Drug interaction of contraceptive medication with methadone: Clinic, treatment and therapeutic drug monitoring

Introduction:

Drug therapy in patients with methadone and oral contraceptive can be challenging cause of relevant drug interactions which should be taken into account in clini- cal practice. Here we present a case of a 22 year old women. Patient additionally suffered from metha- done addiction, affective disorder, attention deficit disorder, Hashimoto-Thyreoiditis and was treated with methadone, bupropion, doxepine and oral contraceptive steroids ethinyl estradiol.

The metabolism of racemic methadone is stereoselective, CYP2B6 preferentially metabo- lizes (S)-methadone, CYP2C19 preferentially (R)-methadone, and CYP3A4 has no prefe- rence 1. Methadone's major metabolite, 2-ethylidene-1,5-dimethyl- 3,3-diphenylpyrrolidine, does not exhibit pharmacologic activity. At 10 mg/mL of methadone, CYP2C9 and CYP2D6 also generate 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine in vitro but in at least 10- fold lower quantities than CYP2B6.1 – 4 These CYP enzymes have large interindividual variability and the potential for interactions with inducers and/or inhibitors is well known.

Methods:

Clinical course documentation, measurement of drug levels.

Results:

Methadone is in high range before taking ethinyl estradiol (in serum 653 ng/ml, therapeutic range 50 – 400 ng/ml). Methadone serum-level decreased after two month du- ring ethyl estradiol intake (154 ng/ml, 75 ng/ml). After stop oral contraceptives serum level of methadone increase due to 373 ng/ml. Due to the insufficient low methadone serum le- vel, patient suffer of withdrawals like mydriasis, dreams of drugs, depressive mood. Due to the withdrawals of methadone a combination of doxepine and bupropion was cho- sen, both effected a sufficient plasma level.

Conclusion:

Methadone serum-level decreased during ethinyl estradiol intake and increasing after stop taken pills. The treatment of methadone addiction and oral contraceptives indi- cates the necessity of individualized treatment, taking account of TDM before through and after contraceptives therapy.