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Fosphenytoin

Classification: C

Drug products: Pro-Epanutin, Pro-Epanutin®

ATC code: N03AB05

Substances: fosphenytoin, fosphenytoin sodium

Summary

Fosphenytoin is a pro-drug of phenytoin and the anticonvulsant effect can thus be attributed to phenytoin.

Physiologic changes during pregnancy may decrease plasma concentration if the same dose is used and thus a risk of increased seizure frequency. If phenytoin is used during pregnancy, more frequent monitoring of phenytoin concentration is motivated.

Fosphenytoin can affect the metabolism of oral contraceptives and additional contraception should be used.

Additional information

Pharmacokinetics and dosing

A study (39 men, 24 women) found no difference between men and women in phenytoin clearance, distribution volume or half-life. Men and women received the same daily dose (4.8 mg/kg/day) of phenytoin or fosphenytoin and trough phenytoin concentrations were similar between men and women [1].

Phenytoin pharmacokinetics is altered during pregnancy and an increase of seizure frequency may occur in pregnant women if the same dose is used. For appropriate dose adjustment in pregnant women, monitoring of plasma phenytoin concentrations is recommended [2].

Effects

Fosphenyotin is a pro-drug of phenytoin and accordingly, its anticonvulsant effects are attributable to phenytoin [2].

Adverse effects

No studies with a clinically relevant sex analysis regarding adverse effects of fosphenytoin have been found.

Reproductive health issues

Fosphenytoin may affect the metabolism of estrogens and progestogens. Thus, the effect of these can be reduced. Additional contraceptive method should be used [4]. Regarding drug-drug interactions aspects, please consult Janusmed Interactions (in Swedish, Janusmed interaktioner).

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Updated: 2020-03-20

Date of litterature search: 2019-10-14

References

  1. Ahn JE, Cloyd JC, Brundage RC, Marino SE, Conway JM, Ramsay RE et al. Phenytoin half-life and clearance during maintenance therapy in adults and elderly patients with epilepsy. Neurology. 2008;71:38-43. PubMed
  2. Cerebyx (fosphenytoin). DailyMed [www]. US National Library of Medicine. [updated 2019-07-26, cited 2019-10-14]. länk
  3. Pro-Epanutin (fosfenytoin). Summary of Products Characteristics. Swedish Medical Products Agency [updated 2019-07-08, cited 2019-10-14].
  4. Patsalos PN, Perucca E. Clinically important drug interactions in epilepsy: general features and interactions between antiepileptic drugs. Lancet Neurol. 2003;2:347-56. PubMed
  5. Concise (INSIKT). Kalmar: eHälsomyndigheten. 2018 [cited 2019-03-14.] länk

Authors: Linnéa Karlsson Lind

Reviewed by: Mia von Euler, Carl-Olav Stiller

Approved by: Karin Schenck-Gustafsson