Comment
Author: Admin | 2025-04-28
Data from clinical studies (Figure 1).Patients With Hepatic impairmentHepatic impairment does not have any impact on the exposure of semaglutide. The pharmacokinetics of semaglutide were evaluated in patients with different degrees of hepatic impairment (mild, moderate, severe) compared with subjects with normal hepatic function in a study with 10 consecutive days of once daily oral doses of semaglutide.Patients With Disease In The Upper GI TractUpper GI disease (chronic gastritis and/or gastroesophageal reflux disease) does not impact semaglutide pharmacokinetics in a clinically relevant manner. This was shown in a study in patients with type 2 diabetes with or without upper GI disease dosed for 10 consecutive days with once daily oral doses of semaglutide.Pediatric PatientsSemaglutide has not been studied in pediatric patients.Drug Interaction StudiesIn vitro studies have shown very low potential for semaglutide to inhibit or induce CYP enzymes, and to inhibit drug transporters.The delay of gastric emptying with semaglutide may influence the absorption of concomitantly administered oral medicinal products. Trials were conducted to study the potential effect of semaglutide on the absorption of oral medications taken with semaglutide administered orally at steady-state exposure.No clinically relevant drug-drug interaction with semaglutide (Figure 2) was observed based on the evaluated medications. Total exposure (AUC) of thyroxine (adjusted for endogenous levels) was increased by 33% following administration of a single dose of levothyroxine 600 μg concurrently administered with semaglutide. Maximum exposure (Cmax) was unchanged [see DRUG INTERACTIONS].Figure 2. Impact of semaglutide on the exposure of treatment with other oral medications Relative exposure in terms of AUC and Cmax for each medication when given with semaglutide compared to without semaglutide. Metformin and oral contraceptive drug (ethinylestradiol/levonorgestrel) were assessed at steady state. Effect on levothyroxine is measured as baseline corrected total T4 (thyroxine) concentration. Lisinopril, warfarin (S-warfarin/R-warfarin), digoxin, furosemide, rosuvastatin and levothyroxine were assessed after a single dose. Abbreviations: AUC: area under the curve. Cmax: maximum concentration. CI: confidence interval. No clinically relevant change in semaglutide exposure was observed when taken with omeprazole.ImmunogenicityThe observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of semaglutide or of other semaglutide products.During the 26-78 week treatment periods in 5 clinical trials [see Clinical Studies] and 1 clinical trial in Japanese adults with type 2 diabetes mellitus, 14/2924 (0.5%) of RYBELSUS-treated patients developed anti-semaglutide antibodies. Of these 14 RYBELSUS-treated patients, 7 patients (0.2% of the total RYBELSUS-treated study population) developed antibodies that cross-reacted with native GLP-1. No identified clinically significant effect of anti-semaglutide antibodies on pharmacokinetics of RYBELSUS was observed.There is insufficient information to
Add Comment