CALBERZOL XL

Posology Adults The dosage for Bezafibrate is one tablet daily, equivalent to 400mg bezafibrate. The tablets should be swallowed whole with sufficient fluid after a meal either at night or in the morning. Paediatric population At present there is inadequate information regarding an appropriate dosage in children.

Elderly Bezafibrate prolonged-release tablets should not be used in elderly as the creatinine clearance after 70 years of age is normally lower than 60ml/min. Renal impairment In dialysis patients the use of Bezafibrate 400mg prolonged release tablets is contraindicated.

Bezafibrate is contra-indicated in patients with renal impairment with serum creatinine > 135 micromol/l or creatinine clearance < 60ml/min. Such patients may be treated with conventional Bezafibrate tablets (200mg bezafibrate) using an appropriately reduced daily dosage.

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Treatment should be withdrawn if an adequate response has not been achieved within 3 to 4 months.

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), Uncommon (>1/1,000 and <1/100),Rare ( ≥ 1/10,000 and <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:

Cholelithiasis Skin and subcutaneous tissue disorders: Uncommon: Pruritus, urticaria, photosensitivity reaction, alopecia, rash.

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, 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). - 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) Lactose Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

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

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