Lansoprazole is metabolized through the cytochrome P450 system, specifically through the CYP3A and CYP2C19 isozymes. Studies have shown that lansoprazole does not have clinically significant interactions with other drugs metabolized by the cytochrome P450 system such as warfarin, antipyrine, indomethacin, ibuprofen, phenytoin, propanolol, prednisolone, diazepam, clarithromycin, or terfenadine in healthy subjects. These compounds are metabolized through various cytochrome P450 isozymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A. When lansoprazole was administered concomitantly with theophylline (CYP1A2, CYP3A), a minor increase (10%) in the clearance of theophylline was seen. Because of the small magnitude and the direction of the effect on theophylline clearance, this interaction has not been considered to be clinically significant. Nonetheless, individual patients may require additional titration of their theophylline dosage when lansoprazole is started or stopped to ensure clinically effective blood levels.
In a study of healthy subjects neither the pharmacokinetics of warfarin enantiomers nor prothrombin time were affected following single or multiple 60mg doses of lansoprazole. However, there have been reports of increased International Normalized Ratio (INR) and prothrombin time in patients receiving proton pump inhibitors, including lansoprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time. Lansoprazole has also been shown to have no clinically significant interaction with amoxicillin. In a single-dose crossover study examining lansoprazole 30mg and omeprazole 20mg each administered alone and concomitantly with sucralfate 1gram, absorption of the proton pump inhibitors was delayed and their bioavailability was reduced by 17% and 16%, respectively, when administered concomitantly with sucralfate. Therefore, proton pump inhibitors should be taken at least 30 minutes prior to sucralfate. In clinical trials, antacids were administered concomitantly with PREVACID FDT this did not interfere with its effect. Lansoprazole causes a profound and long-lasting inhibition of gastric acid secretion; therefore, it is theoretically possible that lansoprazole may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (e.g., ketoconazole, ampicillin esters, iron salts, digoxin).
HIV Protease Inhibitors: Co-administration of lansoprazole is not recommended with HIV protease inhibitors for which absorption is dependent on acidic intragastric pH such as atazanavir, nelfinavir; due to significant reduction in their bioavailability.
Methotrexate: Concomitant use with high-dose Methotrexate may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities.
Clopidogrel: Concomitant administration of lansoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition. No dose adjustment of clopidogrel is necessary when administered with an approved dose of lansoprazole.
Warfarin: Co-administration of lansoprazole 60mg and warfarin did not affect the pharmacokinetics of warfarin or INR. However, there have been reports of increased INR and prothrombin time in patients receiving PPIs and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with lansoprazole and warfarin concomitantly may need to be monitored for increase in INR and prothrombin time.
Tacrolimus: Concomitant administration of lansoprazole and tacrolimus may increase whole blood levels of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19.
Drugs that Inhibit or Induce CYP2C19: (Tacrolimus, Fluvoxamine): Concomitant administration of lansoprazole and tacrolimus may increase whole blood levels of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19. Inhibitors of CYP2C19 such as fluvoxamine would likely increase the systemic exposure of to lansoprazole. Inducers of CYP2C19 would likely decrease the systemic exposure to lansoprazole.