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Phenytoin - Interactions and Warnings

Both phenytoin and isradipine have been shown to bind to calcium channels and to inhibit calcium entry into the cells. Binding of isradipine to the brain has been described in humans and animals, and calcium-channel blockers have been shown to cause potentiation of anticonvulsant action of phenytoin. Acute pharmacokinetic and pharmacodynamic interactions between phenytoin and isradipine were probably responsible for the lethargy, dysarthria, ataxia, and weakness the patient developed. The combination of phenytoin and calcium-channel blockers should be used with caution.
- Ann Pharmacother 2002 Sep;36(9):1399-402 -- Phenytoin/Isradipine interaction causing severe neurologic toxicity. -- Cachat F, Tufro A.

Vitamin K deficiency may occur in pregnant women and the child after birth for women taking hepatic enzyme-inducing anti-epileptic drugs.
- Curr Treat Options Neurol 2002 Jan;4(1):31-40 -- Epilepsy in Pregnant Women. -- Bruno MK, Harden CL.

Phenytoin is likely to interact with hormones.
- Epilepsia 1991;32 Suppl 6:S60-7 -- Effects of antiepileptic drugs on hormones. -- Ramsay RE, Slater JD.

Patients taking drugs with a narrow therapeutic index such as phenytoin should be discouraged from using herbal products. All drugs with a narrow therapeutic index may either have increased adverse effects or be less effective when used in conjunction with herbal products.
- Crit Care Nurse 2002 Apr;22(2):22-8, 30, 32; quiz 34-5 -- Herbal remedies: drug-herb interactions. -- Kuhn MA.

Long term use may have an adverse effect on the absorption of calcium.
- in Pharmacol Ther 1981 Oct;30(4):506-12 -- Long-term anticonvulsant therapy and intestinal calcium absorption. -- Wahl TO, Gobuty AH, Lukert BP.

Anticonvulsant therapy causes changes in calcium and bone metabolism and may lead to decreased bone mass with the risk of osteoporotic fractures. The two widely used antiepileptic drugs phenytoin and carbamazepine are recognized to have direct effects on bone cells. Beside alterations in calcium and vitamin D homeostasis leading to osteomalazia, direct effects of anticonvulsant drugs on bone cells may contribute to the damaging effects on the skeletal system.
- Exp Clin Endocrinol Diabetes 2000;108(1):37-43 -- Long-term anticonvulsant therapy leads to low bone mineral density--evidence for direct drug effects of phenytoin and carbamazepine on human osteoblast-like cells. -- Feldkamp J, Becker A, Witte OW, Scharff D, Scherbaum WA.

Phenytoin may cause a folic acid deficiency.
- Clin Neuropharmacol 1999 Sep-Oct;22(5):268-72 -- Phenytoin-folic acid interaction: a lesson to be learned. -- Seligmann H, Potasman I, Weller B, Schwartz M, Prokocimer M.

last update: November 2008

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