Darunavir/Cobicstat versus Ethinyl Estradiol/Drosperinone
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Study Design
Study was an open label, two cohort (n=18/cohort), fixed sequence Phase 1 study in healthy female subjects that evaluated the DDI potential between multiple dose Atazanavir/Cobicistat (ATV/COBI) 300 mg / 150 mg) or Darunavir/Cobicistat (DRV+COBI 800 mg+150 mg) and single dose OC drospirenone/ethinyl estradiol (EE).
Study Results
In Study , drospirenone exposures (AUCinf) were 1.6-fold and 2.3-fold higher upon coadministration of drospirenone/EE with DRV+COBI or ATV+COBI respectively, compared to drospirenone/EE alone. EE AUCinf decreased 30% following treatment with drospirenone/EE and DRV+COBI, and was unchanged following treatment with ATV+COBI with drospirenone/EE, compared with drospirenone/EE alone. Most subjects completed treatment with ATV+COBI (14/18) and DRV+COBI (15/18). All study discontinuations were due to study drug-related adverse events (AEs; Grade 1 maculopapular rash). The majority of AEs were mild; no Grade 3 or 4 AEs were observed.
Study Conclusions
The authors concluded that the increase in progestin (drospirenone) levels was consistent with known CYP3A inhibition by cobicistat. Further, the decrease in EE exposure has been seen in previous drug interaction studies utilizing OCs with darunavir+ritonavir. The findings in this study were expected and such align with the prescribing recommendations for combining these agents. For drospirenone/EE, clinical monitoring is recommended when coadministered with COBI-containing regimens due to potential for hyperkalemia. This recommendation is aligned with the prescribing information of drospirenone/EE.
References
Majeed S, West S, Jiang S, Andrews J, Singha S, Ling K. Confirmation of the drug-drug interaction (ddi) potential between cobicistat-boosted antiretroviral regimens and hormonal contraceptives. International Workshop On Clinical Pharmacology Of Antiviral Therapy . Chicago, IL, USA. 18; June 2017.
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