Adverse reactions : תופעות לוואי

4.8 Undesirable effects
The following undesirable effects may occur during treatment with Bezafibrate400 mg retard film- coated tablets:

Skin and skin appendages
Occasionally, allergic skin reactions such as pruritus, urticaria and other skin manifestations may occur. In isolated cases, generally reversible photoallergic or phototoxic reactions may occur, even after several months of complication-free treatment, in association with erythema, pruritus, blister formation and lichenoid changes. Very rarely, erythema multiforme, Stevens- Johnson syndrome and toxic epidermal necrolysis may occur. In this case, treatment with Bezafibrate400 mg retard film-coated tablets must be stopped immediately and appropriate treatment measures instituted.

Gastrointestinal tract
Occasionally, gastrointestinal disorders, such as sensation of fullness, nausea and loss of appetite, can occur.

Nervous system
Occasionally, headaches and dizziness may occur.
The above side effects are generally transient and do not require cessation of treatment.

Liver
In isolated cases, impaired liver function (e.g. increase in transaminases, cholestasis) has been observed.
Blood
In isolated cases a slight drop in haemoglobin and leukocyte count has been observed. A drop in platelet count with haemorrhage in some cases (e.g. purpura) has also been observed in isolated cases.
Isolated cases have also been reported of a simultaneous drop in all three blood-cell elements (pancytopenia).

Miscellaneous
In rare cases, hair loss, and in isolated cases, impaired potency have occurred.

Most of the above-mentioned side effects generally rapidly subsided following cessation of treatment with Bezafibrate400 mg retard film-coated tablets.

Hypersensitivity
In isolated cases, generalised hypersensitivity reactions associated with tightness in the chest, dyspnoea, tachycardia, skin manifestations, hypotension, oedema, cardiovascular collapse, shivering and syncope have been observed. These allergic reactions require appropriate emergency treatment measures as well as the immediate cessation of treatment.


Kidneys
Long-term treatment frequently leads to slight elevations of serum creatinine.

Muscles
An important but rare side effect is myotoxicity associated with muscular pains, muscle weakness and muscle spasms. Creatine phosphokinase (CPK) must be determined in such cases. Rarely, significant CPK elevations can occur along with clinical symptoms of drug-related rhabdomyolysis. This is often due to excessively high doses, due for example to accumulation of the drug in patients with renal insufficiency (see paragraph 4.2. Posology and method of administration). In case of suspected rhabdomyolysis, treatment with bezafibrate should be suspended immediately and kidney function monitored carefully.

Gallbladder
Bezafibrate alters the composition of bile. Whether, as has been observed with other drugs with similar action, long-term treatment with bezafibrate leads to an increase in gallstones, or whether the gallstones present during treatment with bezafibrate increase in size, is disputed. Gallstone formation has been reported in isolated cases.

Abnormal laboratory findings
The following abnormal laboratory findings have been reported during clinical studies and in the post- marketing phase:
Elevation of transaminase levels (occasionally).