Bezafibrate Medomie

/ Medomie Pharma Ltd, Israel

The recommended dosage is one tablet, equivalent to 400mg Bezafibrate, and should be swallowed whole with sufficient fluid after a meal either in the morning or at night.

This medicinal product is indicated as an adjunct to diet and other non- pharmacological treatment (e.g. exercise, weight reduction) for the following:
– Treatment of severe hypertriglyceridaemia

– Hypersensitivity to the active substance, other fibrates, or to any of the excipients.
– Significant hepatic disease (other than fatty infiltration of the liver associated with raised triglyceride values).
– Gall-bladder diseases with or without cholelithiasis.
– Patients with nephrotic syndrome and severe renal failure (serum creatinine > 135μmol/l; creatinine clearance <60ml/min) and patients undergoing dialysis.
– Combination therapy (concomitant use) of bezafibrate with HMG CoA reductase inhibitors (statins) in patients with predisposing factors for myopathy.
– Known photoallergic or phototoxic reactions to fibrates.

– Bezafibrate should be used as an adjunct to diet and measures such as physical activity, weight loss and adequate treatment of other metabolic disorders (e.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. Combination therapy should not be used in patients with predisposing factors for myopathy.
– Bezafibrate alters the composition of bile. There have been isolated reports of the development of gallstones.
– As bezafibrate could cause cholelithiasis appropriate diagnostic procedures should be performed if cholelithic symptoms and signs occur.
– 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.
– When bezafibrate is given in combination with anion-exchange resins (e.g. colestyramine), the two drugs should be taken at least 2 hours apart.
– Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Common: Decreased appetite, gastrointestinal disorders.
See prescribing information for more details.

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% 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 this medicinal product.
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. A pharmacodynamic interaction between these two classes of drugs may, in some cases, also contribute to an increase in the risk of myopathy for specific dose recommendations of statins refer also to the SPC of the relevant product.

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

No specific effects of acute overdose are known apart from rhabdomyolysis. There is no specific antidote. Thus, appropriate symptomatic therapy is recommended in cases of overdose.
In cases of rhabdomyolysis, bezafibrate must be stopped immediately and renal function carefully monitored.