Valproic acid (drug interactions)
Valproic acid is a widely utilized anticonvulsant medication, prescribed for seizure disorders and other conditions, including migraine prevention and bipolar disorder management. While effective, it has significant drug interactions that require careful consideration. Co-administration with certain herbs and supplements, such as biotin, carnitine, vitamin D, and folate, can alter the absorption and effectiveness of valproic acid, potentially leading to adverse effects. For instance, valproic acid may reduce the body's levels of folate, which is critical for preventing certain congenital disabilities. Additionally, interactions with medications like St. John's wort and dong quai may increase the risk of skin sensitivity.
Moreover, combining valproic acid with supplements like glutamine or herbs like ginkgo can pose risks, including heightened seizure susceptibility. Patients should be particularly cautious with combinations that could lead to liver damage, as valproic acid itself carries a risk of serious hepatotoxicity. Due to these potential interactions and the associated health risks, it is crucial for individuals to consult with healthcare providers before starting or stopping valproic acid or any other related supplements or medications.
Valproic acid (drug interactions)
DEFINITION: A commonly used anticonvulsant treatment.
INTERACTIONS: Biotin, carnitine, dong quai, folate, ginkgo, glutamine, melatonin, St. John’s wort, vitamin A, vitamin D, white willow, kava, folic acid, vitamin K, many other herbs and supplements
TRADE NAMES: Depakene, Depakote, Stavzor
DRUGS IN THIS FAMILY: Depakene syrup, depakote, depakote sprinkle, divalproex sodium, sodium valproate
Overview
Valproic acid is a substance commonly used as an anticonvulsant to treat various seizure disorders. As a medication, it may also be known as divalproex sodium or valproate sodium and appears under various brand names. Other uses include the prevention of migraine headaches and the treatment of manic episodes associated with bipolar disorder. It may be taken in various tablet, capsule, or syrup forms.
Using valproic acid can cause dangerous and potentially fatal liver damage. This risk is higher for those under two years old (especially those taking multiple medications for seizures), with certain genetic disorders such as urea cycle disorder and Alpers-Huttenlocher syndrome, or with liver disease. Serious, life-threatening pancreas damage is also possible. As with all medications, patients should not begin or stop taking valproic acid without first consulting their doctor.
Valproic acid is known to interact with many other substances. These interactions can be positive or negative for patients and should be carefully considered by anyone taking or considering taking valproic acid. Some of the key drug interactions are described below.
Carnitine
Effect: Supplementation Possibly Helpful
Carnitine is an amino acid used for heart conditions, Alzheimer’s disease, and intermittent claudication. Intermittent claudication is a possible complication of atherosclerosis, in which impaired blood circulation causes severe pain in calf muscles while walking or exercising.
Long-term therapy with anticonvulsant agents, particularly valproic acid, is associated with low levels of carnitine. However, it is unclear whether the anticonvulsants cause the carnitine deficiency or whether it occurs for other reasons. It has been hypothesized that low carnitine levels may contribute to valproic acid’s damaging effects on the liver. The risk of this liver damage increases in children younger than twenty-four months, and carnitine supplementation does seem to be protective. However, in one double-blind crossover study, carnitine supplementation produced no real improvement in “well-being” as assessed by parents of children receiving either valproic acid or carbamazepine. L-carnitine supplementation may be advisable in certain cases, such as in infants and young children (especially those younger than two years) who have neurologic disorders and are receiving valproic acid and multiple anticonvulsants.
Vitamin D
Effect: Supplementation Possibly Helpful
Valproic acid slows down the liver’s conversion of vitamin D into the active form of the vitamin that the body can use. This effect might reduce calcium absorption since the body needs active vitamin D to absorb calcium properly. Therefore, taking vitamin D supplements at the US Adequate Intake (AI) dosage might be advisable.
Folate
Effect: Supplementation Possibly Helpful
Folate (also known as folic acid) is a B vitamin that plays an important role in many vital aspects of health, including preventing neural tube congenital disabilities and possibly reducing the risk of heart disease. Because inadequate intake of folate is widespread, if one takes any medication that depletes or impairs folate even slightly, one may need supplementation. Valproic acid appears to decrease the body’s absorption of folate, and other antiseizure drugs can also reduce folate levels in the body. The low serum folate caused by anticonvulsants can raise homocysteine levels, a condition believed to increase the risk of heart disease.
Adequate folate intake is also necessary to prevent neural tube congenital disabilities, such as spina bifida and anencephaly. Because anticonvulsant drugs deplete folate, babies born to women taking anticonvulsants are at increased risk for such congenital disabilities. Anticonvulsants may also play a more direct role in the development of congenital disabilities.
However, the case for taking extra folate during anticonvulsant therapy is not as simple as it might seem. It is possible that folate supplementation might itself impair the effectiveness of anticonvulsant drugs, and physician supervision is necessary.
Melatonin
Effect: Supplementation Possibly Helpful
One double-blind study in children found that using melatonin improved general quality of life in children on valproic acid. The most obvious way melatonin might help would involve improvements in sleep, as melatonin is a widely used treatment for insomnia. Another rather theoretical study by the same author suggests it might help in more subtle ways involving the body’s biochemistry.
Biotin
Effect: Supplementation Possibly Helpful, but Take at a Different Time of Day
Many antiseizure medications, including valproic acid, are believed to interfere with the absorption of biotin. For this reason, persons taking valproic acid may benefit from extra biotin. Biotin should be taken two to three hours apart from antiseizure medication. One should stay within the recommended daily intake because too much biotin might interfere with the effectiveness of the medication.
Vitamin A
Effect: Possible Increased Risk of Birth Defects
Both valproic acid and vitamin A can increase the risk of congenital disabilities. The effect might be additive, indicating that pregnant women should avoid such combination treatment.
Glutamine
Effect: Theoretical Harmful Interaction
Because valproic acid works (at least in part) by blocking glutamate pathways in the brain, high dosages of glutamine might overwhelm the drug and increase the risk of seizures.
White Willow
Effect: Possible Negative Interaction
The herb white willow contains substances very similar to aspirin. On this basis, combining white willow with valproic acid might not be advisable.
Ginkgo
Effect: Possible Harmful Interaction
The herb ginkgo is widely used for improving memory and mental function. Seizures also have been reported with the use of ginkgo leaf extract in people with previously well-controlled epilepsy; in one case, the seizures were fatal. One possible explanation is the contamination of ginkgo leaf products with ginkgo seeds. It has also been suggested that ginkgo might interfere with the effectiveness of some antiseizure medications, including phenytoin. Finally, it has been noted that the drug tacrine (also used to improve memory) has been associated with seizures, and ginkgo may affect the brain in ways similar to tacrine.
Dong Quai, St. John’s Wort
Effect: Possible Harmful Interaction
Valproic acid has been reported to cause increased sensitivity to the sun, amplifying the risk of sunburn or skin rash. Because St. John’s wort and dong quai (female ginseng) may also cause this problem, taking them during treatment with this drug might add to this risk.
Other Interactions
There are several other notable interactions between valproic acid and herbs and supplements. Like St. John's wort, kava may inhibit the breakdown of valproic acid, leading to potential situations of toxicity. Saw palmetto, valerian root, and passionflower may also affect the way the body metabolizes valproic acid. Folic acid and vitamin K may decrease the absorption of valproic acid. When combined with valproic acid, kava, black cohosh, and comfrey may cause liver damage. Garlic and ginger may increase the risk of bleeding when taken with valproic acid.
Bibliography
De Vivo, D. C., et al. "L-carnitine Supplementation in Childhood Epilepsy: Current Perspectives." Epilepsia, vol. 39, 1998, pp. 1216-1225.
Granger, A. S. "Ginkgo biloba Precipitating Epileptic Seizures." Age and Ageing, vol. 30, 2001, pp. 523-525.
Gupta, M., S. Aneja, and K. Kohli. "Add-on Melatonin Improves Quality of Life in Epileptic Children on Valproate Monotherapy." Epilepsy and Behavior, vol. 5, 2004, pp. 316-321.
Kupiec, T., and V. Raj. "Fatal Seizures Due to Potential Herb-Drug Interactions with Ginkgo biloba." Journal of Analytical Toxicology, vol. 29, 2006, pp. 755-758.
Lewis, D. P., et al. "Drug and Environmental Factors Associated with Adverse Pregnancy Outcomes: Part 1–Antiepileptic Drugs, Contraceptives, Smoking, and Folate." Annals of Pharmacotherapy, vol. 32, 1998, pp. 802-817.
Multum, Cerner. "Valproic Acid." Drugs.com, 3 Mar. 2020, www.drugs.com/mtm/valproic-acid.html. Accessed 30 June 2020.
"Valproic Acid." MedlinePlus, 10 Aug. 2023, medlineplus.gov/druginfo/meds/a682412.html. Accessed 15 Sept. 2024.
"Valproic Acid: Medicine Used for Bipolar Disorder, Epilepsy and Migraine." NHS, 23 Feb. 2024, www.nhs.uk/medicines/valproic-acid. Accessed 15 Sept. 2024.
"Valproic Acid (Oral Route) Before Using." Mayo Clinic, 1 Sept. 2024, www.mayoclinic.org/drugs-supplements/valproic-acid-oral-route/before-using/drg-20072931. Accessed 15 Sept. 2024.