Phenytoin Contraceptives, combined hormonal

Almost all of the interactions of the hormonal contraceptives described in this publication involve the combined hormonal contraceptives. Most of the elinically important interactions with the eombined hormonal contraceptives involve increased metabolism. The major route for hepatic metabolism of ethinylestradiol is hydroxylation by the cytochrome P450 isoenzyme CYP3A4, and progestagens are also substrates for this enzyme. Thus, inducers of this enzyme can increase the clearance ofthe contraceptive steroids and possibly increase breakthrough bleeding and decrease contraceptive efficacy (see Hormonal contraceptives + Antiepileptics Barbiturates or Phenytoin , p.985). The drugs that have been shown to induce the metabolism of hormonal contraceptives are listed in Table 28.1 , (see below). Conversely, inhibitors of CYP3A4 may... 

Co-cyprindiol is a mixture of the anti-androgenic progestogen, cyproter-one acetate 2 mg, with ethinylestradiol 35 micrograms. It is used for the treatment of acne and moderately severe hirsutism in women who may also wish to use it as an oral contraceptive, and its contraceptive efficacy is expected to be reduced by the same hepatic enzyme inducers (see Table 28. r, (p.975)) that interact with conventional combined oral contraceptives. The precautions described in this section for the combined hormonal contraceptives with the various drugs listed in Table 28.1 , (p.975), should therefore be followed, see Hormonal contraceptives + Antiepileptics Barbiturates or Phenytoin , p.985. 

It is likely that nevirapine induces the metabolism of the components of the oral contraceptive by cytochrome P450 isoenzymes. Although it is not known whether these modest reductions in levels would reduce the anti-ovulatory efficacy of the combined oral contraceptive, it would be prudent to assume they could. The manufacturers recommend that combined oral contraceptives and other hormonal methods of birth control should not be used as the sole method of contraception in women taking nevirapine. They suggest that a barrier method (e.g. condoms) should also be used, and note that this is also advisable to reduce the risk of HTV transmission. The Faculty of Family Planning and Reproductive Health Care (FFPRHC) Clinical Effectiveness Unit notes that nevirapine can induce liver enzymes and may reduce the levels of ethinylestradiol and progestogens. They therefore recommend that their guidance on hormonal contraceptives and liver enzyme inducers is followed, see Hormonal contraceptives + Antiepileptics Barbiturates or Phenytoin , p.985 for fiir-ther detail. 

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