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Zonisamide

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Zonisamide

Drug Information

Anticonvulsants are a family of drugs that depress abnormal nerve activity in the brain, thereby blocking seizures. Barbiturates and benzodiazepines are commonly used to prevent and treat seizure disorders , as well as other conditions. Though some people are maintained on a single drug, most take two or more anticonvulsant medications to prevent seizures. Consequently, many studies report interactions that occur in individuals taking several anticonvulsants.

Common brand names:

Zonegran

Summary of Interactions with Vitamins, Herbs, & Foods

Types of interactions: Beneficial Adverse Check

Replenish Depleted Nutrients

  • Biotin

    Several controlled studies have shown that long-term anticonvulsant treatment decreases blood levels of biotin.1 , 2 , 3 , 4 In children, a deficiency of biotin can lead to withdrawn behavior and a delay in mental development. Adults with low biotin levels might experience a loss of appetite, feelings of discomfort or uneasiness, mental depression , or hallucinations. To avoid side effects, individuals taking anticonvulsants should supplement with biotin either alone or as part of a multivitamin .

  • L-Carnitine

    Several controlled and preliminary studies showed that multiple drug therapy for seizures results in dramatic reductions in blood carnitine levels.5 , 6 , 7 Further controlled research is needed to determine whether children taking anticonvulsants might benefit by supplementing with L-carnitine, since current studies yield conflicting results. For example, one controlled study indicated that children taking valproic acid and carbamazepine received no benefit from supplementing with L-carnitine.8 However, another small study revealed that children taking valproic acid experienced less fatigue and excessive sleepiness following L-carnitine supplementation.9 Despite the lack of well-controlled studies, individuals who are taking anticonvulsants and experiencing side effects might benefit from supplementing with L-carnitine.

  • Vitamin A

    Anticonvulsant drugs can occasionally cause birth defects when taken by pregnant women, and their toxicity might be related to low blood levels of vitamin A. One controlled study showed that taking multiple anticonvulsant drugs results in dramatic changes in the way the body utilizes vitamin A.10 Further controlled research is needed to determine whether supplemental vitamin A might prevent birth defects in children born to women on multiple anticonvulsant therapy. Other research suggests that ingestion of large amounts of vitamin A may promote the development of birth defects, although the studies are conflicting.

  • Vitamin B12

    Anemia is an uncommon side effect experienced by people taking anticonvulsant drugs. Though many researches believe that low blood levels of folic acid are involved, the effects might be caused by a vitamin B12 deficiency. Deficiencies of folic acid and vitamin B12 can lead to nerve and mental problems. One study revealed that individuals on long-term anticonvulsant therapy, despite having no laboratory signs of anemia, had dramatically lower levels of vitamin B12 in their cerebrospinal fluid (the fluid that bathes the brain) when compared with people who were not taking seizure medications. Improvement in mental status and nerve function was observed in a majority of symptomatic individuals after taking 30 mcg of vitamin B12 daily for a few days.11 Another study found that long-term anticonvulsant therapy had no effect on blood levels of vitamin B12.12 The results of these two studies indicate that people taking anticonvulsant drugs might experience side effects of vitamin B12 deficiency, and that the deficiency is not easily detected by the usual blood tests. Therefore, individuals taking anticonvulsant drugs for several months or years might prevent nerve and mental problems by supplementing with vitamin B12.

  • Vitamin B6

    One controlled study revealed that taking anticonvulsant drugs dramatically reduces blood levels of vitamin B6.13 A nutritional deficiency of vitamin B6 can lead to an increase in homocysteine blood levels, which has been associated with atherosclerosis . Vitamin B6 deficiency is also associated with symptoms such as dizziness, fatigue, mental depression , and seizures. On the other hand, supplementation with large amounts of vitamin B6 (80–200 mg per day) has been reported to reduce blood levels of some anticonvulsant drugs, which could theoretically trigger seizures. People taking multiple anticonvulsant drugs should discuss with their doctor whether supplementing with vitamin B6 is advisable.

  • Vitamin D

    Though research results vary, long-term use of anticonvulsant drugs appears to interfere with vitamin D activity,14 which might lead to softening of bones ( osteomalacia ). One study showed that blood levels of vitamin D in males taking anticonvulsants were lower than those found in men who were not taking seizure medication.15 In a controlled study, bone strength improved in children taking anticonvulsant drugs who were supplemented with the activated form of vitamin D and 500 mg per day of calcium for nine months.16 Some research suggests that differences in exposure to sunlight—which normally increases blood levels of vitamin D—might explain why some studies have failed to find a beneficial effect of vitamin D supplementation. In one controlled study, blood vitamin D levels in children taking anticonvulsants were dramatically lower in winter months than in summer months.17 Another study of 450 people in Florida taking anticonvulsants found that few had drug-induced bone disease.18 Consequently, people taking anticonvulsant drugs who do not receive adequate sunlight should supplement with 400 IU of vitamin D each day to help prevent osteomalacia.

  • Vitamin E

    Two studies showed that individuals taking phenytoin and phenobarbital had lower blood vitamin E levels than those who received no treatment for seizures.19 , 20 Though the consequences of lower blood levels of vitamin E are unknown, people taking multiple anticonvulsant drugs might supplement with 100 to 200 IU of vitamin E daily to help prevent a deficiency.

Reduce Side Effects

  • Vitamin D

    Though research results vary, long-term use of anticonvulsant drugs appears to interfere with vitamin D activity,21 which might lead to softening of bones ( osteomalacia ). One study showed that blood levels of vitamin D in males taking anticonvulsants were lower than those found in men who were not taking seizure medication.22 In a controlled study, bone strength improved in children taking anticonvulsant drugs who were supplemented with the activated form of vitamin D and 500 mg per day of calcium for nine months.23 Some research suggests that differences in exposure to sunlight—which normally increases blood levels of vitamin D—might explain why some studies have failed to find a beneficial effect of vitamin D supplementation. In one controlled study, blood vitamin D levels in children taking anticonvulsants were dramatically lower in winter months than in summer months.24 Another study of 450 people in Florida taking anticonvulsants found that few had drug-induced bone disease.25 Consequently, people taking anticonvulsant drugs who do not receive adequate sunlight should supplement with 400 IU of vitamin D each day to help prevent osteomalacia.

Support Medicine

  • none

Reduces Effectiveness

  • none

Potential Negative Interaction

  • none

Explanation Required 

  • Vitamin K

    Some studies have shown that babies born to women taking anticonvulsant drugs have low blood levels of vitamin K, which might cause bleeding in the infant.26 Though some researchers recommend vitamin K supplementation prior to delivery,27 , 28 not all agree that supplementation for women taking anticonvulsant drugs is necessary.29 Until more information is available, pregnant women or women who might become pregnant while taking anticonvulsant drugs should discuss vitamin K supplementation with their healthcare practitioner.

The Drug-Nutrient Interactions table may not include every possible interaction. Taking medicines with meals, on an empty stomach, or with alcohol may influence their effects. For details, refer to the manufacturers’ package information as these are not covered in this table. If you take medications, always discuss the potential risks and benefits of adding a new supplement with your doctor or pharmacist.

References

1. Mock DM, Dyken ME. Biotin catabolism is accelerated in adults receiving long-term therapy with anticonvulsants. Neurology 1997;49:1444–7.

2. Mock DM, Mock NI, Nelson RP, Lombard KA. Disturbances in biotin metabolism in children undergoing long-term anticonvulsant therapy. J Pediatr Gastroenterol Nutr 1998;26:245–50.

3. Krause KH, Bonjour JP, Berlit P, Kochen W. Biotin status of epileptics. Ann NY Acad Sci 1985;447:297–313.

4. Krause KH, Bonjour JP, Berlit P, et al. Effect of long-term treatment with antiepileptic drugs on the vitamin status. Drug Nutr Interact 1988;5:317–43.

5. Hiraoka A, Arato T, Tominaga I. Reduction in blood free carnitine levels in association with changes in sodium valproate (VPA) disposition in epileptic patients treated with VPA and other anti-epileptic drugs. Biol Pharm Bull 1997;20:91–3.

6. Morita J, Yuge K, Yoshino M. Hypocarnitinemia in the handicapped individuals who receive a polypharmacy of antiepileptic drugs. Neuropediatrics 1986;17:203–5.

7. Hug G, McGraw CA, Bates SR, Landrigan EA. Reduction of serum carnitine concentrations during anticonvulsant therapy with phenobarbitol, valproic acid, phenytoin and carbamazepine in children. J Pedr 1991;119:799–802.

8. Freeman JM, Vining EP, Cost S, Singhi P. Does carnitine administration improve the symptoms attributed to anticonvulsant medications?: A double-blinded, crossover study. Pediatrics 1994;93:893–5.

9. Van Wouwe JP. Carnitine deficiency during valproic acid treatment. Int J Vitam Nutr Res 1995;65:211–4.

10. Nau H, Tzimas G, Mondry M, et al. Antiepileptic drugs alter endogenous retinoid concentrations: a possible mechanism of teratogensis of anticonvulsant therapy. Life Sci 1995;57:53–60.

11. Frenkel EP, McCall MS, Sheehan RG. Cerebrospinal fluid folate, and vitamin B12 in anticonvulsant-induced megaloblastosis. J Lab Clin Med 1973;81:105–15.

12. Schwaninger M, Ringleb P, Winter R, et al. Elevated plasma concentrations of homocysteine in antiepileptic drug treatment. Epilepsia 1999;40:345–50.

13. Schwaninger M, Ringleb P, Winter R, et al. Elevated plasma concentrations of homocysteine in antiepileptic drug treatment. Epilepsia 1999;40:345–50.

14. Nettekoven S, Strohle A, Trunz B, et al. Effects of antiepileptic drug therapy on vitamin D status and biochemical markers of bone turnover in children with epilepsy.Eur J Pediatr 2008;167:1369–77.

15. Telci A, Cakatay U, Kurt BB, et al. Changes in bone turnover and deoxypyridinoline levels in epileptic patients Clin Chem Lab Med 2000 38:47–50.

16. Jekovec-Vrhovsek M, Kocijancic A, Prezelj J. Effect of vitamin D and calcium on bone mineral density in children with CP and epilepsy in full-time care. Dev Med Child Neurol 2000;42:403–5.

17. Riancho JA, Del Arco C, Arteaga R, et al. Influence of solar irradiation on vitamin D levels in children on anticonvulsant drugs. Acta Neurol Scand 1989;79:296–9.

18. Williams C, Netzloff M, Folkerts L, et al. Vitamin D metabolism and anticonvulsant therapy: effect of sunshine on incidence of osteomalacia. South Med J 1984;77:834.

19. Higashi A, Tamari H, Ikeda T, et al. Serum vitamin E concentration in patients with severe multiple handicaps treated with anticonvulsants. Pediatr Pharmacol (New York) 1980;1:129–34.

20. Higashi A, Ikeda T, Matsukura M, Matsuda I. Serum zinc and vitamin E concentrations in handicapped children treated with anticonvulsants. Dev Pharmacol Ther 1982;5:109–13.

21. Nettekoven S, Strohle A, Trunz B, et al. Effects of antiepileptic drug therapy on vitamin D status and biochemical markers of bone turnover in children with epilepsy.Eur J Pediatr 2008;167:1369–77.

22. Telci A, Cakatay U, Kurt BB, et al. Changes in bone turnover and deoxypyridinoline levels in epileptic patients Clin Chem Lab Med 2000 38:47–50.

23. Jekovec-Vrhovsek M, Kocijancic A, Prezelj J. Effect of vitamin D and calcium on bone mineral density in children with CP and epilepsy in full-time care. Dev Med Child Neurol 2000;42:403–5.

24. Riancho JA, Del Arco C, Arteaga R, et al. Influence of solar irradiation on vitamin D levels in children on anticonvulsant drugs. Acta Neurol Scand 1989;79:296–9.

25. Williams C, Netzloff M, Folkerts L, et al. Vitamin D metabolism and anticonvulsant therapy: effect of sunshine on incidence of osteomalacia. South Med J 1984;77:834.

26. Cornelissen M, Steegers-Theunissen R, Kollee L, et al. Increased incidence of neonatal vitamin K deficiency resulting from maternal anticonvulsant therapy. Am J Obstet Gynecol 1993;168:923–8.

27. Nulman I, Laslo D, Koren G. Treatment of epilepsy in pregnancy. Drugs 1999;57:535–44 [review].

28. Cornelissen M, Steegers-Theunissen R, Kollee L, et al. Supplementation of vitamin K in pregnant women receiving anticonvulsant therapy prevents neonatal vitamin K deficiency. Am J Obstet Gynecol 1993;168:884–8.

29. Hey E. Effect of maternal anticonvulsant treatment on neonatal blood coagulation. Arch Dis Child Fetal Neonatal Ed 1999;81:F208–10.

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