Valproic Acid with Olanzapine Interaction Details
Brand Names Associated with Valproic Acid
- Depakene®
- Depakote®
- Depakote® ER
- Depakote® Sprinkle
- Divalproex sodium
- Valproate sodium
- Valproic Acid
Brand Names Associated with Olanzapine
- Olanzapine
- Symbyax® (as a combination product containing Fluoxetine, Olanzapine )
- Zyprexa®
- Zyprexa® Zydis
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 03, 2023
Interaction Effect
Decreased olanzapine plasma concentrations
Interaction Summary
Concomitant use of olanzapine 5 to 20 mg/day and valproate up to 2000 mg/day for 4 weeks resulted in significantly decreased olanzapine plasma concentrations in subjects with bipolar or schizoaffective disorder (n=18). In this study, increased valproate concentrations and smoking were associated with lower olanzapine concentrations. Older age was associated with higher olanzapine concentrations. Concurrent use with valproate was well-tolerated, with mild adverse effects that resolved over time. Induction, competitive inhibition, and protein binding displacement are all postulated mechanisms for this interaction. Because of the decreased olanzapine concentrations with concomitant use, monitoring olanzapine levels may be necessary.
Severity
Moderate
Onset
Delayed
Evidence
Established
How To Manage Interaction
Concomitant use of olanzapine and valproate has resulted in decreased olanzapine plasma concentrations. Therefore, monitoring olanzapine concentrations may be warranted.
Mechanism Of Interaction
Unknown
Literature Reports
A) Concomitant use of olanzapine and valproate resulted in decreased olanzapine plasma concentrations in subjects with bipolar or schizoaffective disorder (n=18). A consistent olanzapine dose of 5 to 20 mg/day was given for 1 month prior to valproate initiation. Valproate was adjusted based on clinical response and maintained at a stable dose of 600 to 2000 mg/day. After 2 and 4 weeks of coadministration, a mean baseline olanzapine concentration of 32.9 +/- 9.7 nanogram/mL (ng/mL; 105.3 +/- 31 nanomol/L) had decreased to 27.4 +/- 9.8 ng/mL (87.7 +/- 31 nanomol/L) and 26.9 +/- 9.2 ng/mL (86.1 +/- 29.4 nanomol/L). In an analysis adjusted for age, smoking, valproate treatment duration, and individual variances, an increase in valproate concentrations was associated with a decrease in olanzapine concentrations that was dependent on the number of treatment weeks. With a 1 mcg/mL (7 mcmol/L) valproate concentration increase at 2 and 4 weeks, olanzapine concentrations decreased 0.37 ng/mL (1.18 nanomol/L) and 0.21 ng/mL (0.67 nanomol/L). Olanzapine concentrations were 5.9 ng/mL (18.9 nanomol/L) lower in smokers compared with nonsmokers. Age progression was associated with higher olanzapine concentrations. Sex did not affect olanzapine concentrations. Concurrent use of olanzapine and valproate was well-tolerated with only mild adverse effects .
Valproic Acid Overview
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Valproic acid is used alone or with other medications to treat certain types of seizures. Valproic acid is also used to treat mania (episodes of frenzied, abnormally excited mood) in people with bipolar disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). It is also used to prevent migraine headaches but not to relieve headaches that have already begun. Valproic acid is in a class of medications called anticonvulsants. It works by increasing the amount of a certain natural substance in the brain.
Olanzapine Overview
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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.
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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.