Zemiglo Drug Interactions

In vitro assessment of interactions: The responsible enzyme for the metabolism of gemigliptin is CYP3A4. In vitro studies indicated that gemigliptin and its active metabolite are not an inhibitor of CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 or 3A4 and are not an inducer of CYP1A2, 2C8, 2C9, 2C19, or 3A4. Therefore, gemigliptin is unlikely to cause interactions with other drugs that utilize these metabolic pathways. In vitro studies further indicated that gemigliptin did not induce P-glycoprotein (P-gp) while mildly inhibited P-gp mediated transport at high concentration. Therefore, gemigliptin is unlikely to cause interactions with other P-gp substrates at therapeutic concentrations.
In vivo assessment of interactions: Effects of gemigliptin on other medicinal products: In clinical studies, gemigliptin did not meaningfully alter the pharmacokinetics of metformin, pioglitazone, glimepiride, rosuvastatin, dapagliflozin, and empagliflozin providing in vivo evidence of a low propensity for causing drug interactions with substrates of CYP2C8, CYP2C9, CYP3A4 and organic cation transporter (OCT), and UDP-glucuronosyltransferase (UGT).
Metformin: Repeated co-administration of 50 mg gemigliptin with 2000 mg metformin, a substrate of OCT1 and OCT2, decreased the C_max of metformin by 13% but did not affect the AUC of metformin at steady state.
Pioglitazone: Repeated co-administration of 200 mg gemigliptin with 30 mg pioglitazone, a substrate of CYP2C8 and 3A4, decreased the AUC and C_max of pioglitazone by 15% and 17%, respectively. However, those of the active metabolites of pioglitazone were not changed at steady state.
Glimepiride: Co-administration of multiple doses of 50 mg gemigliptin with a single dose of 4 mg glimepiride, a substrate of CYP2C9, did not meaningfully alter the pharmacokinetics of glimepiride at steady state.
Rosuvastatin: Repeated co-administration of 50 mg gemigliptin with 20 mg rosuvastatin, a substrate of CYP2C9 and 3A4, did not meaningfully alter the pharmacokinetics of rosuvastatin at steady state.
Dapagliflozin: Repeated co-administration of 50 mg gemigliptin with 10 mg of dapagliflozin, substrate of UGT1A9, did not meaningfully alter the pharmacokinetics of dapagliflozin at steady state.
Empagliflozin: Repeated co-administration of 50 mg gemigliptin with 25 mg of empagliflozin, substrate of UGT2B7, UGT1A3, UGT1A8, and UGT1A9, did not meaningfully alter the pharmacokinetics of empagliflozin at steady state.
Effects of other medical products on gemigliptin: In clinical studies, metformin, pioglitazone, rosuvastatin, dapagliflozin, and empagliflozin did not meaningfully alter the pharmacokinetics of gemigliptin. Ketoconazole did not meaningfully alter the pharmacokinetics of gemigliptin and its active metabolite. Therefore, strong and moderate CYP3A4 inhibitors would not cause clinically meaningful drug interactions. Rifampicin (rifampin), on the other hand, significantly decreased exposure of gemigliptin. Therefore, co-administration with other strong CYP3A4 inducers, including rifampicin (rifampin), dexamethasone, phenytoin, carbamazepine, rifabutin and phenobarbital, is not recommended.
Metformin: Repeated co-administration of 50 mg gemigliptin with 2000 mg metformin did not meaningfully alter the pharmacokinetics of gemigliptin at steady state.
Pioglitazone: Repeated co-administration of 200 mg gemigliptin with 30 mg of pioglitazone did not meaningfully alter the pharmacokinetics of gemigliptin and its active metabolite at steady state.
Ketoconazole: Co-administration of multiple doses of 400 mg ketoconazole once daily, a strong inhibitor of CYP3A4, with a single dose of 50 mg gemigliptin increased the AUC of active moiety, the sum of gemigliptin and its active metabolite, by 1.9-fold at steady state.
Rifampicin: Co-administration of multiple doses of 600 mg rifampicin once daily, a strong inducer of CYP3A4, with a single dose of 50 mg gemigliptin, decreased the AUC and C_max of gemigliptin by 80% and 59%, respectively. The C_max of active metabolite of gemigliptin was not significantly affected while the AUC was decreased by 36% at steady state.
Rosuvastatin: Repeated co-administration of 50 mg gemigliptin with 20 mg rosuvastatin did not meaningfully alter the pharmacokinetics of gemigliptin at steady state.
Dapagliflozin: Repeated co-administration of 50 mg gemigliptin with 10 mg of dapagliflozin did not meaningfully alter the pharmacokinetics of gemigliptin at steady state.
Empagliflozin: Repeated co-administration of 50 mg gemigliptin with 25 mg of empagliflozin did not meaningfully alter the pharmacokinetics of gemigliptin at steady state.