K-Cab Drug Interactions

Drugs Dependent on Gastric pH for Absorption: Due to its effects on gastric acid secretion, tegoprazan can reduce the absorption of drugs where gastric pH is an important determinant of their bioavailability. Like with other drugs that decrease intragastric acidity, the absorption of drugs such as ketoconazole, itraconazole, ampicillin ester, atazanavir, iron salts, erlotinib, gefitinib and mycophenolate mofetil (MMF) can decrease during treatment with tegoprazan. While absorption of drugs such as digoxin can increase during treatment with tegoprazan.
Because tegoprazan inhibits gastric acid secretion, co-administration of atazanavir, nelfinavir and rilpivirin with tegoprazan is expected to decrease plasma concentration of atazanavir, nelfinavir or rilpivirin which is dependent on gastric pH for absorption, results in a loss of the therapeutic effect. Therefore, concomitant use of atazanavir, nelfinavir and rilpivirine with tegoprazan is contraindicated.
Tegoprazan is mainly metabolized by CYP3A4. Concomitant use of clarithromycin, a CYP3A4 inhibitor, with tegoprazan has increased AUC_T of tegoprazan and clarithromycin by 2.5 times and 1.25 times, respectively.
Tegoprazan has been shown to have no effects on the pharmacokinetic profiles of amoxicillin.
Tegoprazan has been shown to have no effects on the pharmacokinetic profiles of atorvastatin.
Effects of other drugs on tegoprazan: Tegoprazan is metabolized in liver by CYP3A4. In vitro studies have shown that ketoconazole, a CYP3A4 inhibitor, significantly inhibited the metabolism of tegoprazan, and while inhibitors of CYP1A2, CYP2C9, CYP2C19, CYP2D6 did not significantly reduced the metabolism of tegoprazan. Concomitant use of tegoprazan with CYP3A4 inhibitors may elevate exposure of tegoprazan.
Tegoprazan is a substrate of P-gp. In vitro studies have shown that the efflux ratio of tegoprazan was decreased by verapamil, a P-gp inhibitor. Co-administration of tegoprazan and P-gp inhibitors may result in increase of exposure by increasing gastrointestinal absorption of tegoprazan.
In healthy adult subjects, co-administration of tegoprazan with clarithromycin (substrates and inhibitors of CYP3A4 and P-gp) resulted in increase of Css,max and AUC_T of tegoprazan by 1.65 times and 2.5 times, respectively. AUC_T of clarithromycin increased slightly by 1.25 times and there was no significant increase of Css,max. Neither adverse reactions nor adverse drug reactions clinically significant were observed.
In healthy adult subjects, co-administration of tegoprazan with metronidazole, tetracycline and bismuth resulted in decrease of the AUC0-12 and Css,max of tegoprazan by 0.78 times and 0.75 times, respectively, and the AUC0-12 of tegoprazan metabolite M1 decreased by 0.77 times and Css,max by 0.84 times, compared to when tegoprazan was administered alone. However, no clinically significant adverse reactions or adverse drug reactions were observed.
Effects of tegoprazan on other drugs: In vitro studies have shown that tegoprazan showed competitive inhibition against CYP2C8 and CYP3A4. But, the IC50 values were approximately 25-fold greater than the peak plasma concentration of the recommended human dose.
For OATP1B1, there was a difference in the inhibitory activity of tegoprazan depending on substrates and it is expected that the plasma concentrations of some drugs which are substrate for OATP1B1 may be increased slightly considering the Cmax at the clinical doses.
As a result of co-administration of tegoprazan with metronidazole, tetracycline and bismuth to healthy adults, compared to the co-administration of metronidazole, tetracycline and bismuth, the pharmacokinetics of metronidazole was not affected, and the AUC0-6 of tetracycline was decreased by 0.62 times, Css,max decreased by 0.64 times, AUC0-6 of bismuth increased by 1.55 times, and Css,max increased by 1.38 times, but no clinically significant adverse reactions or adverse drug reactions were observed.