Coadministration of ethinyl estradiol, levonorgestrel and oral cabotegravir increased ethinyl estradiol AUC by 2%, decreased Cmax by 8% and had no effect on Ctau. Levonorgestrel AUC, Cmax and Ctau increased by 12%, 5% and 7%, respectively. Cabotegravir did not significantly change ethinyl estradiol and levonorgestrel plasma concentrations to a clinically relevant extent. No dose adjustment of oral contraceptives is necessary when coadministered with Vocabria.

Based on drug interaction study results, oral contraceptives containing levonorgestrel and ethinyl estradiol can be coadministered with cabotegravir or given after discontinuation of cabotegravir without a dose adjustment. Coadministration of ethinylestradiol (0.03 mg once daily) and oral cabotegravir (30 mg once daily) was studied in 19 subjects. Ethinylestradiol Cmax decreased by 8%, AUC increased by 2% and there was no change in Ctau. Coadministration of levonorgestrel (0.15 mg once daily) and oral cabotegravir (30 mg once daily) was studied in 19 subjects. Levonorgestrel Cmax, AUC and Ctau increased by 5%, 12% and 7%.

Coadministration of oral cabotegravir (30 mg once daily) and an oral contraceptive containing ethinylestradiol/levonorgestrel (0.03/0.15 mg once daily) was studied in 19 female subjects. Ethinylestradiol AUC increased by 2% and Cmax decreased by 7%; levonorgestrel AUC and Cmax increased by 12% and 5%. Steady-state cabotegravir pharmacokinetic parameters were comparable to historical values. There was no apparent difference in mean luteinizing hormone, follicle-stimulating hormone, and progesterone concentrations. These results support cabotegravir coadministration with ethinylestradiol/levonorgestrel oral contraceptives in clinical practice.

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.