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Drug Interactions between cholecalciferol / folic acid and phensuximide

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

folic acid phensuximide

Applies to: cholecalciferol / folic acid and phensuximide

MONITOR: Anticonvulsants including, but not limited to, carbamazepine, lamotrigine, phenobarbital, phenytoin, primidone, and valproic acid have been shown to impair folate absorption and increase the metabolism of circulating folate. The precise mechanism of interaction has not been established.

MONITOR: Coadministration with folate therapy may reduce the anticonvulsant effects of phenytoin, phenobarbital, primidone, and succinimides. The exact mechanism of interaction is unknown. Available data pertain primarily to phenytoin. Some investigators suggest that folic acid may serve as a cofactor in the metabolism of phenytoin, thus clearance is increased in the presence of folic acid. In one study, administration of folic acid for 14 days reduced the serum levels of phenytoin in normal subjects without significantly altering the bound fraction. Urinary excretion of phenytoin and its metabolite, meta-hydroxydiphenylhydantoin, was increased. In another study, three of four folate-deficient male patients receiving phenytoin monotherapy for epilepsy demonstrated a 7.5% to 47.6% decrease in total phenytoin plasma concentration following the addition of folic acid 1 mg/day for 180 or 300 days. Ratios of urinary metabolites to parent drug increased in these patients, suggesting an increase in phenytoin oxidative metabolism. The interaction is further supported by case reports describing subtherapeutic phenytoin levels and/or breakthrough seizures following the addition of folate therapy, including one case involving folinic acid (leucovorin). Limited data are available for phenobarbital and primidone. In one study, the addition of folic acid 15 mg/day increased the frequency and severity of seizures in 13 of 26 folate-deficient epileptic patients receiving two or more anticonvulsant drugs, including phenytoin, phenobarbital, and primidone. Nine of them required discontinuation of folic acid therapy. No data are available for other hydantoins.

MANAGEMENT: Caution is advised when folate therapy is coadministered with anticonvulsants. Close monitoring for clinical and laboratory evidence of diminished therapeutic response to both treatments is recommended. Patients should be advised to notify their physician if they experience loss of seizure control.

References

  1. Furlanut M, Benetello P, Avogaro A, Dainese R "Effects of folic acid on phenytoin kinetics in healthy subjects." Clin Pharmacol Ther 24 (1978): 294-7
  2. Carl GF, Smith ML "Phenytoin-folate interactions: differing effects of the sodium salt and the free acid of phenytoin." Epilepsia 33 (1992): 372-5
  3. Berg MJ, Fincham RW, Ebert BE, Schottelius DD "Phenytoin pharmacokinetics: before and after folic acid administration." Epilepsia 33 (1992): 712-20
  4. MacCosbe PE, Toomey K "Interaction of phenytoin and folic acid." Clin Pharm 2 (1983): 362-9
  5. Robenberg IH "Drugs and folic acid absorption." Gastroenterology 63 (1972): 353-7
  6. Ch'ien LT, Krumdieck CL, Scott CW Jr, Butterworth CE Jr "Harmful effect of megadoses of vitamins: electroencephalogram abnormalities and seizures induced by intravenous folate in drug- treated epileptics." Am J Clin Nutr 28 (1975): 51-8
  7. Katz M "Potential danger of self-medication with folic acid." N Engl J Med 289 (1973): 1095
  8. Yuen GJ "Interaction of phenytoin and folic acid: an alternative explanation." Clin Pharm 3 (1984): 116,119
  9. Berg MJ, Rivey MP, Vern BA, Fischer LJ, Schottelius DD "Phenytoin and folic acid: individualized drug-drug interaction." Ther Drug Monit 5 (1983): 395-9
  10. Berg MJ, Fischer LJ, Rivey MP, Vern BA, Lantz RK, Schottelius DD "Phenytoin and folic acid interaction: a preliminary report." Ther Drug Monit 5 (1983): 389-94
  11. Berg MJ, Stumbo PJ, Chenard CA, Fincham RW, Schneider PJ, Schottelius D "Folic acid improves phenytoin pharmacokinetics." J Am Diet Assoc 95 (1995): 352-6
  12. Lewis DP, Van Dyke DC, Willhite LA, Stumbo PJ, Berg MJ "Phenytoin-folic acid interaction." Ann Pharmacother 29 (1995): 726-35
  13. "Product Information. Wellcovorin (leucovorin)." Glaxo Wellcome, Research Triangle Park, NC.
  14. Seligmann H, Potasman I, Weller B, Schwartz M, Prokocimer M "Phenytoin-folic acid interaction: A lesson to be learned." Clin Neuropharmacol 22 (1999): 268-72
  15. Veldhorst-Janssen NM, Boersma HH, de Krom MC, van Rijswijk RE "Oral tegafur/folinic acid chemotherapy decreases phenytoin efficacy." Br J Cancer 90 (2004): 745
  16. Steinweg DL, Bentley ML "Seizures following reduction in phenytoin level after orally administered folic acid." Neurology 64 (2005): 1982
  17. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  18. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  19. Cerner Multum, Inc. "Australian Product Information." O 0
  20. "Product Information. Levoleucovorin (levoleucovorin)." Spectrum Chemical (2008):
  21. Agencia Española de Medicamentos y Productos Sanitarios Healthcare "Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html" (2008):
  22. "Product Information. L-Methylfolate Calcium (l-methylfolate)." Virtus Pharmaceuticals LLC (2018):
View all 22 references

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Drug and food interactions

Moderate

folic acid food

Applies to: cholecalciferol / folic acid

MONITOR: Ethanol may increase folic acid elimination and folic acid absorption is decreased in chronic alcoholics. Excessive alcohol consumption may lead to folate deficiency.

MANAGEMENT: Monitoring of patient response to folic acid supplementation if they also consume alcohol regularly may be recommended.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. Agencia Española de Medicamentos y Productos Sanitarios Healthcare "Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html" (2008):
  4. Cerner Multum, Inc "ANVISA Bulário Eletrônico." O 0 (2015):
  5. "Product Information. Folic Acid (folic acid)." Method Pharmaceuticals, LLC (2017):
View all 5 references

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Moderate

phensuximide food

Applies to: phensuximide

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc. (1990):
  3. "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
  4. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
View all 4 references

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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