Phenobarbital (drug interactions)

• INTERACTIONS: Biotin, dong quai, folate, ginkgo biloba, glutamine, hops, kava, passionflower, St. John’s wort, valerian, vitamin D, vitamin K, various prescription medications
• TRADE NAMES: Bellatal, Solfoton
• RELATED DRUGS: Mebaral, mephobarbital, methylphenobarbital

DEFINITION: Medications used to control seizures.

Folate

Effect: Supplementation Possibly Helpful

Phenobarbital can reduce folate levels by increasing the vitamin breakdown rate. Over time, such a decrease can cause anemia. Taking folate supplements can correct this anemia. Anticonvulsant-induced folate deficiency might also cause congenital anomalies. Women who plan to become pregnant while taking phenobarbital should be sure to take a supplement to prevent folate deficiencies.

Vitamin D

Effect: Supplementation Possibly Helpful

Phenobarbital appears to interfere with the normal absorption or metabolism of vitamin D. In turn, this can impair calcium absorption. Getting enough vitamin D (and calcium) should help prevent problems from developing.

Vitamin K

Effect: Supplementation Helpful for Pregnant Women

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

Biotin

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

Many antiseizure medications, including phenobarbital, are believed to interfere with the absorption of biotin. For this reason, persons taking phenobarbital may benefit from extra biotin. Biotin should be taken two to three hours apart from antiseizure medication. One should not exceed the recommended daily intake, because too much biotin might interfere with the effectiveness of the medication.

Dong Quai, St. John’s Wort

Effect: Possible Harmful Interaction

Phenobarbital 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. One should use sunscreen or wear protective clothing during sun exposure if taking one of these herbs while using this anticonvulsant.

Ginkgo biloba

Effect: Possible Harmful Interaction

The herb ginkgo (Ginkgo biloba) has been used to treat Alzheimer’s disease and age-related memory loss, among many other conditions. The possible harmful interaction involves potential contaminants in ginkgo, not ginkgo itself.

One study found that a natural nerve toxin in the seeds of Ginkgo biloba made its way into standardized ginkgo extracts prepared from the leaves. This toxin has been associated with convulsions and death in laboratory animals.

The detected amounts of this toxic substance are considered harmless. However, given the lack of satisfactory standardization of herbal formulations in the United States, some batches of the product might contain higher contents of the toxin, depending on the season of harvest. In light of these findings, taking a ginkgo product that happens to contain significant levels of the nerve toxin might theoretically prevent an anticonvulsant from working as well as expected.

Hops, Kava, Passionflower, Valerian

Effect: 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, one should avoid combining these herbs with anticonvulsants or other drugs that also have sedative or depressant effects, such as phenobarbital, unless advised by a physician.

Glutamine

Effect: Theoretical Harmful Interaction

Because phenobarbital 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.

Other Interactions

Several other serious interactions exist between phenobarbital and other medications. Taking phenobarbital with central nervous system depressants, such as alcohol or benzodiazepines, can increase the sedative effects of both medications to dangerous levels, leading to serious respiratory depression. Some medications, including the cancer drug apalutamide, the anticoagulant apixaban, and the antipsychotic lurasidone, can interact with phenobarbital and alter drug levels in the body. As phenobarbital can reduce the effectiveness of oral contraceptives, women who do not wish to become pregnant should use a backup method of birth control when taking this medication. Phenobarbital can also affect the metabolism of antifungals such as fluconazole. Finally, phenobarbital can decrease the effectiveness of certain antibiotics, anticoagulants, and corticosteroids.

Bibliography

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Lewis, D. P., et al. "Drug and Environmental Factors Associated with Adverse Pregnancy Outcomes: Part I–Antiepileptic Drugs, Contraceptives, Smoking, and Folate." Annals of Pharmacotherapy, vol. 32, 1998, pp. 802-17, doi:10.1345/aph.17297. Accessed 11 Dec. 2025.

"Phenobarbital." MedlinePlus, 15 May 2020, medlineplus.gov/druginfo/meds/a682007.html. Accessed 11 Dec. 2025.

"Phenobarbital: Uses, Interactions & Side Effects." Cleveland Clinic, my.clevelandclinic.org/health/drugs/18614-phenobarbital-tablets. Accessed 11 Dec. 2025.