INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo ZAPTO-25 TABLETS
ZAPTO-50 TABLETS
SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

ZAPTO-25 TABLETS
ZAPTO-50 TABLETS

COMPOSITION:
Each tablet contains 25 mg or 50 mg captopril.

PHARMACOLOGICAL CLASSIFICATION:
A 7.1 Vasodilators, hypotensive medicine.

PHARMACOLOGICAL ACTION:
The effects of ZAPTO result primarily from suppression of the renin-angiotensin-aldosterone system. Captopril prevents the conversion of angiotensin I to angiotensin II by inhibition of angiotensin-converting enzyme. This leads to a decrease in the pressor substance, angiotensin II, and an increase in plasma renin activity. Reduced concentrations of aldosterone are also found in the blood and urine.
The Survival and Ventricular Enlargement (SAVE) study was a multicentre randomised, double-blind, placebo-controlled trial conducted in 2231 patients (age 21 - 79 years) who survived the acute phase of a myocardial infarction and did not have active ischaemia. Patients had left ventricular dysfunction (LVD), defined as a resting left ventricular ejection fraction ˜40%, but at the time of randomisation were not sufficiently symptomatic to require ACE inhibitor therapy for heart failure. About half the patients had had symptoms of heart failure in the past. Patients were given a test dose of 6,25 mg oral Captopril and were randomised within 3-16 days post-infarction to receive either Captopril or placebo in addition to conventional therapy. Captopril was initiated at 6,25 mg or 12,5 mg three times a day and after two weeks titrated to a target maintenance dose of 50 mg three times a day. About 80% of patients were receiving the target dose at the end of the study. Patients were followed for a minimum of two years for up to five years, with an average follow-up of up to 3,5 years.
Baseline blood pressure was 113/70 mm Hg and 112/70 mm Hg for the placebo and Captopril groups, respectively. Blood pressure increased slightly in both treatment groups during the study and was somewhat lower in the Captopril group (119/74 vs. 125/77 mm Hg at 1 year). Therapy with Captopril improved long term survival and clinical outcomes compared to placebo. The risk reduction for all cause mortality was 19% (P=0,02) and for cardiovascular death was 21% (P=0,014). Captopril treated subjects had 22% (P=0,034) fewer first hospitalizations for heart failure. Compared to placebo, 22% fewer patients receiving Captopril developed symptoms of overt heart failure. There was no significant difference between groups in total hospitalizations for all causes (2056 placebo; 2306 Captopril).
ZAPTO reduces peripheral arterial resistance and lowers blood pressure in hypertensive patients.

INDICATIONS:
ZAPTO is indicated for the treatment of mild to moderate hypertension in adult patients as well as for the treatment of patients with congestive heart failure in whom vasodilation is indicated and who have not responded adequately to, or cannot be controlled by conventional therapy with diuretics and/or digitalis. Captopril is indicated to improve survival following myocardial infarction in clinically stable patients with left ventricular dysfunction manifested as an ejection fraction ˜ 40%.

CONTRA-INDICATIONS:
A history of previous hypersensitivity to captopril.
Severe renal and/or hepatic insufficiency.
Patients with aortic stenosis or outflow tract obstruction.
Safety in pregnancy, lactation and childhood has not been established.

WARNINGS:
Should a woman become pregnant while receiving ZAPTO, the treatment must be stopped promptly and an alternative medicine used.
Should a women contemplate pregnancy, the doctor should consider alternative medication.
ACE-inhibitors pass through the placenta and can be presumed to cause disturbance in foetal blood pressure regulatory mechanisms. Oligohydramnios as well as hypotension, oliguria and anuria in newborns have been reported after administration of ACE-inhibitors in the second and third trimester. Cases of defective skull ossification have been observed. Prematurity and low birth mass can occur.
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 (e.g. 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 and be fatal. Emergency therapy includes subcutaneous administration of 1:1000 solution of adrenaline, promptly.
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 minimized by starting with a low dose of captopril and giving the initial dose at night.

DOSAGE AND DIRECTIONS FOR USE:
Dosage must be individualized. ZAPTO should be taken one hour before food intake.
See warnings regarding hypotension in salt and volume depleted patients.
ADULTS:
Hypertension:                 The initial dose is 12,5 mg twice daily, increased gradually at intervals of 2 to 4 weeks according to the response. The usual maintenance dose is 25 to 50 mg twice daily and should not exceed 150 mg daily. An initial dose of 6,25 mg twice daily is recommended if ZAPTO are given in combination with a diuretic, to elderly patients, or to those with renal impairmen.
Congestive heart failure: The initial dose is 6,25 to 12,5 mg given under close medical supervision. The usual maintenance dose is 25 mg two or three times daily and should not exceed 150 mg daily.
Left ventricular dysfunction following myocardial infarction: An initial dose of 6,25 mg by mouth 3 days after myocardial infarction and then increased over several weeks to 150 mg daily in divided doses if tolerated.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Adverse effects tend to be dose-related and more frequent in patients with impaired renal function.
The commonest adverse effects are skin rashes, which may be accompanied by pruritus, fever, and eosinophilia, a persistent dry cough, and taste disturbances, which may sometimes be associated with weight loss. The skin rash is usually pruritic and maculopapular and generally occurs during the first 4 weeks of treatment. The taste impairment is usually reversible after 2 to 3 months. The rash usually disappears with dosage reductions or withdrawal, or administration of an antihistamine.
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 hypovolemia. Captopril administration has also been associated with increases in blood-potassium concentrations.
Neutropenia and agranulocytosis may occur, mostly in patients with renal failure, and in those with collagen vascular disorders such as systemic lupus erythematosus and scleroderma. Thrombocytopenia and anaemia, including aplastic anaemia, have also been reported.
All patients receiving captropril should be told to report any signs of infection (e.g. sore throat, fever). A complete white blood cell count should be done immediately when infection is present. If the infection occurs during the first three months of therapy, captopril should be discontinued until the results of the blood count are known.
Other adverse effects reported with captopril include angioedema, tachycardia, headache, paraesthesias, lymphadenopathy, photosensitivity, stomatitis, gastro-intestinal irritation and disturbances, abdominal pain, and rare cases of hepatocellular injury and jaundice.
Renal function should be assessed in all patients prior to administration of captopril. Regular white blood cell counts should be made during the initial stages of therapy.
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 antihypertensive 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.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
See side-effects and special precautions.
Overdosage will lead to hypotension. Captopril can be removed by haemodialysis. Treatment is symptomatic and supportive.

IDENTIFICATION:
25,0 mg: A white, flat, bevelled edged tablet, quadrisected on one side.
50,0 mg: A white, flat, bevelled edged tablet, bisected and embossed with C2 on one side.

PRESENTATION:
25,0 mg: Blister packs of 60 tablets.
50,0 mg: Blister packs of 60 tablets.

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

REGISTRATION NUMBERS:
25,0 mg:         29/7.1/0416
50,0 mg:         29/7.1/0396

NAME AND BUSINESS ADDRESS OF APPLICANT:
Pharmacare Limited
Building 12
Healthcare Park
Woodlands Drive
Woodmead
Sandton
2148

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
15/02/1995

        A210

New addition to this site: March 2005
Source: Community Pharmacy

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