captopril

General

Genetic Implications: Genetic Implications

Pronunciation:
kap-toe-pril


Trade Name(s)

  • Capoten

Ther. Class.

antihypertensives

Pharm. Class.

ace inhibitors

Indications

  • Hypertension (as monotherapy or in combination with other antihypertensives).
  • HF.
  • Reduction of risk of death, HF-related hospitalizations, and development of overt HF following MI.
  • Treatment of diabetic nephropathy in patients with type 1 diabetes mellitus and retinopathy.

Action

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 Effect(s):

  • 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 and 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†)

ROUTEONSETPEAKDURATION
PO15–60 min60–90 min6–12 hr
†Full effects may not be noted for several wk.

Contraindication/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:  Black Box:  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);
  • Genetic implication Black patients (monotherapy for hypertension less effective; may require additional therapy; higher risk of angioedema);
  • Rep:  Black Box:  Women of reproductive potential;
  • Geri:  Initial dose ↓ recommended in older adults.

Exercise Extreme Caution in:

History of angioedema.

Adverse 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

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

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  potassium supplements,  potassium-sparing diuretics, or  potassium-containing salt substitutes.
  • ↑ risk of hyperkalemia, renal dysfunction, hypotension, and syncope with  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 ↑ risk of renal impairment.
  • May ↑ levels and risk of toxicity of  lithium.
  • May ↑ 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); titrate 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 HR frequently during initial dose adjustment and periodically during therapy. Notify health care provider of significant changes.

    • Assess patient for signs of angioedema (swelling of face, extremities, eyes, lips, or 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 ↑ BUN and serum creatinine. If ↑ BUN or serum creatinine concentrations occur, may require dose ↓ or discontinuation.

  • May cause hyperkalemia.
  • May ↑ AST, ALT, alkaline phosphatase, and serum bilirubin.
  • Assess urine protein before 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 1st 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 ↓ in BP during first 1–3 hr following 1st dose. Risk of hypotension may be ↓ by discontinuing diuretics or cautiously ↑ salt intake 2–3 days before beginning captopril. Monitor BP closely. Resume diuretics if BP 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 ≥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 provider.

    • Caution patient to avoid salt substitutes containing potassium or foods containing high levels of potassium or sodium unless directed by health care provider. 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 ↑ orthostatic hypotension.
    • Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider 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 provider 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 provider 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 provider if cough becomes bothersome. Also notify health care provider if nausea, vomiting, or diarrhea occurs and continues.
    • Advise patients with diabetes to monitor blood glucose closely, especially during first months of therapy; may cause hypoglycemia.
    • Emphasize the importance of follow-up examinations to evaluate effectiveness of medication.

    Black Box:  Rep:  May cause fetal harm. Advise women of reproductive potential to use effective contraception, notify health care provider immediately if pregnancy is planned or suspected, and avoid breastfeeding. Captopril should be discontinued as soon as possible when pregnancy is detected. Conduct serial ultrasound exams in pregnant patients exposed to captopril; may cause oligohydramnios. Monitor infants exposed to captopril in utero for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occurs, support BP and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.

    • 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, 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 provider.

Evaluation/Desired Outcomes

  • Decrease in BP without appearance of excessive side effects.
  • Improvement in survival and reduction of symptoms in HF.
  • Reduction of risk of death or development of HF following MI.
  • Decrease in progression of diabetic nephropathy.