INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
CAPTORETIC ® tablets
CAPTORETIC ® HS tablets

CPRP2

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

CAPTORETIC ^® tablets
CAPTORETIC ^® HS tablets

COMPOSITION:
Each tablet contains:
CAPTORETIC - Captopril 50 mg and Hydrochlorothiazide 25 mg.
CAPTORETIC HS - Captopril 25 mg and Hydrochlorothiazide 12,5 mg.

PHARMACOLOGICAL CLASSIFICATION
A.7.1.3. Other hypotensives

PHARMACOLOGICAL ACTION
CAPTORETIC consists of 2 components: an angiotensin converting enzyme (ACE) inhibitor (captopril) and a diuretic (hydrochlorothiazide).
The diuretic treatment results in decreased blood pressure and blood volume, causing a rise in Angiotensin II levels, which reduces the hypotensive effect.
Captopril inhibits the increase in Angiotensin II.
These two components have a different but complementary hypotensive effect and concurrent administration may allow for the use of lower doses of each medicine.
Since captopril reduces the production of Aldosterone, its combination with hydrochlorothiazide may minimize diuretic induced hypokalaemia.

INDICATIONS
Treatment of mild to moderate hypertension in patients stabilized on the same doses of the individual components.

CONTRA-INDICATIONS
Hypersensitivity to captopril or other ACE inhibitors, thiazides or any sulphonamide derived medicine.
Safety and efficacy in patients less than 18 years has not been established.
Patients with a history of angioneurotic oedema relating to previous treatment with an ACE-inhibitor - see warnings.

WARNINGS

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

ACE inhibitors cross the placenta and are presumed to cause disturbances in foetal blood pressure oligo-hydramnios, hypotension, oliguria and anuria in newborns has 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.
2.        ANGIOEDEMA -
Patients should report any signs or symptoms of oedema e.g. swelling of extremities, face, eyes, lips, larynx, mucous membranes or difficulty in swallowing or breathing and hoarseness, to their physician. Therapy should be discontinued.
If angio oedema involves the tongue, glottis and larynx airway obstruction may occur and may be fatal. Emergency therapy includes sub cutaneous administration of a 1:1000 solution of adrenaline.
Swelling confined to the face, mucous membranes of the mouth, lips and extremities has usually resolved with discontinuation of captopril ; some cases require medical therapy. (see side effects and special precautions).
3.        HAEMATOLOGICAL -
Neutropaenia, agranulocytosis, thrombocytopaenia and anaemia have been reported in patients receiving captopril, usually within three months after commencement of therapy.
Do not routinely use captopril in patients with pre-existing impaired renal function, collagen vascular disease, those receiving immunosuppresant therapy, allopurinol or procainamide or a combination of these factors, since neutropaenia has been limited almost exclusively to this group. Patients in this group receiving captopril therapy, should have white blood cell counts and differential counts performed prior to therapy, every two weeks during therapy and periodically thereafter. Some of these patients developed serious infections which in a few instances did not respond to intensive antibiotic therapy.
Patients receiving CAPTORETIC should be instructed to report any sign of infection e.g. persistent sore throat and a differential white blood cell count should be performed.
If Neutropaenia (Neutrophils less than 1000/mm³) is proven or suspected captopril and other concomitant medication should be discontinued. After discontinuation of captopril the neutrophil count usually returns to normal.
4.        HYPOTENSION -
Exaggerated hypotensive responses can occur in patients who are receiving diuretic therapy especially those with severe renin dependent hypotension, usually within one hour of receiving the initial captopril dose.
This transient fall in bloodpressure may occur after any of the initial doses of captopril. Symptoms include mild lightheadedness which may be coupled with arrhythmia or conductive defects. To lessen the possibility of this occurrence patients must discontinue or reduce the diuretic dose for four to seven days prior to initiation of CAPTORETIC tablets. This exaggerated hypotensive response can be rapidly reversed by IV normal saline infusion.
A hypotensive episode following the initial dose of CAPTORETIC does not preclude further episodes.
5.        PROTEINURIA -
This has been reported mainly in patients who had previous renal disease.
Protein estimation (dipstick) should be performed prior to treatment and periodically thereafter.
Some patients, with renal disease, particularly those with bilateral renal artery stenosis, may develop increases in blood urea nitrogen and serum creatinine after reduction of blood pressure with captopril, generally administered with a diuretic.
Azotaemia may be caused by thiazides in renally impaired patients.
CAPTORETIC, therefore, would not be appropriate for patients with renal impairment since loop diuretics (e.g. Furosemide) rather than a thiazide are preferred for such patients.
In patients with impaired renal function, cumulative effects of the thiazides may develop.
6.         PATIENTS WITH RENAL FAILURE -
CAPTORETIC is not recommended for use in patients with renal impairment

DOSAGE AND DIRECTIONS FOR USE
Dosage should be individualized. See Warnings regarding : hypotension in salt and volume depleted patients.
Usual dose:        1 CAPTORETIC tablet once per day
If a satisfactory reduction of blood pressure has not been achieved after 4 weeks, the dose of captopril may be increased to not more than 150 mg per day in divided doses.
The dose may be titrated, by using the other strength of CAPTORETIC as necessary, to suit the patient.

SIDE EFFECTS AND SPECIAL PRECAUTIONS
A.        CAPTOPRIL:
1.        SKIN -       
A dose related rash, usually macropapular and pruritic (less frequently urticarial) may occur It may respond to antihistamine therapy but is usually self limiting and reversible. Pruritis angioedema, flushing, photosensitivity and pemphigoid lesions have been reported.
2.        GASTRO-INTESTINAL-TRACT
Decreased or loss of taste perception which is usually self limiting and reversible. Weight loss associated with loss of taste sensation. Liver enzyme elevation has been reported - no causal relationship has been established. Hepatocellular damage with or without cholestasis has been reported. Gastro intestinal tract irritation and abdominal pain have been reported. Stomatitis.
3.        RENAL -
See Warnings. Increase in serum potassium concentrations and acidosis.
Transient elevations of blood urea and creatinine
4.        HAEMATOLOGICAL -
See Warnings. Neutropaenia, thrombocytopaenia and anaemias have been reported.
5.        CARDIOVASCULAR SYSTEM -
See Warnings. Tachycardia has been observed in volume depleted patients.
Hypotension may occur after initiation of captopril therapy in patients with heart failure, renin dependent hypertension or who are significantly volume depleted (see warnings)
6.        ANAPHALACTOID REACTIONS -
Anaphylactoid type reactions have occurred in patients receiving ACE-inhibitors,during haemodialysis with high flux dialysis membranes.
7.        OTHER:
Paraesthesias of the hands, cough, bronchospasm serum sickness and lymphadenopathy, have been reported with captopril use.
Alopecia, chest pain, pancreatitis, mood and sleep disturbances, impotence, dizziness, fatigue and headache.
Angioedema of the face, eyes, lips, mucous membranes, tongue, glottis or larynx and the extremities can occur.
CAPTORETIC should be used with extreme caution in patients with aortic stenosis due to the potentially harmful consequences of reduced coronary perfusion secondary to the reduced blood pressure. Patients being treated for severe congestive cardiac failure should be warned to increase their physical activity slowly.

B.        HYDROCHLOROTHIAZIDE
1.        SKIN -
Stevens-Johnson syndrome as well as other hypersensitivity reactions, such as skin rashes.
2.        HAEMOTOLOGIC -
Agranulocytosis, thrombocytopaenia, leucopaenia, aplastic and haemolytic anaemia have occurred
3.        OTHER:
Dizziness, vertigo, headache, xanthopsia, hyperglycaemia, glycosurea, hyperuricaemia, weakness, restlessness, muscle spasm, gastric irritation, jaundice, pancreatitis, respiratory distress, interstitial nephritis, glycosurea, electrolyte imbalance (including hyponatraemia) anorexia, transient blurred vision have been reported while on thiazide therapy. Nausea, vomiting, constipation, diarrhoea, photosensitivity reactions, postural hypotension, parasthesia, impotence, yellow vision.
CAPTORETIC should be used with caution in patients with impaired liver function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. Cholestatic jaundice and pancreatitis may occur.
Patients treated with CAPTORETIC should be monitored for clinical signs of thiazide induced fluid or electrolyte imbalance. Should hypokalaemia occur, the toxic effects of digitalis (e.g. increased ventricular irritability) can be exaggerated.
Because captopril reduces the production of aldosterone, its combination with hydrochlorothiazide may minimize diuretic induced hypokalaemia, however, some patients may still require potassium supplements.
Hyperuricaemia may occur or gout may be precipitated by the thiazides, in certain patients.
Insulin requirements in diabetic patients may be altered by thiazides and latent diabetes mellitus may emerge.
Pathologic changes in the parathyroid gland with hypercalcaemia and hyperphosphataemia have been observed during prolonged thiazide therapy. A rise in serum cholesterol has been noted after use of diuretics.
Thiazide diuretics should not be given to patients with pre-existing hypercalcaemia. Elderly patients are particularly susceptible to electrolyte imbalance.
Sensitivity reactions to thiazide may occur in patients with a history of allergy or bronchial asthma. Exacerbation or activation of Systemic lupus erythematosus has been reported.
Thiazide diuretics should not be given to patients with Addison’s disease.
4.        SURGERY / ANAESTHESIA -
CAPTORETIC may cause hypotension which can be corrected by volume expansion.

INTERACTIONS
Captopril decreases Aldosterone production, thus elevating serum potassium, especially in patients with renal failure or diabetes mellitus. Potassium sparing diuretics (e.g. Spironolactone) or other medicines increasing potassium in the serum e.g. Heparin), should thus be used with caution. Potassium supplements and salt substitutes containing potassium, should also be used with caution.
AGENTS HAVING VASODILATOR ACTIVITY
Data is not available, therefore nitroglycerine or other nitrates or other agents having vasodilatory activity should, if possible, be discontinued before starting CAPTORETIC.
If these agents are administered during CAPTORETIC therapy, they should be administered cautiously and possibly at a low dose.
AGENTS AFFECTING SYMPATHETIC ACTIVITY
The sympathetic nervous system is important in supporting blood pressure in patients receiving Captopril alone or with diuretics. Therefore agents affecting sympathetic activity should be used with caution.
INHIBITORS OF ENDOGENOUS PROSTAGLANDIN SYNTHESIS
Indomethacin may reduce the anti-hypertensive effect of Captopril, especially in cases of low renin hypertension. Other non-steroidal anti-inflammatory agents may also have this effect.
LITHIUM
Increased serum Lithium levels and symptoms of Lithium toxicity have been reported in patients receiving concomitant lithium and ACE inhibitor therapy. These agents should thus be co-administered with caution and frequent monitoring of serum lithium levels. If a diuretic is also used it may raise the risk of Lithium toxicity.
OTHERS
Caution should be exercised in prescribing captopril with immunosuppressants, procainamide and other agents causing neutropaenia.
Thiazides potentiate the action of peripheral or ganglionic blocking drugs. Thiazides may increase the responsiveness to Tubocurarine and may decrease arterial responsiveness to noradrenaline.
Captopril may cause a false positive urine test for acetone.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
Hypotension and electrolyte depletion pose the greatest threat during overdosage.
To normalize the blood pressure, IV infusion of normal saline, is recommended.
Captopril is removed by haemodialysis.

IDENTIFICATION

CAPTORETIC	A round, uniformly white to off-white coloured, biconvex tablet,one sided score. The tablet dimensions are 10 +0,2mm x 3,8 +0,1mm and the tablet surface should be smooth.
CAPTORETIC HS	A round, uniformly white to off-white coloured, biconvex tablet one sided score. The tablet dimensions are 7 +0,2mm x 3,4 +0,1mm

PRESENTATION
Amber glass bottles containing 30 (100) tablets
Polypropylene securitainers containing 30 (100) tablets.

STORAGE INSTRUCTIONS
Store at room temperature not exceeding 25°C.
Protect from light and moisture.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS
Captoretic - 31/7.1.3/0478
Captoretic HS - 31/7.1.3 /0494

NAME AND BUSINESS ADDRESS OF APPLICANT
Hexal Pharma (SA) Pty Ltd
10 Fangio Road
Mahogany Ridge
Westmead
3610

DATE OF PUBLICATION OF THIS PACKAGE INSERT
May 1998

        CPRP2

Updated on this site: April 2005
Source: Pharmaceutical Industry
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