Lack of effect of oral cabotegravir on the pharmacokinetics of a levonorgestrel/ethinyl oestradiol‐containing oral contraceptive in healthy adult women

Abstract

AimsThis study aimed to investigate whether cabotegravir (CAB), an integrase inhibitor in development for treatment and prevention of human immunodeficiency virus‐1, influences the pharmacokinetics (PK) of a levonorgestrel (LNG) and ethinyl oestradiol (EO)–containing oral contraceptive (OC) in healthy women.MethodsIn this open‐label, fixed‐sequence crossover study, healthy female subjects received LNG 0.15 mg/EO 0.03 mg tablet once daily Days 1–10 alone and with oral CAB 30 mg once daily Days 11–21. At the end of each treatment period, subjects underwent predose sampling for concentrations of follicle‐stimulating hormone, luteinizing hormone, and progesterone and serial PK sampling for plasma LNG, EO, and CAB concentrations.ResultsTwenty women were enrolled, and 19 completed the study. One subject was withdrawn due to an adverse event unrelated to study medications. Geometric least squares mean ratios (90% confidence interval) of LNG + CAB vs. LNG alone for LNG area under the plasma concentration–time curve over the dosing interval of duration τ and maximum observed plasma concentration were 1.12 (1.07–1.18) and 1.05 (0.96–1.15), respectively. Geometric least squares mean ratio (90% confidence interval) of EO + CAB vs. EO alone for EO area under the plasma concentration–time curve over the dosing interval of duration τ and maximum observed plasma concentration were 1.02 (0.97–1.08) and 0.92 (0.83–1.03), respectively. Steady‐state CAB PK parameters were comparable to historical values. There was no apparent difference in mean luteinizing hormone, follicle‐stimulating hormone, and progesterone concentrations between periods. No clinically significant trends in laboratory values, vital signs, or electrocardiography values were observed.ConclusionsRepeat doses of oral CAB had no significant effect on LNG/EO PK or pharmacodynamics, which supports CAB coadministration with LNG/EO OCs in clinical practice.

Pharmacokinetics and Drug–Drug Interactions of Long-Acting Intramuscular Cabotegravir and Rilpivirine

“…2 a Impact of oral cabotegravir on co-medication pharmacokinetics from drug-drug interaction crossover studies in healthy volunteers. [34,70,71,85,86,94] ◂ that predicts drug pharmacokinetics using anatomical, physiological and biological data for the population of interest and in vitro data describing the absorption, distribution, metabolism and elimination of the drug of interest [89]. PBPK modelling enables simulation of clinical scenarios and therefore constitutes a useful approach to predict DDIs with intramuscular cabotegravir and rilpivirine.…”

<p>Evaluating cabotegravir/rilpivirine long-acting, injectable in the treatment of HIV infection: emerging data and therapeutic potential</p>

“…There is no interaction between cabotegravir and levonorgestrel or ethinyl oestradiol-containing oral contraceptives in healthy adult women65 nor was a change in cabotegravir concentrations detected with any form of hormonal contraception in women in the HPTN 077 study 66. To date, we are not aware of any data on interactions between LA CR and depot contraceptives.…”

Potential risk of drug–drug interactions with hormonal contraceptives and antiretrovirals: prevalence in women living with HIV

“…Present evidence suggests no clinically significant interactions with cabotegravir, currently an investigational INSTI, and HCs; however, further research is needed as oral formulations of contraceptives followed by cabotegravir in cisgender women not living with HIV have been associated with lower peak cabotegravir concentrations. 22 , 23 …”