Class: Cardiovascular System
Dosage Form: Tablets
Description: ACE Inihibitor for hypertension and heart failure therapy
Captopril………………………..25, 50 mg
Microcrystalline cellulose, collodial silicon dioxide, talc purified.
Capotril is a sulfhydryl-containing ACE inhibitor. It prevents the conversion of angiotensin I to angiotensin II by inhibition of ACE (angiotensin converting enzyme). Angiotensin II is a potent endogenous vasoconstrictor and stimulates sodium and fluid retention. Inhibition of ACE results in decreased plasma angiotensin II, leading to decreased circulating aldosterone associated with a potassium-sparing effect, along with sodium and fluid loss, and increased prostaglandin synthesis also may be involved. Peripheral resistance is lowered by vasodilation.
Capotril decreases systemic vascular resistance (after-load) and pulmonary capillary wedge pressure (pre-load), thus increasing cardiac output in patients with heart failure.
After oral administration, about 60-75% captopril is absorbed from the gastrointestinal tract and peak plasma concentrations are achieved within about an hour. Absorption is reduced in the presence of food in the gastrointestinal tract. About 30% of the absorbed captopril is bound to plasma proteins. Captopril is distributed in all tissues except CNS, it crosses the placenta, and it is distributed into breast milk. The duration of action is dose-dependent and may persist for 6 to 12 hours. About 50% of captopril is metabolized in the liver, elminiation half-life is less than 3 hours, but this is increased in renal impairment. Captopril is primarily excreted in the urine; about 45% as unchanged drug and the remainder as disulphide dimer of captopril and other metabolites.
Capotril is indicated in:
- Hypertension: Capotril is used alone or in combination with other antihypertensive drugs, especially thiazide-type diuretics. The effects of Capotril and thaizides are additive
- Heart failure: Capotril is usually indicated in combination with diuretics and digitalis
- Left ventricular dysfunction following myocardial infarction
- Diabetic nephropathy
Capotril is contraindicated in:
- Hypersensitivity to the product or an other ACE inhibitor
- Bilateral renal artery stenosis or solitary kidney
- Pre-existing neutropenia as in immunocompromised patients
The following interactions are to be noted:
- Excessive hypotension may occur when Capotril is used concurrently with diuretics, other antihypertensives, or other agents that lower blood pressure
- An additive hyperkalemic effect is possible in patients receiving Capotril with potassium-sparing diuretics, potassium supplements, or other drugs that can cause hyperkalemia such as cyclosporine or indomethacin. Potassium-sparing diuretics and potassium supplements should be stopped before initiating Capotril in patients with heart failure
- NASIDs may decrease the antihypertensive effect of Capotril and the patient should be monitored closely
- Probenecid decreases Capotril elimination and increases its effect
- Capotril causes false positive results in tests for acetone in urine
- Concomitant administration of oral antidiabetics and Capotril leads to increased risk of hypoglycemia, so patients should be monitored closely
- Licorice can cause sodium retention and increased blood pressure interfering with the therapeutic effect of Capotril, so it’s use is discouraged
As for ACE inhibitors, the side effects include: hypotension, dizziness, fatigue, headache, gastrointestinal disturbances, taste disturbances, persistent dry cough and other upper respiratory tract symptoms, skin rashes, angioedema, hypersensitivity reactions, renal impairment, hyperkalemia, hyponatremia, neutropenia, agranulocytosis, or thrombocytopenia.
Other side effects reported include chest pain, palpitations, stomatitis, abdominal pain, muscle cramps and sleep disturbances.
Elevations of liver transaminases, alkaline phosphatase, and serum bilirubin have occurred.
Dosage and Administration:
Dosage must be individualized. Capotril should be taken one hour before meals.
a) Initial dose: 50 mg daily in one or two divided doses. Concomitant sodium restriction may be beneficial when Capotril (hydrochlorothiazide, 25 mg daily) is used alone. The dose of Capotril in hypertension usually does not exceed 50 mg three times daily. If the blood pressure has not been satisfactorily controlled after one to two weeks at this dose, (and the patient is not already receiving a diuretic), a modest dose of a thiazide-type diuretic mg daily) should be added. The diuretic dose maybe increased at 1 —2 week intervals until its highest usual antihypertensive dose is reached, If further blond pressure reduction is required, the dose of Capotril may by increased to 100 mg two times or three times daily, and then, if necessary, to 150 mg two times or three times daily (while continuing the diuretic). The usual dose range is 25 mg to 150 mg two times or three times daily. A maximum daily dose of 450 mg Capotril should not be exceeded. The daily dose of Capotril may be increased under continuous medical supervision until a satisfactory response is obtained or the maximum dose of Capotril is reached. Addition of a more potent diuretic, e.g. furosemide, may may also be indicated. An initial dose of 6.25 mg twice daily is recommended if Capotril is given in addition to a diuretic or to elder patients.
b) Children: Use Capotril only when the other measures for controlling blood pressure have not been effective. The recommended dose: initially 0.3 – 0.5 mg/kg/dose and titrate upward too a maximum dose of 6 mg/kg/day divided into 2-4 doses.
2. Heart failure:
a) Initial dose:
- 6.25 – 12.5 mg under medical supervision, then 25 mg as maintenance dose 2 – 3 times daily
- Maximum 150 mg daily in divided doses
- Capotril should be initiated under very close medical supervision and in conjunction with a diuretic and digitalis
3. Post-Myocardial Infarction:
Capotril may be initiated as early as there days following a myocardial infarction. After an initial dose of 6.25 mg. Capotril therapy should be increased to 37.5mg daily in divided doses as tolerated. The dose should then be increased as tolerated to 75 mg a day in divided doses during the next several days and to a final target dose of 150 mg daily in divided doses over the next several weeks.
Capotril may be used in patients treated with other post-myocardial infarction therapies, e.g. thrombolytics, aspirin, beta-blockers.
4. Diabetic Nephropathy:
a) Recommended daily dose:
- 75 mg – 100 mg of Capotril in divided doses
In geriatric patients and in patients with renal impairment, the dose of Capotril should be reduced or the dosage interval should be increased, depending on their creatinine clearance:
- Creatinine clearance 21 to 40 ml/minute: Initial daily dose 12.5 mg and maximum daily dose 100 mg
- Creatinine clearance 10 to 20 ml/minute: Initial daily dose 12.5 mg and maximum daily dose 75 mg
- Creatinine clearance below 10 ml/minute: Initial daily dose 6.35 mg and maximum daily dose 37.5 mg
Pregnancy and Lactation:
Capotril is contraindicated during pregnancy (category D) and lactation.
Capotril should be used cautiously in patients with renal impairment, diabetes mellitus, potassium-sparing diuretics or potassium supplements, and this is due to its hyperkalemic effect.
Geriatric patients may need lower doses because of imapired drug clearance, or becasue they also may be more sensitive to the hypotensive effects of captopril.
Pack of 2 strips of 10 tablets each.
Store at room temperature, below 25°C.