Coadministration with a levonorgestrel-containing combined oral contraceptive (COC) has not been studied but can be considered. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Coadministration is predicted to increase levonorgestrel exposure. When used in combined pill, the estrogen component is expected to be reduced. This is unlikely to impair contraceptive efficacy, particularly considering the short duration of nirmatrelvir/ritonavir treatment, though it may increase the risk of irregular bleeding. However, it should be noted that the Paxlovid product labels state patients using combined hormonal contraceptives should be advised to use an effective alternative contraceptive method or an additional barrier method of contraception during treatment with nirmatrelvir/ritonavir, and until one menstrual cycle after stopping nirmatrelvir/ritonavir.