AnticonvulsantMedicationsHydantoinDerivatives

Table of Contents > Depletions > Anticonvulsant Medications, Hydantoin Derivatives

Anticonvulsant Medications

Hydantoin Derivatives

Phenytoin

(Dilantin®)

Depletions

Calcium

Osteoporosis (bone loss) is the primary disease associated with long-term calcium deficiency; it may be associated with bone pain and spinal deformity. Depleted levels can also cause muscle cramps, irregular heartbeat, and depression.

Vitamin B1 (Thiamine)

Symptoms of depleted levels of thiamine include weakness, fatigue, anorexia, constipation, memory loss, confusion, and depression. Deficiency may lead to beriberi, a condition characterized by inflammation of nerves, heart irregularities, and fluid retention.

Vitamin B9 (Folic Acid)

Low levels of folic acid have been linked to anemia, heart disease, and birth defects.

Vitamin H (Biotin)

Low levels of biotin are associated with changes in skin color, inflammation of the skin, hair loss, muscle pain, anemia, loss of appetite, depression, insomnia, and elevated levels of cholesterol.

Vitamin D

Vitamin D deficiency leads to abnormal bone formation (rickets) in children and softening of the bones (osteomalacia) in adults. Vitamin D deficiency interferes with calcium absorption, leading to deficiency of that nutrient with all of the associated symptoms (such as increased risk of fractures, osteoporosis (bone loss), and muscle weakness). Because this nutrient is fat-soluble, prolonged periods of deficiency are required to produce these symptoms.

Editorial Note

The selected depletions information presented here identifies some of the nutrients that may be depleted by certain medications. The signs and symptoms associated with nutrient deficiency may also indicate conditions other than nutrient deficiency. If you are experiencing any of the signs or symptoms mentioned, it does not necessarily mean that you are nutrient deficient. Nutrient depletion depends upon a number of factors, including your medical history, diet, and lifestyle as well as the length of time you have been taking the medication. Please consult your healthcare provider; he or she can best assess and address your individual healthcare needs, and determine if you are at risk for nutrient depletions from these medications as well as others not listed here.

Supporting Research

Ames BN. Micronutrient deficiencies: A major cause of DNA damage. Ann NY Acad Sci. 2000;889:87-106.

Bell RD, Pak CY, Zerwekh J, et al. Effect of phenytoin on bone and vitamin D metabolism. Ann Neurol. 1979;5(4):374-378.

Berg MJ, Fincham RW, Ebert BE, et al. Phenytoin pharmacokinetics: before and after folic acid administration. Epilepsia. 1992;33(4):712-720.

Berg MJ, Stumbo PJ, Chenard CA, et al. Folic acid improves phenytoin pharmacokinetics. J Am Diet Assoc. 1995;95(3):352-256.

Botez MI, et al. Thiamine and folate treatment of chronic epileptic patients: a controlled study with the Wechsler IQ scale. Epilepsy Res. 1993;16(2):157-163.

Botez MI, Joyal C, Maag U, et al. Cerebrospinal fluid and blood thiamine concentrations in phenytoin-treated epileptics. Can J Neurol Sci. 1982;9(1):37-39.

Cashman K, Flynn A. Optimal nutrition: calcium, magnesium and phosphorus. Proc Nutr Soc. 1999;58:477-487.

Covington T, ed. Nonprescription Drug Therapy Guiding Patient Self-Care. St Louis, MO: Facts and Comparisons; 1999:467-545.

Dastur D, Dave U. Effect of prolonged anticonvulsant medication in epileptic patients: serum lipids, vitamins B6, B12 and folic acid, proteins and fine structure of liver. Epilepsia. 1987;28:147-159.

Foss MC, Meneghelli UG, Verissimo JM. The effect of the anticonvulsants phenobarbital and diphenylhydantoin on intestinal absorption of calcium. Acta Physiol Lat Am. 1979;29(4-5):223-228.

Gascon-Barre M, Villeneuve JP, Lebrun LH. Effect of increasing doses of phenytoin on the plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations. J Am Coll Nutr. 1984;3(1):45-50.

Gough H, Goggin T, Bissessar A, et al. A comparative study of the relative influence of different anticonvulsant drugs, UV exposure and diet on vitamin D and calcium metabolism in out-patients with epilepsy. Q J Med. 1986;59(230):569-577.

Holick MF, Krane SM, Potts JT. Calcium, phosphorus, and bone metabolism: calcium-regulating hormones. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison's Principles of Internal Medicine. 14^th ed. New York: McGraw-Hill Companies Health Professional Division; 1998:2221-2222.

Krause KH, Berlit P, Bonjour JP, et al. Impaired biotin status in anticonvulsant therapy. Ann Neurol. 1982;12(5):485-486.

Krause KH, Bonjour JP, Berlit P, et al. Biotin status of epileptics. Ann NY Acad Sci. 1985;447:297-313.

Lewis DP, Van Dyke DC, Willhite LA, et al. Phenytoin-folic acid interaction. Ann Pharmacother. 1995;29(7-8):726-735.

Mock DM, Mock NI, Nelson RP, et al. Disturbances in biotin metabolism in children undergoing long-term anticonvulsant therapy. J Pediatr Gastroenterol Nutr. 1998;26(3):245-250.

National Research Council. Recommended Dietary Allowances. 10^th ed. Washington, DC: National Academy Press; 1989.

Potts JT. Diseases of the parathyroid gland and other hyper- and hypocalcemic disorders. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison's Principles of Internal Medicine. 14^th ed. New York: McGraw-Hill Companies Health Professional Division; 1998:2241.

Rao DS. Perspective on assessment of vitamin D nutrition. J Clin Densitom. 1999:2(4):457-464.

Reunanen MI, Sotaniemi EA, Hakkarainen HK. Serum calcium balance during early phase of diphenylhydantoin therapy. Int J Clin Pharmacol Biopharm. 1976;14(1):15-19.

Schwaninger M, Ringleb P, Winter R, et al. Elevated concentrations of homocysteine in antiepileptic drug treatment. Epilepsia. 1999;40(3):345-350.

Shafer RB, Nuttall FQ. Calcium and folic acid absorption in patients taking anticonvulsant drugs. J Clin Endocrinol Metab. 1975;41(6):1125-1129.

Somerman MJ, Rifkin Br, Pointon-Miska S, et al. Effect of phenytoin on rat bone resorption in vitro. Arch Oral Biol. 1986;31(4):267-268.

Valimaki MJ, Tiihonen M, Laitinen K, et al. Bone mineral density measured by dual-energy x-ray absorptiometry and novel markers of bone formation and resorption in patients on antiepileptic drugs. Bone Miner Res. 1994;9(5):631-637.

Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999;69:842-856.

Review Date: October 2000

Reviewed By: All depletions monographs have been reviewed by a team of experts including Derrick M. DeSilva, Jr., MD, Raritan Bay Medical Center, Perth Amboy, NJ; Jacqueline A. Hart, MD, Department of Internal Medicine, Newton-Wellesley Hospital, Harvard University and Senior Medical Editor, A.D.A.M., Inc., Boston, MA; John Hinze, PharmD, NMD, Woodbine, IA; Ruth Marlin, MD, Medical Director and Director of Medical Education, Preventive Medicine Research Institute, Sausalito, CA; Brian T Sanderoff, PD, BS in Pharmacy, Clinical Assistant Professor, University of Maryland School of Pharmacy; President, Your Prescription for Health, Owings Mills, MD; Leonard Wisneski, MD, FACP, George Washington University, Rockville, MD; Ira Zunin, MD, MPH, MBA, President and Chairman, Hawaii State Consortium for Integrative Medicine, Honolulu, HI.

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