Xenical (Orlistat) Interactions
- Acitretin
- Amiodarone
Antidiabetic Agents
- Beta-Carotene
- Bexarotene
- Calcifediol
- Calcitriol
- Cyclosporine
- Doxercalciferol
- Ergocalciferol, Vitamin D2
- food
- Isotretinoin
- Phytonadione, Vitamin K1
- Pravastatin
- Propafenone
- Tretinoin, ATRA
- Vitamin A
- Vitamin E
- Warfarin
Xenical (Orlistat) Interactions
Due to orlistat’s mechanism of action, the potential exists for the malabsorption of drugs and dietary supplements. Orlistat inhibited the absorption of a vitamin E acetate supplement by 60%. Beta-carotene supplement absorption was reduced by 30% when administered concomitantly with orlistat. The effect on absorption of the vitamin supplements D and A and nutritionally-derived vitamin K from food is not known at this time. However, patients who received orlistat without vitamin supplementation during clinical studies developed significantly lower levels of vitamin A, vitamin D, vitamin E, and beta-carotene over a 1 to 2 year period when compared with the placebo group. Patients should be advised to take a multivitamin supplement once per day that contains fat soluble vitamins A, D, E, K and beta-carotene. Mega doses of vitamin E may antagonize the action of vitamin K and are not recommended. The manufacturer recommends that fat-soluble vitamin supplements (and analogues) be administered at least 2 hours before or after the administration of orlistat to limit effects on oral absorption.
Orlistat reduced the absorption of fat-soluble vitamins absorption during clinical trials. The bioavailability of orally administered retinoids (vitamin A analogs) or vitamin D analogs may also be decreased. In patients receiving orally-administered retinoids (e.g., oral acitretin, bexarotene, isotretinoin, and tretinoin, ATRA) or vitamin D analogs (e.g., calcifediol, calcitriol, dihydrotachysterol, doxercalciferol, and ergocalciferol, vitamin D2) along with orlistat, close monitoring is recommended. In addition, the manufacturer recommends that fat-soluble vitamin analogues be administered at least 2 hours before or after the administration of orlistat to limit effects on oral absorption.
Warfarin therapy can be affected by changes in dietary intake of vitamin K. 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. Orlistat doses of 120 mg three times per day administered orally for 16 days in 12 normal-weight subjects did not appear to alter undercarboxylated osteocalcin, a marker of vitamin K nutritional status. No changes in the pharmacokinetics or pharmacodynamics (PT and serum Factor VII) of warfarin were noted following a single 30 mg dose of Coumadin® in a placebo-controlled, randomized, third-party blind, two-way crossover study. However, vitamin K levels tended to decrease in patients taking orlistat. Since vitamin K1 (phytonadione, vitamin K1) absorption may be affected by orlistat, patients on chronic stable doses of warfarin should be monitored closely for changes in coagulation parameters when orlistat is prescribed; some experts recommend that the INR be monitored weekly during the first month of orlistat therapy.
Orlistat decreases the absorption of fat by inhibiting gastrointestinal lipases and as cyclosporine is dependent on lipid absorption, especially the Sandimmune® formulation, the absorption of cyclosporine is inhibited. The FDA has received reports of transplant recipients with subtherapeutic cyclosporine concentrations after the initiation of orlistat therapy. In a randomized, crossover study, all but 1 of 30 healthy adults had a decrease in steady state cyclosporine concentrations with concomitant orlistat administration. The average reduction in systemic cyclosporine exposure over 12 hours after dosing was 30%. Separating the doses of the 2 drugs by 3 hours did not alter the results. Caution is advised with the concomitant use of orlistat and cyclosporine therapy. More frequent cyclosporine concentration monitoring may be needed. To reduce the chance of a drug-drug interaction, cyclosporine should be administered at least 2 hours before or after orlistat in patients taking both drugs; although, as noted, separation of administration times may not always alter the course of the interaction.
The pharmacodynamic (blood glucose-lowering) or pharmacokinetic properties of a single dose of glyburide were not altered in 12 normal-weight subjects who received 80 mg of orlistat three times per day for 5 days. However, changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. A statistically significant number of obese, type 2 diabetics stabilized on sulfonylureas who received orlistat during a one-year double-blind, placebo-controlled study required a reduction in dose or discontinuation of drug therapy compared to the placebo group. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
Serum concentrations of pravastatin increased by approximately 30% when administered with orlistat 120 mg three times per day for 10 days in a parallel study of 24 normal-weight, mildly hypercholesterolemic subjects. Orlistat produced additive lipid-lowering effects when used concomitantly with pravastatin. However, another study failed to show any changes in pravastatin pharmacokinetics when coadministered with orlistat. Use caution and monitor patients carefully if using these drugs together.
Drug interaction studies indicate that orlistat dosed at 120 mg tid in normal-weight subjects had no effect on the pharmacokinetics and/or pharmacodynamics of ethanol or oral contraceptives, and single doses of digoxin, nifedipine (extended-release tablets), and phenytoin. In addition, ethanol did not alter the pharmacodynamics of orlistat.
Orlistat reduces the absorption of amiodarone (and active metabolite) by about 25% using parameters of Cmax and AUC, without clinically significant differences in half-life or time to peak concentration. Monitor the clinical response to amiodarone more closely if orlistat is initiated during chronic amiodarone therapy.
Orlistat may limit the fraction of propafenone available for absorption. In post-marketing reports, abrupt cessation of orlistat in patients stabilized on propafenone therapy has resulted in severe adverse events including convulsions, AV block and acute circulatory failure.
[ Last revised: 9/15/2005 2:16:00 PM ]
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