Olanzapine drug interactions

List of drug interactions
General CYP1A2 or glucuronyl transferase enzymes Cimetidine and Antacids Carbamazepine Ethanol Fluoxetine Fluvoxamine Warfarin Lithium Valproate

General
The risks of using olanzapine in combination with other drugs have not been extensively evaluated in systematic studies. Given the primary CNS effects of olanzapine, caution should be used when olanzapine is taken in combination with other centrally acting drugs and alcohol. Because of its potential for inducing hypotension, olanzapine may enhance the effects of certain antihypertensive agents. Olanzapine may antagonize the effects of levodopa and dopamine agonists.Return to top

CYP1A2 or glucuronyl transferase enzymes
Agents that induce CYP1A2 or glucuronyl transferase enzymes, such as omeprazole and rifampin, may cause an increase in olanzapine clearance. Inhibitors of CYP1A2 could potentially inhibit olanzapine clearance. Although olanzapine is metabolized by multiple enzyme systems, induction or inhibition of a single enzyme may appreciably alter olanzapine clearance. Therefore, a dosage increase (for induction) or a dosage decrease (for inhibition) may need to be considered with specific drugs. Return to top

Charcoal
The administration of activated charcoal (1 g) reduced the Cmax and AUC of olanzapine by about 60%. As peak olanzapine levels are not typically obtained until about 6 hours after dosing, charcoal may be a useful treatment for olanzapine overdose. Return to top

Cimetidine and Antacids
Single doses of cimetidine (800 mg) or aluminum- and magnesium-containing antacids did not affect the oral bioavailability of olanzapine. Return to top

Carbamazepine
Carbamazepine therapy (200 mg bid) causes an approximately 50% increase in the clearance of olanzapine. This increase is likely due to the fact that carbamazepine is a potent inducer of CYP1A2 activity. Higher daily doses of carbamazepine may cause an even greater increase in olanzapine clearance. Return to top

Ethanol
Ethanol (45 mg/70 kg single dose) did not have an effect on olanzapine pharmacokinetics. Return to top

Fluoxetine
Fluoxetine (60 mg single dose or 60 mg daily for 8 days) causes a small (mean 16%) increase in the maximum concentration of olanzapine and a small (mean 16%) decrease in olanzapine clearance. The magnitude of the impact of this factor is small in comparison to the overall variability between individuals, and therefore dose modification is not routinely recommended. Return to top

Fluvoxamine
Fluvoxamine, a CYP1A2 inhibitor, decreases the clearance of olanzapine. This results in a mean increase in olanzapine Cmax following 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. Return to top

Warfarin
Warfarin (20 mg single dose) did not affect olanzapine pharmacokinetics. Effect of Olanzapine on Other Drugs — In vitro studies utilizing human liver microsomes suggest 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. Return to top

Lithium
Multiple doses of olanzapine (10 mg for 8 days) did not influence the kinetics of lithium. Therefore, concomitant olanzapine administration does not require dosage adjustment of lithium. Return to top

Valproate
Studies in vitro using human liver microsomes determined that olanzapine has little potential to inhibit the major metabolic pathway, glucuronidation, of valproate. Further, valproate has little effect on the metabolism of olanzapine in vitro. In vivo administration of olanzapine (10 mg daily for 2 weeks) did not affect the steady state plasma concentrations of valproate. Therefore, concomitant olanzapine administration does not require dosage adjustment of valproate. Return to top