Bezafibrate

In isolated cases, a pronounced though reversible impairment of renal function (accompanied by a corresponding increase in serum creatinine level) has been reported in organ transplant patients receiving immuno-suppressant therapy and concomitant bezafibrate. Accordingly, renal function should be closely monitored in these patients and, in the event of relevant significant changes in laboratory parameters, bezafibrate, should if necessary, be discontinued.

MAO-inhibitors (with hepatotoxic potential) should not be administered together with bezafibrate.

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 bezafibrate.

Care is required in administering bezafibrate to patients taking coumarin-type anticoagulants, the action of which may be potentiated. The dosage of anticoagulant should be reduced by up to 50 per cent and then readjusted by regular monitoring of blood coagulation.

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 bezafibrate as the absorption of bezafibrate otherwise may be impaired.

When bezafibrate is given in combination with anion-exchange resins (e.g. colestyramine), the two drugs should be taken at least 2 hours apart.

Since oestrogens may lead to a rise in lipid levels, the prescribing of bezafibrate in patients taking oestrogens or oestrogen-containing contraceptives must be critically considered on an individual basis.

Bezafibrate and other fibrates may cause myopathy, manifested as muscle weakness or pain, often accompanied by a considerable increase in creatine kinase (CPK). In isolated cases severe muscle damage (rhabdomyolysis) has been observed. The risk of rhabdomyolysis may be increased when higher than recommended doses of bezafibrate are used, most frequently in the presence of impaired renal function and in patients with predisposing factors for myopathy, (including renal impairment, elderly (aged >65 years), personal or familial history of hereditary muscular disorders and previous history of muscular toxicity with a fibrate or other lipid lowering drugs, hypothyroidism, severe infection, trauma, surgery, disturbances of hormone or electrolyte imbalance and a high alcohol intake).

There are limited data from the use of bezafibrate in pregnant women. Animal studies are insufficient with respect to reproductive toxicity. The potential risk for humans is unknown. Bezafibrate is not recommended during pregnancy and in women of childbearing potential not using contraception.

There is insufficient information on the excretion of bezafibrate or its metabolites in human milk. A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from bezafibrate therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Bezafibrate has been shown to cause dizziness and can have a minor to moderate effect on the ability to drive or use machines. Patients should not drive or use machines if they are affected.