Yes

Angiotensin-Converting Enzyme (ACE) Inhibitors

Management of hypertension; treatment of congestive heart failure, left ventricular dysfunction after myocardial infarction, diabetic nephropathy

C/D (2nd and 3rd trimesters)

Clinical effects on the fetus: No data available on crossing the placenta. Cranial defects, hypocalvaria/acalvaria, oligohydramnios, persistent anuria following delivery, hypotension, renal defects, renal dysgenesis/dysplasia, renal failure, pulmonary hypoplasia, limb contractures secondary to oligohydramnios and stillbirth reported. ACE inhibitors should be avoided during pregnancy.

Breast-feeding/lactation: Crosses into breast milk. American Academy of Pediatrics considers compatible with breast-feeding.

Hypersensitivity to captopril or any component; angioedema related to previous treatment with an ACE inhibitor; primary hyperaldosteronism; patients with idiopathic or hereditary angioedema; bilateral renal artery stenosis; pregnancy (2nd or 3rd trimester)

Anaphylactic reactions can occur. Angioedema can occur at any time during treatment (especially following first dose). Careful blood pressure monitoring with first dose (hypotension can occur especially in volume depleted patients). Dosage adjustment needed in renal impairment. Use with caution in hypovolemia; collagen vascular diseases; valvular stenosis (particularly aortic stenosis); hyperkalemia; or before, during, or immediately after anesthesia. Avoid rapid dosage escalation which may lead to renal insufficiency. Neutropenia/agranulocytosis with myeloid hyperplasia can rarely occur. If patient has renal impairment then a baseline WBC with differential and serum creatinine should be evaluated and monitored closely during the first 3 months of therapy. Hypersensitivity reactions may be seen during hemodialysis with high-flux dialysis membranes (eg, AN69). Deterioration in renal function can occur with initiation. Use with caution in unilateral renal artery stenosis and pre-existing renal insufficiency.

1% to 10%:

Cardiovascular: Hypotension (1% to 2.5%), tachycardia (1%), chest pain (1%), palpitation (1%)

Dermatologic: Rash (maculopapular or urticarial) (4% to 7%), pruritus, (2%); In patients with rash, a positive ANA and/or eosinophilia has been noted in 7% to 10%

Endocrine & metabolic: Hyperkalemia (1% to 11%)

Renal: Proteinuria (1%), increased serum creatinine, worsening of renal function (may occur in patients with bilateral renal artery stenosis or hypovolemia)

Respiratory: Cough (0.5% to 2%)

Miscellaneous: Hypersensitivity reactions (rash, pruritus, fever, arthralgia, and eosinophilia) have occurred in 4% to 7% of patients (depending on dose and renal function); dysgeusia - loss of taste or diminished perception (2% to 4%)

Neutropenia may occur in up to 3.7% of patients with renal insufficiency or collagen-vascular disease.

Incidence not determined: Angioedema, renal insufficiency, renal failure, nephrotic syndrome, polyuria, oliguria, urinary frequency, anemia, thrombocytopenia, pancytopenia, agranulocytosis, flushing, pallor, angina, myocardial infarction, Raynaud's syndrome, congestive heart failure, increased serum transaminases, increased serum bilirubin, increased alkaline phosphatase, anaphylactoid reactions, asthenia, gynecomastia, cardiac arrest, cerebrovascular insufficiency, rhythm disturbances, orthostatic hypotension, syncope, bullous pemphigus, erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, pancreatitis, glossitis, dyspepsia, anemia, anemia, jaundice, hepatitis, hepatic necrosis (rare), cholestasis, hyponatremia (symptomatic), myalgia, myasthenia, ataxia, confusion, depression, nervousness, somnolence, bronchospasm, eosinophilic pneumonitis, rhinitis, blurred vision, impotence

<1% (frequency less than or equal to to placebo) (Limited to important or life-threatening symptoms): Gastric irritation, abdominal pain, nausea, vomiting, diarrhea, anorexia, constipation, aphthous ulcers, peptic ulcer, dizziness, headache, malaise, fatigue, insomnia, xerostomia, dyspnea, alopecia, paresthesia, angina, glomerulonephritis, cholestatic jaundice, psoriasis, hyperthermia, myalgia, arthralgia

Case reports: Aplastic anemia, hemolytic anemia, bronchospasm, alopecia, systemic lupus erythematosus, Kaposi's sarcoma, pericarditis, exacerbations of Huntington's disease, Guillain-Barré syndrome, seizures (in premature infants). A syndrome which may include fever, myalgia, arthralgia, interstitial nephritis, vasculitis, rash, eosinophilia, and elevated ESR has been reported for captopril and other ACE inhibitors.

Mild hypotension has been the only toxic effect seen with acute overdose. Bradycardia may also occur; hyperkalemia occurs even with therapeutic doses, especially in patients with renal insufficiency and those taking NSAIDs.

Following initiation of essential overdose management, toxic symptom treatment and supportive treatment should be initiated. Hypotension usually responds to I.V. fluids or Trendelenburg positioning.

CYP2D6 enzyme substrate

Alpha₁ blockers: Hypotensive effect increased.

Aspirin and NSAIDs may decrease ACE inhibitor efficacy and/or increase adverse renal effects.

Diuretics: Hypovolemia due to diuretics may precipitate acute hypotensive events or acute renal failure.

Insulin: Risk of hypoglycemia may be increased.

Lithium: Risk of lithium toxicity may be increased; monitor lithium levels, especially the first 4 weeks of therapy.

Mercaptopurine: Risk of neutropenia may be increased.

Potassium-sparing diuretics (amiloride, potassium, spironolactone, triamterene): Increased risk of hyperkalemia.

Potassium supplements may increase the risk of hyperkalemia.

Trimethoprim (high dose) may increase the risk of hyperkalemia.

Unstable in aqueous solutions; to prepare solution for oral administration, mix prior to administration and use within 10 minutes

Competitive inhibitor of angiotensin-converting enzyme (ACE); prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor; results in lower levels of angiotensin II which causes an increase in plasma renin activity and a reduction in aldosterone secretion

Onset of effect: Maximal decrease in blood pressure 1-1.5 hours after dose

Duration: Dose related, may require several weeks of therapy before full hypotensive effect is seen

Absorption: Oral: 60% to 75%; food decreases absorption of captopril 30% to 40%

Protein binding: 25% to 30%

Metabolism: 50%

Half-life (dependent upon renal and cardiac function):

Adults, normal: 1.9 hours

Congestive heart failure: 2.06 hours

Anuria: 20-40 hours

Time to peak: Within 1-2 hours

Elimination: 95% excreted in urine in 24 hours

Note: Dosage must be titrated according to patient's response; use lowest effective dose. Oral:

Children: Initial: 0.5 mg/kg/dose; titrate upward to maximum of 6 mg/kg/day in 2-4 divided doses

Older Children: Initial: 6.25-12.5 mg/dose every 12-24 hours; titrate upward to maximum of 6 mg/kg/day

Adolescents: Initial: 12.5-25 mg/dose given every 8-12 hours; increase by 25 mg/dose to maximum of 450 mg/day

Adults:

Hypertension:

Initial dose: 12.5-25 mg 2-3 times/day; may increase by 12.5-25 mg/dose at 1- to 2-week intervals up to 50 mg 3 times/day; add diuretic before further dosage increases

Maximum dose: 150 mg 3 times/day

Congestive heart failure:

Initial dose: 6.25-12.5 mg 3 times/day in conjunction with cardiac glycoside and diuretic therapy; initial dose depends upon patient's fluid/electrolyte status

Target dose: 50 mg 3 times/day

Maximum dose: 150 mg 3 times/day

LVD after MI: Initial dose: 6.25 mg followed by 12.5 mg 3 times/day; then increase to 25 mg 3 times/day during next several days and then over next several weeks to target dose of 50 mg 3 times/day

Diabetic nephropathy: 25 mg 3 times/day; other antihypertensives often given concurrently

Dosing adjustment in renal impairment:

Cl_cr 10-50 mL/minute: Administer at 75% of normal dose.

Cl_cr <10 mL/minute: Administer at 50% of normal dose.

Note: Smaller dosages given every 8-12 hours are indicated in patients with renal dysfunction; renal function and leukocyte count should be carefully monitored during therapy.

Hemodialysis: Moderately dialyzable (20% to 50%); administer dose postdialysis or administer 25% to 35% supplemental dose.

Peritoneal dialysis: Supplemental dose is not necessary.

Should be administered at least 1 hour before or 2 hours after eating; absorption of captopril may be reduced by food; long-term use of captopril may result in a zinc deficiency which can result in a decrease in taste perception; zinc supplements may be used

BUN, serum creatinine, urine dipstick for protein, complete leukocyte count, and blood pressure

BUN, creatinine, potassium, positive Coombs' [direct]; cholesterol (S); may cause false-positive results in urine acetone determinations using sodium nitroprusside reagent

The duration of action of captopril is limited compared to other ACE inhibitors and it is important that every 8-hour dosing be employed for effective treatment. However, when captopril is combined with hydrochlorothiazide, the duration of action of captopril may be prolonged.

ACE-inhibitor therapy may elicit rapid increases in potassium and creatinine, especially when used in patients with bilateral renal artery stenosis. When ACE inhibition is introduced in patients with pre-existing diuretic therapy who are hypovolemic, the ACE inhibitor may induce acute hypotension. In those patients experiencing cough on an ACE inhibitor, the ACE inhibitor may be discontinued and, if necessary, angiotensin-receptor blocker therapy instituted. Because of the potent teratogenic effects of ACE inhibitors, these drugs should be avoided, if possible, when treating women of childbearing potential not on effective birth control measures.

May cause drowsiness or insomnia

May rarely cause agranulocytosis; use caution with clozapine and carbamazepine; may decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity; monitor serum lithium levels

No information available to require special precautions

No effects or complications reported

Take exactly as directed; do not discontinue without consulting prescriber. Take first dose at bedtime. Take all doses on an empty stomach (30 minutes before or 2 hours after meals). This drug does not eliminate need for diet or exercise regimen as recommended by prescriber. Do not use potassium supplements or salt substitutes containing potassium without consulting prescriber. May cause dizziness, fainting, lightheadedness (use caution when driving or engaging in tasks that require alertness until response to drug is known); postural hypotension (use caution when rising from lying or sitting position or climbing stairs); nausea, vomiting, abdominal pain, dry mouth, or transient loss of appetite (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help) - report if these persist. Report chest pain or palpitations; mouth sores; fever or chills; swelling of extremities, face, mouth, or tongue; skin rash; numbness, tingling, or pain in muscles; difficulty in breathing or unusual cough; other persistent adverse reactions. Pregnancy precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptive measures.

Watch for hypotensive effect within 1-3 hours of first dose or new higher dose

Tablet: 12.5 mg, 25 mg, 50 mg, 100 mg

Captopril has limited stability in aqueous preparations. The addition of an antioxidant (sodium ascorbate) has been shown to increase the stability of captopril in solution; captopril (1 mg/mL) in syrup with methylcellulose is stable for 7 days stored either at 4°C or 22°C; captopril (1 mg/mL) in distilled water (no additives) is stable for 14 days if stored at 4°C and 7 days if stored at 22°C; captopril (1 mg/mL) with sodium ascorbate (5 mg/mL) in distilled water is stable for 56 days at 4°C and 14 days at 22°C. Captopril 0.75 mg/mL was found stable for up to 60 days at 5°C and 25°C in a 1:1 mixture of Ora-Sweet® and Ora-Plus®, in Ora-Sweet® SF and Ora-Plus®, and in cherry syrup.

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