Valproic Acid with Clomipramine Interaction Details
Brand Names Associated with Valproic Acid
- Depakene®
- Depakote®
- Depakote® ER
- Depakote® Sprinkle
- Divalproex sodium
- Valproate sodium
- Valproic Acid
Brand Names Associated with Clomipramine
- Anafranil®
- Clomipramine
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 08, 2023
Interaction Effect
An increased risk of clomiPRAMINE toxicity (agitation, confusion, hallucinations, urinary retention, tachycardia, seizures, coma)
Interaction Summary
Comedication with clomiPRAMINE and valproic acid may increase serum levels of clomiPRAMINE resulting in increased side effects. ClomiPRAMINE toxicity developed in a patient twelve days after valproic acid therapy was initiated. Metabolism of clomiPRAMINE is mediated through N-demethylation, hydroxylation, and glucuronidation, and valproic acid appears to inhibit the enzymes responsible for this mode of metabolism.
Severity
Moderate
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Monitor serum clomiPRAMINE levels to avoid overdosing as a result of elevated concentrations of clomiPRAMINE when comedicating with valproic acid. The clomiPRAMINE dose may need to be reduced when valproic acid is added to therapy.
Mechanism Of Interaction
Inhibition of cytochrome P450 2C-mediated metabolism of clomiPRAMINE
Literature Reports
A) A case report describes a 46-year-old female with personality disorder whose serum clomiPRAMINE concentrations became elevated after she began concomitant therapy with valproic acid. Antidepressant therapy with clomiPRAMINE and lorazepam was initiated while being hospitalized for treatment of her psychiatric disorder. These two agents were chosen to reduce the frequency of panic attacks and to improve symptoms of suicidal and self-destructive behavior. A target dose of clomiPRAMINE 150 mg/day resulted in serum clomiPRAMINE levels in the normal range. Lorazepam was initiated at a dose of 2 mg/day After two weeks of therapy valproate was initiated at 1000 mg/day because emotional instability and self-destructive behavior remained unimproved. After five days of therapy the serum levels of clomiPRAMINE and desmethylclomipramine increased to 447 ng/mL and 85 ng/mL, respectively. Valproate serum concentration was 63.2 mcg/mL. The valproate dose was subsequently adjusted to 1400 mg/day. Seven days after the increase in valproate dose, clomiPRAMINE and desmethylclomipramine serum concentrations were 479 ng/mL and 269 ng/mL respectively. Conversely, the valproate serum level was 55 mcg/mL. The patient noted a feeling of numbness and exaggerated sleep disturbances. After the clomiPRAMINE dose was reduced to 75 mg/day, these symptoms resolved. The author concludes that the increase in serum clomiPRAMINE concentrations was primarily due to comedication with valproate .
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.
Clomipramine Overview
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Clomipramine is used to treat people with obsessive-compulsive disorder (a condition that causes repeated unwanted thoughts and the need to perform certain behaviors over and over). Clomipramine is in a group of medications called tricyclic antidepressants. It works by increasing the amount of serotonin, a natural substance in the brain that is needed to maintain mental balance.
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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.