Trade Names


Like phenobarbital, to which it is closely related, primidone is used to control epileptic seizures.

Supplementation Possibly Helpful

Primidone can reduce folate levels perhaps by increasing the rate of breakdown of the vitamin. Over time, such a decrease can cause anemia.1–5 Taking folate supplements will correct this anemia.6 Anticonvulsant-induced folate deficiency might also cause birth defects. Women who plan to become pregnant while on primidone should be sure to take a supplement to prevent deficiency.7,8

Supplementation Possibly Helpful

Primidone appears to interfere with the normal absorption or metabolism of vitamin D.9,10 This in turn impairs calcium absorption, with many potential complications.11 To help avoid this problem, you should make sure that you get enough vitamin D.

Supplementation Possibly Helpful for Pregnant Women

Children born to women taking primidone while pregnant may be deficient in vitamin K.12,13 This might lead to bleeding disorders and facial bone abnormalities. Supplementing with vitamin K during pregnancy should help; however, physician supervision is recommended.

Supplementation Possibly Helpful, but Take at a Different Time of Day

Many antiseizure medications including primidone are believed to interfere with the absorption of biotin.14,15 For this reason, individuals taking primidone 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.

Theoretical Harmful Interaction

Because many anti-epilepsy drugs, including primidone, work by blocking glutamate stimulation in the brain, high dosages of glutamine might counteract the drugs' effects, and pose a risk of increased seizures.

Potentially Dangerous Interaction

Niacinamide (a form of vitamin B 3) might increase blood levels of primidone, possibly requiring reduction in drug dosage.16

Possible Harmful Interaction

Primidone 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.

It may be a good idea to wear a sunscreen or protective clothing during sun exposure if you take one of these herbs while using this anticonvulsant.

Possible Harmful Interaction

The herb ginkgo (Ginkgo biloba) has been used to treat Alzheimer's disease and ordinary age-related memory loss, among many other conditions.

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.17 This toxin has been associated with convulsions and death in laboratory animals.18,19,20

Fortunately, the detected amounts of this toxic substance are considered harmless.21 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.

Possible Harmful Interaction

The herb kava (Piper methysticum) has a sedative effect and is used for anxiety and insomnia.

Combining kava with anticonvulsants, which possess similar depressant effects, could result in "add-on" or excessive physical depression, sedation, and impairment.

Because of the potentially serious consequences, you should avoid combining these herbs with anticonvulsants or other drugs that also have sedative or depressant effects, such as primidone, unless advised by your physician.


1. Kishi T, Fujita N, Eguchi T, and Ueda K. Mechanism for reduction of serum folate by antiepileptic drugs during prolonged therapy. J Neurol Sci 145: 109–112, 1997.

2. McNamara J. Drugs effective in the therapy of the epilepsies. As cited in Goodman L and Gilman A. The pharmacological basis of therapeutics, 9th ed. Hardman J, et al., eds. New York: McGraw-Hill, 1996: 472.

3. Reynolds EH, et al. Anti-convulsant therapy, megaloblastic haematopoesis, and folic acid metabolism. Quart J Med 35: 521–537, 1966.

4. Ono H, Sakamoto A, Eguchi T, et al. Plasma total homocysteine concentrations in epileptic patients taking anticonvulsants. Metabolism 46: 959–962, 1997.

5. Reynolds EH. Mental effects of anticonvulsants, and folic acid metabolism. Brain 91: 197–214, 1968.

6. Berg MJ, Stumbo PJ, Chenard CA, et al. Folic acid improves phenytoin pharmacokinetics. J Am Diet Assoc 95: 352–356, 1995.

7. Lewis DP, Van Dyke DC, Stumbo PJ, et al. Drug and environmental factors associated with adverse pregnancy outcomes. Part I: Antiepileptic drugs, contraceptives, smoking, and folate. Ann Pharmacother 32: 802–817, 1998.

8. Biale Y and Lewenthal H. Effect of folic acid supplementation on congenital malformations due to anticonvulsive drugs. Eur J Obstet Gynecol Reprod Biol 18: 211–216, 1984.

9. Holmes T and Kummerow F. The relationship of adequate and excessive intake of vitamin D to health and disease. J Am Coll Nutr 2: 173–199, 1983.

10. Shils M, et al., eds. Modern nutrition in health and disease. 9th ed. Baltimore: Williams and Wilkins, 1999: 1634.

11. Wahl TO, Gobrity AH, and Lukert BP. Long-term anticonvulsant therapy and intestinal calcium absorption. Clin Pharmacol Ther 30: 506–512, 1981.

12. Cornelissen M, Steegers-Theunissen R, Kolle L, et al. Increased incidence of neonatal vitamin K deficiency resulting from maternal anticonvulsant therapy. Am J Obstet Gynecol 168: 923–928, 1993.

13. Cornelissen M, Steegers-Theunissen R, Kolle L, et al. Supplementation of vitamin K in pregnant women receiving anticonvulsant therapy prevents neonatal vitamin K deficiency. Am J Obstet Gynecol 168: 884–888, 1993.

14. Krause K-H, Bonjour J-P, Berlit P, et al. Biotin status of epileptics. Ann N Y Acad Sci 447: 297–313, 1985.

15. Said HM, Redha R, and Nylander W. Biotin transport in the human intestine: inhibition by anticonvulsant drugs. Am J Clin Nutr 49: 127–131, 1989.

16. Bourgeois BFD, Dodson WE, and Ferrendelli JA. Interactions between primidone, carbamazepine, and nicotinamide. Neurology 32: 1122–1126, 1982.

17. Arenz A, Klein M, Fiehe K, et al. Occurrence of neurotoxic 4'-O-methylpyridoxine in Ginkgo biloba leaves, ginkgo medications and Japanese ginkgo food. Planta Med 62: 548–551, 1996.

18. Mizuno N, Kawakami K, and Morita E. Competitive inhibition between 4'-substituted pyridoxine analogues and pyridoxal for pyridoxal kinase from mouse brain. J Nutr Sci Vitaminol (Tokyo) 26: 535–543, 1980.

19. Wada K, Ishigaki S, Ueda K, et al. An antivitamin B 6, 4'-methoxypyridoxine, from the seed of Ginkgo biloba L. Chem Pharm Bull (Tokyo) 33: 3555–3557, 1985.

20. Yagi M, Wada K, Sakata M, et al. Studies on the constituents of edible and medicinal plants. IV. Determination of 4-O-methylpyridoxine in serum of the patient with gin-nan food poisoning [in Japanese; English abstract]. Yakugaku Zasshi 113: 596–599, 1993.

21. Arenz A, Klein M, Fiehe K, et al. Occurrence of neurotoxic 4'-O-methylpyridoxine in Ginkgo biloba leaves, ginkgo medications and Japanese ginkgo food. Planta Med 62: 548–551, 1996.

Last reviewed December 2015 by EBSCO CAM Review Board

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