Liverpool HIV Interactions

No Interaction Expected

Cabotegravir/rilpivirine [long acting] (CAB/RPV LA)

Ethinylestradiol

Quality of Evidence: Very Low

Summary:

Coadministration with intramuscular cabotegravir and rilpivirine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of oral cabotegravir (30 mg once daily) with an oral contraceptive containing ethinylestradiol (0.03 mg) and levonorgestrel (0.15 mg) did not significantly affect ethinylestradiol and levonorgestrel plasma concentrations to a clinically relevant extent. Ethinylestradiol Cmax decreased by 8%, AUC increased by 2% and there was no change in Ctau; levonorgestrel Cmax, AUC and Ctau increased by 5%, 12% and 7%, respectively. Coadministration of ethinylestradiol/norethindrone (0.035/1 mg once daily) and oral rilpivirine (25 mg once daily) had no effect on rilpivirine Cmax, AUC or Cmin when compared to historic controls (n=15). Ethinylestradiol Cmax, AUC and Cmin increased by 17%, 14% and 9%, respectively. Norethindrone Cmax, AUC and Cmin decreased by 6%, 11% and 1%, respectively. Similarly, no interaction is expected with intramuscular cabotegravir/rilpivirine. No dose adjustment of oral contraceptives is necessary when coadministered with cabotegravir/rilpivirine. Note, use of ethinylestradiol as part of gender affirming treatment is not recommended due to thrombotic risks.

Description:

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.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

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.

Rekambys (rilpivirine prolonged release injection) European Summary of Product Characteristics, Janssen-Cilag, January 2021.

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%.

Cabenuva (cabotegravir/rilpivirine extended release injection) US Prescribing Information, ViiV Healthcare, January 2021.

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.

Lack of effect of oral cabotegravir on the pharmacokinetics of a levonorgestrel/ethinyl oestradiol-containing oral contraceptive in healthy adult women. Trezza C, Ford SL, Gould E, et al. Br J Clin Pharmacol. 2017 Jul;83(7):1499-1505.

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.

Hormonal contraception use and cabotegravir pharmacokinetics in HIV-uninfected women enrolled in HPTN 077. Blair CS, Li S, Chau G, et al. J Acquir Immune Defic Syndr. 2020;85(1):93-97.

View all available interactions with Cabotegravir/rilpivirine [long acting] (CAB/RPV LA) by clicking here.