Olandus/Olandus ODT Drug Interactions

Olandus 5/Olandus 10: Given the primary CNS effects of Olanzapine, caution should be used when Olanzapine tablets are taken in combination with other centrally acting drugs and alcohol. Because of its potential for inducing hypotension, Olanzapine tablets may enhance the effects of certain antihypertensive agents. Olanzapine may antagonize the effects of levodopa and dopamine agonists. The metabolism of Olanzapine is mediated to some extent by the cytochrome P450 isozyme CYP1A2. Concomitant administration of drugs which inhibit or act as a substrate to this isozyme may affect plasma concentrations of Olanzapine. The clearance of Olanzapine is increased by tobacco smoking.
Olandus ODT 5/Olandus ODT 10: 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 coadministration of alcohol (i.e., ethanol) with olanzapine potentiated the orthostatic hypotension observed with olanzapine.
Inhibitors of 1A2: Fluvoxamine: Fluvoxamine, a CYP1A2 inhibitor, decreases the clearance of olanzapine. This results in a mean increase in olanzapine C_max 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.
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 olanzapine and fluoxetine in combination.
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 C_max 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 coadministration 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.
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.
Olandus ODT 15: Given the primary central nervous system effects of Olanzapine, caution should be used when it is taken in combination with other centrally acting drugs and alcohol. As it exhibits in vitro dopamine antagonism, Olanzapine may antagonise the effects of direct and indirect dopamine agonists.
Caution should be exercised when Olanzapine is used concomitantly with medicines known to cause electrolyte imbalance or to increase QT interval.
Potential for other medicines to affect Olanzapine: Single-doses of antacids (containing aluminium and magnesium) or cimetidine do not affect the oral bioavailability of Olanzapine. The concomitant administration of activated charcoal reduces the oral bioavailability of Olanzapine by 50 to 60%.
Fluoxetine (60 mg single dose or 60 mg daily for 8 days) caused a 16% increase in the maximum plasma concentration of Olanzapine and a 16% decrease in Olanzapine clearance. The magnitude of this is small in comparison to the overall variability between individuals and therefore dose modification is not routinely recommended.
The metabolism of Olanzapine may be induced by concomitant smoking (the clearance of olanzapine is 33% lower and the terminal elimination half-life is 21% longer in non-smokers compared to smokers) or carbamazepine therapy (clearance is increased 44% and the terminal elimination half-life is reduced by 20% when administered with carbamazepine). Smoking and carbamazepine therapy induce P450-1A2 activity. The pharmacokinetics of theophylline, which is metabolised by P450-1A2, is not altered by olanzapine.
Fluvoxamine, a CYP1A2 inhibitor, decreases the clearance of Olanzapine. This results in a mean increase in Olanzapine C_max following fluvoxamine of 54% in female non-smokers 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 or any other P450-1A2 inhibitor, such as ciprofloxacin.
Potential for Olanzapine to affect other medicines: In clinical trials with single doses of olanzapine, no inhibition of the metabolism of imipramine/ desipramine (P450-2D6, P450- 3A or P450-1A2), warfarin (P450-2C19), theophylline (P450-1A2) or diazepam (P450-3A4 and P450-2C19) was evident. Olanzapine showed no interaction when coadministered with lithium or biperiden. The in vitro ability of Olanzapine to inhibit metabolism by five principle cytochromes has been examined. These studies found inhibitory constants for 3A4 (491 mcM), 2C9 (751 mcM), 1A2 (36 mcM), 2C19 (920 mcM), 2D6 (89 mcM) that compared to Olanzapine plasma concentrations of approximately 0.2 mcM, would mean maximum inhibition of these P450 systems by Olanzapine would be less than 0.7%. The clinical relevance of these findings is unknown.
Steady state concentrations of Olanzapine had no effect on the pharmacokinetics of ethanol (45 mg/70 kg). However, additive pharmacological effects such as increased sedation may occur when ethanol is ingested together with Olanzapine.
Studies in vitro using human liver microsomes showed that Olanzapine has little potential to inhibit the major metabolic pathway of valproate, which is glucuronidation. Further, valproate was found to have little effect on the oxidative metabolism of Olanzapine in vitro. Daily concomitant in vivo administration of 10 mg Olanzapine for 2 weeks did not affect steady state plasma concentrations of valproate. Therefore, concomitant Olanzapine administration does not require dosage adjustment of valproate.