Bezalip

Bezalip 200 mg film-coated tablets
bezafibrate
Pharmacotherapeutic category
Lipid-lowering agent.
Therapeutic indications
Bezalip belongs to a group of medicines commonly known as fibrates. These medicines are used to lower levels of fats (lipids) in the blood, such as triglycerides.
Bezalip is used, together with a low-fat diet and other non-medical treatments such as physical exercise and weight loss, to reduce fat levels in the blood.
Contraindications
Bezafibrate must not be administered to patients with:

• hepatic disorders (with the exception of hepatic steatosis, which is frequently associated with hypertriglyceridemia);
• biliary tract disorders with or without gallstones;
• renal insufficiency and patients undergoing dialysis;
• concomitant treatment with HMG-CoA reductase inhibitors (statins) in patients with predisposing factors for myopathy (reduced renal function, severe infections, trauma, surgery, or disturbances in hormonal or electrolyte balance) (see Interactions);
• known hypersensitivity to bezafibrate, other fibrates, or any of the excipients;
• documented photoallergic or phototoxic reactions to fibrates;
• pregnancy and lactation (see Pregnancy and lactation).
  Precautions for use
  Adherence to diet and other measures improving lipid metabolism disorders—such as physical activity, weight loss, and adequate treatment of other metabolic disorders (e.g., diabetes, gout)—is of utmost importance.
  The patient's response to therapy should be monitored regularly, and treatment should be discontinued if no adequate response is achieved within 3 to 4 months.
  The use of bezafibrate in children should be considered with particular caution. A precise dosage recommendation for children cannot be provided.
  Since estrogens may increase lipid levels, the prescription of bezafibrate in patients taking estrogens or estrogen-containing contraceptives should be critically evaluated on an individual basis.
  In patients with hypoalbuminemia (e.g., nephrotic syndrome) and in those with impaired renal function, renal function should be monitored regularly. Acute renal failure may develop in patients with existing renal impairment if dosage recommendations based on serum creatinine or creatinine clearance are not strictly followed.
  Muscle weakness, myalgia, and muscle cramps—often accompanied by a marked increase in creatine kinase (CK)—may occur. In rare cases, severe muscle damage (rhabdomyolysis) has been observed. In most cases, this syndrome resulted from overdosage or inappropriate use of bezafibrate, often in the presence of impaired renal function.
  Due to the risk of rhabdomyolysis, concomitant administration of bezafibrate with HMG-CoA reductase inhibitors (statins) should be limited to exceptional cases where it is strictly indicated. Patients receiving combination therapy must be carefully informed about the symptoms of myopathy and closely monitored. Combination therapy must be immediately discontinued at the first signs of myopathy.
  Bezafibrate alters bile composition. Gallstone formation has occasionally been reported. It is unclear whether long-term treatment with bezafibrate increases gallstone formation—as observed with other drugs having a similar mechanism of action—or whether pre-existing gallstones increase in size during treatment with bezafibrate.
  Gallstone formation (cholelithiasis) cannot be excluded as a possible adverse effect of bezafibrate therapy; therefore, if symptoms or signs suggestive of cholelithiasis occur, appropriate diagnostic procedures should be performed (see Undesirable effects).
  When administering bezafibrate in combination with anion-exchange resins (e.g., cholestyramine), the two drugs should be taken at least 2 hours apart.
  Interactions
  Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription.
  When bezafibrate is used concomitantly with other drugs or substances, the following interactions should be considered:
• Bezafibrate may enhance the effect of coumarin-type anticoagulants. Therefore, at the start of bezafibrate treatment, the anticoagulant dose should be reduced by 30–50%, and subsequently adjusted according to coagulation parameters.
• Bezafibrate may enhance the effect of sulfonylureas and insulin due to improved glucose utilization, resulting in a simultaneous reduction in insulin requirements.
• In isolated cases, in organ transplant patients receiving concomitant immunosuppressive therapy with bezafibrate, a pronounced (though reversible) impairment of renal function (accompanied by a corresponding increase in serum creatinine levels) has been reported. Therefore, careful monitoring of renal function is required in these patients, and bezafibrate should be discontinued if significant laboratory changes occur.
• When bezafibrate is used concomitantly with anion-exchange resins (e.g., cholestyramine), an interval of at least 2 hours between administrations should be ensured due to impaired absorption of bezafibrate.
• Perhexiline maleate hydrogenated and MAO inhibitors (potentially hepatotoxic) must not be administered together with bezafibrate.
• The interaction between HMG-CoA reductase inhibitors (statins) and fibrates may vary in nature and intensity depending on the drugs used. The pharmacodynamic interaction between these two drug classes may increase the risk of myopathy (see Contraindications).
  Special warnings
  Pregnancy and lactation
  Due to lack of adequate clinical experience, bezafibrate is contraindicated during confirmed or suspected pregnancy and during breastfeeding.
  Effects on ability to drive and use machines
  Since the medicine may occasionally cause dizziness and drowsiness, patients should be advised to exercise caution when operating machinery, including driving vehicles.
  Dosage, method and timing of administration
  Start with 3 film-coated tablets daily (1 after each main meal), swallowed whole with some liquid.
  If favorable results are obtained, particularly in patients with hypertriglyceridemia, a daily dose of 2 film-coated tablets may be tried. In particularly resistant dyslipidemic forms, the dose may be increased up to 4–5 film-coated tablets daily.
  Patients with gastric sensitivity
  Bezafibrate should be administered with caution in patients with gastric sensitivity (see Precautions for use).
  Patients with impaired renal function
  Bezalip 200 mg is contraindicated in patients with impaired renal function (serum creatinine > 6 mg/100 ml or creatinine clearance < 15 ml/min) (see Contraindications).
  Creatinine clearance is the most reliable parameter (especially in elderly patients).
  The use of bezafibrate is contraindicated in dialyzed patients (see Contraindications).
  Elderly patients
  Renal function is physiologically reduced with age. Treatment with bezafibrate should therefore be evaluated based on serum creatinine levels and creatinine clearance.
  Duration of treatment
  Treatment with bezafibrate is normally long-term.
  If you have any doubts about the use of this medicine, consult your doctor or pharmacist.
  Overdose
  Except for rhabdomyolysis, no specific clinical picture of bezafibrate intoxication is known. In case of overdose, appropriate symptomatic therapy should be administered. There is no specific antidote.
  In cases of rhabdomyolysis (predominantly in patients with impaired renal function), bezafibrate administration must be immediately discontinued and renal function carefully monitored.
  In case of accidental ingestion of an excessive dose, contact your doctor immediately or go to the nearest hospital.
  Undesirable effects
  Like all medicines, this medicine can cause adverse effects, although not everybody will experience them.
  The overall safety profile of bezafibrate is based on clinical data and post-marketing experience.
  A total of 3581 patients were enrolled in 48 clinical studies. Adverse effects observed during clinical development and subsequent clinical use consist mainly of transient gastrointestinal symptoms, which rarely led to discontinuation of the drug. Myopathy (rhabdomyolysis) has been observed primarily when dose reduction was not implemented in patients with impaired renal function. It is believed that none of the adverse effects affect long-term safety, as they usually occurred within the first months of treatment and were transient in nature or resolved upon discontinuation of the drug.
  The table below lists the frequency of adverse drug reactions (uncommon (≥ 1/1,000 and < 1/100), very rare (< 1/10,000)).

Laboratory test abnormalities
The following laboratory test abnormalities have been observed in clinical studies
and have also been reported post-marketing:
reduction in alkaline phosphatase (uncommon).
reduction in gamma-glutamyl transferase (uncommon).
Reduction in gamma-glutamyl transferase and, in parallel, alkaline phosphatase may
be used as an indicator of patient compliance.
Following the instructions contained in the package leaflet reduces the risk of
adverse effects.
If any of the adverse effects worsens, or if you notice any adverse effect not listed
in this leaflet, inform your doctor or pharmacist.

Expiry and storage
Expiry: see the expiry date stated on the packaging.
Warning: do not use the medicine after the expiry date stated on the packaging.
The expiry date indicated refers to the product in intact packaging, stored correctly.
Keep the medicine out of the reach and sight of children.
Medicines must not be disposed of via wastewater or household waste. Ask your
pharmacist how to dispose of medicines no longer in use. This will help protect
the environment.

Composition
1 tablet contains: bezafibrate 200 mg.
Excipients: maize starch, pregelatinized starch, microcrystalline cellulose, anhydrous colloidal silica, sodium starch glycolate (Type A), magnesium stearate, polyvinyl alcohol, macrogol 3350, titanium dioxide, talc.

Pharmaceutical form and contents
50 film-coated tablets.

Marketing Authorization Holder
Marketing Authorization Holder: AUROBINDO PHARMA ITALIA SRL, Via San Giuseppe 102, 21047 – Saronno, Varese

Manufacturer and final controller
Manufactured and controlled by:
Cenexi, 52, Rue Marcel et Jacques Gaucher, 94120 Fontenay-Sous-Bois (France)

Batch release:
Cenexi, 52, Rue Marcel et Jacques Gaucher, 94120 Fontenay-Sous-Bois (France)
July 2011

Bezalip 400 mg prolonged-release tablets
bezafibrate

Pharmacotherapeutic category
Hypolipidaemic agent.

Therapeutic indications
Bezalip belongs to a group of medicines commonly known as fibrates. These medicines
are used to lower levels of fats (lipids) in the blood, such as triglycerides.
Bezalip is used, together with a low-fat diet and other non-medical treatments such as
exercise and weight loss, to reduce fat levels in the blood.

Contraindications
Bezafibrate must not be administered to patients with:
hepatic disorders (with the exception of hepatic steatosis, which is frequently associated
with hypertriglyceridaemia);
gallbladder disorders with or without gallstones;
renal insufficiency and patients undergoing dialysis;
concomitant treatment with HMG-CoA reductase inhibitors (statins) in patients with
predisposing factors for myopathy (reduced renal function, severe infections, trauma,
surgical procedures, or disturbances in hormonal or electrolyte balance) (see Interactions);
known hypersensitivity to bezafibrate, other fibrates, or any of the excipients;
known photoallergic or phototoxic reactions to fibrates;
pregnancy and breastfeeding (see Pregnancy and breastfeeding).

Precautions for use
Adherence to diet and other measures improving lipid metabolism disorders, such as
physical activity, weight loss, and adequate treatment of other metabolic disorders (e.g.
diabetes, gout), is of utmost importance.
The patient's response to therapy should be monitored regularly, and treatment should
be discontinued if no adequate response is achieved within 3 to 4 months.
The use of bezafibrate in children should be considered with particular caution.
A precise dosage recommendation cannot be provided for children.
Since estrogens may increase lipid levels, the prescription of bezafibrate in patients
taking estrogens or estrogen-containing contraceptives should be critically evaluated on
an individual basis.
In patients with hypoalbuminemia (e.g. nephrotic syndrome) and in those with impaired
renal function, renal function should be monitored regularly. In patients with existing
renal impairment, acute renal failure may develop if dosage recommendations based on
serum creatinine or creatinine clearance are not strictly followed.
Muscle weakness, myalgia, and muscle cramps may occur, often accompanied by a
marked increase in creatine kinase (CK). In rare cases, severe muscle damage (rhabdomyolysis) has been observed. In most cases, this syndrome resulted from overdosage or inappropriate use of bezafibrate, most often in the presence of impaired renal function.
Due to the risk of rhabdomyolysis, concomitant administration of bezafibrate with HMG-CoA reductase inhibitors should be limited to exceptional cases where it is strictly indicated. Patients receiving combination therapy must be carefully informed about symptoms of myopathy and closely monitored. Combination therapy should be immediately discontinued at the first signs of myopathy.
Bezafibrate alters bile composition. Occasionally, gallstone formation has been reported. It is unclear whether long-term treatment with bezafibrate increases gallstone formation, as observed with other drugs of similar mechanism of action, or whether pre-existing gallstones increase in size during bezafibrate treatment.
Cholelithiasis cannot be ruled out as a potential side effect of bezafibrate therapy; therefore, if symptoms or signs related to cholelithiasis occur, appropriate diagnostic procedures should be performed (see Adverse effects).
When bezafibrate is administered concomitantly with anion-exchange resins (e.g. cholestyramine), the two drugs should be taken at least 2 hours apart.

Interactions
Inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including those without a prescription.
When bezafibrate is used concurrently with other medicines or substances, the following interactions should be considered:
Bezafibrate may enhance the effect of coumarin-type anticoagulants. Therefore, at the start of bezafibrate treatment, the anticoagulant dose should be reduced by 30–50%, and subsequently adjusted based on coagulation parameters.
Bezafibrate may increase the activity of sulfonylureas and insulin due to improved glucose utilization, resulting in a simultaneous reduction in insulin requirements.
In isolated cases, in organ transplant recipients receiving concomitant immunosuppressive therapy with bezafibrate, a pronounced, although reversible, impairment of renal function (accompanied by a corresponding increase in serum creatinine) has been reported. Therefore, close monitoring of renal function is necessary in these patients, and bezafibrate should be discontinued if significant changes in laboratory parameters occur.
When bezafibrate is used concomitantly with anion-exchange resins (e.g. cholestyramine), an interval of at least 2 hours between administrations should be maintained due to impaired absorption of bezafibrate.
Perhexiline maleate and MAO inhibitors (potentially hepatotoxic) must not be administered together with bezafibrate.
The interaction between HMG-CoA reductase inhibitors (statins) and fibrates may vary in nature and intensity depending on the drugs used. The pharmacodynamic interaction between these two drug classes may increase the risk of myopathy (see Contraindications).

Special warnings
Bezalip 400 mg contains lactose: if you have been diagnosed with an intolerance to certain sugars, consult your doctor before taking this medicine.

Pregnancy and breastfeeding
Due to lack of adequate clinical experience, bezafibrate is contraindicated during confirmed or suspected pregnancy and during breastfeeding.

Effects on ability to drive and use machines
Since the medicine may occasionally cause dizziness and somnolence, patients should be advised to exercise caution when operating machinery, including driving vehicles.

Dosage, method and timing of administration
1 tablet daily, taken in the morning or evening with a meal, swallowed whole with sufficient liquid.

Patients with gastric sensitivity
Bezafibrate should be administered with caution in patients with gastric sensitivity (see Precautions for use).

Patients with impaired renal function
Bezalip 400 mg is contraindicated in patients with impaired renal function (serum creatinine > 1.5 mg/100 ml or creatinine clearance < 60 ml/min) (see Contraindications).
Creatinine clearance is the most reliable parameter (especially in elderly patients).
Use of bezafibrate is contraindicated in dialysed patients (see Contraindications).

Elderly patients
Renal function is physiologically reduced with age. Treatment with bezafibrate should therefore be evaluated based on serum creatinine and creatinine clearance values.
Bezalip 400 mg should not be used in elderly patients, as creatinine clearance is normally below 60 ml/min after the age of 70.

Duration of treatment
Treatment with bezafibrate is normally long-term.
If you have any doubts about using this medicine, consult your doctor or pharmacist.

Overdose
Except for rhabdomyolysis, there is no specific clinical picture of bezafibrate intoxication. In case of overdose, appropriate symptomatic therapy should be administered. There is no specific antidote.
In cases of rhabdomyolysis (predominantly in patients with impaired renal function), bezafibrate administration should be immediately discontinued and renal function carefully monitored.
In case of accidental ingestion of an excessive dose, contact your doctor immediately or go to the nearest hospital.

Adverse effects
Like all medicines, this one can cause adverse effects, although not everyone experiences them.
The overall safety profile of bezafibrate is based on clinical data and post-marketing experience.
A total of 3581 patients were enrolled in 48 clinical studies. The adverse effects observed during clinical development and subsequent clinical use are mainly gastrointestinal symptoms, usually transient, and rarely leading to drug discontinuation. Myopathy (rhabdomyolysis) has been observed primarily when dose reduction was not implemented in patients with impaired renal function. It is considered that none of the adverse effects impact long-term safety, as they usually occurred within the first few months of treatment and were transient or resolved upon discontinuation of the drug.
The table below lists the frequency of adverse drug reactions (uncommon (≥ 1/1,000 and < 1/100), very rare (< 1/10,000)).

Laboratory test abnormalities
The following laboratory test abnormalities have been observed during clinical studies
and have also been reported post-marketing:
decrease in alkaline phosphatase (uncommon).
decrease in gamma-glutamyl transferase (uncommon).
Reduction in gamma-glutamyl transferase and, in parallel, in alkaline phosphatase may
be used as an indicator of patient compliance.
Following the instructions contained in this leaflet reduces the risk of adverse effects.
If any of the adverse effects worsens, or if you notice any adverse effect not listed in this
leaflet, inform your doctor or pharmacist.
Expiry and storage
Expiry date: see the expiry date stated on the packaging.
Warning: do not use the medicinal product after the expiry date stated on the packaging.
The expiry date stated refers to the product in its original packaging, stored properly.
Keep the medicinal product out of the reach and sight of children.
Medicines must not be disposed of via wastewater or household waste. Ask your
pharmacist how to dispose of medicines no longer used. This will help protect the
environment.
Composition
1 tablet contains: bezafibrate 400 mg.
Excipients: monohydrate lactose, povidone K25, sodium lauryl sulfate, hypromellose 100 mPas,
anhydrous colloidal silica, magnesium stearate, poly (ethylacrylate, methyl methacrylate),
hypromellose 3 mPas, macrogol 10,000, talc, titanium dioxide, polysorbate 80, sodium citrate.
Pharmaceutical form and contents
30 prolonged-release tablets.
Marketing Authorization Holder
AUROBINDO PHARMA ITALIA SRL Via San Giuseppe 102, 21047 –Saronno Varese
Manufacturer and final controller
Manufactured and controlled by:
Cenexi 52, Rue Marcel et Jacques Gaucher 94120 Fontenay-Sous-Bois (France)
Batch release:
Cenexi 52, Rue Marcel et Jacques Gaucher 94120 Fontenay-Sous-Bois (France)