Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Generics [UK] Ltd t/a Mylan, Station Close, Potters Bar, Herts, EN6 1TL
Bezafibrate is contraindicated in patients with:
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, 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 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).
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 (see sections 4.3 and 4.5).
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 signs or symptoms occur (see section 4.8).
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.
When bezafibrate is given in combination with anion-exchange resins (e.g. colestyramine), the two drugs should be taken at least 2 hours apart.
Bezafibrate Film-coated Tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
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.
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 at least 2 hours between the intake of the resin and bezafibrate, otherwise the absorption of bezafibrate 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 immunosuppressant 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 (see section 4.3 and 4.4) for specific dose recommendations of statins refer also to the SPC of the relevant product.
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.
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: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000).
Very rare: Pancytopenia, thrombocytopenic purpura.
Uncommon: Hypersensitivity reactions including anaphylactic reactions.
Common: Decreased appetite.
Rare: Depression, insomnia.
Uncommon: Dizziness, headache.
Rare: Peripheral neuropathy, paraesthesia.
Very rare: Interstitial lung disease.
Common: Gastrointestinal disorders
Uncommon: Abdominal distension, diarrhoea, nausea, abdominal pain, constipation, dyspepsia.
Rare: Pancreatitis
Uncommon: Cholestasis.
Very rare: Cholelithiasis.
Uncommon: Pruritus, urticaria, photosensitivity reaction, alopecia, rash.
Very rare: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Uncommon: Muscular weakness, myalgia, muscle cramp.
Very rare: Rhabdomyolysis.
Uncommon: Acute renal failure.
Uncommon: Erectile dysfunction NOS.
Uncommon: Increased blood creatinine phosphokinase, blood creatinine increased, decreased gamma-glutamyl transferase and in parallel alkaline phosphatase
Very rare: Haemoglobin decreased, platelet increased, white blood cell count decreased, gamma-glutamyl transferase increased, transaminase increased.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Not applicable.
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