Modafinil slightly reduces levels of ethinylestradiol given aspart of a combined oral contraceptive
Clinical evidence,mechanism, importance and management
In 16 healthy women taking a combined oral contraceptive (ethinylestradiol/norgestimate), modafinil 200mg daily for 7 days followed by 400mg daily for 21 days decreased AUC and maximum plasma levels of ethinylestradiol by 18 % and 11%, respectively. Increases in plasma FSH and LH were not significant (See reference number 1). Modafinil is an inducer of cytochrome P450 isoenzyme CYP3A4, which is partially responsible for metabolism of ethinylestradiol. These small changes are lower than those seen with other enzyme inducers known to reduce reliability of combined oral contraceptives (e.g. see phenytoin’,). However,it cannot be ruled out that they would be sufficient to cause failure of combined oral contraceptives in very rare cases. The UK manufacturer recommends that additional or alternative methods of contraception should be used during and for up to 2 cycles after stopping modafinil (See reference number 2). The US manufacturer gives similar guidance but advises that additional or alternative contraceptive methods need only be continued for one month after stopping modafinil (See reference number 3). Note that this advice applies to other forms of hormonal contraception including implants and patches (See reference number 3,4). The Faculty of Family Planning and Reproductive Health Care (FFPRHC) Clinical Effectiveness Unit has issued guidance on use of liver enzyme inducers with hormonal contraceptives,(See reference number 4)see ‘Hormonal contraceptives + Antiepileptics; Barbiturates or Phenytoin, for further information.
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