BEZAFIBRATE

Posology Adults The recommended dosage for Bezafibrate tablets is one tablet three times a day, equivalent to 600mg bezafibrate. Each tablet should be swallowed whole with sufficient fluid after a meal. Occasionally gastro-intestinal symptoms may occur.

In susceptible patients a slowly increasing dosage over 5 to 7 days may help to avoid such symptoms. Elderly In elderly patients there is a physiological reduction of the renal function with age. Bezafibrate dosage should be adjusted based on serum creatinine clearance values (see Renal impairment below).

Paediatric population At present there is inadequate information regarding an appropriate dosage in children. Renal impairment In dialysis patients the use of bezafibrates is contraindicated. In patients with renal insufficiency the dose should be adjusted according to serum creatinine levels or creatinine clearance as shown in the following table; Serum creatinine ( μmol/l) Creatinin e clearance (ml/min) Dosage (tablets/d ay) Up to 135 Over 60 3 136 – 225 60 – 40 2 226 – 530 40 – 15 1 every 1 or 2 days Over 530 Less than 15 Contra- indicated The response to therapy is normally rapid, although a progressive improvement may occur over a number of weeks.

Treatment should be withdrawn if an adequate response has not been achieved within 3 to 4 months.

). - 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. g. colestyramine), the two drugs should be taken at least 2 hours apart.

Excipient(s) Sodium This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’. 5 Interaction with other medicinal products and other forms of interaction Care is required in administering Bezafibrate to patients taking coumarin-type anti-coagulants, the action of which may be potentiated.

The dosage of anti- coagulant should be reduced by up to 50% and readjusted by monitoring blood coagulation. 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.

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. 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.

Interaction between HMG CoA reductase inhibitors and fibrates may vary in nature and intensity depending on the combination of the administered drugs. 4) for specific dose recommendations of statins refer also to the SPC of the relevant product.

g. diabetes, gout). - Secondary causes of dyslipidaemia, such as uncontrolled type 2 diabetes mellitus, hypothyroidism, nephritic syndrome, dysproteinemia, obstructive liver disease, pharmacological treatment, alcoholism should be adequately treated before Bezafibrate therapy is initiated.

- 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 of 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).

- Bezafibrate should be used with caution in combination with HMG CoA reductase inhibitors as the combination of HMG CoA inhibitors and fibrates has been shown to increase the incidence and severity of myopathy. Patients should be informed of symptoms and monitored for signs of myopathy and increased CPK activity and combination therapy discontinued if signs of myopathy develop.

5). - Bezafibrate alters the composition of bile. There have been isolated reports of the development of gallstones. 8 Undesirable effects). - 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.

g. colestyramine), the two drugs should be taken at least 2 hours apart. Excipient(s) Sodium This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

1. - Significant hepatic disease (other than fatty infiltration of the liver associated with raised triglyceride values). - Gall-bladder diseases with or without cholelithiasis. 2). 4. 5) - Known photoallergic or phototoxic reactions to fibrates.