Olanzapine with Fosamprenavir Interaction Details
Brand Names Associated with Olanzapine
- Olanzapine
- Symbyax® (as a combination product containing Fluoxetine, Olanzapine )
- Zyprexa®
- Zyprexa® Zydis
Brand Names Associated with Fosamprenavir
- Fosamprenavir
- Lexiva®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 03, 2023
Interaction Effect
Reduced olanzapine exposure
Interaction Summary
Coadministration of olanzapine (CYP1A2 and UGT substrate) and fosamprenavir boosted with ritonavir (CYP1A2 and UGT inducer) may result in decreased olanzapine exposure. Increasing the olanzapine dose by 50% (from 10 to 15 mg/day) when coadministered with fosamprenavir/ritonavir compensated for the induction of CYP1A2- and UGT-mediated olanzapine metabolism and resulted in olanzapine exposure that was comparable to when olanzapine was administered alone in a randomized trial in 20 healthy volunteers .
Severity
Moderate
Onset
Unspecified
Evidence
Established
How To Manage Interaction
Coadministration of olanzapine (CYP1A2 and UGT substrate) and fosamprenavir boosted with ritonavir (CYP1A2 and UGT inducer) may result in decreased olanzapine exposure. Increasing the olanzapine dose by 50% (from 10 to 15 mg/day) when coadministered with fosamprenavir/ritonavir compensated for the induction of CYP1A2- and UGT-mediated olanzapine metabolism and resulted in olanzapine exposure that was comparable to when olanzapine was administered alone in a randomized trial in 20 healthy volunteers .
Mechanism Of Interaction
Induction of CYP1A2- and glucuronosyl transferase-mediated metabolism of olanzapine by fosamprenavir boosted with ritonavir
Literature Reports
A) Increasing the olanzapine dose by 50% when coadministered with fosamprenavir/ritonavir compensated for the induction of CYP1A2- and UGT-mediated olanzapine metabolism and resulted in olanzapine exposure that was comparable to when olanzapine was administered alone in a randomized, crossover trial in 20 healthy volunteers. Fosamprenavir 700 mg/ritonavir 100 mg twice daily (for 16 days) was given with a single olanzapine 15 mg (on day 13), and when compared with olanzapine 10 mg alone resulted in similar AUC (438.3 vs 436.9 mcg x hr/L), increased Cmax by 32% (17.4 vs 13.2 mcg/L), and decreased the t(1/2) by 32% (22.7 vs 33.4 hours). A higher Cmax is due to induction by fosamprenavir/ritonavir having no effect on the absorption phase and was not associated with a higher incidence of olanzapine-associated adverse events in the combination group .
B) An open-label study involving 14 healthy volunteers revealed a significant alteration in pharmacokinetic parameters and a reduction in systemic exposure of olanzapine when administered in the presence of ritonavir. Each volunteer received a single dose of olanzapine 10 mg. After a 14-day washout period, subjects received ritonavir 300 mg BID for 3 days, then 400 mg BID for 4 days, then 500 mg BID for 4 days. Significant reductions were seen in the mean olanzapine AUC by 53% (501 to 235 nanograms x hr/mL), t(1/2) by 50% (from 32 to 16 hours), and Cmax by 40% (from 15 to 9 nanograms/mL). The oral clearance of olanzapine increased by 115% (from 20 to 43 L/hr) .
Olanzapine Overview
-
Olanzapine is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions) in adults and teenagers 13 years of age and older. It is also used to treat bipolar disorder (manic depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods) in adults and teenagers 13 years of age and older. Olanzapine is in a class of medications called atypical antipsychotics. It works by changing the activity of certain natural substances in the brain.
Fosamprenavir Overview
-
Fosamprenavir is used along with other medications to treat human immunodeficiency virus (HIV) infection. Fosamprenavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although fosamprenavir does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex and making other life-style changes may decrease the risk of transmitting the HIV virus to other people.
Return To Our Drug Interaction Homepage
Feedback, Question Or Comment About This Information?
Ask Dr. Brian Staiger, PharmD, our medical editor, directly! He's always more than happy to assist.
Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.