Interactions : אינטראקציות

8. DRUG INTERACTIONS

8.1. Potential for ORILISSA to Affect Other Drugs
Elagolix is:
•   A weak to moderate inducer of cytochrome P450 (CYP) 3A. Co-administration with ORILISSA may decrease plasma concentrations of drugs that are substrates of CYP3A (see Table 7).
•   A weak inhibitor of CYP 2C19. Co-administration with ORILISSA may increase plasma concentrations of drugs that are substrates of CYP2C19 (see Table 7).
•   An inhibitor of efflux transporter P-glycoprotein (P-gp). Co-administration with ORILISSA may increase plasma concentrations of drugs that are substrates of P-gp (see Table 7).
The effects of co-administration of ORILISSA on concentrations of concomitant drugs and the clinical recommendations for these drug interactions are summarized in Table 7.

Table 7. Drug Interactions: Effects of ORILISSA on Other Drugs
Concomitant           Effect on Plasma
Drug Class:           Exposure of          Clinical Recommendations
Drug Name             Concomitant Drug
↑ digoxin            Increase monitoring of digoxin concentrations and potential signs and symptoms of clinical toxicity when
Cardiac glycosides: initiating ORILISSA in patients who are taking digoxin.
digoxin
If ORILISSA is discontinued, increase monitoring of digoxin concentrations.
↓ midazolam          Consider increasing the dose of midazolam by no more Benzodiazepines: than 2-fold and individualize midazolam therapy based oral midazolam on the patient’s response.

Statins:                    ↓ rosuvastatin             Monitor lipid levels and adjust the dose of rosuvastatin, if rosuvastatin                                           necessary.
↑ omeprazole               No dose adjustment needed for omeprazole 40 mg once Proton pump daily when co-administered with ORILISSA. When inhibitors:
ORILISSA is used concomitantly with higher doses of omeprazole omeprazole, consider dosage reduction of omeprazole.
Combined hormonal ↑ethinyl estradiol                   Advise women to use effective non-hormonal contraceptives:          ↓levonorgestrel               contraception during treatment with ORILISSA and for oral ethinyl                                           28 days after discontinuing ORILISSA.
estradiol/levonorgestrel
See Tables 10 and 11 [see Clinical Pharmacology (12.3)].
The direction of the arrow indicates the direction of the change in the area under the curve (AUC) (↑= increase, ↓ = decrease).


8.2. Potential for Other Drugs to Affect ORILISSA
Elagolix is a substrate of CYP3A, P-gp, and OATP1B1.
Concomitant use of ORILISSA 200 mg twice daily and strong CYP3A inhibitors for more than 1 month is not recommended. Limit concomitant use of ORILISSA 150 mg once daily and strong CYP3A inhibitors to 6 months.
Co-administration of ORILISSA with strong CYP3A inducers may decrease elagolix plasma concentrations and may result in a decrease of the therapeutic effects of ORILISSA.
Concomitant use of ORILISSA 200 mg twice daily and rifampin is not recommended. Limit concomitant use of ORILISSA 150 mg once daily and rifampin to 6 months.
The effect of concomitant use of P-gp inhibitors or inducers on the pharmacokinetics of ORILISSA is unknown. OATP1B1 inhibitors that are known or expected to significantly increase elagolix plasma concentrations are contraindicated due to increased risk of elagolix- associated adverse reactions [see Contraindications (4)].