Drug Interactions between capivasertib and elagolix / estradiol / norethindrone

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations and pharmacologic effects of capivasertib. The proposed mechanism is accelerated clearance of capivasertib due to induction of the CYP450 3A4 isoenzyme, which is the primary route of elimination of capivasertib. In a clinical study, coadministration with the potent CYP450 3A4 inducer enzalutamide decreased the systemic exposure (AUC) of capivasertib by approximately 40% to 50%. Additionally, physiologically based pharmacokinetic (PBPK) modeling predicted that rifampin may decrease capivasertib's AUC and peak plasma concentration (Cmax) by 70%, and 60%, respectively. Coadministration with the moderate CYP450 3A4 inducer efavirenz, is also predicted to decrease capivasertib AUC by 60% and Cmax by 50%. Reduced therapeutic efficacy of capivasertib may occur.

MANAGEMENT: Coadministration of capivasertib with moderate CYP450 3A4 inducers should generally be avoided. However, some authorities advise caution and monitoring for reduced therapeutic efficacy with their concomitant use. Consultation of individual product labeling is advisable for further guidance.

Estradiol and other estrogen-containing medications may reduce the effectiveness of elagolix in treating your condition. If you require contraception, it is recommended that you use a non-hormonal form of contraception during treatment with elagolix and for one week after its discontinuation. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with capivasertib may increase the plasma concentrations of drugs that are substrates of CYP450 3A4 via inhibition of the isoenzyme. Based on clinical studies and model-informed approaches, concomitant use of capivasertib and midazolam, a sensitive CYP450 3A4 substrate, increased midazolam systemic exposure (AUC) by 1.8-fold on day 4 and by 1.2-fold on day 7 of capivasertib treatment.

MANAGEMENT: Caution is advised if capivasertib is coadministered with CYP450 3A4 substrates, particularly sensitive substrates, or those with a narrow therapeutic range. Some authorities recommend avoiding their concomitant use; however, if coadministration cannot be avoided, they advise to adjust the dosage of the CYP450 3A4 substrate in accordance with that drug's approved product labeling. Clinical and laboratory monitoring may be appropriate whenever capivasertib is added to or withdrawn from therapy.

Elagolix may reduce the blood levels and effects of norethindrone. If you are using low-dose oral contraceptives, you may have an increased risk of breakthrough bleeding and unintended pregnancy. You should discuss the use of alternative or additional methods of birth control with your healthcare provider. If you take hormone replacement for menopause, notify your doctor if your medication is no longer controlling your symptoms or you experience abnormal bleeding. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.