The interaction of phenytoin and carbamazepine with combined oral contraceptive steroids.

Abstract

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 ,ug, and levonorgestrel (Ng); 250 p,g 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-' h (P < 0.05) and for Ng from 33.6 ± 7.8 to 19.5 ± 3.8 ng ml-' h (P < 0.05). Carbamazepine reduced the AUC for EE2 from 1163 ± 466 to 672 ± 211 pg ml-' h (P < 0.05) and for Ng from 22.9 ± 9.4 to 13.8 ± 5.8 ng ml-' h (P < 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 ,ug EE2 daily) to achieve adequate contraceptive effects.

Levetiracetam Does Not Alter the Pharmacokinetics of an Oral Contraceptive in Healthy Women

“…Older AEDs, such as PHT, PB, and CBZ, potently induce CYP-drug metabolizing enzymes, and they also increase sex hormone-binding globulin levels (1,27,28). Both mechanisms may contribute to reduced steroid contraceptive levels during concomitant administration of these older AEDs and OCs, resulting in unplanned pregnancy (3)(4)(5)(6)(7). A second group of AEDs includes TPM, FBM, and OCBZ, which are less potent inducers of CYP but have been shown to alter plasma concentrations of the contraceptive steroids (12,29).…”

“…Contraceptive failure and unplanned pregnancy have been well documented in women with epilepsy treated concomitantly with CYP-inducing AEDs and OCs (3)(4)(5)(6)(7). Newer AEDs, including topiramate (TPM), felbamate (FBM), and oxcarbazepine (OCBZ), are less potent inducers of CYP, but they also may interfere with the metabolism of OCs, thereby altering plasma concentrations of the contraceptive steroids and potentially decreasing their efficacy (8)(9)(10)(11)(12).…”

Efeitos endócrinos e metabólicos das drogas antiepilépticas

“…As DAE indutorhepáticas elevam os níveis da globulina ligadora dos hormônios sexuais (SHBG), reduzindo os níveis de estradiol e testosterona livre. Por outro lado, elas reduzem a eficácia dos contraceptivos hormonais orais ao diminuí-rem os níveis de etinilestradiol e levonorgestrel, aumentando a possibilidade de gravidez (35). Carbamazepina, fenitoína, fenobarbital, etosuximide, primidona e oxcarbazepina são as DAE que podem afetar a eficácia dos anticoncepcionais.…”

Lack of effect of oral cabotegravir on the pharmacokinetics of a levonorgestrel/ethinyl oestradiol‐containing oral contraceptive in healthy adult women

“…EO and LNG are primarily metabolized by the CYP pathway and are impacted by agents that induce or inhibit these metabolizing enzymes. Coadministration with agents known to induce this metabolic pathway may reduce plasma concentrations of these exogenous hormones, permitting escape ovulation and potentially resulting in contraceptive failure 9, 10. Since EO and LNG are not known inhibitors or inducers of CYP or glucuronyl transferase activity, it is unlikely that either would impact the PK of CAB.…”