Valproic Acid with Trihexyphenidyl Interaction Details
Brand Names Associated with Valproic Acid
- Depakene®
- Depakote®
- Depakote® ER
- Depakote® Sprinkle
- Divalproex sodium
- Valproate sodium
- Valproic Acid
Brand Names Associated with Trihexyphenidyl
- Artane®
- Tremin®
- Trihexyphenidyl
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 08, 2023
Interaction Effect
Decreased plasma levels of valproate sodium and loss of seizure control
Interaction Summary
Use caution when using trihexyphenidyl together with valproate sodium. Concomitant use of trihexyphenidyl and valproate sodium may result in decreased plasma levels of valproate sodium. A 3-year-old girl with extrapyramidal cerebral palsy developed increased seizure frequency and decreased valproate sodium levels after 3 months of trihexyphenidyl treatment. Consider monitoring valproate sodium levels and the patient for seizure control if concomitant therapy is necessary. An adjustment in the dose of valproate sodium or discontinuation of trihexyphenidyl may be necessary.
Severity
Moderate
Onset
Delayed
Evidence
Theoretical
How To Manage Interaction
Use caution when prescribing trihexyphenidyl to patients who take valproate sodium. Concomitant use of trihexyphenidyl and valproate sodium may result in decreased plasma levels of valproate sodium. Consider monitoring valproate sodium levels and the patient for seizure control if concomitant therapy is necessary. An adjustment in the dose of valproate sodium or discontinuation of trihexyphenidyl may be necessary.
Mechanism Of Interaction
Unknown
Literature Reports
A) A 3-year-old girl with extrapyramidal cerebral palsy developed increased seizure frequency and decreased valproate sodium levels after 3 months of trihexyphenidyl treatment. The patient was receiving valproate sodium at a dose of 30 mg/kg/day via percutaneous endoscopic gastrostomy (PEG) since the presentation of epilepsy at 8 months of age with therapeutic valproate sodium levels (mean concentration, 70 to 80 mcg/mL); levetiracetam was also given concurrently (40 mg/kg/day). Seizures were well controlled within 6 months of valproate sodium/levetiracetam therapy with a reduction of seizures from daily/weekly to 3 to 4 per month. Trihexyphenidyl was initiated at 33 months of age to reduce generalized dystonia at an initial dose of 0.5 mg once daily, titrated up to 1 mg twice daily (0.16 mg/kg/day). Increased seizure frequency (occurring daily) was noted after 3 months of trihexyphenidyl therapy along with a subtherapeutic valproate sodium serum level of 40 mcg/mL. An increase in the valproate sodium dose to 45 mg/kg/day failed to normalize valproate sodium levels (remained at 48 mcg/mL) and improve seizure control. Valproate sodium levels increased to a therapeutic level of 74 mcg/mL with improvement in seizure control when trihexyphenidyl therapy was discontinued. The authors concluded that trihexyphenidyl decreased valproate sodium absorption, possibly due to its anticholinergic action of reducing gastrointestinal motility .
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.
Trihexyphenidyl Overview
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Trihexyphenidyl is used along with other medications to treat the symptoms of Parkinson's disease (PD; a disorder of the nervous system that causes difficulties with movement, muscle control, and balance) and to control extrapyramidal symptoms (tremor, slurred speech) caused by certain medications. Trihexyphenidyl is in a class of medications called antimuscarinics. It works by relaxing muscles and nerve impulses that control the function of muscles.
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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.