Bezalip 200mg Tablets

Primary hyperlipidaemia types IIa, IIb, III, IV and V (Fredrickson classification) corresponding to groups I, II and III of the European Atherosclerosis Society guidelines: when diet alone or improvements in lifestyle such as increased exercise or weight reduction do not lead to an adequate response. Secondary hyperlipidaemias, e.g. severe hypertriglyceridaemias, when sufficient improvement does not occur after correction of the underlying disorder (e.g. diabetes mellitus).

The basis of the treatment of all disorders of lipid metabolism is by weight loss, physical activity and adequate treatment of other metabolic disorders (e.g. diabetes, gout). This should be prescribed by the doctor. Obese patients should lose weight.

The dose is generally one BEZALIP 200 mg tablet taken 2 or 3 times daily as determined by the doctor. The tablet should be swallowed whole, with a little fluid, after the 3 main meals.

The standard dosage for BEZALIP RETARD 400 mg is 1 tablet once daily. The tablet should be taken in the morning or evening with or after meals. The tablets should be swallowed whole with sufficient fluid.

In patients with sensitive stomachs, the dose may be started slowly. Start with 1 tablet daily, adding the second tablet after 3 to 4 days and the third after a further 3 to 4 days.

The dosage in patients with renal insufficiency must be adjusted according to serum creatinine levels. Treatment with BEZALIP should be monitored over the first 8 weeks of treatment by the determination of the triglyceride, total cholesterol and HDL-cholesterol levels at least three times. If no significant reduction of triglyceride and total cholesterol is obtained, treatment should be discontinued.

• BEZALIP tablets are contraindicated in patients who are hypersensitive to bezafibrate, or fibrates or other components of BEZALIP.
• BEZALIP is contraindicated in patients with liver dysfunction. BEZALIP may be beneficial for patients with fatty liver concomitant with hyperlipidaemia, but caution should be exercised.
• Gall-bladder diseases with or without cholelithiasis (as a possible liver involvement cannot be excluded).
• BEZALIP 200 mg is contraindicated in patients undergoing dialysis and with impaired renal function (serum creatinine > 530 u03bcmol/u2113 or creatinine clearance < 15 mu2113/min). As BEZALIP is normally highly protein bound, it should not be given to patients with nephrotic syndrome.
• BEZALIP RETARD 400 mg is contraindicated in patients undergoing dialysis and with impaired renal function (serum creatinine > 135 u03bcmol/u2113 or creatinine clearance < 60 mu2113/min).
• Combination therapy of BEZALIP with HMG-CoA reductase inhibitors in patients with predisposing factors for myopathy e.g. impaired renal function, severe infection, trauma, and surgery, disturbances of the hormonal or electrolyte balance.
• Known photoallergic or phototoxic reactions to fibrates.

There is insufficient experience in children to recommend the use of BEZALIP in children. Since oestrogens may lead to a rise in lipid levels the prescribing of BEZALIP in patients taking oestrogens or oestrogen containing contraceptives must be critically considered on an individual basis.

Due to the risk of rhabdomyolysis, BEZALIP should only be administered together with HMG-CoA reductase inhibitors in exceptional cases when strictly indicated. Patients receiving this combination therapy must be fully informed of the symptoms of myopathy and monitored closely. Combination therapy must be discontinued immediately at the first signs of myopathy.

BEZALIP alters the composition of bile. There have been reports of the development of gallstones. Appropriate diagnostic procedures should be performed if cholelithiasis related signs and symptoms should occur (refer to SIDE EFFECTS).

Muscular weakness, myalgia and muscle cramps, often accompanied by a considerable increase in creatinine kinase (CK) may occur. In isolated cases, severe muscular damage (rhabdomyolysis) has been observed. In most cases, this syndrome resulted from overdosage of BEZALIP or from inappropriate usage of BEZALIP RETARD, most frequently in the presence of impaired renal function.

BEZALIP contains lactose. Patients with the rare hereditary conditions of galactose intolerance e.g. galactosaemia, Lapp lactase deficiency, glucose-galactose malabsorption should not take BEZALIP.

When BEZALIP is used concurrently with cholestyramine, an interval of 2 hours should be maintained between taking the two medicaments, since the absorption of BEZALIP is impaired by cholestyramine.

BEZALIP may interact with oral coumarin anti-coagulants and the dosage of these agents may have to be reduced. Adjustments should be made by means of checks on the blood clotting status.

BEZALIP may potentiate the action of sulphonylureas and insulin.

MAO-inhibitors with hepatotoxic potential must not be administered together with BEZALIP. Interaction between HMG-CoA reductase inhibitors (statins) 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 perhaps, in some cases, also contribute to an increased risk of myopathy.

In isolated cases, a pronounced though reversible, impairment of renal function (accompanied by a corresponding increase in the serum creatinine level) has been reported in organ transplant patients receiving immune suppressant therapy and concomitant BEZALIP. Accordingly, renal function should be closely monitored in these patients and, in the event of relevant significant changes in laboratory parameters, BEZALIP should, if necessary, be discontinued.

Due to lack of adequate clinical experience, BEZALIP is contraindicated during pregnancy and lactation.

Not specified in the provided text.

A total of 3 581 patients were enrolled into 48 clinical studies. Side effects observed during the clinical development and subsequent use in clinical practice consisted mainly of symptoms of gastro intestinal disturbances which were usually transient and rarely led to discontinuation of the medicine. Myopathy (rhabdomyolysis) was mostly observed when dose reduction was not implemented in patients with impaired renal function. None of the side effects could be considered to affect long term safety, as they usually occurred within the first few months of therapy and were either transient or disappeared upon withdrawal of the medicine.

The frequency of adverse drug reactions (ADRs) according to MedDRA System Organ Class is displayed in the table below:

MedDRA System Organ Class

• Very rare: (<10 000)
• Uncommon: (>1/1 000 and <1/100)
• Common

Blood and the Lymphatic System Disorders

• Pancytopenia
• Thrombocytopenia

Immune System Disorders

• Hypersensitivity reactions

Metabolism and Nutrition Disorders

• Decreased appetite

Nervous System Disorders

• Dizziness
• Headache

Gastrointestinal Disorders

• Abdominal distension
• Nausea

Hepatobiliary Disorders

• Cholelithiasis
• Cholestasis

Skin and Subcutaneous Tissue Disorders

• Thrombocytopenic purpura
• Erythema multiforme
• Pruritis
• Urticaria
• Photosensitivity
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis reaction
• Alopecia

Musculoskeletal, Connective Tissue and Bone Disorders

• Rhabdomyolysis
• Muscular weakness
• Myalgia
• Muscle cramp

Renal and Urinary Disorders

• Acute renal failure

Reproductive Systems and Breast Disorders

• Erectile dysfunction

Investigations

• Haemoglobin decreased
• Platelet increased
• White blood cell count decreased
• Gamma-glutamyl transferase increased
• Transaminase increased
• Increased blood creatinine phosphokinase
• Blood creatinine increased
• Blood alkaline phosphatase increased

Laboratory abnormalities: The following laboratory abnormalities have been observed during clinical trials and also reported during post marketing period:

• Increased blood creatinine phosphokinase (uncommon)
• Increased platelets (uncommon)
• Decreased haemoglobin (uncommon)
• Decreased haematocrit (uncommon)
• Decreased white blood cells (uncommon)
• Increased transaminase (uncommon)
• Decreased alkaline phosphatase (uncommon).
• Decreased gamma-glutamyl transferase (uncommon) and in parallel alkaline phosphatase could be used as an indicator of patient compliance.

Specific clinical picture of BEZALIP intoxication (apart from rhabdomyolysis) is unknown. Thus, appropriate symptomatic therapy as necessary in case of overdose. There is no specific antidote. In cases of rhabdomyolysis (mostly in patients with impaired renal function), administration of BEZALIP/BEZALIP RETARD must be stopped immediately and renal function must be carefully monitored.