Lack of a clinically important pharmacokinetic interaction between sofosbuvir or ledipasvir and hormonal oral contraceptives norgestimate/ethinyl estradiol in HCV-uninfected female subjects
German, P.; Moorehead, L.; Pang, P.; Vimal, M.; Mathias, A.
Journal of Clinical Pharmacology 54(11): 1290-1298
2014
ISSN/ISBN: 1552-4604 PMID: 24925712 DOI: 10.1002/jcph.346Document Number: 582134
This study evaluated the potential for a drug-drug interaction between HCV direct-acting antivirals sofosbuvir or ledipasvir and oral hormonal contraceptive (OC) norgestimate/ethinyl estradiol (norgestimate 0.18/0.215/0.25 mg with ethinyl estradiol 25 μg). This was a 112-day, open-label, fixed-sequence pharmacokinetic (PK) study in healthy female subjects that included a lead-in cycle (OC only; N = 21), cycle 1 (OC only; N = 15), cycle 2 (OC + sofosbuvir; N = 15), and cycle 3 (OC + ledipasvir; N = 15). Administration of sofosbuvir with OC did not alter PK of norelgestromin (primary norgestimate metabolite) or ethinyl estradiol. Small increases in norgestrel (secondary norgestimate metabolite) AUC(tau) (19%) and C(tau) (23%) with sofosbuvir were noted. Ledipasvir did not impact PK of norelgestromin or norgestrel but modestly increased ethinyl estradiol C(max) (40%). Sofosbuvir, GS- 331007 (predominant circulating metabolite of SOF), and ledipasvir PK were similar to historical data. Pharmacodynamic markers luteinizing hormone, follicle-stimulating hormone, and progesterone values were generally comparable in all cycles. No loss in contraceptive efficacy is expected upon administration of sofosbuvir or ledipasvir/sofosbuvir with oral contraceptives containing norgestimate and ethinyl estradiol. The use of sofosbuvir or ledipasvir/sofosbuvir FDC with oral contraceptives is permitted.