Oral semaglutide does not significantly alter the of ethinylestradiol and levonorgestrel.
The area under the curve (AUC) for ethinylestradiol and levonorgestrel remained stable when co-administered with oral semaglutide.
AUC ratios for ethinylestradiol and levonorgestrel were 1.06, indicating no significant interaction.
Furosemide and rosuvastatin showed a notable increase in AUC values when taken with oral semaglutide, with ratios of 1.28 and 1.41, respectively.
Sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC) did not impact the pharmacokinetics of ethinylestradiol, levonorgestrel, or rosuvastatin.
Adverse events reported were consistent with those previously documented for glucagon-like peptide-1 receptor agonists.
Simplified
BACKGROUND: The first oral glucagon-like peptide-1 receptor agonist (GLP-1RA) comprises semaglutide co-formulated with the absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC). Oral semaglutide may alter the of co-administered drugs via effects of semaglutide or SNAC. Two separate one-sequence crossover trials investigated the effects of oral semaglutide and SNAC on the pharmacokinetics of ethinylestradiol, levonorgestrel, furosemide and rosuvastatin.
METHODS: Healthy, postmenopausal women (n = 25) received once-daily combined ethinylestradiol and levonorgestrel (Trial 1) and healthy male and female subjects (n = 41) received single doses of furosemide and rosuvastatin (Trial 2), either alone, with SNAC alone or with oral semaglutide. Lack of drug-drug interaction was concluded if 90% confidence intervals (CIs) for the ratio of area under the plasma concentration-time curve (AUC) or maximum concentration (C), with/without oral semaglutide, were within a pre-specified interval (0.80-1.25). max
RESULTS: The AUC values of ethinylestradiol and levonorgestrel were not affected by oral semaglutide co-administration (estimated ratios [90% CI] 1.06 [1.01-1.10] and 1.06 [0.97-1.17], respectively); Cwas not affected. The no-effect criterion was not met for furosemide or rosuvastatin for the AUC (1.28 [1.16-1.42] and 1.41 [1.24-1.60], respectively) or C. SNAC alone did not affect the AUC or Cof ethinylestradiol, levonorgestrel or rosuvastatin; the Cof furosemide was slightly decreased. Adverse events were similar to those previously observed for GLP-1RAs (both trials). max max max max
CONCLUSION: Co-administration with oral semaglutide did not affect the pharmacokinetics of ethinylestradiol or levonorgestrel. There was a small increase in exposure of furosemide and rosuvastatin; however, these increases are not expected to be of clinical relevance.
CLINICAL TRIAL REGISTRATION NUMBERS: NCT02845219 and NCT03010475.
Key numbers
28%
Increase in furosemide exposure
Furosemide exposure increased when co-administered with oral semaglutide.
41%
Increase in rosuvastatin exposure
Rosuvastatin exposure increased when co-administered with oral semaglutide.
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Tine A. Bækdal, Erik Christiansen, Azadeh Houshmand-Øregaard, Easwaran Manigandan and Andreas B. Jordy are Novo Nordisk employees. Tine A. Bækdal, Thomas W. Anderson, Erik Christiansen, Azadeh Houshmand-Øregaard and Easwaran Manigandan own stocks or shares in Novo Nordisk. Thomas W. Anderson is a former employee of Novo Nordisk.
