The interaction of phenytoin and carbamazepine with combined oral contraceptive steroids.
Patients taking oral contraceptive steroids (OCS) are known to suffer contraceptive failure while taking anticonvulsants such as phenobarbitone, phenytoin and carbamazepine. We have studied the single dose kinetics of ethinyloestradiol (EE2); 50 micrograms, and levonorgestrel (Ng); 250 micrograms in groups of women before and 8-12 weeks after starting therapy with phenytoin (n = 6) and carbamazepine (n = 4). The area under the plasma concentration-time curve (AUC) was measured over a 24 h period for each steroid and significant reductions were seen with both anticonvulsants. Phenytoin reduced the AUC for EE2 from 806 +/- 50 (mean +/- s.d.) to 411 +/- 132 pg ml-1 h (P less than 0.05) and for Ng from 33.6 +/- 7.8 to 19.5 +/- 3.8 ng ml-1 h (P less than 0.05). Carbamazepine reduced the AUC for EE2 from 1163 +/- 466 to 672 +/- 211 pg ml-1 h (P less than 0.05) and for Ng from 22.9 +/- 9.4 to 13.8 +/- 5.8 ng ml-1 h (P less than 0.05). These changes are compatible with the known enzyme inducing effects of phenytoin and carbamazepine. Patients taking these anticonvulsants will need to be given increased doses of OCS (equivalent to 50-100 micrograms EE2 daily) to achieve adequate contraceptive effects.
Crawford
P
P
Regional Neurosciences Centre, Walton Hospital, Liverpool.
Chadwick
D J
DJ
Martin
C
C
Tjia
J
J
Back
D J
DJ
Orme
M
M
D000293:Adolescent; D000328:Adult; D002220:Carbamazepine / Q000097:blood / Q000494:pharmacology*; D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000493:pharmacokinetics; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000493:pharmacokinetics; D004347:Drug Interactions; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D016912:Levonorgestrel; D009644:Norgestrel / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010672:Phenytoin / Q000097:blood / Q000494:pharmacology*
D003271:Contraceptive Agents, Female; D003277:Contraceptives, Oral, Combined; D002220:Carbamazepine; D009644:Norgestrel; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D010672:Phenytoin