Coadministration of oral rilpivirine and ethinylestradiol/norethindrone (0.035/1 mg once daily) had no effect on ethinylestradiol AUC or Cmin, but increased Cmax by 17%; there was no change in norethindrone AUC, Cmin or Cmax. Rilpivirine AUC, Cmin and Cmax were unchanged based on historical controls. No dose adjustment is required.

Based on drug interaction study results, the ethinyl estradiol and norethindrone can be coadministered with rilpivirine or given after discontinuation of rilpivirine. Coadministration of ethinylestradiol/norethindrone (0.035/1 mg once daily) and oral rilpivirine (25 mg once daily) was studied in 15 subjects. There was no effect on rilpivirine Cmax, AUC or Cmin when compared to historic controls. Ethinylestradiol Cmax, AUC and Cmin increased by 17%, 14% and 9%, respectively. Norethindrone Cmax, AUC and Cmin decreased by 6%, 11% and 1%, respectively.

The effect of hormonal contraceptive use on intramuscular cabotegravir (CAB) pharmacokinetics was evaluated in the framework of the HPTN077 clinical study. Participants received 4-week daily oral cabotegravir lead-in, followed by CAB-LA 800 mg injection every 12 weeks (cohort 1) or 600 mg every 8 weeks (after 4-week initial interval between injections, cohort 2), over 41 weeks. Differences in CAB-LA PK parameters were evaluated against self-reported hormonal contraceptive use. Compared to women reporting no hormonal contraception (n=6), oral contraceptive use (n=18) was associated with lower CAB-LA Cmax but was not associated with differences in other PK parameters. No other hormonal contraceptive type (injectable, implants, and other) was associated with significant differences in CAB-LA PK parameters. Cabotegravir Cmax, AUC and Ctrough decreased by 25%, 19% and 9% with contraceptive use. Although oral contraceptive use was associated with differences in CAB-LA Cmax, no differences were observed in other PK parameters, suggesting that this association is not likely to be clinically significant. However, these data highlight the need for further research exploring potential drug-drug interactions between CAB-LA and hormonal contraceptives.