Source: Υπουργείο Υγείας (CY) Revision Year: 2018 Publisher: Remedica Ltd, Aharnon Street, Limassol Industrial Estate, 3056 Limassol, Cyprus
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 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 (see section 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 symptoms and signs occur (see section 4.8 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.
When bezafibrate is given in combination with anion-exchange resins (e.g. colestyramine), the two drugs should be taken at least 2 hours apart.
Care is required in administering Lacromid 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 Lacromid.
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 cyclosporine 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.
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 Lacromid as the absorption of bezafibrate otherwise may be impaired.
Concomitant therapy with HMG CoA reductase inhibitors and fibrates has been reported to increase the risk of myopathy (see section 4.4 Special warnings and precautions). The underlying mechanism for this remains unclear; the available data do not suggest a pharmacokinetic interaction between bezafibrate and HMG CoA reductase inhibitors.
MAO-inhibitors (with hepatotoxic potential) should not be administered together with bezafibrate.
Since oestrogens may lead to a rise in lipid levels, the necessity for treatment with Lacromid in patients receiving oestrogens or oestrogen containing preparations should be considered on an individual basis.
Although the drug substance has not been shown in animal studies to have any adverse effects on the foetus, it is recommended that Lacromid should not be administered to either pregnant women or to those who are breast-feeding.
Lacromid 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, urticarial, photosensitivity reaction, alopecia, rash.
Very rare: erythema multiform, 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 gamm-aglutamyl transferase and in parallel alkaline phosphatase
Very rare: haemoglobin decreased, platelet increased, white blood cell count decreased, gamma-glutamyl tranferase increased, transaminase increased.
Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continue monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system: Cyprus, Pharmaceutical Services, Ministry of Health, CY-1475 Nicosia, Fax: +357 22608649, Website: www.moh.gov.cy/phs.
None known.
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