ATC kod: N03AB02
Det saknas kontrollerade studier om skillnader mellan könen avseende effekt, säkerhet eller farmakokinetik för fenytoin förutom i samband med graviditet.
Fysiologiska förändringar vid graviditet kan förändra plasmakoncentrationen av fenytoin och därmed kan anfallsfrekvensen hos kvinnan öka. Tätare koncentrationsmätning av fenytoin under graviditet är därför rekommenderat.
Fenytoin kan påverka metabolismen av p-piller och kompletterande antikonceptiv metod bör användas.
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 [4].Also, a randomized controlled trial in healthy subjects (12 men, 12 women) showed that the mean AUC, normalized for the mg/kg phenytoin dose, was about 30% lower in women than men. This might be explained by a more rapid elimination in women. This counterbalance the generally lower body weight in women that results in higher phenytoin concentration levels [5]. Dose regimens for phenytoin do not need to be adjusted based on patient’s sex, since the more rapid elimination in women counterbalance the generally lower weight that result in higher phenytoin concentration levels [5].
A study examining binding characteristics of phenytoin to serum proteins in healthy adults (40 men, 40 women) on monotherapy found no sex differences. The affinity of phenytoin to serum proteins was similar in men and women, and patient’s sex does not have a significant effect on binding characteristics of phenytoin to serum proteins in adult patients [6].
No studies with a clinically relevant sex analysis regarding effects of phenytoin have been found.
A retrospective analysis (320 men, 343 women) of patients on antiepileptic drug treatment showed fertile women to have a higher risk for skin reactions than men when treated with phenytoin [7].
Enzyme-inducing antiepileptic drugs, such as carbamazepine, phenytoin and phenobarbital, may have potentially negative effects on reproductive endocrine function in men and women. These antiepileptic drugs increase concentrations of sex hormone-binding globulin (SHBG) and thereby reducing the concentrations of unbound biologically active androgens [1-3]. This may result in sexual dysfunction.
Phenytoin pharmacokinetics is altered during pregnancy resulting in lower plasma concentrations and thus, an increased risk of seizures. For appropriate dose adjustment in pregnant women, monitoring of plasma phenytoin concentrations is recommended [8]. Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Phenytoin may affect the metabolism of estrogens and progestogens. Thus, the effect of these can be reduced. Additional contraceptive method should be used [9]. Regarding drug-drug interactions aspects, please consult Janusmed Interactions (in Swedish, Janusmed interaktioner).
Fler män än kvinnor hämtade ut läkemedel innehållande fenytoin (ATC-kod N03AB02) på recept i Sverige år 2019, totalt 2 071 män och 1 724 kvinnor. Det motsvarar 0,4 respektive 0,3 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 60 år och äldre hos båda könen. I genomsnitt var läkemedel innehållande fenytoin 1,4 gånger vanligare hos män [10].
Uppdaterat: 2020-04-03
Litteratursökningsdatum: 2019-10-11
Faktagranskat av: Mia von Euler, Carl-Olav Stiller, Diana Rydberg
Godkänt av: Karin Schenck-Gustafsson