FIBRAZATE XL

Posology Adults The recommended daily dose for Fibrazate® XL 400mg Tablets is one tablet, equivalent to 400mg bezafibrate, after a meal either in the morning or at night. Older people Fibrazate® XL 400mg Tablets should not be prescribed/administered to older people whose creatinine clearance is below 60ml/min (see Renal impairment below).

Paediatric population Information available to date is not adequate for a dose recommendation in children. Renal impairment Fibrazate® XL 400mg Tablets are contraindicated in dialysis patients. Bezafibrate should not be given to patients with renal impairment with serum creatinine > 135 micromol/l or creatinine clearance < 60 ml/min.

Such patients may be treated with conventional tablets using an appropriately reduced daily dose. For patients with a history of gastric sensitivity, the dosage may be gradually increased over 5-7 days to the maintenance level. 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Treatment should be withdrawn if an adequate response has not been achieved within 3 to 4 months. Method of administration Swallow whole tablet with sufficient fluid.

The overall safety profile of bezafibrate is based on a combination of clinical study data and post-marketing experience. The frequency of adverse drug reactions (ADRs) according to MedDRA System Organ Class is displayed below.

Frequency of reporting:

Common (≥ 1/100 to <1/10), Uncommon (≥ 1/1,000 to <1/100), Rare (≥ 1/10,000 to <1/1000), Very rare (<1/10,000).

Blood and lymphatic system disorders:

Very rare: Pancytopenia, thrombocytopenic purpura.

Immune system disorders:

Uncommon: Hypersensitivity reactions including anaphylactic reactions.

Metabolism and nutrition disorders:

Common: Decreased appetite.

Nervous system disorders:

Uncommon: Dizziness, headache.

Rare:

Peripheral neuropathy, paraesthesia.

Psychiatric disorders:

Rare: Depression, insomnia.

Gastrointestinal disorders:

Common: Gastrointestinal disorders.

Uncommon:

Abdominal pain, constipation, dyspepsia, abdominal distension, diarrhoea, nausea.

Rare:

Pancreatitis Hepatobiliary disorders: Uncommon: Cholestasis.

Very rare:

g. diabetes, gout). - Secondary causes of dyslipidaemia, such as uncontrolled type 2 diabetes mellitus, hypothyroidism, nephrotic 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, older (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). - 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.

Significant hepatic disease (other than fatty infiltration of the liver associated with raised triglyceride values). - Gall bladder disease with or without cholelithiasis. ) and patients undergoing dialysis. 5). - Hypersensitivity to bezafibrate or any component of the product or to other fibrates.

- Known photoallergic or phototoxic reactions to fibrates.