Are there any known pharmacological interactions between combined oral contraceptives and interfero

Fråga: Are there any known pharmacological interactions between combined oral contraceptives and interferon beta?

A woman is treated with interferon beta for multiple sclerosis. She has recently ceased breast-feeding her child and wants to swap from a gestagen-only to a combined oral contraceptive.

Sammanfattning: There are no reports of pharmacological interactions between interferon beta and oral contraceptives. Theoretically, the former drug could cause reduced hepatic metabolism of the latter. Although it seems unlikely that such an inhibition would cause any toxic effects, a low-dose oral contraceptive may be the best choice in this patient.

Svar: No reports of pharmacological interactions between combined oral contraceptives and interferon beta were found in Medline, Drugline or standard pharmacological literature.

Interferon beta is extensively metabolised in the liver, although the exact enzymes involved are not known (1). Since oral contraceptives may alter the activity of hepatic enzymes such as CYP3A4 (cytochrome P450 3A4) (2) and CYP2C19 (3), they could theoretically interfere with the metabolism of interferon beta. However, of all reported drug interactions involving interferon beta, none is caused by alterations of its metabolism, indicating a wide therapeutic range (2, 4-5). Hence, such interactions seem less likely to occur in co-medication with oral contraceptives.

Interferon beta, on the other hand, is known to reduce the activity of several hepatic drug-metabolising enzymes, and this could hypothetically cause increased plasma levels of the estrogenic and gestagenic components of oral contraceptives (1). Fortunately, the toxicity potential of those substances appears to be small and it seems unlikely that an incomplete inhibition of their metabolism would cause any clinical problems (6). This notion is further supported by the fact that most pharmacokinetic interactions with oral contraceptives involve induction rather than inhibition of their metabolism (4).

Based on the adverse effects profiles and mechanisms of the substances, there are no obvious reasons to anticipate pharmacodynamic interactions. Nevertheless, the complex actions of these drugs make it very difficult to draw any certain conclusions in this regard. 1 Dollery C Sir, editor. Therapeutic drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1999. p. I54-5. 2 Levy RH, Thummel KE, Trager WF, Hansten PD, Eichelbaum M. Metabolic drug interactions. Philadelphia: Williams & Wilkins; 2000. p. 125, 450, 547. 3 Hägg S, Spigset O, Dahlqvist R. Influence of gender and oral contraceptives on CYP2D6 and CYP2C19 activity in healthy volunteers. Br J Clin Pharmacol 2001;51:169-73. 4 Griffin JP, d´Arcy PF. A manual of adverse drug interactions. 5th ed. Amsterdam: Elsevier; 1997. p. 439-451, 513. 5 Stockley IH. Drug interactions. 6th ed. London: The Pharmaceutical Press; 2002. p. 160, 182, 271, 491. 6 Persson H, Sjöberg G. Överdosering av läkemedel. FASS 2002. p. 1623-62.