Trulicity Drug Interactions

Dulaglutide delays gastric emptying and has the potential to impact the rate of absorption of concomitantly administered oral medicinal products. Dulaglutide should be used with caution in patients receiving oral medicinal products that require rapid gastrointestinal absorption. For some prolonged release formulations, an increased release due to an extended gastric residence time may slightly increase drug exposure.
Paracetamol: Following a first dose of 1 and 3 mg dulaglutide, paracetamol C_max was reduced by 36 % and 50 %, respectively, and the median t_max occurred later (3 and 4 hours, respectively). After coadministration with up to 3 mg of dulaglutide at steady state, there were no statistically significant differences on AUC_(0-12), C_max or t_max of paracetamol. No dose adjustment of paracetamol is necessary when administered with dulaglutide.
Atorvastatin: Coadministration of dulaglutide with atorvastatin decreased C_max and AUC_(0-∞) up to 70 % and 21 %, respectively, for atorvastatin and its major metabolite o-hydroxyatorvastatin. The mean t_1/2 of atorvastatin and o-hydroxyatorvastatin were increased by 17 % and 41 %, respectively, following dulaglutide administration. These observations are not clinically relevant. No dose adjustment of atorvastatin is necessary when administered with dulaglutide.
Digoxin: After coadministration of steady state digoxin with 2 consecutive doses of dulaglutide, overall exposure (AUC) and t_max of digoxin were unchanged; and C_max decreased by up to 22 %. This change is not expected to have clinical consequences. No dose adjustment is required for digoxin when administered with dulaglutide.
Anti-hypertensives: Coadministration of multiple dulaglutide doses with steady state lisinopril caused no clinically relevant changes in the AUC or C_max of lisinopril. Statistically significant delays in lisinopril t_max of approximately 1 hour were observed on Days 3 and 24 of the study. When a single dose of dulaglutide and metoprolol were coadministered, the AUC and C_max of metoprolol increased by 19 % and 32 %, respectively. While metoprolol t_max was delayed by 1 hour, this change was not statistically significant. These changes were not clinically relevant; therefore no dose adjustment of lisinopril or metoprolol is necessary when administered with dulaglutide.
Warfarin: Following dulaglutide coadministration, S- and R-warfarin exposure and R-warfarin C_max were unaffected, and S-warfarin C_max decreased by 22 %. AUC_INR increased by 2 %, which is unlikely to be clinically significant, and there was no effect on maximum international normalised ratio response (INR_max). The time of international normalised ratio response (tINR_max) was delayed by 6 hours, consistent with delays in t_max of approximately 4 and 6 hours for S- and R-warfarin, respectively. These changes are not clinically relevant. No dose adjustment for warfarin is necessary when given together with dulaglutide.
Oral contraceptives: Coadministration of dulaglutide with an oral contraceptive (norgestimate 0.18 mg/ethinyl estradiol 0.025 mg) did not affect the overall exposure to norelgestromin and ethinyl estradiol. Statistically significant reductions in C_max of 26 % and 13 % and delays in t_max of 2 and 0.30 hours were observed for norelgestromin and ethinyl estradiol, respectively. These observations are not clinically relevant. No dose adjustment for oral contraceptives is required when given together with dulaglutide.
Metformin: Following coadministration of multiple dose dulaglutide with steady state metformin (immediate release formula [IR]), metformin AUC increased up to 15 % and C_max decreased up to 12 %, respectively, with no changes in t_max. These changes are consistent with the gastric emptying delay of dulaglutide and within the pharmacokinetic variability of metformin and thus are not clinically relevant. No dose adjustment for metformin IR is recommended when given with dulaglutide.
Sitagliptin: Sitagliptin exposure was unaffected when coadministered with a single dose of dulaglutide. Following coadministration with 2 consecutive doses of dulaglutide, sitagliptin AUC_(0-τ) and C_max decreased by approximately 7.4 % and 23.1 %, respectively. Sitagliptin t_max increased approximately 0.5 hours following coadministration with dulaglutide compared to sitagliptin alone.
Sitagliptin can produce up to 80 % inhibition of DPP-4 over a 24-hour period. Dulaglutide coadministration with sitagliptin increased dulaglutide exposure and C_max by approximately 38 % and 27 %, respectively, and median t_max increased approximately 24 hours. Therefore, dulaglutide does have a high degree of protection against DPP-4 inactivation (see Pharmacology: Pharmacodynamics under Actions). The increased exposure may enhance the effects of dulaglutide on blood glucose levels.