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.
Cyclosporine: Preliminary data from a XENICAL and cyclosporine drug interaction study indicate a
reduction in cyclosporine plasma levels when XENICAL was coadministered with cyclosporine.
Digoxin: 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.
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
Warfarin: 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.