

Lab Test Considerations:

Monitor renal function. May cause ↑ BUN and serum creatinine. If ↑ BUN or serum creatinine concentrations occur, may require dose reduction or withdrawal.
- May cause hyperkalemia.
- May cause ↑ AST, ALT, alkaline phosphatase, and serum bilirubin.
- Assess urine protein prior to and periodically during therapy for up to 1 yr in patients with renal impairment or those receiving > 150 mg/day of captopril. If excessive or increasing proteinuria occurs, re-evaluate ACE inhibitor therapy.
- May cause positive antinuclear antibody titer.
- Monitor CBC with differential prior to initiation of therapy, every 2 wk for the first 3 mo, and periodically for up to 1 yr in patients at risk for neutropenia (patients with renal impairment or collagen-vascular disease) or at first sign of infection. Discontinue therapy if neutrophil count <1000/mm³.
- May cause false-positive test results for urine acetone.

Implementation ⬆ ⬇

Do not confuse captopril with carvedilol.
Correct volume depletion, if possible, before initiation of therapy due to possible precipitous drop in BP during first 1–3 hr following first dose. Risk of hypotension may be decreased by discontinuing diuretics or cautiously increasing salt intake 2–3 days prior to beginning captopril. Monitor BP closely. Resume diuretics if BP is not controlled.
PO: Administer 1 hr before meals or 2 hr after meals. May be crushed if patient has difficulty swallowing. Tablets may have a sulfurous odor.
- An oral solution may be prepared by crushing a 25-mg tablet and dissolving it in 25–100 mL of water. Shake for at least 5 min and administer within 30 min.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take captopril as directed at the same time each day, even if feeling well. Take missed doses as soon as remembered but not if almost time for next dose. Do not double doses. Warn patient not to discontinue ACE inhibitor therapy unless directed by health care professional.
- Caution patient to avoid salt substitutes containing potassium or foods containing high levels of potassium or sodium unless directed by health care professional. See Food Sources for Specific Nutrients.
- Caution patient to change positions slowly to minimize orthostatic hypotension. Use of alcohol, standing for long periods, exercising, and hot weather may increase orthostatic hypotension.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially NSAIDs and cough, cold, or allergy remedies.
- May cause dizziness. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
- Advise patient to inform health care professional of medication regimen prior to treatment or surgery.
- Advise patient that medication may cause impairment of taste that generally resolves within 8–12 wk, even with continued therapy.
- Instruct patient to notify health care professional if immediately rash; mouth sores; sore throat; fever; swelling of hands or feet; irregular heartbeat; chest pain; dry cough; hoarseness; swelling of face, eyes, lips, or tongue; or difficulty swallowing or breathing occurs or if taste impairment or skin rash persists. Persistent dry cough may occur and may not subside until medication is discontinued. Consult health care professional if cough becomes bothersome. Also notify health care professional if nausea, vomiting, or diarrhea occurs and continues.
- Advise patients with diabetes to monitor blood glucose closely, especially during first mo of therapy; may cause hypoglycemia.
- Advise females of reproductive potential to use contraception and notify health care professional immediately if pregnancy is planned or suspected or if breastfeeding. If pregnancy is detected, discontinue medication as soon as possible.
- Emphasize the importance of follow-up examinations to evaluate effectiveness of medication.
Hypertension: Encourage patient to comply with additional interventions for hypertension (weight reduction, low-sodium diet, discontinuation of smoking, moderation of alcohol consumption, regular exercise, and stress management). Medication controls but does not cure hypertension.
- Instruct patient and family on correct technique for monitoring BP. Advise them to check BP at least weekly and to report significant changes to health care professional.

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Pronunciation ⬇

Classifications ⬆ ⬇

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