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  • CLASSES

    Antibiotics for IBS-D
    Intestinal Antibiotics

    DEA CLASS

    Rx

    DESCRIPTION

    Oral, non-systemically absorbed rifamycin antibiotic
    Approved to treat traveler's diarrhea (due to non-invasive strains of Escherichia coli), to reduce risk of hepatic encephalopathy recurrence, and treatment of irritable bowel syndrome with diarrhea (IBS-D)
    No significant drug interactions since not systemically absorbed

    COMMON BRAND NAMES

    Xifaxan

    HOW SUPPLIED

    Xifaxan Oral Tab: 200mg, 550mg

    DOSAGE & INDICATIONS

    For the treatment of traveler's diarrhea due to noninvasive strains of E. coli.
    Oral dosage
    Adults

    200 mg PO 3 times daily for 3 days. Rifaximin is an alternative treatment for severe, nondysenteric diarrhea in areas where invasive pathogens are not common. May reserve use for patients unable to take a quinolone or azithromycin. Antibiotic treatment is not recommended for mild cases, may be considered for moderate cases, and should be used for severe cases.

    Children 12 years and Adolescents

    200 mg PO 3 times daily for 3 days.

    For reduction in risk of overt hepatic encephalopathy recurrence.
    Oral dosage
    Adults

    550 mg PO twice daily. In clinical trials, 91% of subjects were using lactulose concomitantly. Differences in the treatment effect of those subjects not using lactulose concomitantly could not be assessed.

    For the treatment of irritable bowel syndrome (IBS) with diarrhea.
    Oral dosage
    Adults

    550 mg PO three times per day for 14 days. Patients experiencing a recurrence of symptoms may receive the same 14-day dosing regimen up to 2 additional times (maximum of 3 total treatment cycles). Data from two clinical trials showed more patients receiving rifaximin experienced adequate relief of IBS symptoms compared to placebo (41% vs. 31%, p= 0.0125 and 41% vs. 32%, p = 0.0263).  

    For traveler's diarrhea prophylaxis†.
    Oral dosage
    Adults

    200 to 1,100 mg/day PO in 1 to 3 divided doses for travelers at high risk of health-related complications of traveler's diarrhea.

    For the treatment of active Crohn's disease†.
    Oral dosage
    Adults

    In an open-label study, patients ranging in age from 18 to 80 years with active Crohn's disease received rifaximin 200 mg PO three times per day for 16 weeks. At the conclusion of the study, rifaximin was well tolerated and resulted in clinical improvement in patients with active Crohn's disease. Due to the open-label design, a randomized, double-blind, placebo-controlled study is needed to confirm the effectiveness of rifaximin in active Crohn's disease.

    Geriatric

    See adult dosage.

    For the treatment of pseudomembranous colitis† due to C. difficile infection†.
    Oral dosage
    Adults

    400 mg PO 3 times daily for 20 days after 10 days of oral vancomycin for patients with second or subsequent recurrences.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    600 mg/day PO for traveler's diarrhea; 1100 mg/day PO for hepatic encephalopathy; 1650 mg/day for irritable bowel syndrome with diarrhea.

    Geriatric

    600 mg/day PO for traveler's diarrhea; 1100 mg/day PO for hepatic encephalopathy; 1650 mg/day for irritable bowel syndrome with diarrhea.

    Adolescents

    600 mg/day PO for traveler's diarrhea.

    Children

    >= 12 years: 600 mg/day PO for traveler's diarrhea.
    < 12 years: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    There is increased systemic exposure in patients with severe hepatic impairment. Pharmacokinetic trials showed increased Cmax and AUC in patients with Child-Pugh Class A, B, and C (see Pharmacokinetics). Clinical trials were limited to patients with MELD (Model for End-Stage Liver Disease) scores < 25; therefore, caution should be exercised when administering rifaximin to patients with severe hepatic impairment (Child-Pugh class C).

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    Rifaximin tablets may be taken with or without food.

    Extemporaneous Compounding-Oral

    Extemporaneous 20 mg/ml rifaximin oral suspension:
    NOTE: Rifaximin oral suspension is not an FDA approved formulation.
    With a mortar and pestle, crush six 200 mg rifaximin tablets into a fine powder.
    Mix 30 ml Ora-Plus with either 30 ml Ora-Sweet or 30 ml Ora-Sweet Sugar Free and stir vigorously.
    Levigate 30 ml of the Ora-Plus/Ora-Sweet mixture into the rifaximin powder via geometric dilution until a smooth suspension is formed.
    Transfer the mixture into a 2 ounce amber plastic bottle.
    Rinse the mortar with the remainder of the Ora-Plus/Ora-Sweet mixture and add to the amber plastic bottle to bring the final volume to 60 ml.
    Shake well before each use. This suspension is stable 60 days at room temperature (23—25 degrees C).

    STORAGE

    Xifaxan:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Rifamycin hypersensitivity

    Rifaximin is contraindicated in patients with a history of rifamycin hypersensitivity, rifaximin hypersensitivity, or hypersensitivity to any of the components of rifaximin.

    C. difficile-associated diarrhea, diarrhea, fever, pseudomembranous colitis

    Rifaximin was not found to be effective in patients with diarrhea complicated by fever and/or blood in the stool or diarrhea due to pathogens other than E. coli. Discontinue rifaximin if diarrhea symptoms get worse or persist more than 24 to 48 hours and consider alternative antibiotic therapy. Do not use rifaximin in patients where Campylobacter jejuni, Shigella sp., or Salmonella sp. may be suspected as causative pathogens. Rifaximin is not effective in cases of travelers' diarrhea due to Campylobacter jejuni. The effectiveness of rifaximin in travelers' diarrhea caused by Shigella sp. and Salmonella sp. has not been proven. Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including rifaximin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

    Biliary cirrhosis, hepatic disease

    Use caution when administering rifaximin to persons with severe hepatic disease (Child-Pugh class C). There is increased rifaximin systemic exposure in persons with severe hepatic impairment. Clinical trials were limited to subjects with MELD (Model for End-Stage Liver Disease) scores less than 25. Severe cutaneous adverse reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN), as well as cases of rhabdomyolysis have been associated with the use of rifaximin in patients with biliary cirrhosis in postmarketing reports.

    Geriatric

    Clinical studies with rifaximin for travelers' diarrhea did not include sufficient numbers of patients aged 65 and older to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between geriatric and younger patients, but greater sensitivity of some older individuals cannot be ruled out. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities (LTCFs). According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.

    Pregnancy

    There are no available data on rifaximin use in human pregnancy to inform any drug associated risks. However, because systemic absorption of rifaximin after oral administration is minimal, rifaximin is suggested as an alternative agent for travelers' diarrhea in pregnant women in whom quinolones are contraindicated. Pregnant women have a higher risk of experiencing travelers' diarrhea due to decreased gastric acidity and increased GI transit time, and the consequences of fluid loss may be more severe (e.g., premature labor, shock). Teratogenic effects were observed in animal reproduction studies after administration of rifaximin to pregnant rats and rabbits during organogenesis at doses approximately 0.9 to 5 times and 0.7 to 33 times, respectively of the recommended human doses of 600 to 1,650 mg/day. In rabbits, ocular, oral and maxillofacial, cardiac, and lumbar spine malformations were observed. Ocular malformations were observed in both rats and rabbits at doses that caused reduced maternal body weight gain. Advise pregnant women of the potential risk to a fetus.

    Breast-feeding

    There is no information regarding the presence of rifaximin in human milk, the effects of rifaximin on the breast-fed infant, or the effects of rifaximin on milk production. Consider the development and health benefits of breast-feeding along with the mother's clinical need for rifaximin and any potential adverse effects on the breast-fed infant from rifaximin or from the underlying maternal condition.

    ADVERSE REACTIONS

    Severe

    toxic epidermal necrolysis / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    C. difficile-associated diarrhea / Delayed / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known

    Moderate

    peripheral edema / Delayed / 15.0-15.0
    ascites / Delayed / 11.0-11.0
    anemia / Delayed / 8.0-8.0
    depression / Delayed / 7.0-7.0
    dyspnea / Early / 6.0-6.0
    pseudomembranous colitis / Delayed / 0-5.0
    elevated hepatic enzymes / Delayed / 2.0-2.0
    superinfection / Delayed / Incidence not known

    Mild

    nausea / Early / 2.0-14.0
    dizziness / Early / 13.0-13.0
    fatigue / Early / 12.0-12.0
    headache / Early / 10.0-10.0
    abdominal pain / Early / 6.0-9.0
    pruritus / Rapid / 9.0-9.0
    pharyngitis / Delayed / 7.0-7.0
    arthralgia / Delayed / 6.0-6.0
    fever / Early / 6.0-6.0
    rash / Early / 5.0-5.0
    myalgia / Early / 0-5.0
    weight loss / Delayed / 0-2.0
    anorexia / Delayed / Incidence not known
    flushing / Rapid / Incidence not known
    urticaria / Rapid / Incidence not known

    DRUG INTERACTIONS

    Abrocitinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with abrocitinib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and abrocitinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Amiodarone: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with amiodarone is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and amiodarone is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with clarithromycin is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and clarithromycin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Asciminib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with asciminib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and asciminib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Atazanavir; Cobicistat: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with cobicistat is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and cobicistat is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Berotralstat: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with berotralstat is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and berotralstat is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Brigatinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with brigatinib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and brigatinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Cabozantinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with cabozantinib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and cabozantinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Cannabidiol: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with cannabidiol is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and cannabidiol is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Capmatinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with capmatinib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and capmatinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Carvedilol: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with carvedilol is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and carvedilol is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Clarithromycin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with clarithromycin is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and clarithromycin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Cobicistat: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with cobicistat is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and cobicistat is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Conivaptan: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with conivaptan is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and conivaptan is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Cyclosporine: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with cyclosporine is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and cyclosporine is a P-gp inhibitor. Coadministration with cyclosporine increased rifaximin overall exposure by 124-fold.
    Daclatasvir: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with daclatasvir is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and daclatasvir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Darunavir; Cobicistat: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with cobicistat is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and cobicistat is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with cobicistat is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and cobicistat is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with ritonavir is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and ritonavir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Dextromethorphan; Quinidine: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with quinidine is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and quinidine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Dronedarone: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with dronedarone is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and dronedarone is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Elagolix: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with elagolix is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and elagolix is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Elagolix; Estradiol; Norethindrone acetate: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with elagolix is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and elagolix is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Elexacaftor; tezacaftor; ivacaftor: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with ivacaftor is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and ivacaftor is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Eliglustat: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with eliglustat is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and eliglustat is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with cobicistat is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and cobicistat is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with cobicistat is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and cobicistat is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Enasidenib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with enasidenib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and enasidenib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Erdafitinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with erdafitinib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and erdafitinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Erythromycin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with erythromycin is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and erythromycin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Etravirine: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with etravirine is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and etravirine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Flibanserin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with flibanserin is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and flibanserin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Fostamatinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with fostamatinib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and fostamatinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Futibatinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with futibatinib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and futibatinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Gilteritinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with gilteritinib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and gilteritinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Glecaprevir; Pibrentasvir: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with glecaprevir is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and glecaprevir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold. (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with pibrentasvir is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and pibrentasvir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Ibrutinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with ibrutinib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and ibrutinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Isavuconazonium: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with isavuconazonium is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and isavuconazonium is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Istradefylline: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with istradefylline is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and istradefylline is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Itraconazole: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with itraconazole is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and itraconazole is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Ivacaftor: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with ivacaftor is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and ivacaftor is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Ketoconazole: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with ketoconazole is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and ketoconazole is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with clarithromycin is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and clarithromycin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Lapatinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with lapatinib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and lapatinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Lasmiditan: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with lasmiditan is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and lasmiditan is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Ledipasvir; Sofosbuvir: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with ledipasvir is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and ledipasvir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Levoketoconazole: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with ketoconazole is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and ketoconazole is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Lomitapide: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with lomitapide is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and lomitapide is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Lonafarnib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with lonafarnib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and lonafarnib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Lopinavir; Ritonavir: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with ritonavir is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and ritonavir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Lumacaftor; Ivacaftor: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with ivacaftor is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and ivacaftor is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Maribavir: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with maribavir is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and maribavir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Mefloquine: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with mefloquine is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and mefloquine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Mifepristone: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with mifepristone is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and mifepristone is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Mitapivat: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with mitapivat is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and mitapivat is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Nelfinavir: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with nelfinavir is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and nelfinavir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Neratinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with neratinib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and neratinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Nirmatrelvir; Ritonavir: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with ritonavir is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and ritonavir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with ritonavir is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and ritonavir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Osimertinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and osimertinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Pacritinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with pacritinib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and pacritinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Posaconazole: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with posaconazole is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and posaconazole is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Propafenone: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with propafenone is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and propafenone is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Quinidine: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with quinidine is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and quinidine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Quinine: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with quinine is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and quinine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Ranolazine: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with ranolazine is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and ranolazine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Ritonavir: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with ritonavir is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and ritonavir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Rolapitant: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with rolapitant is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and rolapitant is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Saquinavir: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with saquinavir is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and saquinavir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Sarecycline: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with sarecycline is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and sarecycline is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Selpercatinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with selpercatinib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and selpercatinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Sofosbuvir; Velpatasvir: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with velpatasvir is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and velpatasvir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with velpatasvir is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and velpatasvir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold. (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with voxilaprevir is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and voxilaprevir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Sorafenib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with sorafenib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and sorafenib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Sotorasib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with sotorasib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and sotorasib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Telithromycin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with telithromycin is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and telithromycin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Temsirolimus: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with temsirolimus is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and temsirolimus is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Tepotinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with tepotinib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and tepotinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Tezacaftor; Ivacaftor: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with ivacaftor is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and ivacaftor is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Ticagrelor: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with ticagrelor is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and ticagrelor is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Trandolapril; Verapamil: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with verapamil is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and verapamil is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Tucatinib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with tucatinib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and tucatinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Vemurafenib: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with vemurafenib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and vemurafenib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Venetoclax: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with venetoclax is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and venetoclax is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Verapamil: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with verapamil is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and verapamil is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Voclosporin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with voclosporin is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and voclosporin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with clarithromycin is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and clarithromycin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
    Zonisamide: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with zonisamide is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and zonisamide is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no available data on rifaximin use in human pregnancy to inform any drug associated risks. However, because systemic absorption of rifaximin after oral administration is minimal, rifaximin is suggested as an alternative agent for travelers' diarrhea in pregnant women in whom quinolones are contraindicated. Pregnant women have a higher risk of experiencing travelers' diarrhea due to decreased gastric acidity and increased GI transit time, and the consequences of fluid loss may be more severe (e.g., premature labor, shock). Teratogenic effects were observed in animal reproduction studies after administration of rifaximin to pregnant rats and rabbits during organogenesis at doses approximately 0.9 to 5 times and 0.7 to 33 times, respectively of the recommended human doses of 600 to 1,650 mg/day. In rabbits, ocular, oral and maxillofacial, cardiac, and lumbar spine malformations were observed. Ocular malformations were observed in both rats and rabbits at doses that caused reduced maternal body weight gain. Advise pregnant women of the potential risk to a fetus.

    There is no information regarding the presence of rifaximin in human milk, the effects of rifaximin on the breast-fed infant, or the effects of rifaximin on milk production. Consider the development and health benefits of breast-feeding along with the mother's clinical need for rifaximin and any potential adverse effects on the breast-fed infant from rifaximin or from the underlying maternal condition.

    MECHANISM OF ACTION

    Rifaximin is a semi-synthetic derivative of rifampin and acts by binding to the beta-subunit of bacterial DNA-dependent RNA polymerase thereby blocking 1 of the steps in transcription. This results in inhibition of bacterial protein synthesis and consequently inhibits bacterial growth.
     
    Resistance to rifaximin is caused primarily by mutations in the rpoB gene. This changes the binding site on DNA-dependent RNA polymerase and decreases rifaximin binding affinity, thereby reducing efficacy.
     
    Since oral rifaximin is minimally absorbed, it is concentrated in the gastrointestinal tract, where it exerts its effects. In general, oral antibiotics have been used for hepatic encephalopathy to reduce ammonia-producing enteric bacteria.

    PHARMACOKINETICS

    Rifaximin is administered orally, although it is largely unabsorbed by the GI tract. Rifaximin is 67.5% bound to plasma proteins in healthy subjects and 62% bound to plasma proteins in patients with hepatic impairment. In an in vitro study, rifaximin was metabolized mainly by CYP3A4. Rifaximin accounted for 18% of radioactivity in plasma suggesting that the absorbed rifaximin undergoes extensive metabolism. After administration of radiolabeled rifaximin to healthy volunteers, 96.62% of the administered radioactivity was recovered in the feces mostly as unchanged drug and 0.32% was recovered in urine mostly as metabolites with 0.03% as the unchanged drug. Biliary excretion of rifaximin was suggested in a study in which rifaximin was detected in the bile after cholecystectomy in patients with intact gastrointestinal mucosa. The mean half-life in healthy subjects at steady-state is 5.63 hours and 6.08 hours in patients with irritable bowel syndrome with diarrhea.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, P-gp, OATP1A2, OAPT1B1, and OATP1B3
    In vitro studies show that rifaximin is a substrate of CYP3A4, P-gp, and OATP1A2, OAPT1B1, and OATP1B3. In vitro drug interaction studies of rifaximin show that it does not inhibit the CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4 isoenzymes. In vitro studies show rifaximin is an inhibitor of P-gp, OATP1A2, OAPT1B1, and OATP1B3. The clinical significance of potential interaction with substrates of these drug transporters is unknown.

    Oral Route

    In healthy volunteers treated with rifaximin 550 mg 3 times daily for 14 days, the median Tmax was 1 hour. The mean Cmax was 4.04 ng/mL after a single dose on day 1 and 2.39 ng/mL on day 14. The mean AUC was 10.4 ng x hour/mL after a single dose on day 1 and 9.3 ng x hour/mL on day 14. A high-fat meal consumed 30 minutes before a 550 mg dose resulted in a delay in the mean Cmax from 0.75 to 0.8 hours to 1.5 hours and increased systemic AUC by 2-fold. The Cmax of rifaximin was unchanged in the fasting vs. the fed state.
     
    After oral administration of rifaximin 200 mg, 400 mg, and 600 mg, systemic exposure increased dose-dependently by approximately 2-fold for both AUC and Cmax from 200 to 400 mg, but with a less than dose-proportional increase of 1.3-fold for both AUC and Cmax from 400 to 600 mg.
     
    In patients with irritable bowel syndrome with diarrhea treated with rifaximin 550 mg 3 times daily for 14 days, the median Tmax was 1 hour. The mean Cmax was 3.49 ng/mL after a single dose on day 1 and 4.22 ng/mL on day 14. The mean AUC was 9.69 ng x hour/mL after a single dose on day 1 and 16 ng x hour/mL on day 14.
     
    Systemic absorption of rifaximin 200 mg 3 times daily was evaluated in 13 shigellosis patients on days 1 and 3 of a 3-day treatment course. Rifaximin plasma concentrations were low and variable and there was no evidence of drug accumulation after repeated administration for 3 days. Peak plasma concentrations (Cmax) on day 1 and day 3 ranged from 0.81 to 3.4 ng/mL and 0.68 to 2.26 ng/mL, respectively. The AUC estimates were 6.95 +/- 5.15 ng x hour/mL and 7.83 +/- 4.94 ng x hour/mL, on day 1 and day 3 respectively. Rifaximin is not suitable for treating systemic bacterial infections because of the limited systemic exposure after oral rifaximin administration.