Reported Adverse Drug Reaction Cases
Implanon: interactions and failure of contraception
Hepatic enzyme inducing medicines can reduce the efficacy of contraceptives, including implantable contraceptives, leading to unintended pregnancy.
Medicare Australia data indicate that 370,173 etonogestrel-containing contraceptive implants (Implanon) have been dispensed since 2001. The ADRAC database contains 594 reports concerning Implanon, 32 of which describe a suspected interaction between Implanon and another medicine, resulting in unintended pregnancy.
Medicines implicated in a possible interaction with Implanon leading to contraceptive failure include carbamazepine (26), phenytoin (4), methylphenobarbital (1) and rifampicin (1). All but 1 of these interactions involved medicines used to treat epilepsy. The 4 interacting medicines are potent inducers of CYP3A4 and other phase I and phase II enzyme systems in the liver. This enzyme induction is likely to reduce plasma concentrations of etonogestrel which, similar to other contraceptive steroids, is catalysed by CYP3A4.
Other medicines likely to interact with etonogestrel and thus possibly reduce its contraceptive effect or lead to breakthrough bleeding include primidone, oxcarbazepine, rifabutin, griseofulvin and products containing St John's wort. Maximal enzyme induction is generally not seen before two to three weeks but may then be sustained for at least four weeks after cessation of therapy with these medicines.
The Product Information for Implanon advises that women receiving short-term treatment with any of the above medicines or other hepatic enzyme inducing medicines should temporarily use a barrier method in addition to Implanon, i.e. during the time of concomitant medicine administration and for at least seven days after discontinuation. For women taking rifampicin, an additional barrier method should be used during the time of rifampicin administration and for 28 days after its discontinuation.
Prescribers are reminded that in women receiving long-term treatment with hepatic enzyme inducing medicines, the approved prescribing information recommends Implanon should be removed and another, nonhormonal, contraceptive method should be used.
Australian Adverse Drug Reactions Bulletin, Volume 26, Number 4 (August 2007)