Alcohol: Ethanol (45 mg/70 kg single dose) did not have an effect on olanzapine pharmacokinetics. The coadministration of alcohol (i.e., ethanol) with olanzapine potentiated the orthostatic hypotension observed with olanzapine.
Antihypertensive agents: Olanzapine, because of its potential for inducing hypotension, may enhance the effects of certain antihypertensive agents.
Carbamazepine: Causes an approximately 50% increase in olanzapine clearance; this increase is likely due to the fact that carbamazepine is a potent inducer of CYP1A2 activity.
Activated charcoal: The use of activated charcoal (1 g) reduced the Cmax and area under the plasma concentration time curve (AUC) of oral olanzapine by about 60%. As peak olanzapine levels are not typically obtained until about six hours after dosing, charcoal may be a useful treatment for olanzapine overdose.
Central nervous system (CNS) acting drugs: Caution should be used when olanzapine is taken in combination with other CNS acting drugs and alcohol.
Diazepam: The coadministration of diazepam with olanzapine potentiated the orthostatic hypotension observed with olanzapine.
Fluoxetine: Causes a small increase in the maximum concentration of olanzapine and a small decrease in olanzapine clearance. The magnitude of the impact of this factor is small in comparison to the overall variability between individuals, and thus dose modification is not routinely recommended.
Fluvoxamine: Decreases the clearance of olanzapine. This results in a mean increase in olanzapine Cmax after fluvoxamine of 54% in female nonsmokers and 77% in male smokers. The mean increase in olanzapine AUC is 52% and 108%, respectively. Lower doses of olanzapine should be considered in patients receiving concomitant treatment with fluvoxamine.
Levodopa and dopamine agonists: Olanzapine may antagonize the effects of levodopa and dopamine agonists.
Omeprazole and rifampicin: May cause an increase in olanzapine clearance.
Biperiden and theophylline: Did not influence the kinetics of biperiden and theophylline.
Cimetidine and antacids: Single doses of cimetidine or aluminum- and magnesium-containing antacids did not affect the oral bioavailability of olanzapine.
Drug metabolizing enzymes: In vitro studies utilizing human liver microsomes showed that olanzapine has little potential to inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A. Thus, olanzapine is unlikely to cause clinically important drug interactions mediated by these enzymes.
Imipramine/desipramine: Single doses of olanzapine did not affect the pharmacokinetics of imipramine or its active metabolite desipramine.
Lithium: Multiple doses of olanzapine did not influence the kinetics of lithium. Concomitant olanzapine use does not require dosage adjustment of lithium.
Valproate: Olanzapine did not affect the steady state plasma concentrations of valproate. Concomitant olanzapine use does not require dosage adjustment of valproate.
Warfarin: Did not affect olanzapine pharmacokinetics.