Source: Drug labeling information submitted to the Food and Drug Administration (FDA), updated by the National Library of Medicine (NLM).
The risks of using olanzapine in combination with other drugs have not been extensively evaluated in systematic studies.
Potential for Other Drugs to Affect Olanzapine
- Diazepam — The co-administration of diazepam with olanzapine potentiated the orthostatic hypotension observed with olanzapine.
- Cimetidine and Antacids — Single doses of cimetidine (800 mg) or aluminum- and magnesium-containing antacids did not affect the oral bioavailability of olanzapine.
Inducers of CYP1A2
- 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.
- Alcohol — Ethanol (45 mg/70 kg single dose) did not have an effect on olanzapine pharmacokinetics. The co-administration of alcohol (i.e., ethanol) with olanzapine potentiated the orthostatic hypotension observed with olanzapine .
Inhibitors of CYP1A2
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.
Inhibitors of CYP2D6
- Fluoxetine: Fluoxetine (60 mg single dose or 60 mg daily dose 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. When using ZYPREXA and fluoxetine in combination, also refer to the Drug Interactions section of the package insert for Symbyax.
- Warfarin — Warfarin (20 mg single dose) did not affect olanzapine pharmacokinetics.
Inducers of CYP1A2 or Glucuronyl Transferase
- Omeprazole and rifampin may cause an increase in olanzapine clearance.
Charcoal — The administration of activated charcoal (1 g) reduced the Cmax and AUC of oral 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.
Potential for Olanzapine to Affect Other Drugs
CNS Acting Drugs — Given the primary CNS effects of olanzapine, caution should be used when olanzapine is taken in combination with other centrally acting drugs and alcohol.
Antihypertensive Agents — Olanzapine, because of its potential for inducing hypotension, may enhance the effects of certain antihypertensive agents.
Levodopa and Dopamine Agonists — Olanzapine may antagonize the effects of levodopa and dopamine agonists.
Lorazepam (IM) — Administration of intramuscular lorazepam (2 mg) 1 hour after intramuscular olanzapine for injection (5 mg) did not significantly affect the pharmacokinetics of olanzapine, unconjugated lorazepam, or total lorazepam. However, this co-administration of intramuscular lorazepam and intramuscular olanzapine for injection added to the somnolence observed with either drug alone.
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 .
Valproate — 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 .
Effect of Olanzapine on Drug Metabolizing Enzymes — 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.
Imipramine — Single doses of olanzapine did not affect the pharmacokinetics of imipramine or its active metabolite desipramine.
Warfarin — Single doses of olanzapine did not affect the pharmacokinetics of warfarin.
Diazepam — Olanzapine did not influence the pharmacokinetics of diazepam or its active metabolite N-desmethyldiazepam. However, diazepam co-administered with olanzapine increased the orthostatic hypotension observed with either drug given alone .
Alcohol — Multiple doses of olanzapine did not influence the kinetics of ethanol.
Biperiden — Multiple doses of olanzapine did not influence the kinetics of biperiden.
Theophylline — Multiple doses of olanzapine did not affect the pharmacokinetics of theophylline or its metabolites.
Related Olanzapine Information
- Olanzapine Indications: FDA-Approved Uses
- Mechanism of Action and Pharmacodynamics of Olanzapine
- Olanzapine Pharmacokinetics
- Olanzapine Adverse Effects
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