Side effects Xenical

Commonly Observed (based on first year and second year data - XENICAL 120 mg three times a day versus placebo):

Gastrointestinal (GI) symptoms were the most commonly observed treatment-emergent adverse events associated with the use of XENICAL in double-blind, placebo-controlled clinical trials and are primarily a manifestation of the mechanism of action. (Commonly observed is defined as an incidence of ³5% and an incidence in the XENICAL 120 mg group that is at least twice that of placebo.)

Discontinuation of Treatment: In controlled clinical trials, 8.8% of patients treated with XENICAL discontinued treatment due to adverse events, compared with 5.0% of placebo-treated patients. For XENICAL, the most common adverse events resulting in discontinuation of treatment were gastrointestinal.

Incidence in Controlled Clinical Trials: The following table lists other treatment-emergent adverse events from seven multicenter, double-blind, placebo-controlled clinical trials that occurred at a frequency of ≥ 2% among patients treated with XENICAL 120 mg three times a day and with an incidence that was greater than placebo during year 1 and year 2, regardless of relationship to study medication.

Other Clinical Studies or Postmarketing Surveillance

Rare cases of hypersensitivity have been reported with the use of XENICAL. Signs and symptoms have included pruritus, rash, urticaria, angioedema, bronchospasm and anaphylaxis. Very rare cases of bullous eruption, increase in transaminases and in alkaline phosphatase, and exceptional cases of hepatitis that may be serious have been reported. No causal relationship or physiopathological mechanism between hepatitis and orlistat therapy has been established. Reports of decreased prothrombin, increased INR and unbalanced anticoagulant treatment resulting in change of hemostatic parameters have been reported in patients treated concomitantly with orlistat and anticoagulants.

In clinical trials in obese diabetic patients, hypoglycemia and abdominal distension were also observed.

Preliminary data from a XENICAL and cyclosporine drug interaction study indicate a reduction in cyclosporine plasma levels when XENICAL was coadministered with cyclosporine (see WARNINGS).

DRUG INTERACTIONS

Alcohol: In a multiple-dose study in 30 normal weight subjects, coadministration of XENICAL and 40 grams of alcohol (e.g., approximately 3 glasses of wine) did not result in alteration of alcohol pharmacokinetics, orlistat pharmacodynamics (fecal fat excretion), or systemic exposure to orlistat.

Glyburide: In 12 normal-weight subjects receiving orlistat 80 mg three times a day for 5 days, orlistat did not alter the pharmacokinetics or pharmacodynamics (blood glucose-lowering) of glyburide.

Nifedipine (extended-release tablets): In 17 normal-weight subjects receiving XENICAL 120 mg three times a day for 6 days, XENICAL did not alter the bioavailability of nifedipine (extended-release tablets).

Oral Contraceptives: In 20 normal-weight female subjects, the treatment of XENICAL 120 mg three times a day for 23 days resulted in no changes in the ovulation-suppressing action of oral contraceptives.

Phenytoin: In 12 normal-weight subjects receiving XENICAL 120 mg three times a day for 7 days, XENICAL did not alter the pharmacokinetics of a single 300-mg dose of phenytoin.

Pravastatin: In a 2-way crossover study of 24 normal-weight, mildly hypercholesterolemic patients receiving XENICAL 120 mg three times a day for 6 days, XENICAL did not affect the pharmacokinetics of pravastatin.