INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
CAPTOHEXAL® 12.5
CAPTOHEXAL® 25
CAPTOHEXAL® 50

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

CAPTOHEXAL^® 12.5
CAPTOHEXAL^® 25
CAPTOHEXAL^® 50
tablets

COMPOSITION:
Each tablet contains 12.5, 25 or 50 mg Captopril.

PHARMACOLOGICAL CLASSIFICATION:
A 7.1 Vasodilators, hypotensive medicine.

PHARMACOLOGICAL ACTION:
Captopril inhibits angiotensin-converting-enzyme (ACE), the enzyme involved in the conversion of angiotensin I to angiotensin II; this enzyme is identical to bradykininase or kininase II and captopril may also reduce the degradation of bradykinin. The pharmacological actions of captopril are thought to be primarily due to the inhibition of the renin-angiotensin-aldosterone system, but as it also effectively reduces blood pressure in patients with low renin concentrations, other mechanisms are probably also involved.
Captopril produces a reduction in total peripheral arterial resistance and, in patients with congestive heart failure, a reduction in both preload and afterload. Normally renal blood flow is increased without a change in glomerular filtration rate.
Following oral administration, captopril produces a maximum effect within 1 to 2 hours, although the full effect may not develop for several weeks during chronic dosing. The duration of action is dose-dependant and may persist for 6-12 hours.
About 60-75% of a dose of captopril is absorbed from the gastro-intestinal tract. It is about 30% bound to plasma proteins. It crosses the placenta and is found in breast milk at about 1% of maternal blood concentrations. It is largely excreted in the urine, 40 to 50% as unchanged drug, the rest as disulphide and other metabolites.
The elimination half-life has been reported to be 2-3 hours, but this is increased in renal failure. Captopril is removed by dialysis.

INDICATIONS:
CaptoHexal is indicated for the treatment of mild to moderate hypertension in adults. It may be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics, where the blood pressure lowering effects of captopril and thiazides are additive.
CaptoHexal is indicated for the treatment of patients with congestive heart failure and when indicated, in combination with diuretics and/or digitalis.

CONTRA-INDICATIONS:
Hypersensitivity to captopril or the other components of CaptoHexal, or other ACE-inhibitors.
Safety and efficacy in individuals younger than 18 years of age have not been established.
Patients with a history of angioneurotic oedema relating to previous treatment with an ACE-inhibitor.
Severe renal and/or hepatic insufficiency.
Pregnancy.
Captopril should not be used in patients with aortic stenosis or outflow tract obstruction.

WARNINGS:
Captopril should not generally be used in patients with impaired renal function particularly if renovascular disease is present or suspected but is occasionally necessary for severe resistant hypertension in such patients, when it should only be given with great caution and under close specialist supervision. Some authorities consider patients with peripheral vascular diseases or generalised atherosclerosis may be at high risk of renovascular disease.
Captopril should also be used with caution in patients with collagen vascular disorders such as systemic lupus erythematosus or scleroderma. Renal function should be assessed in all patients prior to administration of captopril. Patients with existing renal disease or taking high doses of captopril should be monitored regularly for proteinuria. Regular white blood cell counts should be made during the initial stages of therapy particularly in patients with collagen vascular disorders or impaired renal function and in patients receiving immunosuppressive therapy.
Patients with congestive heart failure and patients who are likely to be salt or water depleted, may experience symptomatic hypotension during the initial stages of captopril therapy - this may be minimised by starting with a low dose, preferably on retiring.

Should a woman become pregnant while receiving an ACE-inhibitor, the treatment must be stopped promptly and the patient switched to a different medicine. Should a woman contemplate pregnancy, the doctor should consider alternative medication.

Angioedema involving the extremities, face, eyes, lips, mucous membranes, tongue, glottis or larynx has been seen in patients treated with captopril. Patients should be advised to immediately report to their doctor, any signs or symptoms suggesting angioedema (eg. swelling of face, eyes, lips, tongue, larynx and extremities, difficulty in swallowing or breathing, hoarseness) and to discontinue therapy. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur, which may be fatal. Emergency therapy including but not necessarily limited to, subcutaneous administration of 1:1000 solution of adrenalin should be promptly instituted. Swelling confined to the face, mucous membranes of the mouth, lips and extremities has usually resolved with discontinuation of captopril, some cases required medical therapy (see side effects and special precautions).
Proteinuria has been seen in patients receiving captopril, but this has been predominantly in those receiving relatively high doses (in excess of 150 mg per day), or those with compromised renal function, or both.. Alterations in renal function (as assessed by blood urea and serum creatinine) were infrequent in these patients and did not occur in those who had prior renal disease. Nephrotic syndrome (hypoalbuminemia, edema and protein excretion greater than 3 grams per day) has also occurred. In most cases, proteinuria subsided or cleared within 6 months whether or not captopril was continued.

DOSAGE AND DIRECTIONS FOR USE:
Dosage must be individualised.
CaptoHexal should be taken an hour before food intake.
Hypertension. An initial dose of 12.5 mg twice daily, which may be increased gradually at intervals of 2-4 weeks according to the response.
The usual maintenance dose is 25 to 50 mg twice daily and should not normally exceed 50 mg three times daily, even in more severe hypertension.
Since there may be a precipitous fall in blood pressure in some patients, the first dose of captopril should preferably be given at bedtime, and if possible diuretic therapy should cease a few days before introducing captopril.
An initial dose of 6,25 mg twice daily is recommended if captopril is given in addition to a diuretic, to elderly patients, or to those with renal impairment.
Congestive heart failure. In the treatment of congestive heart failure severe first-dose hypotension on introduction to captopril is common in patients on loop diuretics, but their temporary withdrawal may cause rebound pulmonary oedema. Thus an initial dose of 6,25 to 12,5 mg of captopril is given under close medical supervision; the usual maintenance dose is 25 mg two or three times daily, and doses should not normally exceed 50 mg three times daily.
Higher doses have occasionally been given under close supervision.

SIDE EFFECTS AND SPECIAL PRECAUTIONS:
The most common adverse effects are skin rashes which may be accompanied by pruritis, fever and eosinophilia; a persistent dry cough; and taste disturbances, which may sometimes be associated with weight loss.
Proteinuria has occurred mainly in patients with existing renal disease and some of these patients develop the nephrotic syndrome. Evidence of deterioration in renal function, including increasing blood concentrations of urea and creatinine, and reversible acute renal failure have been reported in patients with existing renal or renovascular dysfunction and may be aggravated by hypovolaemia.
Captopril administration has also been associated with increases in blood-potassium concentrations.
Neutropenia and agranulocytosis occur less frequently, again mostly in patients with renal failure, and in those with collagen vascular disorders such as systemic lupus erythematosus and scleroderma.
Thrombocytopenia and anaemias, including aplastic anaemia, have also been reported.
Transient hypotension may occur at the start of therapy particularly in patients with congestive heart failure and in sodium- or volume-depleted patients. This can be minimised by starting with a low dose of captopril and giving the initial dose at night.
Other adverse effects reported include angioedema (see warnings), tachycardia, headache, paraesthesias, lymphadenopathy, photosensitivity, stomatitis, gastro-intestinal irritation and disturbances, abdominal pain, and cases of hepatocellular injury and jaundice.
Since raised serum-potassium concentrations may develop, potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes should be used with caution.
The hypotensive effect of captopril is enhanced by diuretics and other anti-hypertensive agents.
Indomethacin has been shown to reduce or abolish the hypotensive action of captopril, and salicylates appear to produce a similar effect.
Captopril may cause false positive results in tests for acetone in urine.
Captopril has been reported to produce harmful effects in animal foetuses following large maternal doses, and is secreted into the breast milk in nursing mothers.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF IT'S TREATMENT:
Volume expansion with an intravenous infusion of sodium chloride injection has been recommended for the treatment of hypotension, the most likely effect of overdosage. Captopril is removed by dialysis.
Treatment is symptomatic and supportive.

IDENTIFICATION:

CaptoHexal 12.5	Round, uniform, white tablets with a 120° "snap tab" break mark on one sides, diameter 6,0-6,2 mm, height 2,4-2,7 mm.
CaptoHexal 25	Round, uniform, white tablets of a cloverleaf shape with a facette and crossed break mark on both sides, diameter 8,0-8,2 mm, height 2,7-3,1 mm.
CaptoHexal 50	Round, uniform, white tablets of a cloverleaf shape with a facette and crossed break mark on both sides, diameter 10,0-10,2 mm, height 3,3-3,7 mm.

PRESENTATION:
CaptoHexal 12.5 are supplied in amber glass bottles, containing 60 or 100 tablets per bottle.
CaptoHexal 25 are supplied in amber glass bottles, containing, 60 or 100 tablets per bottle.
CaptoHexal 50 are supplied in amber glass bottles, containing, 60 or 100 tablets per bottle.

STORAGE INSTRUCTIONS:
Store below 25°C in airtight containers.
KEEP OUT OF REACH OF CHILDREN

REGISTRATION NUMBERS

CaptoHexal 12.5	31/7.1/0039
CaptoHexal 25	31/7.1/0040
CaptoHexal 50	31/7.1/0041

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Hexal Pharma (SA) (Pty) Ltd
10 Fangio Road
Mahogany Ridge
Westmead
Pinetown

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
January 1998

        CPHP2

Updated on this site: April 2002

Source: Hospital Pharmacy
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