DRUG INTERACTIONS
Abrocitinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with abrocitinib is necessary. Rifaximin is a P-gp substrate and abrocitinib is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ratio of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with rifaximin can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If rifaximin is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Dihydrocodeine is partially metabolized by CYP3A4. Rifaximin is a moderate CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with rifaximin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifaximin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifaximin is a moderate CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with rifaximin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifaximin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate; rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Acetaminophen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with rifaximin is necessary; consider increasing the dose of oxycodone as needed. If rifaximin is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and rifaximin is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Amiodarone: (Moderate) Concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and amiodarone, a P-gp inhibitor, may increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During an in vitro study, coadministration with a potent P-gp inhibitor resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and clarithromycin, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Concomitant use of codeine with rifaximin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifaximin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifaximin is a moderate CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with rifaximin can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If rifaximin is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Dihydrocodeine is partially metabolized by CYP3A4. Rifaximin is a moderate CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with rifaximin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifaximin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifaximin is a moderate CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Aspirin, ASA; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with rifaximin is necessary; consider increasing the dose of oxycodone as needed. If rifaximin is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and rifaximin is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Atazanavir: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin and atazanavir may increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. Rifaximin is a substrate for the drug transporters P-gp and organic anion transporting polypeptide (OATP); atazanavir is an inhibitor of OATP1B1. During one in vitro study, coadministration with a combined P-gp and OATP1B1 inhibitor resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively.
Atazanavir; Cobicistat: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin and atazanavir may increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. Rifaximin is a substrate for the drug transporters P-gp and organic anion transporting polypeptide (OATP); atazanavir is an inhibitor of OATP1B1. During one in vitro study, coadministration with a combined P-gp and OATP1B1 inhibitor resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) and organic anion-transporting polypeptide (OATP1A1/1B1/1B3) substrate, with cobicistat, a P-gp and OATP inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp and OATP inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Avapritinib: (Minor) Avoid coadministration of avapritinib with rifaximin in patients with hepatic impairment due to the risk of decreased avapritinib efficacy. Avapritinib is a CYP3A4 substrate. In vitro, rifaximin is a CYP3A4 inducer. In patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. However, it is unknown whether rifaximin can have a significant effect on the pharmacokinetics of CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations. Coadministration with a moderate CYP3A4 inducer is predicted to decrease the AUC and Cmax of avapritinib by 62% and 55%, respectively.
Axitinib: (Moderate) In patients with hepatic impairment, avoid coadministration of axitinib with rifaximin if possible due to the risk of decreased efficacy of axitinib. Selection of a concomitant medication with no or minimal CYP3A4 induction potential is recommended. Axitinib is a CYP3A4/5 substrate. In patients with normal hepatic function, rifaximin is not expected to induce CYP3A4 at the recommended dosing regimen. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Bepridil: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and bepridil, a P-gp inhibitor, may increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During an in vitro study, coadministration with a potent P-gp inhibitor resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively.
Berotralstat: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with berotralstat is necessary. Rifaximin is a P-glycoprotein (P-gp) substrate and berotralstat is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with a P-gp inhibitor decreased the efflux ratio of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Boceprevir: (Moderate) Rifaximin is a substrate of P-gp and boceprevir is a P-gp inhibitor. Coadministation may result in increased plasma concentrations of rifaximin; use caution. In patients with hepatic impairment, reduced drug metabolism may increase the effects of P-gp inhibition.
Brigatinib: (Moderate) In patients with hepatic impairment, avoid coadministration of brigatinib with rifaximin due to decreased plasma exposure to brigatinib which may result in decreased efficacy; brigatinib may be administered with rifaximin in patients with normal hepatic function. If concomitant use is unavoidable in patients with hepatic impairment, after 7 days of concomitant treatment with rifaximin, increase the dose of brigatinib as tolerated in 30 mg increments to a maximum of twice the original brigatinib dose. After discontinuation of rifaximin, resume the brigatinib dose that was tolerated prior to initiation of rifaximin. Brigatinib is a CYP3A4 substrate. In patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations. Coadministration with a moderate CYP3A inducer is predicted to decrease the AUC of brigatinib by approximately 50%.
Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with rifaximin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifaximin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate; rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with rifaximin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifaximin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate; rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with rifaximin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifaximin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifaximin is a moderate CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Cabozantinib: (Moderate) Rifaximin is a substrate of P-gp and cabozantinib is a P-gp inhibitor. Coadministation may result in increased plasma concentrations of rifaximin; use caution. In patients with hepatic impairment, reduced drug metabolism may increase the effects of P-gp inhibition.
Cannabidiol: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with cannabidiol is necessary. Rifaximin is a P-gp substrate and cannabidiol is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ratio of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with rifaximin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifaximin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate; rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with rifaximin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifaximin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate; rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with rifaximin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifaximin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifaximin is a moderate CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with rifaximin can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If rifaximin is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Dihydrocodeine is partially metabolized by CYP3A4. Rifaximin is a moderate CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with rifaximin can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If rifaximin is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Dihydrocodeine is partially metabolized by CYP3A4. Rifaximin is a moderate CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with rifaximin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifaximin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate; rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with rifaximin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifaximin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate; rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with rifaximin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifaximin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate; rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with rifaximin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifaximin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate; rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Clarithromycin: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and clarithromycin, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Cobicistat: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) and organic anion-transporting polypeptide (OATP1A1/1B1/1B3) substrate, with cobicistat, a P-gp and OATP inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp and OATP inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Cobimetinib: (Major) The manufacturer of cobimetinib recommends avoiding concurrent with rifaximin due to decreased cobimetinib efficacy. Cobimetinib is a CYP3A substrate in vitro, and rifaximin is a moderate inducer of CYP3A. Based on simulations, cobimetinib exposure would decrease by 73% when coadministered with a moderate CYP3A inducer. In patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Codeine: (Moderate) Concomitant use of codeine with rifaximin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifaximin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifaximin is a moderate CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with rifaximin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifaximin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifaximin is a moderate CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with rifaximin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifaximin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifaximin is a moderate CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with rifaximin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifaximin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifaximin is a moderate CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with rifaximin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifaximin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifaximin is a moderate CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Conivaptan: (Moderate) Use caution when administering conivaptan and rifaximin concurrently. Conivaptan is an inhibitor of P-glycoprotein (P-gp). Co-administration of conivaptan with P-gp substrates, such as rifaximin, can increase rifaximin exposure leading to increased or prolonged therapeutic effects and adverse events.
Cyclosporine: (Moderate) Concurrent use of rifaximin, a P-glycoprotein (P-gp) and organic anion-transporting polypeptide (OATP1A1/1B1/1B3) substrate, with cyclosporine, a P-gp and OATP inhibitor, increases the systemic exposure and maximum plasma concentration to rifaximin by 83- and 124-fold, respectively. The clinical significance of this increase in systemic exposure is unknown; thus, caution and close monitoring for adverse reactions is advised if these drugs must be administered together.
Dabigatran: (Moderate) Coadministration of dabigatran and rifaximin may result in increased dabigatran serum concentrations, increasing the risk of dabigatran adverse effects. Coadministration of dabigatran and rifaximin should be avoided in patients with severe renal impairment (CrCl <= 30 ml/min). Dabigatran is a substrate of P-glycoprotein (P-gp); rifaximin is a mild P-gp inhibitor. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Daclatasvir: (Major) The dose of daclatasvir, a CYP3A4 substrate, may need to be increased to 90 mg PO once daily when administered in combination with rifaximin. Rifaximin is categorized as a moderate CYP3A4 inducer; however in patients with normal hepatic function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance. Conversely, the therapeutic effects of rifaximin, a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptides (OATP), may be increased by daclatasvir, a P-gp and OATP inhibitor.
Darunavir; Cobicistat: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) and organic anion-transporting polypeptide (OATP1A1/1B1/1B3) substrate, with cobicistat, a P-gp and OATP inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp and OATP inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) and organic anion-transporting polypeptide (OATP1A1/1B1/1B3) substrate, with cobicistat, a P-gp and OATP inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp and OATP inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and ritonavir, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin. (Moderate) Concurrent administration of rifaximin with dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir may result in elevated rifaximin and ombitasvir plasma concentrations and altered concentrations of dasabuvir, paritaprevir, and ritonavir. Rifaximin is a substrate and inhibitor of the drug transporter P-glycoprotein (P-gp); ritonavir and paritaprevir are P-gp inhibitors. Although ritonavir's effect on rifaximin clearance is not defined, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in rifaximin Cmax and AUC, respectively. In patients with hepatic impairment, the reduced metabolism and P-gp inhibition may further increase rifaximin exposure. Dasabuvir, ombitasvir, paritaprevir, and ritonavir are also P-gp substrates. In addition, ritonavir, paritaprevir, and dasabuvir (minor) are substrates of the hepatic isoenzyme CYP3A4. Rifaximin has been shown to be an inducer of CYP3A4, but enzyme induction is not expected when rifaximin is given at FDA-approved dosages in patients with normal liver function. It is not known whether rifaximin has a significant effect on the pharmacokinetics of CYP3A4 substrates in patients with hepatic impairment. Caution and close monitoring are advised if these drugs are administered together. (Moderate) Monitor for an increase in adverse reactions related to either therapy if coadministration is necessary. Rifaximin is a substrate and inhibitor of the drug transporter P-glycoprotein (P-gp); ritonavir is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ration of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold. Dasabuvir, ombitasvir, paritaprevir, and ritonavir are also P-gp substrates. Caution and close monitoring are advised if these drugs are administered together. (Moderate) Monitor for an increase in adverse reactions related to either therapy if coadministration is necessary. Rifaximin is a substrate and inhibitor of the drug transporter P-glycoprotein (P-gp); ritonavir is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ration of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold. Dasabuvir, ombitasvir, paritaprevir, and ritonavir are also P-gp substrates. Caution and close monitoring are advised if these drugs are administered together.
Deflazacort: (Moderate) Monitor for decreased efficacy of deflazacort if concomitant use of deflazacort and rifaximin is necessary. Deflazacort is a CYP3A4 substrate. Rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations. Administration of deflazacort with multiple doses of rifampin (a strong CYP3A4 inducer) resulted in geometric mean exposures that were approximately 95% lower compared to administration alone.
Dextromethorphan; Quinidine: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and quinidine, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with rifaximin can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If rifaximin is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Dihydrocodeine is partially metabolized by CYP3A4. Rifaximin is a moderate CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with rifaximin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifaximin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate; rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Doravirine: (Moderate) Concurrent administration of doravirine and rifaximin may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate. Rifaximin is a moderate CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Concurrent administration of doravirine and rifaximin may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate. Rifaximin is a moderate CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Doxorubicin Liposomal: (Major) Avoid coadministration of rifaximin and doxorubicin if possible. If not possible, monitor doxorubicin closely for increased side effects including myelosuppression and cardiotoxicity. Oral rifaximin is largely unabsorbed and should not result in drug interactions. In vitro, rifaximin is a mild inhibitor of P-glycoprotein (P-gp). Doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin.
Doxorubicin: (Major) Avoid coadministration of rifaximin and doxorubicin if possible. If not possible, monitor doxorubicin closely for increased side effects including myelosuppression and cardiotoxicity. Oral rifaximin is largely unabsorbed and should not result in drug interactions. In vitro, rifaximin is a mild inhibitor of P-glycoprotein (P-gp). Doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin.
Dronabinol: (Moderate) Use caution if coadministration of dronabinol with rifaximin is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate. Rifaximin is a moderate inducer of CYP3A4 in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations. Concomitant use may result in decreased plasma concentrations of dronabinol.
Dronedarone: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and dronedarone, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Elagolix: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with elagolix is necessary. Rifaximin is a P-glycoprotein (P-gp) substrate and elagolix is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ration of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with elagolix is necessary. Rifaximin is a P-glycoprotein (P-gp) substrate and elagolix is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ration of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with ivacaftor is necessary. Rifaximin is a P-glycoprotein (P-gp) substrate and ivacaftor is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ration of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold. (Moderate) Monitor for rifaximin-related adverse reactions during coadministration of elexacaftor; tezacaftor; ivacaftor as concurrent use may increase exposure of rifaximin. Rifaximin is a substrate for the transporters OATP1B1 and OATP1B3; elexacaftor; tezacaftor; ivacaftor may inhibit uptake of OATP1B1 and OATP1B3.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) and organic anion-transporting polypeptide (OATP1A1/1B1/1B3) substrate, with cobicistat, a P-gp and OATP inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp and OATP inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) and organic anion-transporting polypeptide (OATP1A1/1B1/1B3) substrate, with cobicistat, a P-gp and OATP inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp and OATP inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Enasidenib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with enasidenib is necessary. Rifaximin is a P-gp substrate and enasidenib is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ration of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Encorafenib: (Major) Avoid coadministration of encorafenib and rifaximin due to decreased encorafenib exposure and potential loss of efficacy. Although not observed in patients with normal hepatic function, in patients with reduced liver function rifaximin may induce metabolism of CYP3A4 substrates, such as encorafenib. Coadministration with CYP3A4 inducers has not been studied with encorafenib; however, in clinical trials, steady-state encorafenib exposures were lower than encorafenib exposures after the first dose, suggesting CYP3A4 auto-induction.
Entrectinib: (Major) Avoid coadministration of entrectinib with rifaximin due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; rifaximin is a moderate CYP3A4 inducer. In patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Erdafitinib: (Major) If coadministration of erdafitinib and rifaximin is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If rifaximin must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21) in patients with hepatic impairment, increase the dose of erdafitinib up to 9 mg. If rifaximin is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate. In patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Erythromycin: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and erythromycin, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Erythromycin; Sulfisoxazole: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and erythromycin, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Etravirine: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and etravirine, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Fedratinib: (Moderate) Avoid coadministration of fedratinib with rifaximin in patients with hepatic dysfunction as concurrent use may decrease fedratinib exposure which may result in decreased therapeutic response. Fedratinib is a CYP3A4 substrate. In patients with normal hepatic function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with hepatic dysfunction who have elevated rifaximin concentrations. The coadministration of fedratinib with a moderate CYP3A4 inducer has not been evaluated.
Gemfibrozil: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, an organic anion-transporting polypeptide (OATP1A1/1B1/1B3) substrate, with gemfibrozil, an OATP inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, OATP inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively.
Gilteritinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with gilteritinib is necessary. Rifaximin is a P-gp substrate and gilteritinib is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ratio of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Glasdegib: (Major) Avoid coadministration of glasdegib and rifaximin due to the potential for decreased glasdegib exposure and risk of decreased efficacy. If concurrent use cannot be avoided, consider an increase the glasdegib dosage (i.e., from 100 mg PO daily to 200 mg PO daily; or from 50 mg PO daily to 100 mg PO daily) for select patients. Resume the previous dose of glasdegib after rifaximin has been discontinued for 7 days. Glasdegib is a CYP3A4 substrate; rifaximin is a moderate CYP3A4 inducer in vitro. However, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations. Coadministration with another moderate CYP3A4 inducer was predicted to decrease the glasdegib AUC value by 55%.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of pibrentasvir and rifaximin as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Rifaximin is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide (OATP) 1B1/3; pibrentasvir is an inhibitor of these drug transporters. Additionally, pibrentasvir is a substrate of P-gp while rifaximin is an inhibitor of P-gp. (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with glecaprevir is necessary. Rifaximin is a P-glycoprotein (P-gp) substrate and glecaprevir is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ration of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with rifaximin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifaximin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate; rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with rifaximin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifaximin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate; rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with rifaximin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifaximin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate; rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with rifaximin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifaximin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate; rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with rifaximin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifaximin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate; rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with rifaximin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifaximin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate; rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Concomitant use of hydrocodone with rifaximin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifaximin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate; rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with rifaximin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifaximin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate; rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with rifaximin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifaximin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate; rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Ibuprofen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with rifaximin is necessary; consider increasing the dose of oxycodone as needed. If rifaximin is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and rifaximin is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Itraconazole: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and itraconazole, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Ivacaftor: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with ivacaftor is necessary. Rifaximin is a P-glycoprotein (P-gp) substrate and ivacaftor is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ration of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Ketoconazole: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and ketoconazole, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and clarithromycin, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Lapatinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with lapatinib is necessary. Rifaximin is a P-glycoprotein (P-gp) substrate and lapatinib is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ration of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Ledipasvir; Sofosbuvir: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and ledipsavir, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Lefamulin: (Major) Avoid coadministration of lefamulin with rifaximin unless the benefits outweigh the risks as concurrent use may decrease lefamulin exposure and efficacy. Lefamulin is a CYP3A4 substrate; rifaximin is a moderate CYP3A4 inducer. In patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Lemborexant: (Moderate) Avoid coadministration of lemborexant and rifaximin as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate. Rifaximin is a moderate CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Levoketoconazole: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and ketoconazole, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Lonafarnib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with lonafarnib is necessary. Rifaximin is a P-glycoprotein (P-gp) substrate and lonafarnib is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ration of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Loperamide: (Moderate) If coadministration is necessary, monitor closely for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest). The plasma concentration of loperamide, a P-glycoprotein (P-gp) substrate, may be altered when administered concurrently with rifaximin, a mild inhibitor of P-gp.
Loperamide; Simethicone: (Moderate) If coadministration is necessary, monitor closely for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest). The plasma concentration of loperamide, a P-glycoprotein (P-gp) substrate, may be altered when administered concurrently with rifaximin, a mild inhibitor of P-gp.
Lopinavir; Ritonavir: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin and lopinavir may increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. Rifaximin is a substrate for the drug transporter organic anion transporting polypeptide (OATP); lopinavir is an inhibitor of OATP1B1. In patients with hepatic impairment, the effects of reduced metabolism and transporter inhibition may further increase exposure to rifaximin. (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and ritonavir, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Lumacaftor; Ivacaftor: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with ivacaftor is necessary. Rifaximin is a P-glycoprotein (P-gp) substrate and ivacaftor is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ration of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Lumateperone: (Major) Avoid coadministration of lumateperone and rifaximin if possible as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A4 substrate. Rifaximin is a moderate CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Maraviroc: (Minor) Use caution and closely monitor for increased adverse effects with the coadministration of maraviroc and rifaximin as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp); rifaximin is a mild inhibitor of P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
Maribavir: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with maribavir is necessary. Rifaximin is a P-gp substrate and maribavir is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ratio of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Mefloquine: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and mefloquine, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Midazolam: (Minor) Studies have shown rifaximin to be largely unabsorbed following oral administration with most of the drug recovered in feces. A clinical drug-drug interaction study showed that rifaximin administered as 200 mg PO tid for 3 or 7 days did not alter the pharmacokinetics of IV or PO midazolam presystemically or systemically, demonstrating a lack of induction of intestinal or hepatic CYP 3A4 isoenzyme. Rifaximin was also administered as 550 mg PO bid for 7 or 14 days with oral midazolam in healthy subjects. The mean AUC of a single 2 mg oral dose of midazolam was 3.8 to 8.8% lower than when midazolam was administered alone. The mean Cmax of midazolam was decreased by 4 to 5% when administered for 7 to 14 days prior to midazolam administration. However, this degree of interaction was not considered clinically significant.
Mitapivat: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with mitapivat is necessary. Rifaximin is a P-gp substrate and mitapivat is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ratio of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with rifaximin is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate. Rifaximin is a moderate CYP3A4 inducer, although in patients with normal liver function, rifaximin at the recommended dosage regimen is not expected to induce CYP3A4.
Nelfinavir: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and nelfinavir, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Neratinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with neratinib is necessary. Rifaximin is a P-glycoprotein (P-gp) substrate and neratinib is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ratio of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Nirmatrelvir; Ritonavir: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and ritonavir, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Obeticholic Acid: (Moderate) Obeticholic acid may increase the exposure to rifaximin. Rifaximin is a substrate of OATP1B1 and OATP1B3 and obeticholic acid inhibits OAT1B1 and OATP1B3 in vitro. Caution and close monitoring is advised if these drugs are used together.
Olaparib: (Minor) Monitor for a decrease in the efficacy of olaparib if coadministration with rifaximin is necessary in patients with hepatic insufficiency. Olaparib is a CYP3A substrate. In patients with normal liver function, rifaximin is not expected to induce CYP3A4 at the recommended dosing regimen. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who may have elevated rifaximin concentrations.
Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and ritonavir, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin. (Moderate) Concurrent administration of rifaximin with dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir may result in elevated rifaximin and ombitasvir plasma concentrations and altered concentrations of dasabuvir, paritaprevir, and ritonavir. Rifaximin is a substrate and inhibitor of the drug transporter P-glycoprotein (P-gp); ritonavir and paritaprevir are P-gp inhibitors. Although ritonavir's effect on rifaximin clearance is not defined, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in rifaximin Cmax and AUC, respectively. In patients with hepatic impairment, the reduced metabolism and P-gp inhibition may further increase rifaximin exposure. Dasabuvir, ombitasvir, paritaprevir, and ritonavir are also P-gp substrates. In addition, ritonavir, paritaprevir, and dasabuvir (minor) are substrates of the hepatic isoenzyme CYP3A4. Rifaximin has been shown to be an inducer of CYP3A4, but enzyme induction is not expected when rifaximin is given at FDA-approved dosages in patients with normal liver function. It is not known whether rifaximin has a significant effect on the pharmacokinetics of CYP3A4 substrates in patients with hepatic impairment. Caution and close monitoring are advised if these drugs are administered together. (Moderate) Monitor for an increase in adverse reactions related to either therapy if coadministration is necessary. Rifaximin is a substrate and inhibitor of the drug transporter P-glycoprotein (P-gp); ritonavir is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ration of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold. Dasabuvir, ombitasvir, paritaprevir, and ritonavir are also P-gp substrates. Caution and close monitoring are advised if these drugs are administered together.
Osimertinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with osimertinib is necessary. Rifaximin is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ration of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with rifaximin is necessary; consider increasing the dose of oxycodone as needed. If rifaximin is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and rifaximin is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Pacritinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with pacritinib is necessary. Rifaximin is a P-gp substrate and pacritinib is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ratio of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Posaconazole: (Moderate) Posaconazole and rifaximin should be coadministered with caution. Both posaconazole and rifaximin are substrates and inhibitors of the drug efflux protein, P-glycoprotein. This interaction may cause alterations in the plasma concentrations of both drugs, ultimately resulting in an increased risk of adverse events.
Propafenone: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and propafenone, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Quinidine: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and quinidine, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Ranolazine: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and ranolazine, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Rimegepant: (Major) Avoid coadministration of rimegepant with rifaximin; concurrent use may significantly decrease rimegepant exposure which may result in loss of efficacy. Rimegepant is a CYP3A4 substrate and rifaximin is a moderate CYP3A4 inducer in vitro. However, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Ritonavir: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and ritonavir, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Rivaroxaban: (Moderate) If coadministration is necessary, monitor closely for rivaroxaban-associated adverse reactions, such as increased bleeding risk. The plasma concentration of rivaroxaban, a P-glycoprotein (P-gp) substrate, may be altered when administered concurrently with rifaximin, a mild inhibitor of P-gp.
Romidepsin: (Moderate) Coadministration of romidepsin, a substrate for P-glycoprotein (P-gp) with rifaximin, a P-gp inhibitor may cause an increase in systemic romidepsin concentrations. Use caution when concomitant administration of these agents is necessary.
Saquinavir: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and saquinavir, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Selumetinib: (Major) Avoid coadministration of selumetinib and rifaximin due to the risk of decreased selumetinib exposure which may reduce its efficacy. Selumetinib is a CYP3A4 substrate and rifaximin is a moderate CYP3A4 inducer. In patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations. Coadministration with a moderate CYP3A4 inducer is predicted to decrease selumetinib exposure by 38%.
Simeprevir: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) and organic anion-transporting polypeptide (OATP1A1/1B1/1B3) substrate, with simeprevir, a P-gp and OATP inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp and OATP inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Siponimod: (Moderate) Concomitant use of siponimod and rifaximin is not recommended for patients with CYP2C9*1/*3 and *2/*3 genotypes due to a significant decrease in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; rifaximin is a moderate CYP3A4 inducer. In patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations. Across different CYP2C9 genotypes, a moderate CYP3A4 inducer decreased the exposure of siponimod by up to 52% according to in silico evaluation.
Sofosbuvir; Velpatasvir: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin with velpatasvir may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. Rifaximin is a substrate of the drug transporters P-glycoprotein (P-gp) and organic anion transporting polypeptides OATP1B1 and OATP1B3; velpatasvir is a P-gp, OATP1B1, and OATP1B3 inhibitor. During one in vitro study, coadministration with a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin with velpatasvir may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. Rifaximin is a substrate of the drug transporters P-glycoprotein (P-gp) and organic anion transporting polypeptides OATP1B1 and OATP1B3; velpatasvir is a P-gp, OATP1B1, and OATP1B3 inhibitor. During one in vitro study, coadministration with a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin. (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with voxilaprevir is necessary. Rifaximin is a P-glycoprotein (P-gp) substrate and voxilaprevir is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ration of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Sonidegib: (Major) Avoid the concomitant use of sonidegib and rifaximin; sonidegib levels may be significantly decreased and its efficacy reduced. Sonidegib is a CYP3A4 substrate and rifaximin is a CYP3A4 inducer in vitro. When given at the recommended dosage, rifaximin is not expected to induce the CYP3A4 isoenzyme in patients with normal liver function; however, it is not known whether rifaximin may induce metabolism of CYP3A4 substrates in patients with reduced hepatic function who may have elevated rifaximin concentrations. Physiologic-based pharmacokinetics (PBPK) simulations indicate that the sonidegib geometric mean steady-state AUC (0-24hours) would decrease by 56% in cancer patients who received 14 days of sonidegib 200 mg/day with a moderate CYP3A inducer. Additionally, the PBPK model predicts that the sonidegib geometric mean steady-state AUC (0-24 hours) would decrease by 69% in cancer patients who received sonidegib 200 mg/day with a moderate CYP3A inducer for 4 months.
Sorafenib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with sorafenib is necessary. Rifaximin is a P-glycoprotein (P-gp) substrate and sorafenib is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ratio of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Sotorasib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with sotorasib is necessary. Rifaximin is a P-gp substrate and sotorasib is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ratio of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if rifaximin must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with rifaximin is necessary; consider increasing the dose of sufentanil injection as needed. If rifaximin is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate. In patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with rifaximin as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and rifaximin is a moderate CYP3A4 inducer. In patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Telaprevir: (Moderate) Since rifaximin and telaprevir are substrates and inhibitors of the drug efflux transporter P-glycoprotein (P-gp), coadministation may result in increased plasma concentrations of both drugs. If these drugs are used in combination, monitor patients closely for adverse events.
Telithromycin: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) an organic anion-transporting polypeptide (OATP1A1/1B1/1B3) substrate, with telithromycin, a P-gp and OATP inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp and OATP inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Temsirolimus: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with temsirolimus is necessary. Rifaximin is a P-glycoprotein (P-gp) substrate and temsirolimus is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased the mean rifaximin Cmax by 83-fold and the mean AUC by 124-fold. The effect may be greater in patients with hepatic impairment.
Tepotinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with tepotinib is necessary. Rifaximin is a P-gp substrate and tepotinib is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ratio of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Teriflunomide: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, an organic anion-transporting polypeptide (OATP1A1/1B1/1B3) substrate, with teriflunomide, an OATP inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, an OATP inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively.
Tezacaftor; Ivacaftor: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with ivacaftor is necessary. Rifaximin is a P-glycoprotein (P-gp) substrate and ivacaftor is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ration of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Ticagrelor: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and ticagrelor, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Trandolapril; Verapamil: (Moderate) Rifaximin is a P-glycoprotein (P-gp) substrate. An in vitro study with the P-gp inhibitor verapamil showed that the efflux ratio of rifaximin was reduced more than 50%. Due to the potential for substantially increased systemic exposure to rifaximin, caution is advised when concurrent use of these drugs is required. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin. The clinical significance of this interaction is unknown.
Tucatinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with tucatinib is necessary. Rifaximin is a P-glycoprotein (P-gp) substrate and tucatinib is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ratio of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Ubrogepant: (Major) Consider increasing the initial and second dose of ubrogepant to 100 mg if coadministered with rifaximin in patients with reduced liver function as concurrent use may decrease ubrogepant exposure and reduce its efficacy. Ubrogepant is a CYP3A4 substrate. Rifaximin is a moderate CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Vemurafenib: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and vemurafenib, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Verapamil: (Moderate) Rifaximin is a P-glycoprotein (P-gp) substrate. An in vitro study with the P-gp inhibitor verapamil showed that the efflux ratio of rifaximin was reduced more than 50%. Due to the potential for substantially increased systemic exposure to rifaximin, caution is advised when concurrent use of these drugs is required. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin. The clinical significance of this interaction is unknown.
Vincristine Liposomal: (Moderate) Monitor patients for vincristine toxicity if coadministration of rifaximin, a mild P-glycoprotein (P-gp) inhibitor and vincristine, a P-gp substrate is necessary.
Vincristine: (Moderate) Monitor patients for vincristine toxicity if coadministration of rifaximin, a mild P-glycoprotein (P-gp) inhibitor and vincristine, a P-gp substrate is necessary.
Voclosporin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with voclosporin is necessary. Rifaximin is a P-gp substrate and voclosporin is a P-gp inhibitor. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Coadministration with one P-gp inhibitor decreased the efflux ratio of rifaximin by greater than 50%. Concomitant use with another P-gp inhibitor increased the Cmax and AUC of rifaximin by 83-fold and 124-fold.
Voxelotor: (Major) Avoid coadministration of voxelotor and rifaximin as concurrent use may decrease voxelotor exposure and lead to reduced efficacy. If coadministration is unavoidable, increase voxelotor dosage to 2,500 mg PO once daily. Voxelotor is a substrate of CYP3A4; rifaximin is a moderate CYP3A4 inducer. In patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations. Coadministration with another moderate CYP3A4 inducer is predicted to decrease voxelotor exposure by up to 60%.
Warfarin: (Moderate) Monitor the INR if warfarin is coadministered with rifaximin; concurrent use may decrease the exposure of warfarin leading to reduced efficacy. The R-enantiomer of warfarin is a CYP3A4 substrate. Rifaximin is a moderate CYP3A4 inducer; however, at the recommended dosing regimen in patients with normal liver function, rifaximin is not expected to induce CYP3A4.
Zanubrutinib: (Major) Avoid the concomitant use of zanubrutinib and rifaximin. Coadministration may result in decreased zanubrutinib exposure and reduced efficacy. Zanubrutinib is a CYP3A4 substrate; rifaximin is a moderate CYP3A4 inducer. In patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations. The AUC of zanubrutinib is predicted to decrease by 60% when coadministered with another moderate CYP3A4 inducer.