The Basics
What is Fosphenytoin?
Short-term (five days or fewer) treatment of epilepsy when more widely used means of phenytoin administration are not possible or are ill-advised.
Brand names for Fosphenytoin
Cerebyx
How Fosphenytoin is classified
Anticonvulsants
Fosphenytoin During Pregnancy
Fosphenytoin pregnancy category
Category Not AssignedNote that the FDA has deprecated the use of pregnancy categories, so for some medications, this information isn’t available. We still think it’s useful to list historical info, however, given what a common proxy this has been in the past.
What we know about taking Fosphenytoin while pregnant
In humans, prenatal exposure to phenytoin (the active metabolite of CEREBYX) may increase the risks for congenital malformations and other adverse developmental outcomes. Prenatal phenytoin exposure is associated with an increased incidence of major malformations, including orofacial clefts and cardiac defects. In addition, the fetal hydantoin syndrome, a pattern of abnormalities including dysmorphic skull and facial features, nail and digit hypoplasia, growth abnormalities (including microcephaly), and cognitive deficits has been reported among children born to epileptic women who took phenytoin alone or in combination with other antiepileptic drugs during pregnancy . There have been several reported cases of malignancies, including neuroblastoma, in children whose mothers received phenytoin during pregnancy. Administration of phenytoin to pregnant animals resulted in an increased incidence of fetal malformations and other manifestations of developmental toxicity (including embryofetal death, growth impairment, and behavioral abnormalities) in multiple species at clinically relevant doses . In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Clinical Considerations Disease-Associated Maternal Risk An increase in seizure frequency may occur during pregnancy because of altered phenytoin pharmacokinetics. Periodic measurement of serum phenytoin concentrations may be valuable in the management of pregnant women as a guide to appropriate adjustment of dosage . However, postpartum restoration of the original dosage will probably be indicated. Fetal/Neonatal Adverse Reactions A potentially life-threatening bleeding disorder related to decreased levels of vitamin K-dependent clotting factors may occur in newborns exposed to phenytoin in utero. This drug-induced condition can be prevented with vitamin K administration to the mother before delivery and to the neonate after birth. Data Human Data Meta-analyses using data from published observational studies and registries have estimated an approximately 2.4-fold increased risk for any major malformation in children with prenatal phenytoin exposure compared to controls. An increased risk of heart defects, facial clefts, and digital hypoplasia has been reported. The fetal hydantoin syndrome is a pattern of congenital anomalies including craniofacial anomalies, nail and digital hypoplasia, prenatal-onset growth deficiency, and neurodevelopmental deficiencies. Animal Data Administration of phenytoin to pregnant rats, rabbits, and mice during organogenesis resulted in embryofetal death, fetal malformations, and decreased fetal growth. Malformations (including craniofacial, cardiovascular, neural, limb, and digit abnormalities) were observed in rats, rabbits, and mice at doses as low as 100, 75, and 12.5 mg/kg, respectively.
Taking Fosphenytoin While Breastfeeding
What are recommendations for lactation if you're taking Fosphenytoin?
No information is available on the clinical use of fosphenytoin during breastfeeding. However, fosphenytoin is rapidly metabolized in the body to the active drug phenytoin. Breastfeeding during phenytoin monotherapy does not appear to adversely affect infant growth or development, and breastfed infants had higher IQs and enhanced verbal abilities than nonbreastfed infants at 6 years of age in one study.[1] If phenytoin is required by the mother, it is not necessarily a reason to discontinue breastfeeding. Because of the low levels of phenytoin in breastmilk, amounts ingested by the infant are small and usually cause no difficulties in breastfed infants when used alone except for rare idiosyncratic reactions. Combination therapy with sedating anticonvulsants or psychotropics may result in infant sedation or withdrawal reactions. In one case report, maternal phenytoin dosage requirements decreased as breastfeeding was discontinued.[2]
Maternal / infant drug levels
No information is available on the clinical use of fosphenytoin during breastfeeding. However, fosphenytoin is rapidly metabolized in the body to the active drug phenytoin. Breastfeeding during phenytoin monotherapy does not appear to adversely affect infant growth or development, and breastfed infants had higher IQs and enhanced verbal abilities than nonbreastfed infants at 6 years of age in one study.[1] If phenytoin is required by the mother, it is not necessarily a reason to discontinue breastfeeding. Because of the low levels of phenytoin in breastmilk, amounts ingested by the infant are small and usually cause no difficulties in breastfed infants when used alone except for rare idiosyncratic reactions. Combination therapy with sedating anticonvulsants or psychotropics may result in infant sedation or withdrawal reactions. In one case report, maternal phenytoin dosage requirements decreased as breastfeeding was discontinued.[2]
Possible effects of Fosphenytoin on milk supply
Relevant published information was not found as of the revision date.
Possible alternatives to Fosphenytoin
List of References
Lactation sources: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK501922/1. Meador KJ, Baker GA, Browning N et al. Breastfeeding in children of women taking antiepileptic drugs: Cognitive outcomes at age 6 years. JAMA Pediatr. 2014;168:729-36. PMID: 24934501
2. Puckett JB, Butler WM, McFarland JA. Phenytoin and lactation. Arch Neurol. 1982;39:457-8. Letter. PMID: 7103792
3. Mirkin BL. Diphenylhydantoin: placental transport, fetal localization, neonatal metabolism, and possible teratogenic effects. J Pediatr. 1971;78:329-37. PMID: 5539782
4. Horning MG, Nowlin J, Hickert P et al. Identification of drugs and drug metabolites in breast milk by gas chromatography-mass spectrometry. In: Galli C, Jacini G, Pecile A, eds. Dietary lipids and postnatal development. New York: Raven Press, 1973:257-69.
5. Rane A, Garle M, Borga O et al. Plasma disappearance of transplacentally transferred diphenyl-hydantoin in the newborn studied by mass fragmentography. Clin Pharmacol Ther. 1974;15:39-45. PMID: 4808742
6. Horning MG, Stillwell WG, Nowlin J et al. Identification and quantification of drugs and drug metabolites in human breast milk using GC-MS-COM methods. Mod Probl Pediatr. 1975;15:73-9.
7. Kaneko S, Sato T, Suzuki K. The levels of anticonvulsants in breast milk. Br J Clin Pharmacol. 1979;7:624-7. Letter. PMID: 465285
8. Soderman P, Matheson I. Clonazepam in breast milk. Eur J Pediatr. 1988;147:212-3. Letter. PMID: 3366144
9. Meyer FP, Quednow B, Potrafki A et al. [The perinatal pharmacokinetics of anticonvulsant drugs]. Zentralbl Gynakol. 1988;110:1195-205. PMID: 3239295
10. Shimoyama R, Ohkubo T, Sugawara K et al. 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;17:867-9. PMID: 9682171
11. Sugawara K, Shimoyama R, Ohkubo T. Determinations of psychotropic drugs and antiepileptic drugs by high-performance liquid chromatography and its monitoring in human breast milk. Hirosaki Med J. 1999;51(Suppl):S81-6.
12. Bar-Oz B, Nulman I, Koren G et al. Anticonvulsants and breastfeeding. A critical review. Paediatr Drugs. 2000;2:113-26. PMID: 10937463
13. Steen B, Rane A, Lonnerholm G et al. Phenytoin excretion in human breast milk and plasma levels in nursed infants. Ther Drug Monit. 1982;4:331-4. PMID: 7157456
14. Finch E, Lorber J. Methaemoglobinaemia in the newborn. Probably due to phenytoin excreted in human milk. J Obstet Gynaecol Br Emp. 1954;61:833-4. PMID: 13222209
15. Livingston S. Treatment of epilepsy with diphenylhydantoin sodium (Dilantin sodium). Postgrad Med. 1956;20:584-6.
16. Kok TH, Taitz LS, Bennett MJ et al. Drowsiness due to clemastine transmitted in breast milk. Lancet. 1982;319:914-5. Letter. PMID: 6122135
17. Kaneko S, Suzuki K, Sato T et al. The problems of antiepileptic medication in the neonatal period: is breast-feeding advisable? In: Janz D, Dam M, Richens A et al. Epilepsy, pregnancy and the child. New York: Raven Press, 1982:343-8.
18. Granstrom ML, Bardy AH, Hiilesmaa VK. Prolonged feeding difficulties of infants of primidone mothers during neonatal period: preliminary results from the Helsinki study. In: Janz D et al., eds. Epilepsy, pregnancy and the child. New York: Raven Press, 1982:357-8.
19. Koch S, Gopfert-Geyer I, Hauser I et al. Neonatal behaviour disturbances in infants of epilepetic women treated during pregnancy. Prog Clin Biol Res. 1985;163B:453-61. PMID: 3983173
20. Meador KJ, Baker GA, Browning N et al. Effects of breastfeeding in children of women taking antiepileptic drugs. Neurology. 2010;75:1954-60. PMID: 21106960
Disclaimer: This material is provided for educational purposes only and is not intended for medical advice, diagnosis, or treatment. Consult your healthcare provider with any questions.
