SYMTUZA - Drug Interaction with Ethinyl Estradiol

SUMMARY

• No studies have evaluated a drug-drug interaction between ethinyl estradiol and SYMTUZA administered as either the fixed-dose combination product or the individual drug components administered simultaneously.
• A phase 1 pharmacokinetic (PK) study in 18 healthy women evaluated a potential drug interaction between darunavir (DRV) + cobicistat (COBI) and a hormonal contraceptive containing drospirenone/ethinyl estradiol.¹
  • When the hormonal contraceptive was administered with DRV + COBI, the systemic exposure of drospirenone increased by 58% which was attributed to inhibition of the cytochrome P450 enzyme 3A by COBI.
  • The systemic exposure of ethinyl estradiol decreased by 30% when the hormonal contraceptive was administered with DRV + COBI.

CLINICAL STUDIES

DRV + COBI and Drospirenone/Ethinyl Estradiol

Majeed et al (2020)¹ evaluated the potential drug interaction between DRV + COBI and a hormonal contraceptive that contained drospirenone/ethinyl estradiol.

Study Design/Methods

• Phase 1, open-label, fixed-sequence, single-center study (N=18)
• Participants in the study were healthy, non-pregnant, nonlactating, premenopausal females aged 18-45 years of age with a body mass index 19-30 kg/m².
• Participants received a single dose of drospirenone 3 mg/ethinyl estradiol 0.02 mg on day 1, DRV 800 mg + COBI 150 mg on days 5-17, and a single dose of drospirenone 3 mg/ethinyl estradiol 0.02 mg on day 17.
• Study treatments were administered in the morning with approximately 240 mL of water following an overnight fast, within 5 minutes of completion of a standardized moderate fat breakfast (~600 kcal and 27% fat).
• On PK assessment days, food intake was restricted until after the 4-hour blood sample was collected, and water intake was restricted 1 hour before and 2 hours after dosing of study drug.
• Blood samples for PK analysis were collected over 96 hours after study drug administration on day 1 and day 17.

Results

Efficacy

• Drospirenone and ethinyl estradiol PK are noted in Table: Drospirenone and Ethinyl Estradiol PK Parameters.
• The steady state PK parameters of DRV and COBI are noted in Table: DRV and COBI PK Parameters.

Safety

• A total of 13 participants had an adverse event.
• Four participants experienced adverse events that were considered by the investigator to be drug related.
• Three participants (16.7%) discontinued the study due to grade 1 maculopapular rash.
  • All rash events were assessed by the investigator as related to study treatment and resolved following treatment with topical and/or oral antihistamines or corticosteroids (ie, hydrocortisone 1% cream, oral diphenhydramine, or oral methylprednisolone).
• There were no clinically relevant changes in median laboratory values throughout the study; all laboratory abnormalities were grade 1 or 2 in severity.
• There were increases in serum creatinine and corresponding decreases in estimated glomerular filtration rate calculated using the Cockroft-Gault equation while participants were receiving DRV + COBI (median creatinine increase from baseline of 0.15 mg/dL) that recovered to near baseline at day 21.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 06 August 2025.