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Classification: A

Drug products: Fenemal Meda, Fenobarbital APL, Luminal

ATC code: N03AA02

Substances: phenobarbital, phenobarbital sodium


One study has shown that men treated with phenobarbital had higher prolactin levels compared to controls.

No sex differences in dose-concentration relationship have been shown in children.

Phenobarbital increases the metabolism of oral contraceptives and additional contraception should be used. During pregnancy, serum concentration of phenobarbital decrease 50-55% and even more in primidon derived phenobarbital, up to 70%.

Additional information

Pharmacokinetics and dosing

Several studies have shown that sex does not significantly improve the estimate of phenobarbital clearance, neither in neonatal, infants or elderly [1, 2]. A review article discussion on clinical pharmacokinetics in pediatric patients concludes that no differences on phenobarbital C/D ratios (ratio between plasma concentrations and dose/kg) were found according to sex [3]. 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% [4].


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 [5].

Reproductive health issues

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).

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

Updated: 2017-03-28

Date of litterature search: 2013-04-23


  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-29] länk

Authors: Linnéa Karlsson Lind, Desirée Loikas

Reviewed by: Expertrådet för neurologiska sjukdomar

Approved by: Mia von Euler