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Fenobarbital

Klassificering: A

Preparat: Aphenylbarbit, Fenemal Meda, Fenobarbital APL, Luminal, Phenobarbital Teva, Phenobarbital-neuraxpharm

ATC kod: N03AA02

Substanser: fenobarbital, fenobarbitalnatrium

Sammanfattning

En studie har visat att män som behandlades med fenobarbital fick en signifikant ökning av prolaktinnivåer, jämfört med friska män.

Fenobarbital kan påverka metabolismen av p-piller och kompletterande antikonceptiv metod bör användas. Under graviditet minskar serumkoncentrationen av fenobarbital med 50-55 % och upp till 70 % av primidonderiverad fenobarbital,.

Additional information

Pharmacokinetics and dosing

Several studies have shown that patient’s sex does not significantly improve the estimate of phenobarbital clearance, neither in neonatal, infants or elderly [4, 5]. A review article on clinical pharmacokinetics in pediatric patients concludes that no sex differences on phenobarbital C/D ratios (ratio between plasma concentrations and dose/kg) were found [6].

Effects

No studies with a clinically relevant sex analysis regarding the effects of phenobarbital have been found.

Adverse effects

A study evaluated prolactin secretion in patients with partial or generalized epilepsy (78 men, 56 women; aged 13-60 years) treated with phenobarbital alone or in combination with either phenytoin or benzodiazepines. An increase in baseline prolactin values was observed in men in all treatment groups, but not in women, compared with healthy controls [7]. Abnormal prolactin levels may be associated with sexual dysfunction [8].

Reproductive health issues

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. 

Concurrent administration of phenobarbital and oral contraceptives may decrease the effect of estradiol. Regarding drug-drug interactions aspects, please consult Janusmed Interactions (in Swedish, Janusmed interaktioner).

In pregnant women, the concentration of phenobarbital is decreased up to 50-55%. The lowered serum concentration is even more pronounced in primidone derived phenobarbital, up to 70% [9]. This may necessitate dose adjustments and therapeutic drug monitoring. Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Försäljning på recept

Något fler män än kvinnor hämtade ut läkemedel innehållande fenobarbital (ATC-kod N03AA02) på recept i Sverige år 2019, totalt 824 män och 764 kvinnor. Det motsvarar 0,2 respektive 0,2 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 70 år och äldre hos båda könen. Totalt sett var läkemedel innehållande fenobarbital 1,1 gånger vanligare bland män [10].

Uppdaterat: 2020-04-03

Litteratursökningsdatum: 2019-08-28

Referenser

  1. Duncan S, Blacklaw J, Beastall GH, Brodie MJ. Antiepileptic drug therapy and sexual function in men with epilepsy. Epilepsia. 1999;40:197-204. PubMed
  2. Svalheim S, Sveberg L, Mochol M, Taubøll E. Interactions between antiepileptic drugs and hormones. Seizure. 2015;28:12-7. PubMed
  3. Yogarajah M, Mula M. Sexual Dysfunction in Epilepsy and the Role of Anti-Epileptic Drugs. Curr Pharm Des. 2017;23(37):5649-5661. PubMed
  4. Messina S, Battino D, Croci D, Mamoli D, Ratti S, Perucca E. Phenobarbital pharmacokinetics in old age: a case-matched evaluation based on therapeutic drug monitoring data. Epilepsia. 2005;46:372-7. PubMed
  5. Yukawa M, Yukawa E, Suematsu F, Takiguchi T, Ikeda H, Aki H et al. Population pharmacokinetics of phenobarbital by mixed effect modelling using routine clinical pharmacokinetic data in Japanese neonates and infants: an update. J Clin Pharm Ther. 2011;36:704-10. PubMed
  6. Battino D, Estienne M, Avanzini G. Clinical pharmacokinetics of antiepileptic drugs in paediatric patients Part I: Phenobarbital, primidone, valproic acid, ethosuximide and mesuximide. Clin Pharmacokinet. 1995;29:257-86. PubMed
  7. Bonuccelli U, Murialdo G, Rossi G, Bonura ML, Polleri A, Murri L. Prolactin secretion in epileptic subjects treated with phenobarbital: sex differences and circadian periodicity. Epilepsia. 1986;27:142-8. PubMed
  8. Calafato MS, Austin-Zimmerman I, Thygesen JH, Sairam M, Metastasio A, Marston L et al. The effect of CYP2D6 variation on antipsychotic-induced hyperprolactinaemia: a systematic review and meta-analysis. Pharmacogenomics J. 2020. PubMed
  9. Tomson T, Landmark CJ, Battino D. Antiepileptic drug treatment in pregnancy: changes in drug disposition and their clinical implications. Epilepsia. 2013;54:405-14. PubMed
  10. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2019 [cited 2020-03-10.] länk

Författare: Linnéa Karlsson Lind

Faktagranskat av: Mia von Euler, Carl-Olav Stiller, Diana Rydberg

Godkänt av: Karin Schenck-Gustafsson