Drug Interactions:
Valproic Acid

Trade Names
  • Depakene

Valproic acid is a commonly used anticonvulsant treatment.

Carnitine

Supplementation Possibly Helpful

Carnitine is an amino acid that has been used for heart conditions, Alzheimer's disease, and intermittent claudication (a possible complication of atherosclerosis in which impaired blood circulation causes severe pain in calf muscles during walking or exercising).

Long-term therapy with anticonvulsant agents, particularly valproic acid, is associated with low levels of carnitine.¹ However, it isn't clear 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.^2,3 The risk of this liver damage increases in children younger than 24 months,⁴ and carnitine supplementation does seem to be protective.⁵ 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.⁶

L-carnitine supplementation may be advisable in certain cases, such as in infants and young children (especially those younger than 2 years) who have neurologic disorders and are receiving valproic acid and multiple anticonvulsants.⁷

Vitamin D

Supplementation Possibly Helpful

Valproic acid slows down the liver's conversion of vitamin D into the active form of the vitamin that can be used by the body.⁸ This effect might lead to reduced calcium absorption, since the body needs active vitamin D to absorb calcium properly. Therefore, it might be advisable to take vitamin D supplements at the U.S. Adequate Intake (AI) dosage.

Folate

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 birth defects and possibly reducing the risk of heart disease. Because inadequate intake of folate is widespread, if you are taking any medication that depletes or impairs folate even slightly, you may need supplementation.

Valproic acid appears to decrease the body's absorption of folate,⁹ and other antiseizure drugs can also reduce levels of folate in the body.^10–14

The low serum folate caused by anticonvulsants can raise homocysteine levels, a condition believed to increase the risk of heart disease.¹⁵

Adequate folate intake is also necessary to prevent neural tube birth defects such as spina bifida and anencephaly. Because anticonvulsant drugs deplete folate, babies born to women taking anticonvulsants are at increased risk for such birth defects. Anticonvulsants may also play a more direct role in the development of birth defects.¹⁶

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.

Biotin

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.^17,18 For this reason, individuals taking valproic acid may benefit from extra biotin. Biotin should be taken 2 to 3 hours apart from your antiseizure medication. Do not exceed the recommended daily intake, because it is possible that too much biotin might interfere with the effectiveness of the medication.

Vitamin A

Possible Increased Risk of Birth Defects

Both valproic acid and vitamin A can increase the risk of birth defects. The effect might be additive, indicating that pregnant women should avoid such combination treatment.¹⁹

Glutamine

Theoretical Harmful Interaction

Because valproic acid works (at least in part) by blocking glutamate pathways in the brain, high dosages of glutamine might possibly overwhelm the drug and increase the risk of seizures.

White Willow

Possible Negative Interaction

The herb white willow contains substances very similar to aspirin. On this basis, it might not be advisable to combine white willow with valproic acid.

Ginkgo

Possible Harmful Interaction

This interaction involves potential contaminants in ginkgo, not ginkgo itself.

A recent study found that a natural nerve toxin present in the seeds of Ginkgo biloba made its way into standardized ginkgo extracts prepared from the leaves.²⁰ This toxin has been associated with convulsions and death in laboratory animals.^21,22,23

Fortunately, the detected amounts of this toxic substance are considered harmless.²⁴ However, given the lack of satisfactory standardization of herbal formulations in the United States, it is possible that some batches of product might contain higher contents of the toxin depending on the season of harvest.

In light of these findings, taking a ginkgo product that happened to contain significant levels of the nerve toxin might theoretically prevent an anticonvulsant from working as well as expected.

Dong Quai, St. John's Wort

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 may also cause this problem, taking them during treatment with this drug might add to this risk.

Last reviewed March 2002 by Medical Review Board

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