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Drug Interactions between ethotoin and Prenaissance Next

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

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Interactions between your drugs

Moderate

ethotoin multivitamin, prenatal

Applies to: ethotoin and Prenaissance Next (multivitamin, prenatal)

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

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Drug and food interactions

Moderate

ethotoin food

Applies to: ethotoin

ADJUST DOSING INTERVAL: Phenytoin bioavailability may decrease to subtherapeutic levels when the suspension is given concomitantly with enteral feedings. The mechanism may be related to phenytoin binding to substances in the enteral formula (e.g., calcium, protein) and/or binding to the tube lumen. Data have been conflicting and some studies have reported no changes in phenytoin levels, while others have reported significant reductions.

MONITOR: Acute consumption of alcohol may increase plasma phenytoin levels. Chronic consumption of alcohol may decrease plasma phenytoin levels. The mechanism of this interaction is related to induction of phenytoin metabolism by ethanol during chronic administration. Other hydantoin derivatives may be similarly affected by ethanol.

MANAGEMENT: Some experts have recommended interrupting the feeding for 2 hours before and after the phenytoin dose, giving the phenytoin suspension diluted in water, and flushing the tube with water after administration; however, this method may not entirely avoid the interaction and is not always clinically feasible. Patients should be closely monitored for clinical and laboratory evidence of altered phenytoin efficacy and levels upon initiation and discontinuation of enteral feedings. Dosage adjustments or intravenous administration may be required until therapeutic serum levels are obtained. In addition, patients receiving phenytoin therapy should be warned about the interaction between phenytoin and ethanol and they should be advised to notify their physician if they experience worsening of seizure control or symptoms of toxicity, including drowsiness, visual disturbances, change in mental status, nausea, or ataxia.

References

  1. Sandor P, Sellers EM, Dumbrell M, Khouw V (1981) "Effect of short- and long-term alcohol use on phenytoin kinetics in chronic alcoholics." Clin Pharmacol Ther, 30, p. 390-7
  2. Holtz L, Milton J, Sturek JK (1987) "Compatibility of medications with enteral feedings." JPEN J Parenter Enteral Nutr, 11, p. 183-6
  3. Sellers EM, Holloway MR (1978) "Drug kinetics and alcohol ingestion." Clin Pharmacokinet, 3, p. 440-52
  4. (2001) "Product Information. Dilantin (phenytoin)." Parke-Davis
  5. Doak KK, Haas CE, Dunnigan KJ, et al. (1998) "Bioavailability of phenytoin acid and phenytoin sodium with enteral feedings." Pharmacotherapy, 18, p. 637-45
  6. Rodman DP, Stevenson TL, Ray TR (1995) "Phenytoin malabsorption after jejunostomy tube delivery." Pharmacotherapy, 15, p. 801-5
  7. Au Yeung SC, Ensom MH (2000) "Phenytoin and enteral feedings: does evidence support an interaction?" Ann Pharmacother, 34, p. 896-905
  8. Ozuna J, Friel P (1984) "Effect of enteral tube feeding on serum phenytoin levels." J Neurosurg Nurs, 16, p. 289-91
  9. Faraji B, Yu PP (1998) "Serum phenytoin levels of patients on gastrostomy tube feeding." J Neurosci Nurs, 30, p. 55-9
  10. Marvel ME, Bertino JS (1991) "Comparative effects of an elemental and a complex enteral feeding formulation on the absorption of phenytoin suspension." JPEN J Parenter Enteral Nutr, 15, p. 316-8
  11. Fleisher D, Sheth N, Kou JH (1990) "Phenytoin interaction with enteral feedings administered through nasogastric tubes." JPEN J Parenter Enteral Nutr, 14, p. 513-6
  12. Haley CJ, Nelson J (1989) "Phenytoin-enteral feeding interaction." DICP, 23, p. 796-8
  13. Guidry JR, Eastwood TF, Curry SC (1989) "Phenytoin absorption in volunteers receiving selected enteral feedings." West J Med, 150, p. 659-61
  14. Krueger KA, Garnett WR, Comstock TJ, Fitzsimmons WE, Karnes HT, Pellock JM (1987) "Effect of two administration schedules of an enteral nutrient formula on phenytoin bioavailability." Epilepsia, 28, p. 706-12
  15. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  16. Cerner Multum, Inc. "Australian Product Information."
View all 16 references

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Moderate

multivitamin, prenatal food

Applies to: Prenaissance Next (multivitamin, prenatal)

ADJUST DOSING INTERVAL: Concomitant use of some oral medications may reduce the bioavailability of orally administered iron, and vice versa.

Food taken in conjunction with oral iron supplements may reduce the bioavailability of the iron. However, in many patients intolerable gastrointestinal side effects occur necessitating administration with food.

MANAGEMENT: Ideally, iron products should be taken on an empty stomach (i.e., at least 1 hour before or 2 hours after meals), but if this is not possible, administer with meals and monitor the patient more closely for a subtherapeutic effect. Some studies suggest administration of iron with ascorbic acid may enhance bioavailability. In addition, administration of oral iron products and some oral medications should be separated whenever the bioavailability of either agent may be decreased. Consult the product labeling for specific separation times and monitor clinical responses as appropriate.

References

  1. "Product Information. Feosol (ferrous sulfate)." SmithKline Beecham
  2. (2021) "Product Information. Accrufer (ferric maltol)." Shield Therapeutics

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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.

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