Valproic Acid with Ritonavir Interaction Details

Brand Names Associated with Valproic Acid

Brand Names Associated with Ritonavir

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 08, 2023

Interaction Effect

Reduced valproic acid exposure

Interaction Summary

Concomitant administration of valproate with ritonavir may increase the clearance of valproate. Because of these changes in valproate clearance, monitoring of valproate and ritonavir concentrations should be increased whenever enzyme inducing drugs such as ritonavir are introduced or withdrawn. Coadministering ritonavir with valproic acid may decrease the plasma concentration of valproic acid. A case report suggests the mechanism may be due to ritonavir induction of VPA metabolism via glucuronidation . If needed, consider increasing the dosage of valproate when administered concomitantly with ritonavir and monitoring of valproic acid plasma concentrations is recommended .

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Concomitant administration of valproate with ritonavir may increase the clearance of valproate. Because of these changes in valproate clearance, monitoring of valproate and ritonavir concentrations should be increased whenever enzyme inducing drugs such as ritonavir are introduced or withdrawn. If needed, consider increasing the dosage of valproate when administered concomitantly with ritonavir and monitoring of valproic acid plasma concentrations is recommended .

Mechanism Of Interaction

Ritonavir-induced metabolism of valproic acid

Literature Reports

A) A case report describes a 30-year-old man with bipolar disorder and HIV who became increasingly manic following the addition of lamivudine 150 mg/zidovudine 300 mg twice a day and lopinavir 133 mg/ritonavir 33 mg (3 capsules twice a day) to his drug regimen. The patient had been maintained on valproic acid (VPA) 250 mg 3 times a day, with a serum VPA concentration of 495 mcmol/L, when the antiretrovirals were prescribed during a hospital admission for major depression. Paroxetine 10 mg/day was simultaneously given for the depressive episode. The patient became hypomanic 4 days later, and the paroxetine was switched to sertraline 50 mg/day. Twenty-one days after the initiation of antiretroviral therapy, he became increasingly manic and was again admitted. He had continued all medications except sertraline during this time, including the same VPA dose. Serum VPA concentration 6 to 10 hours post-dose was subtherapeutic at 238 mcmol/L, a decrease of 48% from the previous documented concentration. Olanzapine and an increase in VPA to 1500 mg/day effectively managed the manic episode. The patient adhered to this new drug regimen, including the previously prescribed antiretrovirals, and 10 days later a 14-hour post-dose VPA level measured in the therapeutic range at 392 mcmol/L. Since the patient was not taking concomitant medications known to affect VPA metabolism, it was hypothesized that the decrease in VPA concentrations was due to ritonavir induction of VPA metabolism (via glucuronidation) .

Valproic Acid Overview

• 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.

Ritonavir Overview

• Ritonavir is used along with other medications to treat human immunodeficiency virus (HIV) infection. Ritonavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although ritonavir 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 lifestyle changes may decrease the risk of transmitting the HIV virus to other people.

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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:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.