- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
- 11. Dosimetry
- 12 Instructions for preparation of radiopharmaceuticals
AdultsThe recommended dosage for Bezalip tablets is one tablet three times a day, equivalent to 600mg bezafibrate. Each tablet should be swallowed whole with sufficient fluid after a meal. Occasionally gastro-intestinal symptoms may occur. In susceptible patients a slowly increasing dosage over 5 to 7 days may help to avoid such symptoms.
ElderlyIn elderly patients there is a physiological reduction of the renal function with age. Bezafibrate dosage should be adjusted based on serum creatinine clearance values (see Renal impairment below).
ChildrenAt present there is inadequate information regarding an appropriate dosage in children.
Renal impairmentIn dialysis patients the use of bezafibrates is contraindicated.In patients with renal insufficiency the dose should be adjusted according to serum creatinine levels or creatinine clearance as shown in the following table;
|Serum creatinine (μmol/l)||Creatinine clearance (ml/min)||Dosage (tablets/day)|
|Up to 135||Over 60||3|
|136 225||60 40||2|
|226 530||40 15||1 every 1 or 2 days|
|Over 530||Less than 15||Contraindicated|
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: PancreatitisHepatobiliary disorders: Uncommon: Cholestasis. Very rare: Cholelithiasis.
Skin and subcutaneous tissue disorders:Uncommon: Pruritus, urticaria, photosensitivity reaction, alopecia, rash. Very rare: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Musculoskeletal and connective tissue disorders:Uncommon: Muscular weakness, myalgia, muscle cramp. Very rare: Rhabdomyolysis.
Renal and urinary disorders:Uncommon: Acute renal failure.
Reproductive system and breast disorders:Uncommon: Erectile dysfunction NOS.
Respiratory, thoracic and mediastinal disorders:Very rare: Interstitial lung disease.
Investigations:Uncommon: Increased blood creatinine phosphokinase, blood creatinine increased, decreased gamma-glutamyl transferase and in parallel alkaline phosphataseVery rare: Haemoglobin decreased, platelet increased, white blood cell count decreased, gamma-glutamyl transferase increased, transaminase increased. Reporting of suspected adverse reactions 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.
Mechanism of Action:Bezafibrate lowers elevated blood lipids (triglycerides and cholesterol). Elevated VLDL and LDL are reduced by treatment with bezafibrate, whilst HDL-levels are increased. The activity of triglyceride lipases (lipoprotein lipase and hepatic lipoprotein lipase) involved in the catabolism of triglyceride-rich lipoproteins is increased by bezafibrate. In the course of the intensified degradation of triglyceride-rich lipoproteins (chylomicrons, VLDL), precursors for the formation of HDL are formed which explains an increase in HDL. Furthermore, cholesterol biosynthesis is reduced by bezafibrate, which is accompanied by a stimulation of the LDL-receptor-mediated lipoprotein catabolism. Studies have shown bezafibrate to be effective in treating hyperlipidaemia in patients with diabetes mellitus. Some cases showed a beneficial reduction in fasting blood glucose.Significant reductions in serum fibrinogen levels have been observed in hyperfibrinogenaemic patients treated with bezafibrate.There is evidence that treatment with fibrates may reduce coronary heart disease events but they have not been shown to decrease all cause mortality in the primary or secondary prevention of cardiovascular disease.
Efficacy / Clinical Studies:No data available.
Absorption:Bezafibrate is rapidly and almost completely absorbed from the standard film-coated tablet formulation. A peak plasma concentration of about 8mg/L is reached after 12 hours following a single 200mg dose in healthy volunteers.
DistributionThe protein-binding of bezafibrate in serum is approximately 95% and the apparent volume of distribution is 17 litres.
Metabolism50% of the administered bezafibrate dose is recovered in the urine as unchanged drug and 20% in the form of glucuronides.
Elimination:Elimination is rapid, with excretion almost exclusively renal. Ninety-five percent of the activity of the 14C-labelled drug is recovered in the urine and 3% in the faeces within 48 hours. 50% of the applied dose is recovered in the urine as unchanged drug and 20% in form of glucuronides. The rate of renal clearance ranges from 3.4 to 6.0L/h. The elimination half-life of bezafibrate is 1-2 hours.
Pharmacokinetics in Special Populations:Pharmacokinetic investigations in the elderly suggest that elimination may be delayed in cases of impaired liver function. Liver disease (except fatty liver) is a contraindication for the use of bezafibrate (see 4.3 Contraindications). In elderly patients, there is a physiological reduction of the renal function with age. Bezafibrate dosage should be adjusted based on the serum creatinine and creatinine clearance values as indicated in the above table. The elimination of bezafibrate is reduced in patients with impaired renal function and dosage adjustments are necessary to prevent drug accumulation and toxic effects. Not surprisingly there is a correlation between creatinine clearance and the elimination half-life of bezafibrate; with decreasing creatinine clearance the elimination half-life is increasing. Because of its high protein binding, bezafibrate cannot be dialysed (cuprophane filter). The use of bezafibrate is contraindicated in dialysis patients.
Table core:maize starch, microcrystalline cellulose, colloidal silicon dioxide, sodium starch glycollate, magnesium stearate.
Film-coating:polyvinyl alcohol, titanium dioxide (E171), macrogol,talc.
Actavis UK Ltd
Whiddon Valley, Barnstaple, Devon, EX32 8NS, UK
+44 (0)1271 346 106
+44 (0)1271 311 200
+44 (0)1271 385 257