Last update Aug. 18, 2022

Diphenylhydantoin

Compatible

Safe substance and/or breastfeeding is the best option.

It is an antiepileptic that is used to control the seizures of epilepsy and trigeminal neuralgia. It is also a class Ib antiarrhythmic that has been used to treat cardiac arrhythmias. Oral and intravenous administration.

It is excreted into breast milk in clinically non-significant amount (Bar-Oz 2000, Shimoyama 1998, Meyer 1988, Söderman 1988, Kaneko 1979, Rane 1974, Mirkin 1971) 

No problems have appeared on clinical follow up, and, long-term psychomotor development in infants whose mothers received this treatment. (Meador 2014 & 2010, Mirkin 1971, LIvingston 1956)

Plasma levels in these infants were undetectable or very low. (Steen 1982)

It may appear a withdrawal syndrome with hyperexcitability after abruptly stopping breastfeeding.

It has been authorized for use in infants and newborns.

Expert authors consider the use of this medication safe during lactation (Hale, LactMed, Crettenand 2018, Briggs 2015, Schaefer 2015, Rowe 2013, Davanzo 2013, Mercadé 2012, Mintzer 2011, Harden 2009, O'Connor 2009, Pennell 2006, O'Brien 2005, Hägg 2000)). American Academy of Pediatrics states that it is usually compatible with breastfeeding medication (AAP 2001). WHO List of Essential Medicines 2002: compatible with breastfeeding. (WHO 2002)

Alternatives

Suggestions made at e-lactancia are done by APILAM team of health professionals, and are based on updated scientific publications. It is not intended to replace the relationship you have with your doctor but to compound it. The pharmaceutical industry contraindicates breastfeeding, mistakenly and without scientific reasons, in most of the drug data sheets.

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Other names

Diphenylhydantoin is also known as Phenytoin. Here it is a list of alternative known names::


Diphenylhydantoin in other languages or writings:

Group

Diphenylhydantoin belongs to this group or family:

Tradenames

Main tradenames from several countries containing Diphenylhydantoin in its composition:

List of 40 tradenames

Pharmacokinetics

Variable Value Unit
Oral Bioavail. 70 - 100 %
Molecular weight 252 daltons
Protein Binding 90 %
VD 0.5 - 0.8 l/Kg
pKa 8.49 -
Tmax 1.5 - 3 / 4 - 12 hours
T½ oral: 22 (7 - 42). / iv: 7-15 hours
M/P ratio 0.2 - 0.5 -
Theoretical Dose 0.07 - 0.4 mg/Kg/d
Relative Dose 1.4 - 8 %
Ped.Relat.Dose 1 - 7 %

References

  1. LactMed. Drugs and Lactation Database (LactMed). Internet. Bethesda (MD): National Library of Medicine (US); 2006-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK501922/ 2006 - Consulted on April 16, 2024 Full text (link to original source)
  2. Hale TW. Medications & Mothers' Milk. 1991- . Springer Publishing Company. Available from https://www.halesmeds.com Consulted on April 10, 2024 Full text (link to original source)
  3. Crettenand M, Rossetti AO, Buclin T, Winterfeld U. [Use of antiepileptic drugs during breastfeeding : What do we tell the mother?] Nervenarzt. 2018 Abstract
  4. Briggs GG, Freeman RK, Towers CV, Forinash AB. Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk. Wolters Kluwer Health. Tenth edition (acces on line) 2015
  5. Veiby G, Bjørk M, Engelsen BA, Gilhus NE. Epilepsy and recommendations for breastfeeding. Seizure. 2015 May;28:57-65. Abstract Full text (link to original source)
  6. Schaefer C, Peters P, Miller RK. Drugs During Pregnancy and Lactation. Treatment options and risk assessment. Elsevier, Third Edition. 2015
  7. Meador KJ, Baker GA, Browning N, Cohen MJ, Bromley RL, Clayton-Smith J, Kalayjian LA, Kanner A, Liporace JD, Pennell PB, Privitera M, Loring DW; Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study Group. Breastfeeding in children of women taking antiepileptic drugs: cognitive outcomes at age 6 years. JAMA Pediatr. 2014 Abstract Full text (link to original source) Full text (in our servers)
  8. Rowe H, Baker T, Hale TW. Maternal medication, drug use, and breastfeeding. Pediatr Clin North Am. 2013 Feb;60(1):275-94. Abstract
  9. Davanzo R, Dal Bo S, Bua J, Copertino M, Zanelli E, Matarazzo L. Antiepileptic drugs and breastfeeding. Ital J Pediatr. 2013 Abstract Full text (link to original source) Full text (in our servers)
  10. Mercadé Cerdá JM, Sancho Rieger J, Mauri Llerda JA, López González FJ,Salas Puig X. Guías diagnósticas y terapéuticas de la Sociedad Española de Neurología 2012. 1. Guía oficial de práctica clínica en epilepsia. Guías SEN 2012 Full text (in our servers)
  11. Mintzer S. To test our guess that breast is best: anticonvulsants and breastfeeding. Epilepsy Curr. 2011 Abstract Full text (link to original source) Full text (in our servers)
  12. Meador KJ, Baker GA, Browning N, Clayton-Smith J, Combs-Cantrell DT, Cohen M, Kalayjian LA, Kanner A, Liporace JD, Pennell PB, Privitera M, Loring DW; NEAD Study Group. Effects of breastfeeding in children of women taking antiepileptic drugs. Neurology. 2010 Nov 30;75(22):1954-60. Abstract Full text (link to original source) Full text (in our servers)
  13. O'Connor SE, Zupanc ML. Women and epilepsy. J Pediatr Pharmacol Ther. 2009 Abstract Full text (link to original source) Full text (in our servers)
  14. Harden CL, Pennell PB, Koppel BS, Hovinga CA, Gidal B, Meador KJ, Hopp J, Ting TY, Hauser WA, Thurman D, Kaplan PW, Robinson JN, French JA, Wiebe S, Wilner AN, Vazquez B, Holmes L, Krumholz A, Finnell R, Shafer PO, Le Guen C; American Academy of Neurology; et al. Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of... Neurology. 2009 Abstract Full text (link to original source) Full text (in our servers)
  15. Pennell PB. 2005 AES annual course: evidence used to treat women with epilepsy. Epilepsia. 2006 Abstract Full text (link to original source) Full text (in our servers)
  16. O'Brien MD, Gilmour-White SK. Management of epilepsy in women. Postgrad Med J. 2005 Abstract Full text (link to original source) Full text (in our servers)
  17. Rubin ET, Lee A, Ito S. When breastfeeding mothers need CNS-acting drugs. Can J Clin Pharmacol. 2004 Fall;11(2):e257-66. Epub 2004 Dec 8. Abstract
  18. WHO / UNICEF. BREASTFEEDING AND MATERNAL MEDICATION Recommendations for Drugs in the Eleventh WHO Model List of Essential Drugs. Department of Child and Adolescent Health and Development (WHO/UNICEF) 2002 Abstract Full text (link to original source) Full text (in our servers)
  19. AAP - American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics. 2001 Sep;108(3):776-89. Abstract Full text (link to original source) Full text (in our servers)
  20. Hägg S, Spigset O. Anticonvulsant use during lactation. Drug Saf. 2000 Jun;22(6):425-40. Review. Abstract
  21. Bar-Oz B, Nulman I, Koren G, Ito S. Anticonvulsants and breast feeding: a critical review. Paediatr Drugs. 2000 Mar-Apr;2(2):113-26. Review. Abstract
  22. Shimoyama R, Ohkubo T, Sugawara K, Ogasawara T, Ozaki T, Kagiya A, Saito Y. Monitoring of phenytoin in human breast milk, maternal plasma and cord blood plasma by solid-phase extraction and liquid chromatography. J Pharm Biomed Anal. 1998 Abstract
  23. Meyer FP, Quednow B, Potrafki A, Walther H. [Pharmacokinetics of anticonvulsants in the perinatal period]. Zentralbl Gynakol. 1988 Abstract
  24. Söderman P, Matheson I. Clonazepam in breast milk. Eur J Pediatr. 1988 Abstract
  25. Steen B, Rane A, Lönnerholm G, Falk O, Elwin CE, Sjöqvist F. Phenytoin excretion in human breast milk and plasma levels in nursed infants. Ther Drug Monit. 1982 Abstract
  26. Kaneko S, Sato T, Suzuki K. The levels of anticonvulsants in breast milk. Br J Clin Pharmacol. 1979 Abstract Full text (link to original source) Full text (in our servers)
  27. Rane A, Garle M, Borgå O, Sjöqvist F. Plasma disappearance of transplacentally transferred diphenylhydantoin in the newborn studied by mass fragmentography. Clin Pharmacol Ther. 1974 Abstract
  28. Mirkin BL. Diphenylhydantoin: placental transport, fetal localization, neonatal metabolism, and possible teratogenic effects. J Pediatr. 1971 Abstract
  29. LIVINGSTON S. Treatment of epilepsy with diphenylhydantoin sodium (dilantin sodium). Postgrad Med. 1956 Dec;20(6):584-90. No abstract available. Abstract
  30. FINCH E, LORBER J. Methaemoglobinaemia in the newborn probably due to phenytoin excreted in human milk. J Obstet Gynaecol Br Emp. 1954 Abstract

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