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

Logo COZOLE TABLETS

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

COZOLE TABLETS

COMPOSITION:
Each tablet contains:
Trimethoprim         80 mg
Sulphamethoxazole         400 mg
Nipastat (as preservative)         0,025% m/m

PHARMACOLOGICAL CLASSIFICATION:
A.20.2 Antimicrobial (chemotherapeutic) agents other than antibiotics.

PHARMACOLOGICAL ACTION:
Cozole is a combination of trimethoprim and sulphamethoxazole and results in synergistic effects causing a bacteriocidal action. The action of co-trimoxazole is achieved by the sequential blocking of two enzymes essential in folinic acid synthesis in the organism.

INDICATIONS:
The treatment of infections of upper and lower respiratory tract, the urinary tract and the alimentary and genital tract in both sexes, and skin infections caused by sensitive organisms.

CONTRA-INDICATIONS:
Cozole is contra-indicated in patients with known sulphonamide or trimethoprim hypersensitivity or who are suffering from porphyria.
It should not be used in patients suffering from liver parenchymae damage, or a severe renal insufficiency.
Co-trimoxazole should not be used during pregnancy. Use of the substance in premature or new-born infants during the first few weeks of life, is contra-indicated. Should not be given to patients with megaloblastic anaemia or blood dyscrasia. Should not be given to lactating women. Contra-indicated in the presence of Vitamin B12 and folic acid deficiency states.

WARNINGS:
Erythema multiforme, toxic dermal necrolysis or allergic vasculitis may occur. Treatment should be discontinued immediately when a rash appears because of the danger of severe allergic reactions.
A high incidence of side-effects occurs in immunocompromised patients such as those suffering from AIDS or patients receiving immunosuppressive therapy. The adverse effects include skin rash, recurrent fever, neutropenia, thrombocytopenia and raised liver enzyme values.

DOSAGE AND DIRECTIONS FOR USE:
Adults and children over 12 years: Two tablets every 12 hours for a period of at least 5 days.
Children 6 - 12 years: One tablet every 12 hours for a period of at least 5 days.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Hypersensitivity reactions particularly involving the skin are among the most common adverse effects of co-trimoxazole and are usually due to the sulphamethoxazole components. The Stevens-Johnson and Lyell's syndromes have been reported.
Adverse effects on the gastro-intestinal tract may also occur fairly frequently.
SULPHAMETHOXAZOLE:
Sulphamethoxazole may cause nausea vomiting and diarrhoea.
Hypersensitivity reactions may occur. Those involving the skin include rashes, photosensitivity reactions, exfoliative dermatitis, toxic epidermal necrolysis (Lyell's syndrome), and erythema nodosum. A severe, potentially fatal form of erythema multiforme, associated with widespread lesions of the skin and mucous membranes, termed the Stevens-Johnson syndrome may occur.
Systemic lupus erythematosus, particulary exacerbations of pre-existing disease, has also been reported.
Nephrotoxic reactions, which may result in renal failure, have been attributed to hypersensitivity to sulphamethoxazole. Lumbar pain, haematuria, oliguria and anuria may also occur due to crystallisation in the urine of sulphamethoxazole or it's less soluble acetylated metabolite.
Blood disorders may occur and include agranulocytosis, aplastic anaemia, thrombocytopenia, leucopenia, hypoprothrombinaemia and eosinophilia. Acute haemolytic anaemia associated with glucose-6-phosphate dehydrogenase deficiency may occur.
Other side-effects which may be manifestations of a generalised hypersensitivity reaction to sulphamethoxazole include a syndrome resembling serum sickness, hepatotoxic reactions, myocarditis, pancreatitis, pulmonary eosinophilia and vasculitis including polyarteritis nodosa. Anaphylaxis has been reported.
Sulphamethoxazole may cause cyanosis due to methaemoglobinaemia or sulphaemoglobinaemia.
Other side-effects on the eyes such as optic neuropathy or transient myopia, fever, hypothyroidism and neurological reactions including ataxia, dizziness, fatique, headache, insomnia, peripheral neuritis and vertigo.
Sulphamethoxazole may cause alterations of the bacterial flora in the gastro-intestinal tract. There is, therefore, the possibility that pseudomembranous colitis may occur.
Slow acetylators of sulphamethoxazole may be a greater risk of adverse reactions than fast acetylators.
TRIMETHOPRIM:
Side-effects caused by trimethoprim include pruritis, skin rash, fever, nausea, vomiting and sore mouth.
PRECAUTIONS:
Cozole should be given with caution to patients with actual or possible folate deficiency because of possible interference with human folate metabolism by trimethoprim, and administration of folinic acid could be considered.
Cozole should also be used with caution in patients receiving pyrimethamine as they may develop megaloblastic anaemia due to the trimethoprim component.
Adverse effects on the blood may be more severe in malnourished or elderly patients; there also appears to be an increased risk of thrombocytopenia in elderly patients concurrently receiving diuretics mainly thiazides.
All patients receiving prolonged treatment with Cozole should be given regular blood examinations.
Cozole should be used cautiously and in reduced dosage in patients with impaired renal function. Because of the risk of crystalluria, an adequate fluid intake should be maintained and the administration of alkalis may be necessary if very large doses are used.
INTERACTIONS:
Cross-sensitivity has been observed between sulphamethoxazole and chemically related medicines such as diuretics, particularly acetazolamide and thiazides and the sulphonylurea hypoglycaemic agents. Sulphamethoxazole may potentiate the effects of some medicines such as oral anticoagulants, methotrexate and phenytoin, this may be due to displacement of the plasma protein binding sites or to inhibitation of metabolism. High doses of sulphamethoxazole may have a hypoglycaemic effect; the antidiabetic effect of the sulphonylurea compounds may be enhanced by the concomitant administration of sulphamethoxazole. The action of sulphamethoxazole may be antagonised by p-aminobenzoic acid and compounds derived from it, particularly the procaine group of local anaesthetics.
Paraldehyde has been reported to increase the acetylation of sulphamethoxazole with subsequent increased risk of crystalluria. Sulphamethoxazole may interfere with some diagnostic tests including those of urea, creatinine, and urinary glucose and urobilinogen.
Trimethoprim may potentiate the anticoagulant effect of warfarin. It also prolongs the half-life of phenytoin. Trimethoprim has been reported to interact with a number of medicines by interfering with their clearance; such medicines include digoxin, procainamide and tolbutamide.
Reversible deterioration in renal function has been reported in patients given trimethoprim and cyclosporin following renal transplantation.
Trimethoprim may interfere with some diagnostic tests including serum methotrexate assay where dihydrofolate reductase is used and the Jaffe reaction for creatinine.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF IT'S TREATMENT:
Nausea, vomiting, cyanosis, haematuria, oliguria, or anuria and allergic skin reactions (skin rashes, anaphylaxis, etc.) If megaloblastic changes occur, folinic acid must be given.
Treatment is supportive and symptomatic.

IDENTIFICATION:
Flat white round tablet 12,8 mm in diameter scored on the one side and a "B" embossed on the other side.

PRESENTATION:
In bottles of 20, 100, 500 and 1000 tablets. Patient ready packs of different pack sizes.

STORAGE INSTRUCTIONS:
Store in a cool, dry place, below 25°C. Protect from heat and light.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
R/20.2/279

NAME AND BUSINESS ADDRESS OF APPLICANT:
BE-TABS PHARMACEUTICALS (PTY) LTD.
14 LAUTRE ROAD
STORMILL EXT. 1
ROODEPOORT
1724

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
5 April 1984

CODE: ICZ/5                JETPRINT 12/98

Updated on this site: October 2001

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