Zafibral

Film Coated Tablets containing 200 mg Bezafibrate.

The rationale for the use of BEZAFIBRATE to control abnormal elevations of serum lipids and lipoproteins is to reduce or prevent the long-term adverse effects which have been shown by many major epidemiological studies to be positively and strongly correlated with such dyslipidaemias. The possible beneficial and adverse long-term consequences of some drugs used in the hyperlipidaemias are still the subject of scientific discussion, however, and there is currently no clinical evidence to demonstrate that BEZAFIBRATE is effective in the prevention of heart disease.

BEZAFIBRATE is indicated for use in hyperlipedemias of Type IIa, IIb, III, IV and V.
(Fredrickson Classification) which are illustrated as follows:
Major lipid elevation of Types IIa, IIb, III, IV and V are cholesterol, cholesterol and triglycerides, cholesterol and triglycerides, triglycerides, and triglycerides (possibly cholesterol), respectively.
BEZAFIBRATE is therefore indicated for use only in patients with a fully defined and diagnosed abnormality where diet alone is insufficient to correct the condition and in whom the long-term risks associated with the condition warrant treatment.

The recommended dosage of ZAFIBRAL is three tablets daily, equivalent to 600 mg bezafibrate. The tablets may be taken after food.
Maintenance dosage may occasionally be reduced to two tablets daily, particularly in the treatment of hypertriglyceridaemia.
The initial response to therapy is normally rapidly apparent, although a progressive response over a number of weeks may occur. The patient's response to ZAFIBRAL should be monitored at intervals. Treatment should be terminated if an adequate response has not been achieved within 3 to 4 months.

No serious clinical or biochemical effects are likely to occur in cases of acute overdosage and treatment in such cases, where necessary should be symptomatic.

ZAFIBRAL is contra-indicated in patients with severe liver dysfunction or primary biliary cirrhosis, and in those with severe renal disorders (serum creatinine values above 6 mg/100 mL).
As bezafibrate is normally highly protein bound it should not be given to patients with the nephrotic syndrome.
ZAFIBRAL is contra-indicated in patients hypersensitive to bezafibrate.

The chronic administration of the highest dose of bezafibrate to rats was associated with hepatic tumour formation in females. This dose was in the order of 30-40 times the human dose. No such adverse effect was apparent at reduced intake levels approximating more closely to the lipid-lowering dosage in humans.

Although the drug substance has not been shown, in animal studies, to have any adverse effects on the foetus, it is recommended that BEZAFIBRATE should not be administered either to pregnant women or those who are breast-feeding.

Adverse effects during treatment with ZAFIBRAL most frequently are gastro-intestinal in nature such as loss of appetite, nausea or gastric discomfort. These symptoms generally are transient and do not require withdrawal of therapy. In patients with a sensitive stomach, a slowly increasing dosage over 5 to 7 days may help to avoid such symptoms. More rarely there may be dermal manifestations such as pruritus or urticaria, increased hair loss, disturbances of potency and thyrotoxicity with myasthenia or myalgia in the extremities, with or without raised CPK have been reported. All of these adverse effects generally resolve rapidly following withdrawal of therapy. Rarely headache, decreases of haemoglobin and leucocytes and single cases of increases in transaminases have been reported. Special care is needed in patients with renal disease as progressive increases in the serum creatinine level and/or failure to follow the dosage guidelines may result in myotoxicity (rhabdomyolysis). Bezafibrate may increase the lithogenic index in some patients although studies have shown inconsistent results. However there is no evidence that the administration of ZAFIBRAL is associated with an increased frequency of gallstones.

Care is required in administering ZAFIBRAL to patients receiving anti-coagulant therapy of the coumarin type. The dose of anticoagulant should be reduced by 50 percent initially and then titrated to the patient's needs. As BEZAFIBRATE improves glucose utilisation the action of antidiabetic medication, including insulin, may be potentiated. Hypoglycaemia has not been observed although increased monitoring of the glycaemic status may be warranted for a brief period after introduction of ZAFIBRAL.
Should combined therapy with an ion-exchange resin be considered necessary, there should be an interval of 2 hours between the intake of the resin and ZAFIBRAL, as the absorption of bezafibrate otherwise may be impaired. MAO inhibitors should not be administered with bezafibrate.
Since oestrogens may lead to a rise in lipid levels, the necessity of treatment with ZAFIBRAL in patients receiving oestrogens or oestrogen containing preparations should be considered on an individual basis.

Store in a dry place at a temperature not exceeding 25°C, away from light.

Dyslipidaemic Agents

C10AB02 - bezafibrate ; Belongs to the class of fibrates. Used in the treatment of hyperlipidemia.

POM