In a multiple-dose study in 30 normal-weight subjects, coadministration of XENICAL and 40 grams of alcohol (eg, approximately 3 glasses of wine) did not result in alteration of alcohol pharmacokinetics, orlistat pharmacodynamics (fecal fat excretion), or systemic exposure to orlistat.
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).
In 12 normal-weight subjects receiving XENICAL 120 mg three times a day for 6 days, XENICAL did not alter the pharmacokinetics of a single dose of digoxin.
Fat-soluble Vitamin Supplements and Analogues
A pharmacokinetic interaction study showed a 30% reduction in beta-carotene supplement absorption when concomitantly administered with XENICAL. XENICAL inhibited absorption of a vitamin E acetate supplement by approximately 60%. The effect of orlistat on the absorption of supplemental vitamin D, vitamin A, and nutritionally-derived vitamin K is not known at this time.
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.
Hypothyroidism has been reported in patients treated concomitantly with orlistat and levothyroxine postmarketing (see ADVERSE REACTIONS: Other Clinical Studies or Postmarketing Surveillance). Patients treated concomitantly with orlistat and levothyroxine should be monitored for changes in thyroid function. Administer levothyroxine and orlistat at least 4 hours apart.
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).
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.
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.
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.
In 12 normal-weight subjects, administration of XENICAL 120 mg three times a day for 16 days did not result in any change in either warfarin pharmacokinetics (both R- and S-enantiomers) or pharmacodynamics (prothrombin time and serum Factor VII). Although undercarboxylated osteocalcin, a marker of vitamin K nutritional status, was unaltered with XENICAL administration, vitamin K levels tended to decline in subjects taking XENICAL. Therefore, as vitamin K absorption may be decreased with XENICAL, patients on chronic stable doses of warfarin who are prescribed XENICAL should be monitored closely for changes in coagulation parameters.