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  • CLASSES

    Antibiotics for Tuberculosis
    Rifamycin Antibiotics

    DEA CLASS

    Rx

    DESCRIPTION

    Semisynthetic rifamycin antibiotic
    Primarily used as part of first-line, combination therapy for the treatment of tuberculosis and also used to treat asymptomatic carriers of Neisseria meningitidis
    Potent inducer of hepatic microsomal enzymes and associated with many significant drug interactions

    COMMON BRAND NAMES

    Rifadin, Rimactane

    HOW SUPPLIED

    Rifadin/Rifampin Intravenous Inj Pwd F/Sol: 600mg
    Rifadin/Rifampin/Rimactane Oral Cap: 150mg, 300mg

    DOSAGE & INDICATIONS

    For the treatment of drug-susceptible tuberculosis infection as part of combination therapy.
    For the treatment of drug-susceptible tuberculosis infection in persons without HIV as part of combination therapy.
    Oral dosage
    Adults

    10 mg/kg/dose (Max: 600 mg/dose) PO once daily or 5 days/week, or alternatively, 3 days/week or twice weekly. Daily dosing is preferred and is defined as 5- or 7 days/week. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.  

    Adolescents

    10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily or 5 days/week, or alternatively, 3 days/week or twice weekly. Daily dosing is preferred and is defined as 5- or 7 days/week. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.

    Infants and Children

    10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily or 5 days/week, or alternatively, 3 days/week or twice weekly.[30314] [61094] 20 to 30 mg/kg/dose PO once daily may be considered for infants and toddlers or meningitis and/or disseminated disease. Daily dosing is preferred and is defined as 5- or 7 days/week.[61094] [65619] Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.[61094] [65619]

    Neonates†

    10 to 20 mg/kg/dose PO once daily. Although tuberculosis is rare in neonates, congenital and postnatal cases have been successfully treated with antitubercular agents. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.[53484]

    Intravenous dosage
    Adults

    10 mg/kg/dose (Max: 600 mg/dose) IV once daily or 5 days/week, or alternatively, 3 days/week or twice weekly. Daily dosing is preferred and is defined as 5- or 7 days/week. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.

    Adolescents

    10 to 20 mg/kg/dose (Max: 600 mg/dose) IV once daily or 5 days/week, or alternatively, 3 days/week or twice weekly. Daily dosing is preferred and is defined as 5- or 7 days/week. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.

    Infants and Children

    10 to 20 mg/kg/dose (Max: 600 mg/dose) IV once daily or 5 days/week, or alternatively, 3 days/week or twice weekly. 20 to 30 mg/kg/dose IV once daily may be considered for infants and toddlers or meningitis and/or disseminated disease. Daily dosing is preferred and is defined as 5- or 7 days/week. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.

    Neonates†

    10 to 20 mg/kg/dose IV once daily. Although tuberculosis is rare in neonates, congenital and postnatal cases have been successfully treated with antitubercular agents. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.[53484]

    For the treatment of drug-susceptible tuberculosis infection in persons living with HIV as part of combination therapy.
    Oral dosage
    Adults

    10 mg/kg/dose (Max: 600 mg/dose) PO once daily or 5 days/week.[30314] [34362] [61094] Higher doses may be needed for meningitis.[34362] Daily dosing is defined as 5- or 7 days/week.[61094] Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.[34362] [61094] [65619]

    Adolescents

    10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily or 5 days/week. Higher doses may be needed for meningitis.[34362] Daily dosing is defined as 5- or 7 days/week. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.

    Infants and Children

    10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily or 5 days/week. 20 to 30 mg/kg/dose PO once daily may be considered for infants and toddlers or meningitis and/or disseminated disease. Daily dosing is defined as 5- or 7 days/week. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.

    Neonates†

    10 to 20 mg/kg/dose PO once daily. Although tuberculosis is rare in neonates, congenital and postnatal cases have been successfully treated with antitubercular agents. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.[53484]

    Intravenous dosage
    Adults

    10 mg/kg/dose (Max: 600 mg/dose) IV once daily or 5 days/week.[30314] [34362] [61094] Higher doses may be needed for meningitis.[34362] Daily dosing is defined as 5- or 7 days/week.[61094] Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.[34362] [61094] [65619]

    Adolescents

    10 to 20 mg/kg/dose (Max: 600 mg/dose) IV once daily or 5 days/week. Higher doses may be needed for meningitis.[34362] Daily dosing is defined as 5- or 7 days/week. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.

    Infants and Children

    10 to 20 mg/kg/dose (Max: 600 mg/dose) IV once daily or 5 days/week. 20 to 30 mg/kg/dose IV once daily may be considered for infants and toddlers or meningitis and/or disseminated disease. Daily dosing is defined as 5- or 7 days/week. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.

    Neonates†

    10 to 20 mg/kg/dose IV once daily based. Although tuberculosis is rare in neonates, congenital and postnatal cases have been successfully treated with antitubercular agents. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.[53484]

    For the treatment of drug-resistant tuberculosis infection as part of combination therapy.
    Oral dosage
    Adults

    10 mg/kg/dose (Max: 600 mg/dose) PO once daily.[30314]

    Adolescents

    10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily.[30314]

    Infants and Children

    10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily.[30314] 20 to 30 mg/kg/dose PO once daily may be considered for infants and toddlers or meningitis and/or disseminated disease.

    Intravenous dosage
    Adults

    10 mg/kg/dose (Max: 600 mg/dose) IV once daily.[30314]

    Adolescents

    10 to 20 mg/kg/dose (Max: 600 mg/dose) IV once daily.[30314]

    Infants and Children

    10 to 20 mg/kg/dose (Max: 600 mg/dose) IV once daily.[30314] 20 to 30 mg/kg/dose IV once daily may be considered for infants and toddlers or meningitis and/or disseminated disease.

    For meningococcal carriage eradication in asymptomatic carriers.
    Oral dosage
    Adults

    600 mg PO every 12 hours for 2 days.

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 600 mg/dose) PO every 12 hours for 2 days.

    Neonates

    5 mg/kg/dose PO every 12 hours for 2 days.

    Intravenous dosage
    Adults

    600 mg IV every 12 hours for 2 days.

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 600 mg/dose) IV every 12 hours for 2 days.

    Neonates

    5 mg/kg/dose IV every 12 hours for 2 days.

    For tuberculosis prophylaxis† or latent tuberculosis infection† (LTBI).
    For tuberculosis prophylaxis† or LTBI† in combination with isoniazid.
    Oral dosage
    Adults

    10 mg/kg/dose (Max: 600 mg/dose) PO once daily for 3 to 4 months.

    Infants, Children, and Adolescents

    10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily for 3 to 4 months.

    For tuberculosis prophylaxis† or LTBI† as monotherapy in persons without HIV.
    Oral dosage
    Adults

    10 mg/kg/dose (Max: 600 mg/dose) PO once daily for 3 to 4 months.  

    Infants, Children, and Adolescents

    10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily for 3 to 4 months.

    For tuberculosis prophylaxis† or LTBI† as monotherapy in persons living with HIV.
    Oral dosage
    Adults

    10 mg/kg/dose (Max: 600 mg/dose) PO once daily for 4 months.

    Infants, Children, and Adolescents

    10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily for 4 to 6 months.

    For post-exposure meningococcal infection prophylaxis†.
    Oral dosage
    Adults

    600 mg PO every 12 hours for 2 days. Initiate prophylaxis as soon as possible after exposure (ideally less than 24 hours after identification of index patient); prophylaxis initiated more than 14 days after onset of illness in the index patient has very limited or no value.

    Infants, Children, and Adolescents

    15 to 20 mg/kg/dose (Max: 600 mg/dose) PO every 12 hours for 2 days. Initiate prophylaxis as soon as possible after exposure (ideally less than 24 hours after identification of index patient); prophylaxis initiated more than 14 days after onset of illness in the index patient has very limited or no value.

    Neonates

    5 mg/kg/dose PO every 12 hours for 2 days. Initiate prophylaxis as soon as possible after exposure (ideally less than 24 hours after identification of index patient); prophylaxis initiated more than 14 days after onset of illness in the index patient has very limited or no value.

    For Haemophilus influenzae type B prophylaxis† in carriers who are at high risk of transmitting the disease to children ages 4 years and less.
    Oral or Intravenous dosage
    Adults, Adolescents, and Children

    20 mg/kg PO or IV once daily for 4 days. Maximum daily dose is 600 mg.

    Neonates

    10 mg/kg PO or IV once daily for 4 days.

    For the treatment of leprosy (Hansen's disease)†.
    NOTE: Treatment that is more intensive and of longer duration is preferable.
    For the daily treatment of paucibacillary disease.
    Oral dosage
    Adults

    600 mg PO once daily with dapsone for 12 months.

    Infants, Children, and Adolescents

    10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily with dapsone for 12 months.

    For the monthly treatment of paucibacillary disease.
    Oral dosage
    Adults

    600 mg PO once monthly with dapsone for 12 months or dapsone and clofazimine for 6 months. Monthly treatment is recommended for those receiving prednisone and those receiving treatment through the WHO's Global Leprosy Program. The WHO's Global Leprosy Program also allows for shorter treatment durations.

    Adolescents 15 to 17 years

    600 mg PO once monthly with dapsone for 12 months or dapsone and clofazimine for 6 months. Monthly treatment is recommended for those receiving prednisone and those receiving treatment through the WHO's Global Leprosy Program. The WHO's Global Leprosy Program also allows for shorter treatment durations.

    Children and Adolescents 10 to 14 years weighing more than 40 kg

    10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once monthly with dapsone for 12 months or 450 mg PO once monthly with dapsone and clofazimine for 6 months. Monthly treatment is recommended for those receiving prednisone and those receiving treatment through the WHO's Global Leprosy Program. The WHO's Global Leprosy Program also allows for shorter treatment durations.

    Children and Adolescents 10 to 14 years weighing 20 to 40 kg

    10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once monthly with dapsone for 12 months or 300 mg PO once monthly with dapsone and clofazimine for 6 months. Monthly treatment is recommended for those receiving prednisone and those receiving treatment through the WHO's Global Leprosy Program. The WHO's Global Leprosy Program also allows for shorter treatment durations.

    Infants and Children 1 to 9 years or weighing less than 20 kg

    10 mg/kg/dose PO once monthly with dapsone for 12 months or dapsone and clofazimine for 6 months. Monthly treatment is recommended for those receiving prednisone and those receiving treatment through the WHO's Global Leprosy Program. The WHO's Global Leprosy Program also allows for shorter treatment durations.

    For the daily treatment of multibacillary disease.
    Oral dosage
    Adults

    600 mg PO once daily with dapsone and clofazimine for 24 months.

    Infants, Children, and Adolescents

    10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily with dapsone and clofazimine for 24 months.

    For the monthly treatment of multibacillary disease.
    Oral dosage
    Adults

    600 mg PO once monthly with dapsone and clofazimine for 12 or 24 months. Monthly treatment is recommended for those receiving prednisone and those receiving treatment through the WHO's Global Leprosy Program. The WHO's Global Leprosy Program also allows for shorter treatment durations.

    Adolescents 15 to 17 years

    600 mg PO once monthly with dapsone and clofazimine for 12 or 24 months. Monthly treatment is recommended for those receiving prednisone and those receiving treatment through the WHO's Global Leprosy Program. The WHO's Global Leprosy Program also allows for shorter treatment durations.

    Children and Adolescents 10 to 14 years weighing more than 40 kg

    10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once monthly with dapsone and clofazimine for 24 months or 450 mg PO once monthly with dapsone and clofazimine for 12 months. Monthly treatment is recommended for those receiving prednisone and those receiving treatment through the WHO's Global Leprosy Program. The WHO's Global Leprosy Program also allows for shorter treatment durations.

    Children and Adolescents 10 to 14 years weighing 20 to 40 kg

    10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once monthly with dapsone and clofazimine for 24 months or 300 mg PO once monthly with dapsone and clofazimine for 12 months. Monthly treatment is recommended for those receiving prednisone and those receiving treatment through the WHO's Global Leprosy Program. The WHO's Global Leprosy Program also allows for shorter treatment durations.

    Infants and Children 1 to 9 years or weighing less than 20 kg

    10 mg/kg/dose PO once monthly with dapsone and clofazimine for 12 or 24 months. Monthly treatment is recommended for those receiving prednisone and those receiving treatment through the WHO's Global Leprosy Program. The WHO's Global Leprosy Program also allows for shorter treatment durations.

    For the treatment of infective endocarditis†.
    For the treatment of native valve endocarditis due S. pneumoniae† resistant to cefotaxime.
    Oral dosage
    Adults

    300 mg PO every 8 hours for 4 weeks plus cefotaxime/ceftriaxone and vancomycin.

    Intravenous dosage
    Adults

    300 mg IV every 8 hours for 4 weeks plus cefotaxime/ceftriaxone and vancomycin.

    For the treatment of prosthetic valve endocarditis due to Staphylococcus sp.†.
    Oral dosage
    Adults

    300 mg PO every 8 hours plus nafcillin/oxacillin or vancomycin for at least 6 weeks and gentamicin for 2 weeks.

    Infants, Children, and Adolescents

    15 to 20 mg/kg/day PO divided every 8 hours (Max: 900 mg/day) plus penicillin G, nafcillin/oxacillin, vancomycin, or daptomycin for at least 6 weeks and gentamicin for 2 weeks.

    Neonates

    10 mg/kg/dose PO every 24 hours plus penicillin G, nafcillin/oxacillin, vancomycin, or daptomycin for at least 6 weeks and gentamicin for 2 weeks.

    Intravenous dosage
    Adults

    300 mg IV every 8 hours plus nafcillin/oxacillin or vancomycin for at least 6 weeks and gentamicin for 2 weeks.

    Infants, Children, and Adolescents

    15 to 20 mg/kg/day IV divided every 8 hours (Max: 900 mg/day) plus penicillin G, nafcillin/oxacillin, vancomycin, or daptomycin for at least 6 weeks and gentamicin for 2 weeks.

    Neonates

    10 mg/kg/dose IV every 24 hours plus penicillin G, nafcillin/oxacillin, vancomycin, or daptomycin for at least 6 weeks and gentamicin for 2 weeks.

    For the treatment of culture-negative prosthetic valve endocarditis†.
    Oral dosage
    Adults

    300 mg PO every 8 hours plus vancomycin and cefepime for at least 4 to 6 weeks and gentamicin for at least 2 weeks for early (1 year or less after surgery) infection.

    Infants, Children, and Adolescents

    15 to 20 mg/kg/day PO divided every 8 hours (Max: 900 mg/day) plus vancomycin and cefepime/ceftazidime for 6 weeks and gentamicin for 2 weeks for early (1 year or less after surgery) infection or plus ampicillin; sulbactam with or without vancomycin for at least 6 weeks and gentamicin for 2 weeks for late (more than 1 year after surgery) infection.

    Neonates

    10 mg/kg/dose PO every 24 hours plus vancomycin and cefepime/ceftazidime for 6 weeks and gentamicin for 2 weeks for early (1 year or less after surgery) infection or plus ampicillin; sulbactam with or without vancomycin for at least 6 weeks and gentamicin for 2 weeks for late (more than 1 year after surgery) infection.

    Intravenous dosage
    Adults

    300 mg IV every 8 hours plus vancomycin and cefepime for at least 4 to 6 weeks and gentamicin for at least 2 weeks for early (1 year or less after surgery) infection.

    Infants, Children, and Adolescents

    15 to 20 mg/kg/day IV divided every 8 hours (Max: 900 mg/day) plus vancomycin and cefepime/ceftazidime for 6 weeks and gentamicin for 2 weeks for early (1 year or less after surgery) infection or plus ampicillin; sulbactam with or without vancomycin for at least 6 weeks and gentamicin for 2 weeks for late (more than 1 year after surgery) infection.

    Neonates

    10 mg/kg/dose IV every 24 hours plus vancomycin and cefepime/ceftazidime for 6 weeks and gentamicin for 2 weeks for early (1 year or less after surgery) infection or plus ampicillin; sulbactam with or without vancomycin for at least 6 weeks and gentamicin for 2 weeks for late (more than 1 year after surgery) infection.

    For the treatment of documented Bartonella endocarditis†.
    Oral dosage
    Adults

    300 mg PO every 12 hours for at least 6 weeks plus doxycycline.

    Children and Adolescents

    20 mg/kg/day PO divided every 12 hours (Max: 600 mg/day) for at least 6 weeks plus doxycycline.

    Intravenous dosage
    Adults

    300 mg IV every 12 hours for at least 6 weeks plus doxycycline.

    Children and Adolescents

    20 mg/kg/day IV divided every 12 hours (Max: 600 mg/day) for at least 6 weeks plus doxycycline.

    For the management of methicillin-resistant Staphylococcus aureus (MRSA)-associated bone and joint infections†, including osteomyelitis†, or an orthopedic device-related infection†.
    For the management of methicillin-resistant Staphylococcus aureus (MRSA)-associated osteomyelitis.
    Oral dosage
    Adults

    600 mg PO once daily or 300 to 450 mg PO twice daily as adjuntive therapy. In patients with concurrent bloodstream infections, rifampin should be added after the clearance of the bloodstream infection. A minimum duration of 8 weeks is recommended; however, an additional 1 to 3 months may be necessary.

    For the management of methicillin-resistant Staphylococcus aureus (MRSA)-associated prosthetic joint infections.
    Oral dosage
    Adults

    600 mg PO once daily or 300 to 450 mg PO every 12 hours for 2 weeks as adjunctive therapy in patients with early-onset (less than 2 months after surgery) or acute hematogenous prosthetic joint infections involving a stable implant with short duration (3 weeks or less) of symptoms and debridement (but device retention). Oral therapy should start after the completion of IV therapy and continue for 3 months for hip infections or for 6 months for knee infections.

    For the management of methicillin-resistant Staphylococcus aureus (MRSA)-associated spinal implant infections.
    Oral dosage
    Adults

    600 mg PO once daily or 300 to 450 mg PO every 12 hours as adjunctive therapy in patients with early-onset spinal implant infections (30 days or less after surgery) or implants in an actively infected site. Prolonged oral therapy should follow parenteral therapy; however, the optimal duration of parenteral and/or oral therapy is unclear. Oral therapy should be continued until spine fusion has occurred. Long term oral suppressive therapy may be considered in select cases, especially if device removal is not possible.

    For the treatment of bartonellosis†, including catch scratch disease†, neuroretinitis†, bacillary angiomatosis†, bacillary peliosis† (peliosis hepatis†), CNS infections†, and chronic verruga peruana†.
    NOTE: See endocarditis for treatment of endocarditis.
    For the treatment of severe Bartonella infections, including multifocal disease or with clinical decompensation, in immunocompromised patients†.
    Oral dosage
    Adults

    300 PO every 12 hours for at least 3 months plus doxycycline or erythromycin as first-line therapy or azithromycin or clarithromycin as an alternative.

    Adolescents

    300 PO every 12 hours for at least 3 months plus doxycycline or erythromycin as first-line therapy or azithromycin or clarithromycin as an alternative.

    Intravenous dosage
    Adults

    300 IV every 12 hours for at least 3 months plus doxycycline or erythromycin as first-line therapy or azithromycin or clarithromycin as an alternative.

    Adolescents

    300 IV every 12 hours for at least 3 months plus doxycycline or erythromycin as first-line therapy or azithromycin or clarithromycin as an alternative.

    For the treatment of Bartonella infections involving the central nervous system in immunocompromised patients†.
    Oral dosage
    Adults

    300 mg PO every 12 hours for at least 3 months plus doxycyline as first-line therapy.

    Adolescents

    300 mg PO every 12 hours for at least 3 months plus doxycyline as first-line therapy.

    Intravenous dosage
    Adults

    300 mg IV every 12 hours for at least 3 months plus doxycyline as first-line therapy.

    Adolescents

    300 mg IV every 12 hours for at least 3 months plus doxycyline as first-line therapy.

    For the treatment of Bartonella-related neuroretinitis in immunocompetent patients†.
    Oral dosage
    Adults

    300 mg PO every 12 hours for 4 to 6 weeks plus doxycycline with or without corticosteroids as first-line therapy.

    Infants, Children, Adolescents

    10 mg/kg/dose (Max: 300 mg/dose) PO every 12 hours for 4 to 6 weeks plus azithromycin with or without corticosteroids as first-line therapy.

    Intravenous dosage
    Adults

    300 mg IV every 12 hours for 4 to 6 weeks plus doxycycline with or without corticosteroids as first-line therapy.

    Infants, Children, Adolescents

    10 mg/kg/dose (Max: 300 mg/dose) IV every 12 hours for 4 to 6 weeks plus azithromycin with or without corticosteroids as first-line therapy.

    For the treatment of complicated bacillary angiomatosis† or bacillary peliosis† (peliosis hepatis†) in immunocompetent patients.
    Oral dosage
    Adults

    300 mg PO every 12 hours for 3 months plus doxycycline.

    Intravenous dosage
    Adults

    300 mg IV every 12 hours for 3 months plus doxycycline.

    For the treatment of chronic verruga peruana†.
    Oral dosage
    Adults

    10 mg/kg/dose (Max: 600 mg/dose) PO once daily for 14 to 28 days as second-line therapy.

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 600 mg/dose) PO once daily for 14 to 28 days as second-line therapy.

    For the treatment of atypical hepatosplenic or bony cat scratch disease in immunocompetent patients†.
    Oral dosage
    Adults

    300 mg PO every 12 hours for 4 to 6 weeks with or without gentamicin or doxycycline as first-line therapy.

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 300 mg/dose) PO every 12 hours for 4 to 6 weeks plus azithromycin as first-line therapy.

    Intravenous dosage
    Adults

    300 mg IV every 12 hours for 4 to 6 weeks with or without gentamicin or doxycycline as first-line therapy.

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 300 mg/dose) IV every 12 hours for 4 to 6 weeks plus azithromycin as first-line therapy.

    For the treatment of typical cat scratch disease in immunocompetent patients†.
    Oral dosage
    Adults

    300 mg PO every 12 hours plus doxycycline as an alternative. Most cases resolve without treatment; however, consider treating patients with extensive lymphadenopathy.

    Intravenous dosage
    Adults

    300 mg IV every 12 hours plus doxycycline as an alternative. Most cases resolve without treatment; however, consider treating patients with extensive lymphadenopathy.

    For the treatment of pruritus† secondary to cholestasis.
    Oral dosage
    Adults

    A dose of 10 mg/kg PO once daily has been used.

    For the treatment of central nervous system infections†, including meningitis†, ventriculitis†, cerebrospinal fluid (CSF) shunt infections, brain abscess†, subdural empyema†, spinal epidural abscess†, or septic thrombosis of the cavernous or dural venous sinus†.
    Intravenous dosage
    Adults

    600 mg IV every 24 hours or 300 to 450 mg IV twice daily. The Infectious Diseases Society of America (IDSA) recommends consideration of the addition of rifampin to vancomycin for meningitis due to S. epidermidis or methicillin-resistant S. aureus or vancomycin plus a third-generation cephalosporin for meningitis due to penicillin-resistant S. pneumoniae. For pneumococcal meningitis, the addition of rifampin should be considered for ceftriaxone/cefotaxime MIC of more than 2 mcg/mL. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    Infants, Children, and Adolescents

    10 to 20 mg/kg/day IV in 1 to 2 divided doses (Max: 600 mg/day). The Infectious Diseases Society of America (IDSA) recommends consideration of the addition of rifampin to vancomycin for meningitis due to S. epidermidis or methicillin-resistant S. aureus or vancomycin plus a third-generation cephalosporin for meningitis due to penicillin-resistant S. pneumoniae. For pneumococcal meningitis, the addition of rifampin should be considered for ceftriaxone/cefotaxime MIC of more than 2 mcg/mL. Although rifampin in combination with vancomycin has been used successfully for staphylococcal CNS infections in children, current clinical practice guidelines for methicillin-resistant Staphylococcus aureus (MRSA) infections do not recommend the addition of rifampin to vancomycin in children with CNS infections due to limited data of a clinical benefit. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    Neonates

    Data not available in neonates 7 days and younger; however, 10 to 20 mg/kg/day IV in 2 divided doses is recommended in older neonates. The Infectious Diseases Society of America (IDSA) recommends consideration of the addition of rifampin to vancomycin for meningitis due to S. epidermidis or methicillin-resistant S. aureus or vancomycin plus a third-generation cephalosporin for meningitis due to penicillin-resistant S. pneumoniae. For pneumococcal meningitis, the addition of rifampin should be considered for ceftriaxone/cefotaxime MIC of more than 2 mcg/mL. Although rifampin in combination with vancomycin has been used successfully for staphylococcal CNS infections in neonates, current clinical guidelines for methicillin-resistant Staphylococcus aureus (MRSA) infections do not recommend the addition of rifampin to vancomycin in neonates with CNS infections due to limited data of a clinical benefit. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    Oral dosage
    Adults

    600 mg PO every 24 hours or 300 to 450 mg PO twice daily. The Infectious Diseases Society of America (IDSA) recommends consideration of the addition of rifampin to vancomycin for meningitis due to S. epidermidis or methicillin-resistant S. aureus or vancomycin plus a third-generation cephalosporin for meningitis due to penicillin-resistant S. pneumoniae. For pneumococcal meningitis, the addition of rifampin should be considered for ceftriaxone/cefotaxime MIC of more than 2 mcg/mL. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    Infants, Children, and Adolescents

    10 to 20 mg/kg/day PO in 1 to 2 divided doses (Max: 600 mg/day). The Infectious Diseases Society of America (IDSA) recommends consideration of the addition of rifampin to vancomycin for meningitis due to S. epidermidis or methicillin-resistant S. aureus or vancomycin plus a third-generation cephalosporin for meningitis due to penicillin-resistant S. pneumoniae. For pneumococcal meningitis, the addition of rifampin should be considered for ceftriaxone/cefotaxime MIC of more than 2 mcg/mL. Although rifampin in combination with vancomycin has been used successfully for staphylococcal CNS infections in children, current clinical practice guidelines for methicillin-resistant Staphylococcus aureus (MRSA) infections do not recommend the addition of rifampin to vancomycin in children with CNS infections due to limited data of a clinical benefit. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    Neonates

    Data not available in neonates 7 days and younger; however, 10 to 20 mg/kg/day PO in 2 divided doses is recommended in older neonates. The Infectious Diseases Society of America (IDSA) recommends consideration of the addition of rifampin to vancomycin for meningitis due to S. epidermidis or methicillin-resistant S. aureus or vancomycin plus a third-generation cephalosporin for meningitis due to penicillin-resistant S. pneumoniae. For pneumococcal meningitis, the addition of rifampin should be considered for ceftriaxone/cefotaxime MIC of more than 2 mcg/mL. Although rifampin in combination with vancomycin has been used successfully for staphylococcal CNS infections in neonates, current clinical guidelines for methicillin-resistant Staphylococcus aureus (MRSA) infections do not recommend the addition of rifampin to vancomycin in neonates with CNS infections due to limited data of a clinical benefit. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    For the treatment of persistent Staphylococcus aureus (MRSA) bacteremia† and vancomycin failure†.
    NOTE: Routine use of rifampin for MRSA bacteremia is not recommended.
    Intravenous and Oral dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends high dose daptomycin (See Daptomycin Dosage) in combination with another agent such as rifampin 600 mg daily or 300—450 mg twice daily PO or IV for at least 2 weeks.

    For group A streptococci chronic pharyngeal carriage eradication† in combination with penicillin G benzathine or penicillin V.
    Oral dosage
    Adults

    20 mg/kg/dose PO once daily (Max: 600 mg/day) for 4 days. Rifampin is used for the last 4 days of 10-day penicillin V treatment or with the single benzathine penicillin G dose. Most chronic streptococcal carriers do not need antimicrobial therapy. Treatment may be considered during a community outbreak of acute rheumatic fever, acute poststreptococcal glomerulonephritis or invasive group A streptococcal (GAS) infection; during an outbreak of GAS pharyngitis in a closed or partially closed community; in the presence of a family or personal history of acute rheumatic fever; in a family with excessive anxiety about GAS infections; or when tonsillectomy is being considered only because of carriage.

    Infants, Children, and Adolescents

    20 mg/kg/dose PO once daily (Max: 600 mg/day) for 4 days. Rifampin is used for the last 4 days of 10-day penicillin V treatment or with the single benzathine penicillin G dose. Most chronic streptococcal carriers do not need antimicrobial therapy. Treatment may be considered during a community outbreak of acute rheumatic fever, acute poststreptococcal glomerulonephritis or invasive group A streptococcal (GAS) infection; during an outbreak of GAS pharyngitis in a closed or partially closed community; in the presence of a family or personal history of acute rheumatic fever; in a family with excessive anxiety about GAS infections; or when tonsillectomy is being considered only because of carriage.

    For the treatment of anaplasmosis†.
    Oral
    Adults

    300 mg PO twice daily until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of 5 to 7 days as an alternative for mild disease in the case of pregnancy or documented allergy to tetracycline class drugs.

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 300 mg/dose) PO twice daily until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of 5 to 7 days as an alternative for mild disease in the case of documented allergy to tetracycline class drugs.

    For the treatment of staphylococcal peritoneal dialysis-related peritonitis† and peritoneal dialysis catheter-related infection†.
    For the treatment of peritoneal dialysis-related peritonitis†.
    Oral dosage
    Adults weighing 50 kg or more

    600 mg PO once daily for 5 to 7 days as adjuvant therapy.

    Adults weighing less than 50 kg

    450 mg PO once daily for 5 to 7 days as adjuvant therapy.

    Infants, Children, and Adolescents

    5 to 10 mg/kg/dose (Max: 300 mg/dose) PO every 12 hours as adjuvant therapy.

    For the treatment of peritoneal dialysis catheter-related infection†.
    Oral dosage
    Adults weighing 50 kg or more

    600 mg PO once daily as adjuvant therapy.

    Adults weighing less than 50 kg

    450 mg PO once daily as adjuvant therapy.

    Infants, Children, and Adolescents

    5 to 10 mg/kg/dose (Max: 300 mg/dose) PO every 12 hours as adjuvant therapy.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    10 mg/kg/day (Max: 600 mg/day) PO/IV for tuberculosis treatment; 1,200 mg/day PO/IV for meningococcal prophylaxis.

    Geriatric

    10 mg/kg/day (Max: 600 mg/day) PO/IV for tuberculosis treatment; 1,200 mg/day PO/IV for meningococcal prophylaxis.

    Adolescents

    20 mg/kg/day PO/IV (Max: 600 mg/day PO/IV for tuberculosis treatment; 1,200 mg/day PO/IV for meningococcal prophylaxis).

    Children

    20 mg/kg/day PO/IV (Max: 600 mg/day PO/IV for tuberculosis treatment; 1,200 mg/day PO/IV for meningococcal prophylaxis).

    Infants

    20 mg/kg/day PO/IV.

    Neonates

    20 mg/kg/day PO/IV for tuberculosis treatment has been used off-label; 10 mg/kg/day PO/IV for meningococcal prophylaxis.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Use rifampin in patients with hepatic impairment only in cases of necessity and then under strict medical supervision. Although specific recommendations are not available, dose adjustments of rifampin may be necessary in patients with hepatic impairment.

    Renal Impairment

    Adult patients
    CrCl more than 50 mL/minute: No dosage adjustment needed.
    CrCl less than 50 mL/minute: Administer 50% to 100% of the dose.
     
    Pediatric patients
    No dosage adjustment needed.
     
    Intermittent hemodialysis
    Rifampin is not cleared by hemodialysis; no dosage adjustment needed.
     
    Peritoneal dialysis†
    No dosage adjustment needed.
     
    Continuous renal replacement therapy (CRRT)†NOTE: Various CRRT modalities include continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous high-flux hemodialysis (CVVHFD), continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVHD), and continuous arteriovenous hemodiafiltration (CAVHDF). Dosing should take into consideration patient-specific factors (e.g., intrinsic renal function), type of infection, the duration of renal replacement therapy, the effluent flow rate, and the replacement solution administered.
     
    No dosage adjustment needed.

    ADMINISTRATION

     
    Tuberculosis patients
    Directly observed therapy (DOT) is recommended for all children, adolescents and adults living with HIV, and any regimen consisting of intermittent therapy.[34361] [34362] [61094]

    Oral Administration

    To ensure maximum absorption, administer at least 1 hour before or 2 hours after a meal with a full glass of water.
    Concurrent antacid administration may decrease the absorption of rifampin; administer rifampin at least 1 hour before ingestion of antacids.
    For patients unable to take the capsules, the contents of the capsules may be mixed with applesauce.

    Extemporaneous Compounding-Oral

    Extemporaneous 10 mg/mL oral suspension
    A 1% suspension (10 mg/mL) may be made by combining the contents of four 300-mg or eight 150-mg rifampin capsules with 20 mL of Simple Syrup, Simple Syrup NF, Raspberry syrup, or Syrpalta and shaking vigorously or, alternatively, mixing via trituration (preferred).
    Further dilute this suspension with 100 mL of the chosen diluent.
    Storage: The suspension is stable for 4 weeks when stored in a light-resistant container at room temperature or under refrigeration.
    Shake well before each administration.
     
    Extemporaneous 25 mg/mL oral suspension†
    A 25 mg/mL suspension may be made by combining the contents of ten 300 mg capsules with 20 mL of a 1:1 mixture of Ora-Plus and Ora-Sweet (or Ora-Sweet NF) or cherry syrup in a mortar and mixing into a uniform paste.
    Add the vehicle in geometric proportions and mix thoroughly after each addition.
    Transfer the contents to a bottle and further dilute to a final volume of 120 mL.
    Storage: The suspension is stable for 28 days when stored in a light-resistant container at room temperature or under refrigeration.
    Shake well before each administration.
     
    Extemporaneous 10 mg/mL oral suspension using IV rifampin†
    A 10 mg/mL suspension may be made by mixing 10 mL of IV rifampin solution (60 mg/mL) with 50 mL of Simple Syrup (60 mL total volume).
    Storage: The suspension is stable for 56 days under refrigeration (4 degrees C).

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Reconstitution
    Reconstitute each 600 mg vial with 10 mL of Sterile Water for Injection to give a concentration of 60 mg/mL. Swirl gently to dissolve.
    Storage: Reconstituted solution is stable for up to 30 hours at room temperature.
     
    Dilution
    Dilute appropriate dose in 5% Dextrose Injection or 0.9% Sodium Chloride Injection to a maximum concentration of 6 mg/mL. Other infusion solutions are not recommended.
    Storage: Solutions diluted in 5% Dextrose Injection are stable for up to 8 hours at room temperature. Solutions diluted in 0.9% Sodium Chloride Injection are stable for up to 6 hours at room temperature. However, a compatibility study showed that rifampin 0.1 mg/mL in 0.9% Sodium Chloride Injection underwent up to 7% loss in 8 hours and up to 13% loss in 24 hours at room temperature. Under refrigeration, about 7% loss occurred in 3 days. In 5% Dextrose Injection, rifampin exhibited 5% loss in 8 hours and up to 17% loss in 24 hours at room temperature. Under refrigeration, about 8% loss occurred in 3 days.
     
    Intermittent IV Infusion
    Infuse IV over 30 minutes to 3 hours.

    STORAGE

    Rifadin:
    - Avoid excessive heat (above 104 degrees F)
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in a dry place
    Rimactane:
    - Avoid excessive heat (above 104 degrees F)
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in a dry place

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Rifampin has enzyme induction properties that can enhance the metabolism of endogenous substrates including adrenal hormones, thyroid hormones, and vitamin D. Rifampin has been reported to alter vitamin D metabolism. Reduced concentrations of circulating 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D have been accompanied by reduced serum calcium and phosphate, and elevated parathyroid hormone.

    Rifamycin hypersensitivity

    Rifampin is contraindicated in patients with known rifampin hypersensitivity or any rifamycin hypersensitivity because cross-sensitivity between agents is possible. Symptoms of renal dysfunction may also be associated with hypersensitivity reactions and usually occur during intermittent or interrupted therapy. Monitor patients receiving rifampin for signs and symptoms of hypersensitivity reactions; discontinue treatment and institute appropriate therapy if a reaction occurs.[30314]

    C. difficile-associated diarrhea, diarrhea, pseudomembranous colitis

    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 rifampin, 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.

    Geriatric

    Use rifampin with caution in geriatric patients. 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.

    Contact lenses

    Rifampin may produce a discoloration (i.e., yellow, orange, red, brown) of the teeth, urine, sweat, tears, and sputum. Soft contact lenses may become permanently stained due to rifampin therapy.

    Anticoagulant therapy, hepatic disease, hepatotoxicity, malnutrition, vitamin K deficiency

    Use rifampin in patients with hepatic disease only in cases of necessity and then under strict medical supervision. In these patients, carefully monitor liver function before therapy and then every 2 to 4 weeks during therapy. If signs of hepatic damage occur or worsen, discontinue rifampin. Severe hepatic dysfunction or hepatotoxicity, including fatalities, were reported in patients with hepatic disease and in patients taking rifampin with other hepatotoxic agents. Additionally, rifampin may cause vitamin K-dependent coagulation disorders and bleeding. Monitor coagulation tests during rifampin treatment (e.g., prothrombin time and other coagulation tests) in patients at risk of vitamin K deficiency, such as patients with chronic hepatic disease or malnutrition or those on prolonged antibacterial drugs or anticoagulant therapy. Consider supplementation with vitamin K when appropriate and discontinuation of rifampin if abnormal coagulation tests and/or bleeding occur.[30314] Most combination therapy for active TB disease includes more than 1 agent that may contribute to hepatotoxicity.[61094]

    Acquired immunodeficiency syndrome (AIDS), human immunodeficiency virus (HIV) infection

    Due to drug-drug interactions that complicate the concomitant use of rifampin and protease inhibitors in persons with tuberculosis (TB) and human immunodeficiency virus (HIV) infection, guidelines recommend rifabutin be used in place of rifampin in multidrug regimens for the treatment of active TB in adults and adolescents with HIV. Do not treat persons with TB and HIV infection and/or acquired immunodeficiency syndrome (AIDS) with intermittent (i.e., twice weekly or 3 days/week) TB treatment regimens to avoid recurrent disease and the emergence of drug resistance.

    Diabetes mellitus

    Use rifampin with caution in patients with a history of diabetes mellitus, as diabetes management may be more difficult.

    Extravasation, intramuscular administration, subcutaneous administration

    Rifampin injection is for intravenous use only. Do not administer rifampin by intramuscular administration or subcutaneous administration. Avoid extravasation of rifampin during infusion. Local irritation and inflammation due to extravascular infiltration of the infusion have been observed; if these occur, discontinue rifampin infusion and restart at another site.

    Laboratory test interference

    Rifampin may cause laboratory test interference. Cross-reactivity and false-positive urine screening tests for opioids have been reported in patients receiving rifampin when utilizing the KIMS (Kinetic Interaction of Microparticles in Solution) testing method (e.g., Abuscreen Online opioids assay). Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish rifampin from opioids. Rifampin has been shown to inhibit standard microbiological assays for serum folate and vitamin B12; consider alternate assays. Transient abnormalities in liver function tests and reduced biliary excretion of contrast media used for visualization of the gallbladder have also been observed; therefore, perform these tests before the morning dose of rifampin.

    Serious rash

    Cases of serious rash, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, have been reported with rifampin. If symptoms or signs of severe cutaneous adverse reactions develop, discontinue rifampin immediately and institute appropriate therapy.

    Pregnancy

    Use rifampin during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies of rifampin in pregnant women. Rifampin does cross the placenta. When given during the last few weeks of pregnancy, rifampin can cause postnatal hemorrhages in the mother and infant; vitamin K therapy may be indicated. Rifampin has been shown to be teratogenic in rodents. Congenital malformations, including spina bifida and cleft palate, were increased in the offspring of pregnant rats. Imperfect osteogenesis and embryotoxicity were also observed in pregnant rabbits given oral doses up to about 3-times the maximum recommended human dose based on body surface area.[30314] Rifampin does not appear to be teratogenic in humans. Tuberculosis guidelines support treatment initiation in pregnancy whenever the probability of maternal disease is moderate to high due to the risk of untreated tuberculosis to a pregnant woman and her fetus.[61094]

    Breast-feeding

    Because of the potential for tumorigenicity demonstrated for rifampin in animal studies, the FDA-approved labeling recommends discontinuing breast-feeding or rifampin, taking into consideration the importance of the drug to the mother.[30314] However, previous American Academy of Pediatrics (AAP) recommendations considered rifampin to be compatible with breast-feeding.[27500] Guidelines encourage breast-feeding for women who are noninfectious and taking first-line tuberculosis agents, such as rifampin, as the small concentrations of these drugs measured in breast milk have not been reported to produce toxic effects in the nursing infant.[61094]

    ADVERSE REACTIONS

    Severe

    vasculitis / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    bronchospasm / Rapid / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    pemphigus / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    renal tubular necrosis / Delayed / Incidence not known
    interstitial nephritis / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    hepatotoxicity / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    disseminated intravascular coagulation (DIC) / Delayed / Incidence not known
    intracranial bleeding / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    C. difficile-associated diarrhea / Delayed / Incidence not known
    porphyria / Delayed / Incidence not known
    hemolytic-uremic syndrome / Delayed / Incidence not known
    thrombotic thrombocytopenic purpura (TTP) / Delayed / Incidence not known
    thrombotic microangiopathy / Delayed / Incidence not known

    Moderate

    eosinophilia / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known
    hypotension / Rapid / Incidence not known
    conjunctivitis / Delayed / Incidence not known
    palpitations / Early / Incidence not known
    bone pain / Delayed / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    dyspnea / Early / Incidence not known
    wheezing / Rapid / Incidence not known
    lymphadenopathy / Delayed / Incidence not known
    hematuria / Delayed / Incidence not known
    hyperuricemia / Delayed / Incidence not known
    hemolysis / Early / Incidence not known
    cholestasis / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    hyperbilirubinemia / Delayed / Incidence not known
    confusion / Early / Incidence not known
    psychosis / Early / Incidence not known
    myopathy / Delayed / Incidence not known
    ataxia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    bleeding / Early / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    anemia / Delayed / Incidence not known
    peripheral edema / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known
    superinfection / Delayed / Incidence not known
    vitamin D deficiency / Delayed / Incidence not known
    pneumonitis / Delayed / Incidence not known
    interstitial lung disease / Delayed / Incidence not known

    Mild

    pyrosis (heartburn) / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    vomiting / Early / Incidence not known
    flatulence / Early / Incidence not known
    diarrhea / Early / Incidence not known
    nausea / Early / Incidence not known
    flushing / Rapid / Incidence not known
    syncope / Early / Incidence not known
    chills / Rapid / Incidence not known
    myalgia / Early / Incidence not known
    fever / Early / Incidence not known
    rash / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    urticaria / Rapid / Incidence not known
    cough / Delayed / Incidence not known
    urine discoloration / Early / Incidence not known
    contact lens discoloration / Delayed / Incidence not known
    tooth discoloration / Delayed / Incidence not known
    weakness / Early / Incidence not known
    dizziness / Early / Incidence not known
    fatigue / Early / Incidence not known
    drowsiness / Early / Incidence not known
    headache / Early / Incidence not known
    purpura / Delayed / Incidence not known
    menstrual irregularity / Delayed / Incidence not known
    vitamin B6 deficiency / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abacavir; Dolutegravir; Lamivudine: (Major) When possible, avoid concurrent use of dolutegravir with rifampin in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive or treatment-experienced, but INSTI-naive, adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with rifampin. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Dolutegravir is a CYP3A4 substrate and rifampin is an inducer of CYP3A4.
    Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Minor) Rifampin can accelerate the metabolism of zidovudine, causing a decrease in AUC of approximately 50%. However the effectiveness of zidovudine against HIV does not appear to be altered and no dosage adjustments are required.
    Abemaciclib: (Major) Avoid coadministration of rifampin with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
    Abiraterone: (Major) Avoid the concomitant use of abiraterone and rifampin. If rifampin must be coadministered with abiraterone, increase the abiraterone dosing frequency to twice daily (i.e., 1,000 mg once daily to 1,000 mg twice daily). Reduce the dose back to the previous dose and frequency when rifampin is discontinued. Abiraterone is a substrate of CYP3A4; rifampin is a strong inducer of CYP3A4. Concomitant use may result in decreased concentrations of abiraterone resulting in reduced efficacy. In a drug interaction study, administration of abiraterone with rifampin decreased exposure of abiraterone by 55%.
    Abrocitinib: (Major) Avoid coadministration of abrocitinib with rifampin as the combined exposure of abrocitinib and its 2 active metabolites may be decreased, resulting in reduced therapeutic effect. Abrocitinib is a CYP2C9 substrate and rifampin is a strong CYP2C9 inducer.
    Acalabrutinib: (Major) Avoid the concomitant use of acalabrutinib and rifampin. If coadministration cannot be avoided, increase the acalabrutinib dose to 200 mg PO twice daily. Decreased acalabrutinib exposure occurred in a drug interaction study. Acalabrutinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. In healthy subjects, the Cmax and AUC values of acalabrutinib were decreased by 68% and 77%, respectively, when acalabrutinib was coadministered with rifampin 600 mg/day for 9 days.
    Acetaminophen: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Acetaminophen; Caffeine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with rifamycins is necessary; consider increasing the dose of dihydrocodeine as needed. If the rifamycin is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Rifamycins are inducers of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Concomitant use of dihydrocodeine with rifamycins 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. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Acetaminophen; Chlorpheniramine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Codeine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Moderate) Concomitant use of codeine with rifampin 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 rifampin 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. Rifampin is a strong CYP3A4 inducer.
    Acetaminophen; Dextromethorphan: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Diphenhydramine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Hydrocodone: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Moderate) Concomitant use of hydrocodone with rifampin 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 rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Acetaminophen; Oxycodone: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with rifampin is necessary; consider increasing the dose of oxycodone as needed. If rifampin is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Pentazocine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Propoxyphene: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Pseudoephedrine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetohexamide: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
    Afatinib: (Major) Increase the daily dose of afatinib by 10 mg as tolerated if the concomitant use with rifampin is necessary; resume the previous dose of afatinib 2 to 3 days after discontinuation of rifampin. Afatinib is a P-glycoprotein (P-gp) substrate and rifampin is a P-gp inducer; coadministration may decrease plasma concentrations of afatinib. Pre-treatment with rifampin decreased afatinib exposure by 34%.
    Alendronate; Cholecalciferol: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can decrease the plasma concentrations and possibly the efficacy of cholecalciferol, Vitamin D3. In some cases, reduced concentrations of circulating vitamin D and 1,25-dihydoxy vitamin D have been accompanied by decreased serum calcium and phosphate, and elevated parathyroid hormone. Dosage adjustments of cholecalciferol, Vitamin D3 may be required.
    Alfentanil: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with rifamycins is necessary. If the rifamycin is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of CYP3A4 inducers like rifamycins with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
    Aliskiren; Amlodipine: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Aliskiren; Valsartan: (Minor) Coadministration may increase systemic exposure to valsartan. Valsartan is a substrate of the hepatic uptake transporter OATP1B1 and rifampin is an inhibitor of OATP. Patients should be monitored for adverse effects of valsartan.
    Alogliptin; Pioglitazone: (Minor) Concomitant administration of rifampin with pioglitazone resulted in a decrease in the AUC of pioglitazone. Patients receiving rifampin with pioglitazone should be monitored for changes in glycemic control; dosage adjustments may be necessary.
    Alpelisib: (Major) Avoid coadministration of alpelisib with rifampin due to decreased exposure to alpelisib which could decrease efficacy. Alpelisib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer.
    Alprazolam: (Moderate) Monitor for reduced efficacy of alprazolam and signs of benzodiazepine withdrawal if coadministration with rifampin is necessary. Alprazolam is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease alprazolam concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Altretamine: (Minor) Altretamine undergoes significant metabolism by the cytochrome P450 system. Rifampin is known to induce CYP450 enzymes. In theory, co-administration may increase the rate of altretamine metabolism thus decreasing altretamine effect; one study in mice has suggested that hepatic enzyme induction antagonizes antitumor activity of altretamine.
    Aluminum Hydroxide: (Moderate) Concomitant use of antacids and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of antacids.
    Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Concomitant use of antacids and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of antacids.
    Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Concomitant use of antacids and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of antacids.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Concomitant use of antacids and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of antacids.
    Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Concomitant use of antacids and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of antacids.
    Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of rifampin and aminosalicylate sodium, aminosalicylic acid. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs may be used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Aminosalicylic acid has previously been reported to block the absorption of rifampin; however, this was due to an excipient not included in the aminosalicylic acid granules. Oral administration of a solution of both agents showed full absorption of each product. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
    Amiodarone: (Major) Certain rifamycins, including rifampin, rifabutin, and rifapentine, may induce CYP3A4 metabolism of amiodarone, resulting in decreased serum concentrations of amiodarone and its active metabolite (desethylamiodarone) and potential decreased efficacy. A possible drug interaction has been reported with rifampin and amiodarone in one patient receiving therapy with ICD and amiodarone for history of atrial and ventricular arrhythmias; this patient had evidence of reduced serum amiodarone and metabolite levels, loss of antiarrhythmic efficacy, and required hospitalization.
    Amitriptyline: (Moderate) It may be necessary to adjust the dosage of tricyclic antidepressants if given concurrently with rifampin. Rifampin may induce the metabolism of tricyclic antidepressants; coadministration may result in decreased tricyclic antidepressant plasma concentrations.
    Amlodipine: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Amlodipine; Atorvastatin: (Moderate) Coadministration of atorvastatin with rifampin may result in variable decreases in atorvastatin exposures, with the potential for reduced antilipemic efficacy. If concomitant use of these drugs is required, atorvastatin and rifampin should be simultaneously administered. Atorvastatin is a CYP3A4 and OATP1B1 substrate. Rifampin is a strong CYP3A4 inducer and OATP1B1 inhibitor. As a result of the dual interaction mechanisms, delayed administration of atorvastatin after rifampin administration has been associated with a significant reduction in atorvastatin plasma concentrations. To evaluate this interaction, monitor serum lipid concentrations during coadministration. (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Amlodipine; Benazepril: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Amlodipine; Celecoxib: (Moderate) Rifampin has been reported to induce the hepatic metabolism of celecoxib via cytochrome P450 2C9. It is possible that patients treated with celecoxib and rifampin may have a reduced response to celecoxib. (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Amlodipine; Olmesartan: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Amlodipine; Valsartan: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers. (Minor) Coadministration may increase systemic exposure to valsartan. Valsartan is a substrate of the hepatic uptake transporter OATP1B1 and rifampin is an inhibitor of OATP. Patients should be monitored for adverse effects of valsartan.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers. (Minor) Coadministration may increase systemic exposure to valsartan. Valsartan is a substrate of the hepatic uptake transporter OATP1B1 and rifampin is an inhibitor of OATP. Patients should be monitored for adverse effects of valsartan.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of omeprazole with rifampin due to the risk of decreased omeprazole plasma concentrations which may decrease efficacy. Omeprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Major) Clarithromycin is a substrate and inhibitor of CYP3A4, and rifampin is an inducer of CYP3A4. As compared with the plasma concentration obtained with clarithromycin 500 mg twice daily as monotherapy, the clarithromycin plasma concentration was reduced by 87% when rifampin 600 mg daily was coadministered. Specifically, as monotherapy, the mean serum clarithromycin concentration was 5.4 +/- 2.1 mcg/ml. The mean serum clarithromycin concentration was 0.7 +/- 0.6 mcg/ml when given in combination with rifampin. The mean serum concentrations of 14-OH clarithromycin were similar between the two groups. Alternatives to clarithromycin should be considered in patients who are taking CYP3A4 inducers.
    Amprenavir: (Contraindicated) Concurrent treatment with rifampin and amprenavir is contraindicated. Rifampin decreases amprenavir AUC by 82% and Cmin concentrations by 92%. Coadministration of amprenavir and rifampin may lead to loss of virologic response and possible resistance to amprenavir or to the class of protease inhibitors.
    Anagrelide: (Moderate) Anagrelide is partially metabolized by CYP1A2. Coadministration of anagrelide with drugs that induce CYP1A2, including rifampin, could theoretically increase the elimination of anagrelide and decrease the efficacy of anagrelide. Patients should be monitored for changes in efficacy if anagrelide is coadministered with rifampin.
    Antacids: (Moderate) Concomitant use of antacids and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of antacids.
    Apixaban: (Major) Avoid the concomitant administration of apixaban and drugs that are both strong inducers of CYP3A4 and P-gp, such as rifampin. Concomitant administration of apixaban and rifampin results in decreased exposure to apixaban and an increase in the risk of stroke.
    Apremilast: (Major) The coadministration of apremilast and rifampin is not recommended. Apremilast is metabolized primarily by CYP3A4, with minor metabolism by CYP1A2 and CYP2D6. Rifampin is a strong CYP3A4 inducer and also induces CYP1A2 and CYP2D6. Coadministration of rifampin (600 mg daily for 15 days) with a single dose of apremilast resulted in a decrease in apremilast AUC and Cmax by 72% and 43%, respectively. This reduction in systemic exposure may result in a loss of efficacy of apremilast.
    Aprepitant, Fosaprepitant: (Major) Avoid the concurrent use of rifampin with aprepitant due to substantially decreased exposure of aprepitant. If these drugs must be coadministered, monitor for a decrease in the efficacy of aprepitant. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. Rifampin is a strong CYP3A4 inducer and aprepitant is a CYP3A4 substrate. When a single dose of aprepitant (375 mg, or 3 times the maximum recommended dose) was administered on day 9 of a 14-day rifampin regimen, the AUC of aprepitant decreased approximately 11-fold and the mean terminal half-life decreased by 3-fold.
    Aripiprazole: (Major) Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when a potent CYP3A4 inducer, such as rifampin, is added to aripiprazole therapy with subsequent adjustments based upon clinical response. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is discontinued, the aripiprazole dose in adults should be reduced to the original dose over 1 to 2 weeks. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving Aristada with a strong CYP3A4 inducer, no dosage adjustment is necessary for the 662 mg, 882 mg, or 1,064 mg dose; increase the 441 mg dose to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers.
    Armodafinil: (Major) Armodafinil is partially metabolized via CYP3A4/5 isoenzymes. Drugs that exhibit significant induction of the CYP3A4 isoenzyme, such as rifampin, may potentially increase the metabolism of armodafinil. Decreased serum levels of armodafinil could potentially result in decreased efficacy of the drug.
    Artemether; Lumefantrine: (Contraindicated) Concomitant use of rifampin and artemether; lumefantrine is contraindicated. Rifampin is a potent inducer of CYP3A4 and both components of artemether; lumefantrine are substrates of this isoenzyme; therefore, coadministration may lead to decreased artemether; lumefantrine concentrations and possible reduction in antimalarial activity. Coadministration in 6 HIV and tuberculosis co-infected adults caused reductions in the AUC of artemether, dihydroartemisinin (metabolite of artemether), and lumefantrine by 89%, 85%, and 68%, respectively.
    Artesunate: (Moderate) Monitor for a decrease in antimalarial efficacy if artesunate is coadministered with rifampin. Coadministration may decrease the exposure of the active metabolite of artesunate, dihydroartemisinin (DHA). DHA is a UGT substrate, and rifampin is a strong UGT inducer.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) It may be necessary to adjust the dosage of butalbital if given concurrently with rifampin. Rifampin may induce the metabolism of butalbital; coadministration may result in decreased butalbital plasma concentrations. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Concomitant use of codeine with rifampin 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 rifampin 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. Rifampin is a strong CYP3A4 inducer. (Moderate) It may be necessary to adjust the dosage of butalbital if given concurrently with rifampin. Rifampin may induce the metabolism of butalbital; coadministration may result in decreased butalbital plasma concentrations. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Aspirin, ASA; Caffeine: (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with rifamycins is necessary; consider increasing the dose of dihydrocodeine as needed. If the rifamycin is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Rifamycins are inducers of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Concomitant use of dihydrocodeine with rifamycins 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. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Aspirin, ASA; Carisoprodol: (Minor) Carisoprodol is metabolized via CYP2C19. The formation of meprobamate (active metabolite of carisoprodol) is catalyzed by CYP2C19. If carisoprodol is combined with an inducer of CYP2C19 such as rifampin, the potential exists for increased metabolism of carisoprodol. Theoretically, carisoprodol plasma concentrations could be decreased, and meprobamate (active metabolite) plasma concentrations could be increased. The clinical significance of this interaction is unknown.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with rifampin 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 rifampin 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. Rifampin is a strong CYP3A4 inducer. (Minor) Carisoprodol is metabolized via CYP2C19. The formation of meprobamate (active metabolite of carisoprodol) is catalyzed by CYP2C19. If carisoprodol is combined with an inducer of CYP2C19 such as rifampin, the potential exists for increased metabolism of carisoprodol. Theoretically, carisoprodol plasma concentrations could be decreased, and meprobamate (active metabolite) plasma concentrations could be increased. The clinical significance of this interaction is unknown.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Concomitant use of sodium bicarbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of sodium bicarbonate.
    Aspirin, ASA; Omeprazole: (Major) Avoid coadministration of omeprazole with rifampin due to the risk of decreased omeprazole plasma concentrations which may decrease efficacy. Omeprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Aspirin, ASA; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with rifampin is necessary; consider increasing the dose of oxycodone as needed. If rifampin is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Aspirin, ASA; Pravastatin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of atorvastatin, simvastatin and fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors (Statins). To evaluate this interaction, monitor serum lipid concentrations during coadministration of rifamycins with HMG-CoA reductase inhibitors.
    Atazanavir: (Contraindicated) Atazanavir is contraindicated for use with rifampin. Rifampin induces CYP isoenzymes, thereby decreasing the plasma concentrations and AUC of most protease inhibitors by roughly 90% and leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
    Atazanavir; Cobicistat: (Contraindicated) Atazanavir is contraindicated for use with rifampin. Rifampin induces CYP isoenzymes, thereby decreasing the plasma concentrations and AUC of most protease inhibitors by roughly 90% and leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. (Contraindicated) Coadministration of rifampin with cobicistat is contraindicated. Rifampin induces CYP3A4; cobicistat is a substrate of this enzyme. Concurrent use may result in significant decreases in the plasma concentrations of cobicistat and of the simultaneously administered protease inhibitors (atazanavir or darunavir), leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
    Atogepant: (Major) Use an atogepant dose of 30 or 60 mg PO once daily if coadministered with rifampin. Concurrent use may decrease atogepant exposure and reduce efficacy. Atogepant is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with a strong CYP3A inducer resulted in a 60% reduction in atogepant exposure and a 30% reduction in atogepant peak concentration.
    Atorvastatin: (Moderate) Coadministration of atorvastatin with rifampin may result in variable decreases in atorvastatin exposures, with the potential for reduced antilipemic efficacy. If concomitant use of these drugs is required, atorvastatin and rifampin should be simultaneously administered. Atorvastatin is a CYP3A4 and OATP1B1 substrate. Rifampin is a strong CYP3A4 inducer and OATP1B1 inhibitor. As a result of the dual interaction mechanisms, delayed administration of atorvastatin after rifampin administration has been associated with a significant reduction in atorvastatin plasma concentrations. To evaluate this interaction, monitor serum lipid concentrations during coadministration.
    Atorvastatin; Ezetimibe: (Moderate) Coadministration of atorvastatin with rifampin may result in variable decreases in atorvastatin exposures, with the potential for reduced antilipemic efficacy. If concomitant use of these drugs is required, atorvastatin and rifampin should be simultaneously administered. Atorvastatin is a CYP3A4 and OATP1B1 substrate. Rifampin is a strong CYP3A4 inducer and OATP1B1 inhibitor. As a result of the dual interaction mechanisms, delayed administration of atorvastatin after rifampin administration has been associated with a significant reduction in atorvastatin plasma concentrations. To evaluate this interaction, monitor serum lipid concentrations during coadministration.
    Atovaquone: (Major) The administration of rifampin with atovaquone is not recommended, as rifampin is known to reduce atovaquone levels by 52%. In a small study of HIV-positive subjects, concomitant administration of oral rifampin with atovaquone suspension lead to a substantial decrease in average steady-state plasma atovaquone concentrations and a simultaneous increase in average steady-state plasma rifampin concentrations. The half-life of atovaquone decreased from 82 hours (without rifampin) to 50 hours during rifampin administration. Other rifamycins, (e.g.; rifapentine) may exert similar effects on atovaquone pharmacokinetics, but data are not available.
    Atovaquone; Proguanil: (Major) The administration of rifampin with atovaquone is not recommended, as rifampin is known to reduce atovaquone levels by 52%. In a small study of HIV-positive subjects, concomitant administration of oral rifampin with atovaquone suspension lead to a substantial decrease in average steady-state plasma atovaquone concentrations and a simultaneous increase in average steady-state plasma rifampin concentrations. The half-life of atovaquone decreased from 82 hours (without rifampin) to 50 hours during rifampin administration. Other rifamycins, (e.g.; rifapentine) may exert similar effects on atovaquone pharmacokinetics, but data are not available.
    Avacopan: (Major) Avoid concomitant use of avacopan and rifampin due to the risk of decreased avacopan exposure which may reduce its efficacy. Avacopan is a CYP3A substrate and rifampin is a strong CYP3A inducer. Concomitant use decreased avacopan overall exposure by 93%.
    Avanafil: (Minor) Avanafil is primarily metabolized by CYP3A4, and although no studies have been performed, concomitant administration of CYP3A4 inducers, such as rifampin, may decrease avanafil plasma levels. Concomitant use is not recommended.
    Avapritinib: (Major) Avoid coadministration of avapritinib with rifampin due to the risk of a decrease in the efficacy of avapritinib. Avapritinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the AUC and Cmax of avapritinib by 92% and 74%, respectively.
    Avatrombopag: (Major) In patients with chronic immune thrombocytopenia (ITP), increase the starting dose of avatrombopag to 40 mg PO once daily when used concomitantly with rifampin. In patients starting rifampin while receiving avatrombopag, monitor platelet counts and adjust the avatrombopag dose as necessary. Dosage adjustments are not required for patients with chronic liver disease. Avatrombopag is a CYP2C9 and CYP3A4 substrate, and dual moderate or strong inducers such as rifampin decrease avatrombopag exposure, which may reduce efficacy.
    Axitinib: (Major) Avoid coadministration of axitinib with rifampin 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 and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin significantly decreased the plasma exposure of axitinib in healthy volunteers.
    Bacillus Calmette-Guerin Vaccine, BCG: (Major) Urinary concentrations of rifampin could interfere with the therapeutic effectiveness of BCG. Postpone instillation of BCG if the patient is receiving antibiotics.
    Bedaquiline: (Major) Avoid concurrent use of bedaquiline with rifamycins (e.g., rifampin, rifapentine, and rifabutin). Rifamycins may induce the CYP3A4 metabolism of bedaquiline, resulting in decreased bedaquiline systemic exposure (AUC) and possibly reduced therapeutic effect. One study found bedaquiline AUC decreased by 52% when administered concurrently with rifampin 600 mg PO daily for 21 days.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) It may be necessary to adjust the dosage of phenobarbital if given concurrently with rifampin. Rifampin may induce the metabolism of phenobarbital; coadministration may result in decreased phenobarbital plasma concentrations. Phenobarbital is a CYP29 and CYP2C19 substrate, and rifampin is an inducer of these enzymes.
    Belumosudil: (Major) Increase the dosage of belumosudil to 200 mg PO twice daily when coadministered with rifampin. Belumosudil is a CYP3A4 substrate and rifampin is a strong CYP3A inducer; concomitant use resulted in decreased belumosudil exposure in a drug interaction study. Decreased belumosudil exposure may lead to reduced belumosudil efficacy. Coadministration with rifampin decreased belumosudil exposure by 72% in healthy subjects.
    Bendamustine: (Major) Consider the use of an alternative therapy if rifampin treatment is needed in patients receiving bendamustine. Rifampin may decrease bendamustine exposure, which may result in decreased efficacy. Bendamustine is a CYP1A2 substrate and rifampin is a CYP1A2 inducer.
    Benzhydrocodone; Acetaminophen: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Moderate) Concurrent use of benzhydrocodone with rifampin may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If concomitant use is necessary, consider increasing the benzhydrocodone dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Discontinuation of rifampin may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. If rifampin is discontinued, consider a benzhydrocodone dosage reduction and monitor patients for respiratory depression and sedation at frequent intervals. Benzhydrocodone is a prodrug of hydrocodone. Rifampin is a strong inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of hydrocodone.
    Bepridil: (Major) Rifampin may induce the CYP3A4 metabolism of calcium-channel blockers and thereby reduce their oral bioavailability. The dosage requirements of bepridil may be increased in patients receiving concurrent enzyme inducers.
    Berotralstat: (Major) Avoid coadministration of berotralstat with rifampin. Concurrent use may decrease berotralstat exposure, leading to reduced efficacy. Berotralstat is a P-gp substrate and rifampin is a P-gp inducer.
    Betrixaban: (Major) Avoid the concomitant administration of betrixaban and rifampin. Concomitant administration of betrixaban and rifampin results in decreased plasma concentrations of betrixaban that may be insufficient to achieve the intended therapeutic effect. Betrixaban is a P-glycoprotein (P-gp) substrate and rifampin is a P-gp inducer.
    Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Concomitant use of bictegravir and rifampin is contraindicated due to the potential for decreased bictegravir plasma concentrations which may result in the loss of therapeutic efficacy and development of resistance. Bictegravir is a substrate of CYP3A4; rifampin is a potent inducer of this isoenzyme. In drug interactions studies, coadministration of rifampin and bictegravir decreased the mean AUC of bictegravir by approximately 75%.
    Boceprevir: (Contraindicated) The potential for boceprevir treatment failure exists when boceprevir is administered with rifampin; concurrent use is contraindicated. Rifampin is a potent inducer of CYP3A4, which is partially responsible for boceprevir metabolism. Coadministration may result in decreased boceprevir serum concentrations and impaired virologic response.
    Bortezomib: (Moderate) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of bortezomib.
    Bosentan: (Major) Concomitant administration of a single dose of rifampin (a known inducer of CYP2C9 and CYP3A4) and bosentan in normal volunteers has resulted in increased mean bosentan serum concentrations (trough) by 6-fold; however, coadministration of rifampin with bosentan decreases bosentan serum concentrations at steady-state by about 60%. The effect of bosentan on rifampin serum concentrations has not been assessed. When concomitant use is justified after weighing the risks and benefits, the manufacturer recommends monitoring LFTs weekly for the first 4 weeks, and then to follow routine recommendations for monitoring LFTs during bosentan therapy.
    Bosutinib: (Major) Avoid the concomitant use of bosutinib, a CYP3A4 substrate, and rifampin, a strong CYP3A4 inducer, as a large decrease in bosutinib plasma exposure may occur. In a cross-over trial in 24 healthy volunteers, the Cmax and AUC values of bosutinib were decreased by 86% and 94%, respectively, following a single oral dose of bosutinib 500 mg administered after 6 days of oral rifampin 600 mg/day.
    Brentuximab vedotin: (Moderate) Concomitant administration of brentuximab vedotin and rifampin decreased the exposure of monomethyl auristatin E (MMAE), one of the 3 components released from brentuximab vedotin, by approximately 46%. MMAE is a CYP3A4 substrate and rifampin is a potent CYP3A4 inducer; therefore, the efficacy of brentuximab may be reduced.
    Brexpiprazole: (Major) Because brexpiprazole is partially metabolized by CYP3A4, the manufacturer recommends that the brexpiprazole dose be doubled over 1 to 2 weeks when a strong CYP3A4 inducer, such as rifampin, is added to brexpiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in brexpiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the brexpiprazole dose should be reduced to the original level over 1 to 2 weeks.
    Brigatinib: (Major) Avoid coadministration of brigatinib with rifampin due to decreased plasma exposure to brigatinib, which may result in decreased efficacy. Brigatinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration of rifampin decreased the AUC and Cmax of brigatinib by 80% and 60%, respectively.
    Brivaracetam: (Major) Co-administration of brivaracetam with rifampin decreases brivaracetam plasma concentrations by 45%, likely because of CYP2C19 induction. When metabolized, brivaracetam undergoes hydroxylation that is mediated by CYP2C19. The dose of brivaracetam should be increased by up to 100% in patients in patients taking concomitant rifampin.
    Bromocriptine: (Moderate) Caution and close monitoring are advised if bromocriptine and rifampin are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; rifampin is a strong inducer of CYP3A4.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with rifampin 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 rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with rifampin 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 rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Bupivacaine; Lidocaine: (Moderate) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of lidocaine,
    Buprenorphine: (Moderate) Monitor for decreased efficacy of buprenorphine, and potentially the onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine, if coadministration with rifamycins is necessary; consider increasing the dose of buprenorphine until stable drug effects are achieved. If the rifamycin is discontinued, consider a buprenorphine dose reduction and monitor for signs of respiratory depression. Buprenorphine is a CYP3A4 substrate and rifamycins are CYP3A4 inducers.
    Buprenorphine; Naloxone: (Moderate) Monitor for decreased efficacy of buprenorphine, and potentially the onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine, if coadministration with rifamycins is necessary; consider increasing the dose of buprenorphine until stable drug effects are achieved. If the rifamycin is discontinued, consider a buprenorphine dose reduction and monitor for signs of respiratory depression. Buprenorphine is a CYP3A4 substrate and rifamycins are CYP3A4 inducers.
    Bupropion: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function such as rifampin. Pharmacokinetic studies describe patients who developed subtherapeutic bupropion serum concentrations when enzyme-inducing agents were added. In healthy volunteers, coadministration of bupropion with rifampin reduced the mean AUC of bupropion by 3-fold and the mean half-life from 15.9 hours to 8.2 hours.
    Bupropion; Naltrexone: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function such as rifampin. Pharmacokinetic studies describe patients who developed subtherapeutic bupropion serum concentrations when enzyme-inducing agents were added. In healthy volunteers, coadministration of bupropion with rifampin reduced the mean AUC of bupropion by 3-fold and the mean half-life from 15.9 hours to 8.2 hours.
    Buspirone: (Major) Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as rifampin, may increase the rate of buspirone metabolism. In a study of healthy volunteers, co-administration of buspirone with rifampin decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone. An in vitro study indicated that buspirone did not displace highly protein-bound drugs such as phenytoin. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect.
    Butalbital; Acetaminophen: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Moderate) It may be necessary to adjust the dosage of butalbital if given concurrently with rifampin. Rifampin may induce the metabolism of butalbital; coadministration may result in decreased butalbital plasma concentrations.
    Butalbital; Acetaminophen; Caffeine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Moderate) It may be necessary to adjust the dosage of butalbital if given concurrently with rifampin. Rifampin may induce the metabolism of butalbital; coadministration may result in decreased butalbital plasma concentrations. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Moderate) Concomitant use of codeine with rifampin 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 rifampin 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. Rifampin is a strong CYP3A4 inducer. (Moderate) It may be necessary to adjust the dosage of butalbital if given concurrently with rifampin. Rifampin may induce the metabolism of butalbital; coadministration may result in decreased butalbital plasma concentrations. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Cabotegravir: (Contraindicated) Coadministration of cabotegravir and rifampin is contraindicated due to the potential for significant decreases in the plasma concentrations of cabotegravir, which may result in potential loss of virologic response and development of resistance. Cabotegravir is a substrate for UGT1A1 and UGT1A9; rifampin is an inducer of UGT. Coadministration with rifampin decreased cabotegravir exposure by 59%.
    Cabotegravir; Rilpivirine: (Contraindicated) Coadministration of cabotegravir and rifampin is contraindicated due to the potential for significant decreases in the plasma concentrations of cabotegravir, which may result in potential loss of virologic response and development of resistance. Cabotegravir is a substrate for UGT1A1 and UGT1A9; rifampin is an inducer of UGT. Coadministration with rifampin decreased cabotegravir exposure by 59%. (Contraindicated) Concurrent use of rifampin and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Rifampin is a potent inducer of CYP3A4, which is primarily responsible for the metabolism of rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine.
    Cabozantinib: (Major) Avoid coadministration of cabozantinib with rifampin due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with rifampin 2 to 3 days after discontinuation of rifampin. Cabozantinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased single-dose cabozantinib exposure by 77%.
    Caffeine: (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Caffeine; Sodium Benzoate: (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Calcium Carbonate: (Moderate) Concomitant use of calcium carbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of calcium carbonate.
    Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Concomitant use of calcium carbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of calcium carbonate.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) Concomitant use of calcium carbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of calcium carbonate.
    Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Concomitant use of calcium carbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of calcium carbonate.
    Calcium Carbonate; Risedronate: (Moderate) Concomitant use of calcium carbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of calcium carbonate.
    Calcium Carbonate; Simethicone: (Moderate) Concomitant use of calcium carbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of calcium carbonate.
    Calcium; Vitamin D: (Moderate) Concomitant use of calcium carbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of calcium carbonate. (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can decrease the plasma concentrations and possibly the efficacy of cholecalciferol, Vitamin D3. In some cases, reduced concentrations of circulating vitamin D and 1,25-dihydoxy vitamin D have been accompanied by decreased serum calcium and phosphate, and elevated parathyroid hormone. Dosage adjustments of cholecalciferol, Vitamin D3 may be required.
    Canagliflozin: (Moderate) Monitor for decreased efficacy of canagliflozin if coadministration with rifampin is necessary. In patients taking rifampin who have an eGFR of 60 mL/min/1.73 m2 or greater and are currently tolerating a canagliflozin dose of 100 mg once daily, increase the dose of canagliflozin to 200 mg (taken as two 100 mg tablets) once daily. In patients who are tolerating canagliflozin to 200 mg and who require additional glycemic control, the dose may be increased to 300 mg once daily. In patients taking rifampin who have an eGFR less than 60 mL/min/1.73 m2, and are currently tolerating a canagliflozin dose of 100 mg once daily, increase the dose of canagliflozin to 200 mg (taken as two 100 mg tablets) once daily. Consider other antihyperglycemic therapy in patients who require additional glycemic control. Coadministration of canagliflozin with rifampin, a nonselective inducer of several UGT enzymes, including UGT1A9, UGT2B4, decreased canagliflozin AUC by 51%. This decrease in exposure to canagliflozin may decrease efficacy.
    Canagliflozin; Metformin: (Moderate) Monitor for decreased efficacy of canagliflozin if coadministration with rifampin is necessary. In patients taking rifampin who have an eGFR of 60 mL/min/1.73 m2 or greater and are currently tolerating a canagliflozin dose of 100 mg once daily, increase the dose of canagliflozin to 200 mg (taken as two 100 mg tablets) once daily. In patients who are tolerating canagliflozin to 200 mg and who require additional glycemic control, the dose may be increased to 300 mg once daily. In patients taking rifampin who have an eGFR less than 60 mL/min/1.73 m2, and are currently tolerating a canagliflozin dose of 100 mg once daily, increase the dose of canagliflozin to 200 mg (taken as two 100 mg tablets) once daily. Consider other antihyperglycemic therapy in patients who require additional glycemic control. Coadministration of canagliflozin with rifampin, a nonselective inducer of several UGT enzymes, including UGT1A9, UGT2B4, decreased canagliflozin AUC by 51%. This decrease in exposure to canagliflozin may decrease efficacy.
    Capmatinib: (Major) Avoid coadministration of capmatinib and rifampin due to the risk of decreased capmatinib exposure, which may reduce its efficacy. Capmatinib is a CYP3A substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased capmatinib exposure by 67%.
    Capreomycin: (Moderate) Adverse hepatic effects have been associated with capreomycin, especially with concurrent use of other antituberculosis drugs known to alter hepatic function. Theoretically, coadministration of capreomycin and any of the rifamycins could increase the risk of hepatotoxicity. Monitor patients for changes in liver function if these drugs are coadministered.
    Carbamazepine: (Major) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of carbamazepine. Carbamazepine dosages may need to be adjusted while the patient is receiving rifampin.
    Carbidopa; Levodopa; Entacapone: (Moderate) Entacapone should be given cautiously with drugs known to interfere with biliary excretion, glucuronidation or intestinal beta-glucuronidation such as rifampin. Decreased biliary excretion of entacapone may occur if these agents are given concurrently.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with rifampin 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 rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with rifampin 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 rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Concurrent use of cariprazine with CYP3A4 inducers, such as rifabutin or rifampin, has not been evaluated and is not recommended because the net effect on active drug and metabolites is unclear.
    Carisoprodol: (Minor) Carisoprodol is metabolized via CYP2C19. The formation of meprobamate (active metabolite of carisoprodol) is catalyzed by CYP2C19. If carisoprodol is combined with an inducer of CYP2C19 such as rifampin, the potential exists for increased metabolism of carisoprodol. Theoretically, carisoprodol plasma concentrations could be decreased, and meprobamate (active metabolite) plasma concentrations could be increased. The clinical significance of this interaction is unknown.
    Carvedilol: (Moderate) Concurrent use of carvedilol and rifampin may result in decreased carvedilol concentrations and reduced beta-blocker efficacy. Dosage must be individualized to the patient's response and tolerance. Monitor for signs of altered carvedilol response. During drug interaction studies, rifampin decreased the Cmax and AUC of carvedilol by approximately 70%. Carvedilol is metabolized primarily by CYP2D6 and CYP2C9; rifampin is a known CYP450 hepatic enzyme inducer.
    Caspofungin: (Major) Dose caspofungin as 70 mg IV once daily for adult patients and 70 mg/m2 (Max: 70 mg/day) IV once daily for pediatric patients when coadministered with rifampin. Coadministration of caspofungin with CYP450 enzyme inducers, such as rifampin, may reduce the plasma concentrations of caspofungin. Rifampin has been shown to decrease caspofungin trough concentrations by 30%.
    Cefazolin: (Moderate) Avoid coadministration of rifampin and cefazolin in patients at increased risk of bleeding. If no alternative treatment options are available, closely monitor prothrombin time and other coagulation tests, and administer vitamin K as indicated. Postmarketing reports suggest that concomitant administration of high doses of rifampin and cefazolin may prolong the prothrombin time, leading to severe vitamin K-dependent coagulation disorders that may be life-threatening or fatal.
    Celecoxib: (Moderate) Rifampin has been reported to induce the hepatic metabolism of celecoxib via cytochrome P450 2C9. It is possible that patients treated with celecoxib and rifampin may have a reduced response to celecoxib.
    Celecoxib; Tramadol: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with rifampin is necessary; consider increasing the dose of tramadol as needed. If rifampin is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. (Moderate) Rifampin has been reported to induce the hepatic metabolism of celecoxib via cytochrome P450 2C9. It is possible that patients treated with celecoxib and rifampin may have a reduced response to celecoxib.
    Ceritinib: (Major) Avoid concomitant use of ceritinib with rifampin as ceritinib exposure may be decreased, which may reduce its efficacy. Ceritinib is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased ceritinib exposure by 70%.
    Chloramphenicol: (Moderate) It may be necessary to adjust the dosage of chloramphenicol if given concurrently with rifampin. Rifampin may induce the metabolism of chloramphenicol; coadministration may result in decreased chloramphenicol plasma concentrations.
    Chlordiazepoxide: (Moderate) Several hepatic inducers, such as rifampin, can theoretically increase the clearance of benzodiazpines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations.
    Chlordiazepoxide; Amitriptyline: (Moderate) It may be necessary to adjust the dosage of tricyclic antidepressants if given concurrently with rifampin. Rifampin may induce the metabolism of tricyclic antidepressants; coadministration may result in decreased tricyclic antidepressant plasma concentrations. (Moderate) Several hepatic inducers, such as rifampin, can theoretically increase the clearance of benzodiazpines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations.
    Chlordiazepoxide; Clidinium: (Moderate) Several hepatic inducers, such as rifampin, can theoretically increase the clearance of benzodiazpines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations.
    Chloroquine: (Moderate) Monitor patients more frequently for signs of reduced chloroquine effects if administered with rifampin. Coadministration may decrease the exposure of chloroquine. Chloroquine may be a CYP3A4 substrate in vitro, and rifampin is a strong CYP3A4 inducer.
    Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with rifampin 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 rifampin 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. Rifampin is a strong CYP3A4 inducer.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with rifamycins is necessary; consider increasing the dose of dihydrocodeine as needed. If the rifamycin is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Rifamycins are inducers of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Concomitant use of dihydrocodeine with rifamycins 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.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with rifamycins is necessary; consider increasing the dose of dihydrocodeine as needed. If the rifamycin is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Rifamycins are inducers of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Concomitant use of dihydrocodeine with rifamycins 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.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with rifampin 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 rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with rifampin 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 rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with rifampin 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 rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with rifampin 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 rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Chlorpropamide: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
    Ciprofloxacin: (Moderate) It may be necessary to adjust the dosage of ciprofloxacin if given concurrently with rifampin. Rifampin may induce the metabolism of ciprofloxacin; coadministration may result in decreased ciprofloxacin plasma concentrations. Ciprofloxacin and rifampin have been used concomitantly in some cases for the treatment of MRSA.
    Cisapride: (Moderate) Cisapride is metabolized by the hepatic cytochrome P450 enzyme system, specifically the CYP3A4 isoenzyme. Inducers of CYP3A4, such as rifampin, may increase the clearance of cisapride.
    Citalopram: (Moderate) Monitor for decreased efficacy of citalopram if coadministration with rifampin is necessary. Citalopram is a substrate of CYP3A4 and CYP2C19 and rifampin is a moderate to strong CYP2C19 inducer and strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer did not affect citalopram plasma concentrations, but increased clearance of citalopram with strong CYP3A4 inducers is possible.
    Clarithromycin: (Major) Clarithromycin is a substrate and inhibitor of CYP3A4, and rifampin is an inducer of CYP3A4. As compared with the plasma concentration obtained with clarithromycin 500 mg twice daily as monotherapy, the clarithromycin plasma concentration was reduced by 87% when rifampin 600 mg daily was coadministered. Specifically, as monotherapy, the mean serum clarithromycin concentration was 5.4 +/- 2.1 mcg/ml. The mean serum clarithromycin concentration was 0.7 +/- 0.6 mcg/ml when given in combination with rifampin. The mean serum concentrations of 14-OH clarithromycin were similar between the two groups. Alternatives to clarithromycin should be considered in patients who are taking CYP3A4 inducers.
    Clindamycin: (Moderate) Monitor for loss of clindamycin efficacy with coadministration of rifampin as concurrent use may decrease clindamycin exposure. Clindamycin is a CYP3A4 substrate; rifampin is a strong inducer of CYP3A4.
    Clomipramine: (Moderate) It may be necessary to adjust the dosage of tricyclic antidepressants if given concurrently with rifampin. Rifampin may induce the metabolism of tricyclic antidepressants; coadministration may result in decreased tricyclic antidepressant plasma concentrations.
    Clonazepam: (Moderate) Monitor patients for a change in clonazepam dosage requirements when starting or stopping concomitant rifampin. Clonazepam concentration decreases of approximately 38% have been reported when clonazepam is used with strong CYP3A4 inducers. Clonazepam is a CYP3A4 substrate. Rifampin is a strong CYP3A4 inducer.
    Clopidogrel: (Major) Avoid concomitant use of clopidogrel and rifampin due to the risk of bleeding. Concomitant use results in increased plasma concentrations of clopidogrel's active metabolite and an increase in platelet inhibition. Clopidogrel is primarily metabolized to its active metabolite by CYP2C19; rifampin is a strong CYP2C19 inducer.
    Clorazepate: (Major) Rifampin, a hepatic inducer can theoretically increase the clearance of benzodiazpines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations.
    Clozapine: (Major) Coadministration of clozapine, a CYP3A4 substrate, with a potent inducer of CYP3A4, such as rifampin, is not recommended. If coadministration is necessary, monitor for decreased effectiveness of clozapine and consider increasing the clozapine dose if necessary. If the inducer is discontinued, reduce the clozapine dose based on clinical response. Rifampin may also increase the metabolism of clozapine through induction of CYP1A2.
    Cobicistat: (Contraindicated) Coadministration of rifampin with cobicistat is contraindicated. Rifampin induces CYP3A4; cobicistat is a substrate of this enzyme. Concurrent use may result in significant decreases in the plasma concentrations of cobicistat and of the simultaneously administered protease inhibitors (atazanavir or darunavir), leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
    Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with rifampin due to decreased cobimetinib efficacy. Cobimetinib is a CYP3A substrate in vitro; rifampin is a strong inducer of CYP3A. Based on simulations, cobimetinib exposure would decrease by 83% when coadministered with a strong CYP3A inducer.
    Codeine: (Moderate) Concomitant use of codeine with rifampin 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 rifampin 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. Rifampin is a strong CYP3A4 inducer.
    Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with rifampin 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 rifampin 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. Rifampin is a strong CYP3A4 inducer.
    Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with rifampin 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 rifampin 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. Rifampin is a strong CYP3A4 inducer.
    Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with rifampin 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 rifampin 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. Rifampin is a strong CYP3A4 inducer.
    Codeine; Promethazine: (Moderate) Concomitant use of codeine with rifampin 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 rifampin 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. Rifampin is a strong CYP3A4 inducer.
    Conjugated Estrogens; Bazedoxifene: (Major) Bazedoxifene undergoes metabolism by UGT enzymes in the intestinal tract and liver. The metabolism of bazedoxifene may be increased by concomitant use of substances known to induce UGTs, such as rifampin. A reduction in bazedoxifene exposure may be associated with an increase risk of endometrial hyperplasia. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding. In addition, in vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4, such as rifampin, may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Patients taking these hormones may need to be monitored for reduced clinical effect while on rifampin, with dose adjustments made based on clinical efficacy.
    Conjugated Estrogens; Medroxyprogesterone: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Copanlisib: (Major) Avoid the concomitant use of copanlisib and rifampin; decreased copanlisib exposure occurred in a drug interaction study. Copanlisib is a substrate of CYP3A and P-glycoprotein (P-gp); rifampin is a strong CYP3A inducer and also induces P-gp. The AUC and Cmax values of copanlisib decreased by 60% and 12%, respectively, when a single IV dose of copanlisib 60 mg was administered following 12 days of rifampin 600 mg/day in a drug interaction study in patients with cancer.
    Crizotinib: (Major) Avoid coadministration of crizotinib with rifampin due to decreased plasma concentrations of crizotinib, which may result in decreased efficacy. Crizotinib is primarily metabolized by CYP3A and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the crizotinib AUC and Cmax at steady state by 84% and 79%, respectively.
    Cyclosporine: (Moderate) Closely monitor cyclosporine concentrations and adjust the dose of cyclosporine as appropriate if coadministration with rifamycins is necessary. Concurrent use may decrease cyclosporine exposure resulting in decreased efficacy. Cyclosporine is extensively metabolized by CYP3A4 and has a narrow therapeutic index; rifamycins are CYP3A4 inducers.
    Dabigatran: (Major) In general, avoid coadministration of dabigatran with P-gp inducers, such as rifampin. Concomitant administration of 600 mg rifampin for 7 days followed by a single dose of dabigatran decreased dabigatran AUC and Cmax by 66% and 67%, respectively. Dabigatran exposure returned to normal 7 days after cessation of rifampin therapy.
    Daclatasvir: (Contraindicated) Concomitant use of daclatasvir with rifampin is contraindicated due to the potential for hepatitis C treatment failure. Coadministration reduces systemic exposes to daclatasvir by 79%. Rifampin is a potent inducer of the hepatic isoenzyme CYP3A4; daclatasvir is a substrate of this isoenzyme.
    Dapagliflozin; Saxagliptin: (Minor) Coadministration of saxagliptin and rifampin decreased the maximum serum saxagliptin concentration by 53% and the systemic exposure by 76%. As expected, the maximum serum concentration of the saxagliptin active metabolite was increased by 39%; no significant change in the systemic exposure was noted. Saxagliptin dose adjustment is not advised when coadministered with rifampin, as the plasma dipeptidyl peptidase-4 activity over a 24-hour period was unaffected.
    Dapsone: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with rifampin is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and rifampin is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with rifampin decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage.
    Darifenacin: (Moderate) Monitor for decreased efficacy of darifenacin if coadministration with rifamycins is necessary; coadministration may result in decreased plasma concentrations of darifenacin. Rifamycins are CYP3A4 inducers and darifenacin is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of darifenacin.
    Darolutamide: (Major) Avoid coadministration of darolutamide with rifampin due to the risk of decreased darolutamide plasma concentrations which may decrease efficacy. Rifampin is a P-glycoprotein (P-gp) inducer and a strong inducer of CYP3A4; darolutamide is a CYP3A4 substrate. Concomitant use with rifampin decreased the mean AUC and Cmax of darolutamide by 72% and 52%, respectively.
    Darunavir: (Contraindicated) Darunavir is contraindicated for use with rifampin. Rifampin induces CYP3A4, thereby decreasing the plasma concentrations and AUC of most protease inhibitors by roughly 90% and leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
    Darunavir; Cobicistat: (Contraindicated) Coadministration of rifampin with cobicistat is contraindicated. Rifampin induces CYP3A4; cobicistat is a substrate of this enzyme. Concurrent use may result in significant decreases in the plasma concentrations of cobicistat and of the simultaneously administered protease inhibitors (atazanavir or darunavir), leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. (Contraindicated) Darunavir is contraindicated for use with rifampin. Rifampin induces CYP3A4, thereby decreasing the plasma concentrations and AUC of most protease inhibitors by roughly 90% and leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Coadministration of rifampin with cobicistat is contraindicated. Rifampin induces CYP3A4; cobicistat is a substrate of this enzyme. Concurrent use may result in significant decreases in the plasma concentrations of cobicistat and of the simultaneously administered protease inhibitors (atazanavir or darunavir), leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. (Contraindicated) Darunavir is contraindicated for use with rifampin. Rifampin induces CYP3A4, thereby decreasing the plasma concentrations and AUC of most protease inhibitors by roughly 90% and leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Contraindicated) Coadministration of rifampin and ritonavir results in markedly decreased ritonavir concentrations; HIV treatment failure and virologic resistance would be expected. Rifampin (300 or 600 mg daily for 10 days) decreases the AUC and Cmax of ritonavir (500 mg every 12 hours for 20 days) by 35% and 25%, respectively. Coadministration may lead to loss of virologic response if ritonavir is the sole protease inhibitor and increase the risk of hepatotoxicity. The DHHS/NIH HIV Treatment Guidelines recommend ritonavir and rifampin should not be coadministered and suggest the consideration of alternative antimycobacterial agents, such as rifabutin. However, CDC guidelines suggest no change in ritonavir or rifampin dose when the drugs are coadministered, but this appears to only be in the setting of low-dose ritonavir (i.e., 100 mg or 200 mg twice daily) used to 'boost' concentrations of other protease inhibitors. In this setting it would be less likely to produce adverse events than higher ritonavir doses; however, a net CYP3A4 induction still results when used with rifampin. (Contraindicated) Concomitant use of dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir with rifampin is contraindicated due to the potential for hepatitis C treatment failure. Coadministration may result in reduced systemic exposes to dasabuvir, ombitasvir, paritaprevir and ritonavir. Rifampin is a potent inducer of the hepatic isoenzyme CYP3A4; dasabuvir (minor), paritaprevir and ritonavir are substrates of this isoenzyme. Rifampin also induces CYP2D6 and CYP2C8, enzymes partially responsible for the metabolism of ritonavir and dasabuvir, respectively. In addition, rifampin induces the drug transporter proteins P-glycoprotein (P-gp) and UGT; dasabuvir, ombitasvir, paritaprevir and ritonavir are substrates for P-gp, while dasabuvir, ombitasvir and paritaprevir are also substrates of UGT. (Contraindicated) Concomitant use of dasabuvir; ombitasvir; paritaprevir; ritonavir with rifampin is contraindicated due to the potential for hepatitis C treatment failure. Coadministration may result in reduced systemic exposes to dasabuvir, ombitasvir, paritaprevir and ritonavir. Rifampin is a potent inducer of the hepatic isoenzyme CYP3A4; dasabuvir (minor), paritaprevir and ritonavir are substrates of this isoenzyme. Rifampin also induces CYP2D6 and CYP2C8, enzymes partially responsible for the metabolism of ritonavir and dasabuvir, respectively. In addition, rifampin induces the drug transporter proteins P-glycoprotein (P-gp) and UGT; dasabuvir, ombitasvir, paritaprevir and ritonavir are substrates for P-gp, while dasabuvir, ombitasvir and paritaprevir are also substrates of UGT.
    Dasatinib: (Major) Avoid coadministration of dasatinib and rifampin due to the potential for decreased dasatinib exposure and reduced efficacy. Consider an alternative to rifampin with less potential for enzyme induction. If coadministration cannot be avoided, consider an increased dose of dasatinib and monitor for toxicity. Dasatinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Concurrent use of rifampin decreased the mean Cmax and AUC of dasatinib by 81% and 82%, respectively.
    Deferasirox: (Major) Deferasirox undergoes UGT metabolism, and rifampin is a potent inducer of this enzyme system. The concomitant administration of deferasirox (single dose of 30 mg/kg) and rifampin (i.e., rifampicin 600 mg/day for 9 days) resulted in a decrease in deferasirox AUC by 44%. Avoid the concomitant use of rifampin and deferasirox if possible. If rifampin and deferasirox coadministration is necessary, consider increasing the initial dose of deferasirox. Monitor serum ferritin concentrations and clinical response for further modifications.
    Deflazacort: (Major) Avoid concomitant use of deflazacort and rifampin. Concurrent use may significantly decrease concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in loss of efficacy. Deflazacort is a CYP3A4 substrate; rifampin is a strong inducer of CYP3A4. Administration of deflazacort with multiple doses of rifampin resulted in geometric mean exposures that were approximately 95% lower compared to administration alone.
    Delavirdine: (Contraindicated) Rifampin decreases delavirdine concentrations by 97%. Do not administer delavirdine with rifampin because of the potential for subtherapeutic antiretroviral activity and the subsequent possibility for the development of resistant mutations of HIV.
    Desipramine: (Moderate) It may be necessary to adjust the dosage of tricyclic antidepressants if given concurrently with rifampin. Rifampin may induce the metabolism of tricyclic antidepressants; coadministration may result in decreased tricyclic antidepressant plasma concentrations.
    Desogestrel; Ethinyl Estradiol: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Dexamethasone: (Moderate) Monitor for decreased efficacy of dexamethasone if coadministration with rifampin is necessary; consider increasing the dose of dexamethasone if clinically appropriate. Dexamethasone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Dexlansoprazole: (Major) Avoid coadministration of dexlansoprazole with rifampin due to the risk of decreased dexlansoprazole plasma concentrations which may decrease efficacy. Dexlansoprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Dextromethorphan; Quinidine: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Inducers of CYP3A4 may increase hepatic elimination of quinidine. Rifampin is a potent inducer of this isoenzyme. Quinidine concentrations should be monitored closely after rifampin is added to the treatment regimen. No special precautions appear necessary if rifampin is begun several weeks before quinidine is added but quinidine doses may require adjustment if it is added or discontinued during quinidine therapy.
    Diazepam: (Major) Rifampin is a potent inducer of the hepatic isoenzyme CYP3A4, one of the pathways responsible for the hepatic metabolism of diazepam. Patients receiving rifampin may require higher doses of diazepam to achieve the desired clinical effect.
    Dienogest; Estradiol valerate: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Digoxin: (Moderate) It appears that rifampin decreases serum concentrations of digoxin by inducing intestinal P-glycoprotein and decreasing the oral bioavailability of digoxin by 30.1%. The Cmax and AUC of digoxin were decreased by 43% and 58%, respectively. The manufacturer of digoxin recommends measuring serum digoxin concentrations prior to initiation of rifampin. Continue monitoring during concomitant treatment and increase the digoxin dose by 20 to 40% as necessary.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with rifamycins is necessary; consider increasing the dose of dihydrocodeine as needed. If the rifamycin is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Rifamycins are inducers of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Concomitant use of dihydrocodeine with rifamycins 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.
    Diltiazem: (Major) Avoid coadministration of diltiazem and rifampin due to decreased plasma concentrations of diltiazem. Coadministration with rifampin lowered diltiazem plasma concentrations to undetectable. Diltiazem is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with rifampin 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 rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Disopyramide: (Major) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of disopyramide. Patients should be monitored for loss of disopyramide activity if rifampin is added. In addition, disopyramide doses may need to be reduced if rifampin is stopped and disopyramide therapy is continued. Serum disopyramide concentrations should be monitored closely if hepatic enzyme inducers are either added or discontinued during disopyramide therapy.
    Docetaxel: (Major) Avoid coadministration of docetaxel with rifampin due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
    Dolasetron: (Moderate) Blood concentrations of hydrodolasetron, the active metabolite of dolasetron, may be decreased when dolasetron is administered concomitantly with rifampin, a potent inducer of cytochrome P450.
    Dolutegravir: (Major) When possible, avoid concurrent use of dolutegravir with rifampin in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive or treatment-experienced, but INSTI-naive, adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with rifampin. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Dolutegravir is a CYP3A4 substrate and rifampin is an inducer of CYP3A4.
    Dolutegravir; Lamivudine: (Major) When possible, avoid concurrent use of dolutegravir with rifampin in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive or treatment-experienced, but INSTI-naive, adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with rifampin. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Dolutegravir is a CYP3A4 substrate and rifampin is an inducer of CYP3A4.
    Dolutegravir; Rilpivirine: (Contraindicated) Concurrent use of rifampin and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Rifampin is a potent inducer of CYP3A4, which is primarily responsible for the metabolism of rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine. (Major) When possible, avoid concurrent use of dolutegravir with rifampin in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive or treatment-experienced, but INSTI-naive, adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with rifampin. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Dolutegravir is a CYP3A4 substrate and rifampin is an inducer of CYP3A4.
    Donepezil: (Moderate) Monitor for decreased efficacy of donepezil if coadministration with rifampin is necessary. Donepezil is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Inducers of CYP3A4 could increase the rate of elimination of donepezil.
    Donepezil; Memantine: (Moderate) Monitor for decreased efficacy of donepezil if coadministration with rifampin is necessary. Donepezil is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Inducers of CYP3A4 could increase the rate of elimination of donepezil.
    Doravirine: (Contraindicated) Concurrent administration of doravirine and rifampin is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer.
    Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Contraindicated) Concurrent administration of doravirine and rifampin is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer.
    Doxepin: (Moderate) It may be necessary to adjust the dosage of tricyclic antidepressants if given concurrently with rifampin. Rifampin may induce the metabolism of tricyclic antidepressants; coadministration may result in decreased tricyclic antidepressant plasma concentrations.
    Doxercalciferol: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as rifampin, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Doxorubicin Liposomal: (Major) Rifampin is a potent CYP3A4 inducer, a moderate inducer of P-glycoprotein (P-gp), and a mild inducer of CYP2D6. Doxorubicin is a major substrate of CYP3A4, P-gp, and CYP2D6. Inducers of CYP3A4, CYP2D6, and/or P-gp may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy. Avoid coadministration of rifampin and doxorubicin if possible. If not possible, monitor doxorubicin closely for efficacy.
    Doxorubicin: (Major) Rifampin is a potent CYP3A4 inducer, a moderate inducer of P-glycoprotein (P-gp), and a mild inducer of CYP2D6. Doxorubicin is a major substrate of CYP3A4, P-gp, and CYP2D6. Inducers of CYP3A4, CYP2D6, and/or P-gp may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy. Avoid coadministration of rifampin and doxorubicin if possible. If not possible, monitor doxorubicin closely for efficacy.
    Doxycycline: (Major) Although doxycycline is not appreciably metabolized by the liver, concomitant use of rifampin has been shown to substantially increase doxycycline clearance. It is possible that extrahepatic sites of metabolism (e.g., intestinal mucosa) may be involved since P-450 cytochrome enzymes have been identified in areas such as adrenal cortex, intestinal mucosa, and kidney. A similar effect on doxycycline clearance and half-life has been noted for carbamazepine, pentobarbital, phenobarbital, phenytoin, and primidone. It is likely that all barbiturates exert the same effect on doxycycline pharmacokinetics. The possibility of antibiotic failure should also be considered whenever these enzyme inducers are used with doxycycline.
    Dronabinol: (Moderate) Use caution if coadministration of dronabinol with rifampin is necessary, and monitor for a decrease in the efficacy of dronabinol. Concomitant use may result in decreased plasma concentrations of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; rifampin is a strong inducer of CYP3A4 and a moderate CYP2C9 inducer.
    Dronedarone: (Major) Avoid coadministration of dronedarone with rifampin due to the potential for decreased dronedarone exposure and efficacy. Dronedarone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin significantly decreased dronedarone exposure.
    Drospirenone: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Drospirenone; Estetrol: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Drospirenone; Estradiol: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Drospirenone; Ethinyl Estradiol: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Duvelisib: (Major) Avoid coadministration of duvelisib with rifampin. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; rifampin is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with rifampin for 7 days decreased duvelisib Cmax and AUC by 66% and 82%, respectively.
    Edoxaban: (Major) Coadministration of edoxaban and rifampin should be avoided. Edoxaban is a P-glycoprotein (P-gp) substrate; rifampin is a strong inducer of P-gp. Coadminsitration decreases the serum concentration of edoxaban; reduced serum concentrations of edoxaban are expected to result in decreased efficacy of the anticoagulant.
    Efavirenz: (Major) When efavirenz and rifampin are coadministered, decreased efavirenz concentrations are seen and decreased antiretroviral efficacy is expected. These drugs may be coadministered to patients weighing 50 kg or more if the efavirenz dose is increased to 800 mg PO daily. A small study evaluated this interaction by administering the drugs (both at 600 mg PO daily x 7 days) to 12 subjects, and found decreased mean efavirenz Cmax, AUC, and Cmin of 20%, 26%, and 32%. Of note, reduced efavirenz metabolism is seen in patients with genetic polymorphisms of cytochrome P450 2B6 (primarily in patients of African, Asian, and Hispanic descent). Increasing the dose in these patients can result in a significant increase in efavirenz toxicity; some patients may even require lower doses.
    Efavirenz; Emtricitabine; Tenofovir: (Major) When efavirenz and rifampin are coadministered, decreased efavirenz concentrations are seen and decreased antiretroviral efficacy is expected. These drugs may be coadministered to patients weighing 50 kg or more if the efavirenz dose is increased to 800 mg PO daily. A small study evaluated this interaction by administering the drugs (both at 600 mg PO daily x 7 days) to 12 subjects, and found decreased mean efavirenz Cmax, AUC, and Cmin of 20%, 26%, and 32%. Of note, reduced efavirenz metabolism is seen in patients with genetic polymorphisms of cytochrome P450 2B6 (primarily in patients of African, Asian, and Hispanic descent). Increasing the dose in these patients can result in a significant increase in efavirenz toxicity; some patients may even require lower doses.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) When efavirenz and rifampin are coadministered, decreased efavirenz concentrations are seen and decreased antiretroviral efficacy is expected. These drugs may be coadministered to patients weighing 50 kg or more if the efavirenz dose is increased to 800 mg PO daily. A small study evaluated this interaction by administering the drugs (both at 600 mg PO daily x 7 days) to 12 subjects, and found decreased mean efavirenz Cmax, AUC, and Cmin of 20%, 26%, and 32%. Of note, reduced efavirenz metabolism is seen in patients with genetic polymorphisms of cytochrome P450 2B6 (primarily in patients of African, Asian, and Hispanic descent). Increasing the dose in these patients can result in a significant increase in efavirenz toxicity; some patients may even require lower doses.
    Elagolix: (Contraindicated) The use of rifampin with elagolix is contraindicated. Concomitant use of elagolix and organic anion transporting polypeptide (OATP) 1B1 inhibitors such as rifampin increase exposure to elagolix. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. During drug interaction studies, a single dose of rifampin increased the mean AUC of elagolix by 5.58-fold. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. While induction of CYP3A by rifampin may also occur, particularly with continued use, it appears that elagolix is more influenced by the OATP1B1 activity of rifampin as AUC remained elevated by a mean of 1.65-fold with continued use of rifampin.
    Elagolix; Estradiol; Norethindrone acetate: (Contraindicated) The use of rifampin with elagolix is contraindicated. Concomitant use of elagolix and organic anion transporting polypeptide (OATP) 1B1 inhibitors such as rifampin increase exposure to elagolix. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. During drug interaction studies, a single dose of rifampin increased the mean AUC of elagolix by 5.58-fold. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. While induction of CYP3A by rifampin may also occur, particularly with continued use, it appears that elagolix is more influenced by the OATP1B1 activity of rifampin as AUC remained elevated by a mean of 1.65-fold with continued use of rifampin. (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Elbasvir; Grazoprevir: (Contraindicated) Concurrent administration of elbasvir; grazoprevir with rifampin is contraindicated. Rifampin is a strong CYP3A inducer, while both elbasvir and grazoprevir are substrates of CYP3A. Use of these drugs together is expected to significantly decrease the plasma concentrations of both elbasvir and grazoprevir, and may result in decreased virologic response.
    Elexacaftor; tezacaftor; ivacaftor: (Major) Coadministration of elexacaftor; tezacaftor; ivacaftor with rifampin is not recommended as concurrent use may decrease exposure of elexacaftor; tezacaftor; ivacaftor. Elexacaftor, tezacaftor, and ivacaftor are CYP3A4 substrates (ivacaftor is a sensitive CYP3A4 substrate). Coadministration of rifampin, a strong CYP3A4 inducer, significantly decreased ivacaftor exposure by 89%; elexacaftor and tezacaftor exposures are expected to also decrease during coadministration of strong CYP3A4 inducers. (Major) Coadministration of ivacaftor with rifampin is not recommended due to decreased plasma concentrations of ivacaftor. Ivacaftor is a sensitive CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin significantly decreased ivacaftor exposure by approximately 9-fold. (Major) Do not administer tezacaftor; ivacaftor and rifampin together; coadministration may reduce the efficacy of tezacaftor; ivacaftor. Exposure to ivacaftor is significantly decreased and exposure to tezacaftor may be reduced by the concomitant use of rifampin, a strong CYP3A inducer; both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate). Coadministration of ivacaftor with rifampin decreased ivacaftor exposure 89%.
    Eliglustat: (Major) Coadministration of eliglustat and rifampin significantly decreases eliglustat exposure and is not recommended in extensive, intermediate, or poor metabolizers of CYP2D6 (EMs, IMs, PMs). Rifampin is a strong CYP3A inducer, and eliglustat is a CYP3A substrate. During clinical trials, systemic exposures (Cmax and AUC) of eliglustat decreased by approximately 90% in EMs and IMs after coadministration of eliglustat 127 mg PO twice daily with rifampin 600 mg PO once daily. Of note, the only FDA-approved dose of eliglustat is 84 mg. Additionally, systemic exposures decreased by approximately 95% after coadministration of eliglustat 84 mg PO twice daily with rifampin 600 mg PO once daily in PMs.
    Eltrombopag: (Major) Eltrombopag is metabolized by CYP1A2 and CYP2C8. The significance of administering inducers of CYP1A2 and CYP2C8, such as rifampin, on the systemic exposure of eltrombopag has not been established. Additionally, eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as rifampin, may exhibit an increase in systemic exposure if coadministered with eltrombopag. Monitor patients for a decrease in the efficacy of eltrombopag and for an increase in adverse reactions of rifampin if these drugs are coadministered.
    Eluxadoline: (Major) When administered concurrently with rifampin, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); rifampin is an inhibitor of OATP. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
    Elvitegravir: (Major) Coadministration of rifampin, a potent CYP3A4 inducer, with elvitegravir, a CYP3A4 substrate, is not recommended. Concurrent use may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Coadministration of rifampin with cobicistat is contraindicated. Rifampin induces CYP3A4; cobicistat is a substrate of this enzyme. Concurrent use may result in significant decreases in the plasma concentrations of cobicistat and of the simultaneously administered protease inhibitors (atazanavir or darunavir), leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. (Major) Coadministration of rifampin, a potent CYP3A4 inducer, with elvitegravir, a CYP3A4 substrate, is not recommended. Concurrent use may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Coadministration of rifampin with cobicistat is contraindicated. Rifampin induces CYP3A4; cobicistat is a substrate of this enzyme. Concurrent use may result in significant decreases in the plasma concentrations of cobicistat and of the simultaneously administered protease inhibitors (atazanavir or darunavir), leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. (Major) Coadministration of rifampin, a potent CYP3A4 inducer, with elvitegravir, a CYP3A4 substrate, is not recommended. Concurrent use may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
    Empagliflozin; Linagliptin: (Major) Concomitant use of linagliptin with rifampin is not recommended due to the potential for decreased linagliptin serum concentrations and loss of efficacy. Linagliptin is a substrate of hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); rifampin is a strong inducer of CYP3A4 and an inducer of P-gp. In drug interaction studies, rifampin decreased the mean AUC and Cmax of linagliptin by 40% and 44%, respectively. For patients requiring use of such drugs, an alternative to linagliptin is strongly recommended.
    Empagliflozin; Linagliptin; Metformin: (Major) Concomitant use of linagliptin with rifampin is not recommended due to the potential for decreased linagliptin serum concentrations and loss of efficacy. Linagliptin is a substrate of hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); rifampin is a strong inducer of CYP3A4 and an inducer of P-gp. In drug interaction studies, rifampin decreased the mean AUC and Cmax of linagliptin by 40% and 44%, respectively. For patients requiring use of such drugs, an alternative to linagliptin is strongly recommended.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Contraindicated) Concurrent use of rifampin and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Rifampin is a potent inducer of CYP3A4, which is primarily responsible for the metabolism of rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Contraindicated) Concurrent use of rifampin and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Rifampin is a potent inducer of CYP3A4, which is primarily responsible for the metabolism of rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine.
    Enalapril, Enalaprilat: (Moderate) Concomitant use of rifampin and enalapril may result in decreased concentrations of enalaprilat, the active metabolite of enalapril. Dosage adjustments of enalapril may be required.
    Enalapril; Felodipine: (Major) The metabolism of felodipine may be increased by rifampin, an enzyme inducer. (Moderate) Concomitant use of rifampin and enalapril may result in decreased concentrations of enalaprilat, the active metabolite of enalapril. Dosage adjustments of enalapril may be required.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of rifampin and enalapril may result in decreased concentrations of enalaprilat, the active metabolite of enalapril. Dosage adjustments of enalapril may be required.
    Encorafenib: (Major) Avoid coadministration of encorafenib and rifampin due to decreased encorafenib exposure and potential loss of efficacy. Encorafenib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. 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.
    Enflurane: (Moderate) Caution is advised with the concomitant use of enflurane and rifampin as concurrent use may increase the risk of hepatotoxicity.
    Entacapone: (Moderate) Entacapone should be given cautiously with drugs known to interfere with biliary excretion, glucuronidation or intestinal beta-glucuronidation such as rifampin. Decreased biliary excretion of entacapone may occur if these agents are given concurrently.
    Entrectinib: (Major) Avoid coadministration of entrectinib with rifampin due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration of rifampin decreased the entrectinib AUC by 77% in a drug interaction study.
    Enzalutamide: (Major) Avoid coadministration of enzalutamide with rifampin if possible due to the risk of decreased enzalutamide plasma concentrations. If concomitant use is unavoidable, increase the dose of enzalutamide from 160 mg to 240 mg PO once daily. If rifampin is discontinued, resume the dose of enzalutamide used prior to initiation of rifampin. Enzalutamide is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the composite AUC of enzalutamide plus N-desmethyl enzalutamide by 37%.
    Eravacycline: (Major) Increase the dose of eravacycline to 1.5 mg/kg IV every 12 hours when coadministered with a strong CYP3A4 inducer, such as rifampin. Concomitant use of strong CYP3A4 inducers decreases the exposure of eravacycline, which may reduce its efficacy. When eravacycline was administered with rifampin, the eravacycline AUC was decreased by 35% and its clearance was increased by 54%.
    Erdafitinib: (Major) Avoid the concomitant use of erdafitinib and rifampin due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 and CYP2C9 substrate; rifampin is a strong CYP3A4 and CYP2C9 inducer. Simulations suggested that rifampin may significantly decrease erdafitinib Cmax and AUC.
    Ergotamine; Caffeine: (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Erlotinib: (Major) Avoid coadministration of erlotinib with rifampin if possible due to the risk of decreased erlotinib efficacy. If concomitant use is unavoidable, increase the dose of erlotinib in 50 mg increments at 2-week intervals as tolerated (maximum dose, 450 mg). Erlotinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased erlotinib exposure by 58% to 80%.
    Erythromycin: (Major) Caution is warranted with the concomitant use of erythromycin and rifampin as this may result in reduced erythromycin Cmax and increased clearance. Coadministration of oral erythromycin 500 mg and rifampin 600 mg to healthy patients led to a reduced erythromycin maximum serum concentration (Cmax) and an increased clearance. Specifically, as monotherapy, the median erythromycin Cmax was 1.34 mg/L (range, 0.4 to 3.16), and the median apparent oral clearance was 96 L/hour (range, 37 to 250). In combination with rifampin, the median erythromycin Cmax was 0.72 mg/L (range, 0.06 to 1.66), and the median apparent oral clearance was 197 L/hour (range, 102 to 2015).
    Erythromycin; Sulfisoxazole: (Major) Caution is warranted with the concomitant use of erythromycin and rifampin as this may result in reduced erythromycin Cmax and increased clearance. Coadministration of oral erythromycin 500 mg and rifampin 600 mg to healthy patients led to a reduced erythromycin maximum serum concentration (Cmax) and an increased clearance. Specifically, as monotherapy, the median erythromycin Cmax was 1.34 mg/L (range, 0.4 to 3.16), and the median apparent oral clearance was 96 L/hour (range, 37 to 250). In combination with rifampin, the median erythromycin Cmax was 0.72 mg/L (range, 0.06 to 1.66), and the median apparent oral clearance was 197 L/hour (range, 102 to 2015).
    Escitalopram: (Moderate) Escitalopram is metabolized by CYP3A4. Rifampin can induce the metabolism of escitalopram via induction of CYP3A4. Although no clinical data are available to support a clinically significant interaction, escitalopram may need to be administered in higher doses in patients chronically taking rifampin.
    Esomeprazole: (Major) Avoid coadministration of esomeprazole with rifampin due to the risk of decreased esomeprazole plasma concentrations which may decrease efficacy. Esomeprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Estradiol Cypionate; Medroxyprogesterone: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Estradiol; Levonorgestrel: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Estradiol; Norethindrone: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Estradiol; Norgestimate: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Estradiol; Progesterone: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Estrogens affected by CYP3A inducers: (Major) Women taking both estrogens and rifamycins should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed rifamycins. In some cases, it may be advisable for patients to change to non-hormonal methods of birth control during rifamycin therapy. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of rifamycins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on rifamycins, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and rifamycins are a CYP3A4 inducers. Concurrent administration may increase estrogen elimination.
    Eszopiclone: (Moderate) Monitor for decreased efficacy of eszopiclone if coadministration with rifampin is necessary. Eszopiclone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased racemic zopiclone exposure by 80%; a similar effect would be expected with eszopiclone.
    Ethambutol: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of rifampin and ethambutol. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
    Ethanol: (Major) Rifampin is associated with dose-related hepatoxicity. Daily use of alcohol while receiving rifampin increases the risk of drug-induced hepatitis. Liver-function tests should be conducted prior to and every 2-4 weeks during treatment in patients who consume alcohol routinely while receiving rifampin therapy. (Major) Rifampin is associated with dose-related hepatoxicity. Daily use of ethanol while receiving rifampin increases the risk of drug-induced hepatitis. Liver-function tests should be conducted prior to and every 2-4 weeks during treatment in patients who consume ethanol routinely while receiving rifampin therapy.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Ethinyl Estradiol; Norelgestromin: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Ethinyl Estradiol; Norethindrone Acetate: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Ethinyl Estradiol; Norgestrel: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Ethionamide: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of rifampin and ethionamide. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs may be used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
    Ethotoin: (Major) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of ethotoin. Dosages of ethotoin may need to be adjusted while the patient is receiving rifampin.
    Ethynodiol Diacetate; Ethinyl Estradiol: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Etonogestrel: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Etonogestrel; Ethinyl Estradiol: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Etravirine: (Major) Etravirine should not be coadministered with rifampin, a potent inducer of CYP450 enzymes, as significant decreases in etravirine plasma concentrations and, thus, loss of therapeutic effect could occur.
    Everolimus: (Major) Avoid coadministration of everolimus with rifampin due to the risk of decreased efficacy of everolimus. If concomitant use is unavoidable, coadministration requires a dose increase for some indications and close monitoring for others. For oncology indications and tuberous sclerosis complex (TSC)-associated renal angiomyolipoma, double the daily dose using increments of 5 mg or less; multiple increments may be required. For patients with TSC-associated subependymal giant cell astrocytoma (SEGA) and TSC-associated partial-onset seizures, assess the everolimus whole blood trough concentration 2 weeks after initiation of rifampin and adjust the dose as necessary to remain in the recommended therapeutic range. Also closely monitor everolimus whole blood trough concentrations in patients receiving everolimus for either kidney or liver transplant and adjust the dose as necessary to remain in the recommended therapeutic range. Everolimus is a sensitive CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the Cmax and AUC of everolimus by 58% and 63%, respectively. For indications where everolimus trough concentrations are monitored, the addition of a second strong CYP3A4 inducer in a patient already receiving treatment with a strong CYP3A4 inducer may not require additional dose modification.
    Exemestane: (Major) If coadministration of exemestane with rifampin is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased exemestane exposure by 54%.
    Ezetimibe; Simvastatin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of simvastatin. Monitor for potential reduced cholesterol-lowering and hypotensive efficacy when these drugs are coadministered.
    Fedratinib: (Major) Avoid coadministration of fedratinib with rifampin as concurrent use may decrease fedratinib exposure which may result in decreased therapeutic response. Fedratinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration of fedratinib with rifampin decreased the overall exposure of fedratinib by 81%.
    Felodipine: (Major) The metabolism of felodipine may be increased by rifampin, an enzyme inducer.
    Fenfluramine: (Moderate) Consider an increase in fenfluramine dosage if coadministered with rifampin. Concurrent use may decrease fenfluramine plasma concentrations, which may lower its efficacy. Fenfluramine is a CYP2B6 and CYP1A2 substrate and rifampin is a strong CYP2B6 and CYP1A2 inducer.
    Fentanyl: (Moderate) Consider an increased dose of fentanyl and monitor for evidence of opioid withdrawal if concurrent use of rifampin is necessary. If rifampin is discontinued, consider reducing the fentanyl dosage and monitor for evidence of respiratory depression. Coadministration of a CYP3A4 inducer like rifampin with fentanyl, a CYP3A4 substrate, may decrease exposure to fentanyl resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to fentanyl. Fentanyl plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
    Fexofenadine: (Minor) Rifampin may decrease plasma concentrations of fexofenadine and potentially reduce its antihistaminic effects. Although the therapeutic range of fexofenadine is broad, monitor for potential decreased therapeutic effects of fexofenadine if rifampin is initiated.
    Fexofenadine; Pseudoephedrine: (Minor) Rifampin may decrease plasma concentrations of fexofenadine and potentially reduce its antihistaminic effects. Although the therapeutic range of fexofenadine is broad, monitor for potential decreased therapeutic effects of fexofenadine if rifampin is initiated.
    Finerenone: (Major) Avoid concurrent use of finerenone and rifampin due to the risk for decreased finerenone exposure which may reduce its efficacy. Finerenone is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased overall exposure to finerenone by 90%.
    Flibanserin: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and rifampin, a strong CYP3A4 inducer, is not recommended. In a study of 24 healthy female subjects, rifampin 600 mg once daily for 7 days prior to administration of 100 mg flibanserin significantly decreased flibanserin exposure by 95%.
    Fluconazole: (Moderate) Rifampin is a potent enzyme inducer and can increase the metabolism of fluconazole. Administration of fluconazole 200 mg PO after 15 days of rifampin 600 mg PO daily to 8 healthy male volunteers resulted in a significant decrease in fluconazole AUC and a significant increase in fluconazole apparent oral clearance. The AUC was reduced by about 23% and the apparent oral clearance was increased by about 32%. Fluconazole half-life decreased from approximately 33 hours to approximately 27 hours. The dose of fluconazole may need to be increased in patients also receiving rifampin to assure adequate fluconazole plasma concentrations. Although available data are inconclusive, rifabutin may be less likely than rifampin to interact with fluconazole in this manner.
    Flurazepam: (Major) Rifamycins are hepatic inducers and can theoretically increase the clearance of benzodiazpines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations.
    Fluvastatin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors. Monitor serum lipid concentrations during coadministration of rifampin with fluvastatin.
    Food: (Moderate) The incidence of marijuana associated adverse effects may change following coadministration with rifampin. Rifampin is an inducer of CYP2C9 and CYP3A4, two isoenzymes responsible for the metabolism of marijuana's most psychoactive compound, delta-9-tetrahydrocannabinol (Delta-9-THC). When given concurrently with rifampin, the amount of Delta-9-THC converted to the active metabolite 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC) may be increased. These changes in Delta-9-THC and 11-OH-THC plasma concentrations may result in an altered marijuana adverse event profile.
    Fosamprenavir: (Contraindicated) Fosamprenavir is contraindicated for use in combination with rifampin. Rifampin decreases fosamprenavir Cmax, AUC, and Cmin by 70%, 82%, and 92%, respectively. Coadministration of fosamprenavir and rifampin may lead to loss of virologic response and possible resistance to fosamprenavir or to the class of protease inhibitors.
    Fosphenytoin: (Major) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of fosphenytoin. Dosages of fosphenytoin may need to be adjusted while the patient is receiving rifampin.
    Fostamatinib: (Major) Avoid the concomitant use of fostamatinib with rifampin. Concomitant use of fostamatinib with a strong CYP3A4 inducer decreases exposure to the major active metabolite, R406. R406 is extensively metabolized by CYP3A4; rifampin is a strong CYP3A4 inducer. Concomitant use of fostamatinib with rifampin decreased R406 AUC by 75% and Cmax by 59%.
    Fostemsavir: (Contraindicated) Concomitant use of fostemsavir and rifampin is contraindicated. Use of these drugs together significantly decreases the plasma concentrations of temsavir, the active moiety of fostemsavir, thereby increasing the risk for HIV treatment failure or development of viral resistance. Temsavir is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Gefitinib: (Major) Increase the dose of gefitinib to 500 mg PO once daily if coadministration with rifampin is necessary. If rifampin is discontinued, gefitinib at a dose of 250 mg once daily may be resumed 7 days later. Gefitinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin reduced gefitinib exposure by 83%.
    Gemfibrozil: (Moderate) Coadministration may result in an increase in rifampin exposure. A dose reduction of rifampin may be required if used concomitantly with gemfibrozil. Use rifampin and gemfibrozil together with caution. Rifampin is a substrate of the OATP1B1 transporter. Gemfibrozil inhibits OATP1B1.
    Gilteritinib: (Major) Avoid coadministration of gilteritinib and rifampin due to the potential for decreased gilteritinib exposure and risk of decreased efficacy. Gilteritinib is a P-gp and CYP3A4 substrate; rifampin is a combined P-gp and strong CYP3A4 inducer. Coadministration with rifampin decreased the gilteritinib AUC by 70% in a drug interaction study
    Glasdegib: (Major) Avoid coadministration of glasdegib and rifampin due to the potential for decreased glasdegib exposure and risk of decreased efficacy. Glasdegib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the glasdegib AUC by 70% in a drug interaction study.
    Glecaprevir; Pibrentasvir: (Contraindicated) Coadministration of glecaprevir with rifampin is contraindicated due to the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate for CYP3A4 and P-glycoprotein (P-gp); rifampin is a CYP3A4 and P-gp inducer. Coadministration decreases the plasma concentrations of glecaprevir by 88%. (Contraindicated) Coadministration of pibrentasvir with rifampin is contraindicated due to the potential loss of efficacy of pibrentasvir. Pibrentasvir is a substrate for P-glycoprotein (P-gp); rifampin is an inducer of P-gp. Coadministration decreases the plasma concentrations of pibrentasvir by 87%.
    Glimepiride: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
    Glimepiride; Rosiglitazone: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers. (Minor) The coadministration of rifampin and rosiglitazone may decrease the concentration of rosiglitazone. This interaction is most likely due to rifampin's inhibition of the CYP2C8 and, to a lesser extent, CYP2C9 isozymes. Use caution if rifampin and rosiglitazone are to be coadministered, as decreased rosiglitazone efficacy may be seen. Blood glucose concentrations should be monitored and possible dose adjustments of rosiglitazone may need to be made.
    Glipizide: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
    Glipizide; Metformin: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
    Glyburide: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
    Glyburide; Metformin: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
    Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with rifampin 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 rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with rifampin 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 rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Guanfacine: (Major) Rifampin may significantly decrease guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if these agents are taken together, doubling the recommended dose of guanfacine should be considered; if rifampin is added in a patient already receiving guanfacine, this escalation should occur over 1 to 2 weeks. Upon rifampin discontinuation, decrease the guanfacine ER dosage back to the recommended dose over 1 to 2 weeks. Specific recommendations for immediate-release (IR) guanfacine are not available. Guanfacine is primarily metabolized by CYP3A4, and rifampin is a strong CYP3A4 inducer.
    Haloperidol: (Major) Limited data suggest that rifampin, a potent CYP inducer, can increase the metabolism and/or reduce the bioavailability of haloperidol. In one small study (n=12), plasma levels of haloperidol were decreased by a mean of 70% and mean scores on the Brief Psychiatric Rating Scale (BPRS) were increased from baseline during concurrent use of rifampin. Discontinuation of rifampin has resulted in a mean 3.3-fold increase in haloperidol concentrations in some instances. Haloperidol dosage adjustments should be made as needed when rifampin is added or discontinued. Prolonged use of CYP inducers such as rifampin in patients receiving haloperidol has resulted in significant reductions in haloperidol plasma concentrations.
    Halothane: (Major) Avoid concomitant use of rifampin and halothane. Concurrent use may increase the potential for hepatotoxicity.
    Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with rifampin 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 rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Hydrocodone: (Moderate) Concomitant use of hydrocodone with rifampin 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 rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with rifampin 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 rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with rifampin 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 rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Concomitant use of hydrocodone with rifampin 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 rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with rifampin 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 rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with rifampin 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 rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Hydroxychloroquine: (Major) Avoid concomitant use of hydroxychloroquine and rifampin as lack of efficacy of hydroxychloroquine was reported when administered together. Coadministration may decrease the exposure of hydroxychloroquine. Hydroxychloroquine may be a CYP3A4 substrate in vitro, and rifampin is a strong CYP3A4 inducer.
    Ibrexafungerp: (Major) Avoid concurrent administration of ibrexafungerp with rifampin. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and rifampin is a strong CYP3A inducer.
    Ibrutinib: (Major) Avoid the concomitant use of ibrutinib and rifampin; significantly reduced ibrutinib plasma concentrations have occurred. Ibrutinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. When ibrutinib was administered with rifampin, the Cmax and AUC values of ibrutinib decreased by more than 13-fold and 10-fold, respectively.
    Ibuprofen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with rifampin is necessary; consider increasing the dose of oxycodone as needed. If rifampin is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Idelalisib: (Contraindicated) Avoid concomitant use of idelalisib, a CYP3A4 substrate, with a strong CYP3A4 inducer such as rifampin, as idelalisib exposure may be significantly reduced and efficacy compromised. In healthy subjects, rifampin 600 mg once daily for 8 days administered with a single dose of idelalisib 150 mg resulted in a decrease of the geometric mean idelalisib AUC by 75% and geometric mean Cmax by 58% compared wtih idelalisib administered alone.
    Ifosfamide: (Moderate) Closely monitor for increased ifosfamide-related toxicities (e.g., neurotoxicity, nephrotoxicity) if coadministration with rifampin is necessary; consider adjusting the dose of ifosfamide as clinically appropriate. Ifosfamide is metabolized to its active alkylating metabolites by CYP3A4; rifampin is a strong CYP3A4 inducer. Concomitant use may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde.
    Iloperidone: (Moderate) In vitro studies indicate that CYP3A4 is involved in the metabolism of iloperidone. In theory, potent inducers of CYP3A4 such as rifampin may increase the elimination of iloperidone. The clinical outcome of concurrent administration with iloperidone is unknown.
    Imatinib: (Major) Avoid coadministration of imatinib and rifampin if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
    Imipramine: (Moderate) It may be necessary to adjust the dosage of tricyclic antidepressants if given concurrently with rifampin. Rifampin may induce the metabolism of tricyclic antidepressants; coadministration may result in decreased tricyclic antidepressant plasma concentrations.
    Indinavir: (Contraindicated) Indinavir and rifampin should not be coadministered. Administration of indinavir and rifampin for one week resulted in a 89% decrease in the indinavir AUC. The administration of rifampin with indinavir, alone or in combination with ritonavir, could lead to subtherapeutic concentrations of indinavir.
    Infigratinib: (Major) Avoid concurrent use of infigratinib and rifampin. Coadministration decreased the AUC of infigratinib by 56% which may decrease infigratinib efficacy. Infigratinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Irinotecan Liposomal: (Major) Avoid administration of rifampin during treatment with irinotecan and for at least 2 weeks prior to starting therapy unless there are no therapeutic alternatives. Irinotecan is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Exposure to irinotecan or its active metabolite, SN-38, was substantially reduced in patients treated with other strong CYP3A4 inducers. An appropriate starting dose for patients taking irinotecan with strong CYP3A4 inducers has not been defined.
    Irinotecan: (Major) Avoid administration of rifampin during treatment with irinotecan and for at least 2 weeks prior to starting therapy unless there are no therapeutic alternatives. Irinotecan is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Exposure to irinotecan or its active metabolite, SN-38, was substantially reduced in patients treated with other strong CYP3A4 inducers. An appropriate starting dose for patients taking irinotecan with strong CYP3A4 inducers has not been defined.
    Isavuconazonium: (Contraindicated) Concomitant use of isavuconazonium with rifampin is contraindicated due to the potential for decreased isavuconazole serum concentrations and treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; rifampin is a strong inducer of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inducers is contraindicated. There was a 97% decrease in isavuconazole serum concentrations when coadministered with rifampin.
    Isoflurane: (Moderate) Caution is advised with the concomitant use of isoflurane and rifampin as concurrent use may increase the risk of hepatotoxicity.
    Isoniazid, INH: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of isoniazid, INH and rifampin. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Rifampin can increase the metabolism of isoniazid, INH into a hepatotoxic metabolite (hydrazine). The impact of this drug interaction, however, appears minimal; combination therapy is routinely used in treating tuberculosis. Hepatotoxicity as a result of this interaction may be more significant in INH slow acetylators, patients with preexisting hepatic disease, or patients receiving anesthetics. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of isoniazid, INH and rifampin. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Rifampin can increase the metabolism of isoniazid, INH into a hepatotoxic metabolite (hydrazine). The impact of this drug interaction, however, appears minimal; combination therapy is routinely used in treating tuberculosis. Hepatotoxicity as a result of this interaction may be more significant in INH slow acetylators, patients with preexisting hepatic disease, or patients receiving anesthetics. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program. (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of rifampin and pyrazinamide, PZA. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. The use of the 2-month rifampin plus pyrazinamide latent tuberculosis infection (LTBI) regimen should no longer be offered due to the known increased risk of severe liver injury and death. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
    Isoniazid, INH; Rifampin: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of isoniazid, INH and rifampin. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Rifampin can increase the metabolism of isoniazid, INH into a hepatotoxic metabolite (hydrazine). The impact of this drug interaction, however, appears minimal; combination therapy is routinely used in treating tuberculosis. Hepatotoxicity as a result of this interaction may be more significant in INH slow acetylators, patients with preexisting hepatic disease, or patients receiving anesthetics. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
    Isradipine: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that induce CYP3A4, such as rifampin, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Istradefylline: (Major) Avoid coadministration of istradefylline with rifampin as istradefylline exposure and efficacy may be reduced. Rifampin is a strong inducer. Istradefylline exposure was decreased by 81% when administered with rifampin in a drug interaction study.
    Itraconazole: (Major) The use of rifampin within 2 weeks of itraconazole therapy is not recommended. If coadministration cannot be avoided, monitor for decreased efficacy of itraconazole and increase the dose of itraconazole as necessary. Itraconazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Ivabradine: (Major) Avoid coadministration of ivabradine and rifampin. Ivabradine is primarily metabolized by CYP3A4; rifampin induces CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
    Ivacaftor: (Major) Coadministration of ivacaftor with rifampin is not recommended due to decreased plasma concentrations of ivacaftor. Ivacaftor is a sensitive CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin significantly decreased ivacaftor exposure by approximately 9-fold.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with rifampin due to decreased plasma concentrations of ivosidenib. Ivosidenib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin is predicted to decrease ivosidenib exposure at steady-state by 33%.
    Ixabepilone: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with strong CYP3A4 inducers such as rifampin may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Ixazomib: (Major) Avoid the concomitant use of ixazomib and rifampin; ixazomib levels were significantly decreased in a drug interactions evaluation. Ixazomib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. In subjects who received ixazomib with rifampin, the ixazomib Cmax and AUC values were decreased by 54% and 74%, respectively.
    Ketoconazole: (Major) Ketoconazole and rifampin each affect the pharmacokinetics of the other. Ketoconazole has been shown to reduce serum concentrations of rifampin but the clinical significance of this effect on rifampin concentrations is not known. More significant are the effects of rifampin on ketoconazole pharmacokinetics. Rifampin is a potent inducer of hepatic microsomal enzymes. When rifampin is used in combination with isoniazid, INH, isoniazid appears to intensify the effect of rifampin on the pharmacokinetics of other drugs, despite the fact that isoniazid is generally considered an inhibitor of drug metabolism. The effects of isoniazid with rifampin on ketoconazole have been significant enough to result in antifungal treatment failure. Ketoconazole doses may need to be increased if rifampin, or the combination of rifampin with isoniazid, is used concomitantly. However, it is generally not recommended that ketoconazole be used with INH or rifampin.
    Lamivudine, 3TC; Zidovudine, ZDV: (Minor) Rifampin can accelerate the metabolism of zidovudine, causing a decrease in AUC of approximately 50%. However the effectiveness of zidovudine against HIV does not appear to be altered and no dosage adjustments are required.
    Lamotrigine: (Major) Adjustments in lamotrigine escalation and maintenance dose regimens are necessary with concomitant rifampin use. Monitoring lamotrigine plasma concentrations may be indicated, particularly during dosage adjustments. Lamotrigine is metabolized predominantly by glucuronic acid conjugation, and rifampin induces glucuronidation. During concurrent use of lamotrigine with rifampin in 10 volunteers, rifampin (600 mg/day for 5 days) decreased the AUC of lamotrigine (25 mg single dose) by approximately 40%.
    Lansoprazole: (Major) Avoid coadministration of lansoprazole with rifampin due to the risk of decreased lansoprazole plasma concentrations which may decrease efficacy. Lansoprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of lansoprazole with rifampin due to the risk of decreased lansoprazole plasma concentrations which may decrease efficacy. Lansoprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Major) Clarithromycin is a substrate and inhibitor of CYP3A4, and rifampin is an inducer of CYP3A4. As compared with the plasma concentration obtained with clarithromycin 500 mg twice daily as monotherapy, the clarithromycin plasma concentration was reduced by 87% when rifampin 600 mg daily was coadministered. Specifically, as monotherapy, the mean serum clarithromycin concentration was 5.4 +/- 2.1 mcg/ml. The mean serum clarithromycin concentration was 0.7 +/- 0.6 mcg/ml when given in combination with rifampin. The mean serum concentrations of 14-OH clarithromycin were similar between the two groups. Alternatives to clarithromycin should be considered in patients who are taking CYP3A4 inducers.
    Lansoprazole; Naproxen: (Major) Avoid coadministration of lansoprazole with rifampin due to the risk of decreased lansoprazole plasma concentrations which may decrease efficacy. Lansoprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Lapatinib: (Major) Avoid coadministration of lapatinib with rifampin due to decreased plasma concentrations of lapatinib. If concomitant use is unavoidable, gradually titrate the dose of lapatinib from 1,250 mg per day to 4,500 mg per day in patients receiving concomitant capecitabine (HER2-positive metastatic breast cancer), and from 1,500 mg per day to 5,500 mg per day in patients receiving concomitant aromatase inhibitor therapy (HR-positive, HER2-positive breast cancer) based on tolerability. If rifampin is discontinued, reduce lapatinib to the indicated dose. Lapatinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with another strong CYP3A4 inducer decreased lapatinib exposure by 72%.
    Larotrectinib: (Major) Avoid coadministration of larotrectinib with rifampin due to decreased larotrectinib exposure and risk of decreased efficacy. If coadministration cannot be avoided, double the larotrectinib dose. If rifampin is discontinued, resume the original larotrectinib dose after 3 to 5 elimination half-lives of rifampin. Larotrectinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the larotrectinib AUC by 81% in a drug interaction study.
    Ledipasvir; Sofosbuvir: (Major) Avoid coadministration of ledipasvir with potent inducers of intestinal P-glycoprotein (P-gp), such as rifampin. Taking these drugs together may significantly decrease ledipasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. (Major) Avoid coadministration of sofosbuvir, a P-glycoprotein (P-gp) substrate, with inducers of P-gp, such as rifampin. Taking these drugs together may significantly decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. In a single-dose study, coadministration reduced the sofosbuvir Cmax and AUC to 23% and 28% of normal concentrations, respectively.
    Lefamulin: (Major) Avoid coadministration of lefamulin with rifampin unless the benefits outweigh the risks as concurrent use may decrease lefamulin exposure and efficacy. Lefamulin is a CYP3A4 and P-gp substrate; rifampin is a P-gp and strong CYP3A4 inducer. Coadministration of rifampin decreased the mean AUC of oral and intravenous lefamulin by 72% and 28%, respectively.
    Leflunomide: (Moderate) No dosage adjustment is recommended for leflunomide when coadministered with rifampin. Because of the potential for leflunomide concentrations to increase with multiple dosing, caution should be used if rifampin is added to therapy. Concomitant use of leflunomide and rifampin, a potent inducer of CYP and transporters, increased the plasma concentration of teriflunomide by 40%, probably via induction of metabolism of leflunomide to the active metabolite. However, rifampin administration with the metabolite alone ( teriflunomide) did not alter the pharmacokinetics of the drug.
    Lemborexant: (Major) Avoid coadministration of lemborexant and rifampin as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer.
    Lesinurad: (Moderate) Rifampin may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Rifampin is a CYP2C9 inducer, and lesinurad is a CYP2C9 substrate.
    Lesinurad; Allopurinol: (Moderate) Rifampin may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Rifampin is a CYP2C9 inducer, and lesinurad is a CYP2C9 substrate.
    Letermovir: (Major) Concurrent administration of letermovir and rifampin is not recommended. Use of these drugs together may decrease letermovir plasma concentrations, resulting in a potential loss of letermovir efficacy. Letermovir is a substrate of UDP-glucuronosyltransferase 1A1/3 (UGT1A1/3) and P-glycoprotein (P-gp). Rifampin induces UGT and P-gp.
    Leuprolide; Norethindrone: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Levamlodipine: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Levobupivacaine: (Minor) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of levobupivacaine.
    Levoketoconazole: (Major) Ketoconazole and rifampin each affect the pharmacokinetics of the other. Ketoconazole has been shown to reduce serum concentrations of rifampin but the clinical significance of this effect on rifampin concentrations is not known. More significant are the effects of rifampin on ketoconazole pharmacokinetics. Rifampin is a potent inducer of hepatic microsomal enzymes. When rifampin is used in combination with isoniazid, INH, isoniazid appears to intensify the effect of rifampin on the pharmacokinetics of other drugs, despite the fact that isoniazid is generally considered an inhibitor of drug metabolism. The effects of isoniazid with rifampin on ketoconazole have been significant enough to result in antifungal treatment failure. Ketoconazole doses may need to be increased if rifampin, or the combination of rifampin with isoniazid, is used concomitantly. However, it is generally not recommended that ketoconazole be used with INH or rifampin.
    Levomethadyl: (Major) Agents that induce hepatic cytochrome P450 CYP3A4, such as rifamycins, may reduce serum levels of levomethadyl leading to symptoms of withdrawal in stabilized patients. Dosage adjustments of levomethadyl may be required if given with rifamycins.
    Levonorgestrel: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Levonorgestrel; Ethinyl Estradiol: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Levothyroxine: (Moderate) Rifampin increases thyroid hormone metabolism by inducing uridine 5-diphospho-glucuronosyltransferase (UGT) and leads to lower T4 serum levels. Clinicians should be alert for a decreased response to thyroid hormones if rifampin is used during thyroid hormone therapy.
    Levothyroxine; Liothyronine (Porcine): (Moderate) Rifampin increases thyroid hormone metabolism by inducing uridine 5-diphospho-glucuronosyltransferase (UGT) and leads to lower T4 serum levels. Clinicians should be alert for a decreased response to thyroid hormones if rifampin is used during thyroid hormone therapy.
    Levothyroxine; Liothyronine (Synthetic): (Moderate) Rifampin increases thyroid hormone metabolism by inducing uridine 5-diphospho-glucuronosyltransferase (UGT) and leads to lower T4 serum levels. Clinicians should be alert for a decreased response to thyroid hormones if rifampin is used during thyroid hormone therapy.
    Lidocaine: (Moderate) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of lidocaine,
    Lidocaine; Epinephrine: (Moderate) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of lidocaine,
    Lidocaine; Prilocaine: (Moderate) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of lidocaine,
    Linagliptin: (Major) Concomitant use of linagliptin with rifampin is not recommended due to the potential for decreased linagliptin serum concentrations and loss of efficacy. Linagliptin is a substrate of hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); rifampin is a strong inducer of CYP3A4 and an inducer of P-gp. In drug interaction studies, rifampin decreased the mean AUC and Cmax of linagliptin by 40% and 44%, respectively. For patients requiring use of such drugs, an alternative to linagliptin is strongly recommended.
    Linagliptin; Metformin: (Major) Concomitant use of linagliptin with rifampin is not recommended due to the potential for decreased linagliptin serum concentrations and loss of efficacy. Linagliptin is a substrate of hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); rifampin is a strong inducer of CYP3A4 and an inducer of P-gp. In drug interaction studies, rifampin decreased the mean AUC and Cmax of linagliptin by 40% and 44%, respectively. For patients requiring use of such drugs, an alternative to linagliptin is strongly recommended.
    Linezolid: (Minor) In a study of healthy volunteers (n=16), coadministration of rifampin (600 mg daily administered for 8 days) with oral linezolid (600 mg twice daily administered for 5 days) resulted in a 21% decrease in linezolid Cmax (90% CI, 15-27%) and a 32% decrease in linezolid AUC (90% CI, 27-37%). The clinical significance of this interaction is unknown and the mechanism is not fully understood, but it may be related to the induction of hepatic enzymes. Caution may be warranted if linezolid and rifampin are coadministered.
    Liothyronine: (Moderate) Rifampin increases thyroid hormone metabolism by inducing uridine 5-diphospho-glucuronosyltransferase (UGT) and leads to lower T4 serum levels. Clinicians should be alert for a decreased response to thyroid hormones if rifampin is used during thyroid hormone therapy.
    Lonafarnib: (Contraindicated) Coadministration of lonafarnib and rifampin is contraindicated; concurrent use may decrease lonafarnib exposure, which may reduce its efficacy. Lonafarnib is a sensitive CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the exposure of lonafarnib by 98%.
    Loperamide: (Moderate) The plasma concentration and efficacy of loperamide may be reduced when administered concurrently with rifampin. Loperamide is metabolized by the hepatic enzymes CYP3A4, CYP2C8, CYP2D6, and CYP2B6, and is a substrate for the drug transporter P-glycoprotein (P-gp). Rifampin is an inducer of all 4 enzymes and P-gp.
    Loperamide; Simethicone: (Moderate) The plasma concentration and efficacy of loperamide may be reduced when administered concurrently with rifampin. Loperamide is metabolized by the hepatic enzymes CYP3A4, CYP2C8, CYP2D6, and CYP2B6, and is a substrate for the drug transporter P-glycoprotein (P-gp). Rifampin is an inducer of all 4 enzymes and P-gp.
    Lopinavir; Ritonavir: (Contraindicated) Coadministration of rifampin and ritonavir results in markedly decreased ritonavir concentrations; HIV treatment failure and virologic resistance would be expected. Rifampin (300 or 600 mg daily for 10 days) decreases the AUC and Cmax of ritonavir (500 mg every 12 hours for 20 days) by 35% and 25%, respectively. Coadministration may lead to loss of virologic response if ritonavir is the sole protease inhibitor and increase the risk of hepatotoxicity. The DHHS/NIH HIV Treatment Guidelines recommend ritonavir and rifampin should not be coadministered and suggest the consideration of alternative antimycobacterial agents, such as rifabutin. However, CDC guidelines suggest no change in ritonavir or rifampin dose when the drugs are coadministered, but this appears to only be in the setting of low-dose ritonavir (i.e., 100 mg or 200 mg twice daily) used to 'boost' concentrations of other protease inhibitors. In this setting it would be less likely to produce adverse events than higher ritonavir doses; however, a net CYP3A4 induction still results when used with rifampin. (Contraindicated) The coadministration of lopinavir and rifampin is contraindicated. Concurrent use may lead to loss of virologic response and possible resistance to lopinavir, the class of protease inhibitors, or other antiretroviral agents.
    Lorlatinib: (Contraindicated) Coadministration of lorlatinib with rifampin is contraindicated due to the risk of severe hepatotoxicity as well as decreased lorlatinib exposure which may reduce its efficacy. Discontinue rifampin for 3 plasma half-lives prior to initiating therapy with lorlatinib. Lorlatinib is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased lorlatinib exposure by 85%. Additionally, severe hepatotoxicity occurred, with 50% of patients experiencing grade 4 elevations of ALT/AST, 33% with grade 3 AST/ALT elevations, and 8% with grade 2 ALT/AST elevations. Grade 2 to 4 increases in ALT/AST occurred within 3 days of concomitant use and returned to normal limits within 7 to 34 days (median, 15 days).
    Losartan: (Moderate) Rifampin significantly induces the metabolism of losartan and its more potent metabolite, E-3174, resulting in a decrease in the AUC and half-life of both compounds; monitor for potential loss of losartan activity.
    Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Rifampin significantly induces the metabolism of losartan and its more potent metabolite, E-3174, resulting in a decrease in the AUC and half-life of both compounds; monitor for potential loss of losartan activity.
    Lovastatin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of atorvastatin, simvastatin and fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors (Statins). To evaluate this interaction, monitor serum lipid concentrations during coadministration of rifamycins with HMG-CoA reductase inhibitors.
    Lovastatin; Niacin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of atorvastatin, simvastatin and fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors (Statins). To evaluate this interaction, monitor serum lipid concentrations during coadministration of rifamycins with HMG-CoA reductase inhibitors.
    Lumacaftor; Ivacaftor: (Major) Coadministration of ivacaftor with rifampin is not recommended due to decreased plasma concentrations of ivacaftor. Ivacaftor is a sensitive CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin significantly decreased ivacaftor exposure by approximately 9-fold.
    Lumacaftor; Ivacaftor: (Major) Concomitant use of rifampin and lumacaftor; ivacaftor is not recommended. Rifampin may decrease the therapeutic effect of lumacaftor; ivacaftor by significantly decreasing ivacaftor exposure. Ivacaftor is a sensitive substrate of CYP3A, and rifampin is a potent CYP3A inducer. In a pharmacokinetic study, coadministration of lumacaftor; ivacaftor with rifampin decreased ivacaftor exposure (AUC) by 57%, with minimal effect on the exposure of lumacaftor.
    Lumateperone: (Major) Avoid coadministration of lumateperone and rifampin as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration of lumateperone with rifampin significantly decreased lemborexant exposure.
    Lurasidone: (Contraindicated) Concurrent use of lurasidone with strong CYP3A4 inducers, such as rifampin, is contraindicated. Lurasidone is primarily metabolized by CYP3A4. Decreased blood concentrations of lurasidone are expected when the drug is co-administered with inducers of CYP3A4. When a single dose of lurasidone 40 mg was co-administered with rifampin 1200 mg/day for 8 days, the lurasidone Cmax and AUC values were reduced to one-seventh and one-fifth, respectively, of those seen after administration of lurasidone alone.
    Lurbinectedin: (Major) Avoid coadministration of lurbinectedin and rifampin due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and rifampin is a strong CYP3A inducer.
    Macimorelin: (Major) Discontinue rifampin and allow a sufficient washout period to pass before administering macimorelin. Use of these drugs together can significantly decrease macimorelin plasma concentrations, and may result in a false positive test for growth hormone deficiency. No drug-drug interaction studies have been conducted; however, macimorelin is primarily metabolized by CYP3A4 and rifampin is a strong CYP3A4 inducer.
    Macitentan: (Major) Avoid coadministration of macitentan and rifampin. Rifampin is a strong inducer of CYP3A4 and significantly reduces macitentan exposure.
    Magnesium Hydroxide: (Moderate) Concomitant use of antacids and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of antacids.
    Maraviroc: (Major) Coadministration of maraviroc, a CYP3A/P-glycoprotein (P-gp) substrate, and rifampin, a strong CYP3A inducer and P-gp inducer, without a concomitant strong CYP3A inhibitor significantly decreases maraviroc concentrations. Consider using rifabutin instead of rifampin in patients receiving maraviroc. However, if rifampin must be used, the adult maraviroc dose should be increased to 600 mg PO twice daily when coadministered with rifampin without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and rifampin is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected.
    Maribavir: (Major) Avoid concomitant use of maribavir and rifampin. Coadministration may decrease maribavir exposure resulting in reduced virologic response. Maribavir is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased the exposure of maribavir by 60%.
    Mebendazole: (Moderate) Mebendazole is metabolized by hepatic cytochrome P450 enzymes and other enzymes. Rifamycins induce hepatic microsomal enzymes and may increase the metabolism of mebendazole if given concomitantly.
    Medroxyprogesterone: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Mefloquine: (Moderate) Mefloquine is metabolized by CYP3A4. Rifampin, an inducer of CYP3A4, has been reported to increase the metabolism of mefloquine and reduce mefloquine plasma concentrations in healthy volunteers (decreased mean Cmax by 19% and mean AUC by 68%). Rifampin induces both hepatic and gut wall CYP3A4 and increases the formation of the carboxylic acid mefloquine metabolite. Concomitant administration of rifampin and mefloquine can reduce the clinical efficacy of mefloquine and increase the risk of Plasmodium falciparum resistance during treatment of malaria.
    Melatonin: (Moderate) Potent CYP1A2 inducers, such as rifampin, may reduce plasma concentrations of melatonin and reduce melatonin efficacy. Melatonin is primarily metabolized by CYP1A2, with lesser contributions by CYP1A1, CYP2C9 and CYP2C19.
    Mestranol; Norethindrone: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Metformin; Repaglinide: (Major) Coadministration of rifampin and repaglinide decreases the AUC and Cmax of repaglinide; if coadministration is necessary, a dose increase of repaglinide may be necessary and an increased frequency of glucose monitoring is recommended. Rifampin is a potent CYP3A4 inducer and also a moderate inducer of CYP2C8. Repaglinide is a CYP3A4 substrate and an in vitro sensitive CYP2C8 substrate. Monitor for the possibility of reduced effectiveness of repaglinide and possible symptoms indicating hyperglycemia.
    Metformin; Rosiglitazone: (Minor) The coadministration of rifampin and rosiglitazone may decrease the concentration of rosiglitazone. This interaction is most likely due to rifampin's inhibition of the CYP2C8 and, to a lesser extent, CYP2C9 isozymes. Use caution if rifampin and rosiglitazone are to be coadministered, as decreased rosiglitazone efficacy may be seen. Blood glucose concentrations should be monitored and possible dose adjustments of rosiglitazone may need to be made.
    Metformin; Saxagliptin: (Minor) Coadministration of saxagliptin and rifampin decreased the maximum serum saxagliptin concentration by 53% and the systemic exposure by 76%. As expected, the maximum serum concentration of the saxagliptin active metabolite was increased by 39%; no significant change in the systemic exposure was noted. Saxagliptin dose adjustment is not advised when coadministered with rifampin, as the plasma dipeptidyl peptidase-4 activity over a 24-hour period was unaffected.
    Methadone: (Major) Concurrent administration of rifampin and methadone is associated with a 33 to 68% decrease in methadone levels due to induction of methadone metabolism by rifampin. When effective alternatives exist, rifampin should not be administered to patients receiving chronic methadone therapy. However, if rifampin treatment is necessary, the methadone dosage will need to be increased to maintain adequate suppression of opiate withdrawal symptoms.
    Methylprednisolone: (Moderate) Monitor for decreased corticosteroid efficacy if methylprednisolone is used with rifampin; a dosage increase may be necessary. Concurrent use may decrease the exposure of methylprednisolone. Methylprednisolone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Midazolam: (Major) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of midazolam. Patients receiving rifampin may require higher doses of midazolam to achieve the desired clinical effect.
    Midostaurin: (Major) Avoid the concomitant use of midostaurin and rifampin as midostaurin exposure may be decreased, which may reduce its efficacy. Midostaurin is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the exposure of midostaurin and its metabolites CGP62221 and CGP52421 by 96%, 92%, and 59%, respectively.
    Mifepristone: (Major) When mifepristone is administered for the treatment of Cushing's syndrome, avoid coadministration of rifampin. When mifepristone is administered for pregnancy termination, follow-up assessment to verify that treatment has been successful is recommended in patients receiving rifampin. Coadministration may decrease mifepristone exposure reducing efficacy. Mifepristone is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. The impact of CYP3A4 inducers on mifepristone efficacy is unknown.
    Mirtazapine: (Moderate) Mirtazapine plasma concentrations and pharmacologic action may be decreased in patients taking rifampin. Rifampin is a potent inducer of CYP3A4, and may be a modest inducer of CYP2D6. Rifampin is also a relatively weak inducer of CYP1A2. In vitro studies have identified mirtazapine as a substrate for several CYP450 isoenzymes including 2D6, 1A2, and 3A4. Monitor for reduced effectiveness of mirtazapine during co-administration of rifampin. It may be necessary to increase the mirtazapine dosage during concurrent therapy. Conversely, if rifampin is discontinued, the dosage of mirtazapine may need to be reduced.
    Mitapivat: (Major) Avoid coadministration of mitapivat with rifampin due to decreased mitapivat efficacy. Coadministration decreases mitapivat concentrations. Mitapivat is a CYP3A substrate and rifampin is a strong CYP3A inducer. Rifampin decreased mitapivat overall and peak exposure by 91% and 77%, respectively, after a single mitapivat 50 mg dose. Rifampin decreased mitapivat overall and peak exposure by approximately 95% and 85%, respectively, after mitapivat 5, 20, or 50 mg twice daily.
    Mobocertinib: (Major) Avoid concomitant use of mobocertinib and rifampin. Coadministration may decrease mobocertinib exposure resulting in decreased efficacy. Mobocertinib is a CYP3A substrate and rifampin is a strong CYP3A inducer. Use of a strong CYP3A inducer is predicted to decrease the overall exposure of mobocertinib and its active metabolites by 92%.
    Modafinil: (Major) Rifampin exhibits significant induction of the hepatic microsomal CYP3A4 isoenzyme and may potentially increase the metabolism of modafinil. Decreased serum levels of modafinil could potentially result in decreased efficacy of modafinil.
    Montelukast: (Minor) Monitor for decreased montelukast efficacy if coadministered with rifampin. The systemic exposure of montelukast may be reduced; however, dosage adjustments are not likely to be needed. Montelukast is metabolized by CYP2C8 (primary), and also CYP2C9 and CYP3A4; rifampin is a strong CYP3A4 and moderate CYP2C9 inducer. Coadministration with another strong CYP3A4 and moderate CYP2C9 inducer decreased the exposure of montelukast by approximately 40%.
    Morphine: (Moderate) Rifampin may induce the metabolism of morphine and lead to loss of analgesia if coadministered.
    Morphine; Naltrexone: (Moderate) Rifampin may induce the metabolism of morphine and lead to loss of analgesia if coadministered.
    Moxifloxacin: (Minor) Intermittent rifampin administration during tuberculosis treatment in Indonesian patients resulted in reduced plasma concentrations of moxifloxacin. Rifampin induced phase II metabolism (glucuronide and sulfate conjugation) of moxifloxacin and prolonged the time to peak concentrations (Tmax) of moxifloxacin from 1 hour to 2 hours. The systemic exposure (AUC) and peak serum concentrations (Cmax) of moxifloxacin were reduced by 31% and 32%, respectively. In a study involving healthy volunteers, similar effects were seen on Tmax and AUC but not on Cmax. The effect of daily dosing with rifampin on the pharmacokinetics of moxifloxacin has not been studied. Higher doses of moxifloxacin may be needed when used with rifampin, however, data assessing the efficacy and safety of these higher doses are not available.
    Mycophenolate: (Major) Use of both rifampin and mycophenolate mofetil is not recommended unless the benefit outweighs the risk. Concurrent administration to a heart-lung transplant patient led to a a 67% decrease in mycophenolic acid exposure after correction for dose.
    Naldemedine: (Major) Avoid coadministration of naldemedine with strong CYP3A4 inducers. Naldemedine is metabolized primarily by the CYP3A enzyme system. Strong CYP3A4 inducers, such as rifampin, significantly decrease plasma naldemedine concentrations and may decrease the efficacy of naldemedine treatment.
    Naloxegol: (Major) Coadministration of naloxegol with rifampin is not recommended due to the potential for decreased naloxegol efficacy. Naloxegol is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased naloxegol exposure by 89%.
    Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with rifampin is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 and CYP2C8 substrate. Rifampin is a strong CYP3A4 inducer and a moderate inducer of CYP2C8.
    Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and rifampin due to the risk of decreased sirolimus exposure which may reduce its efficacy. Sirolimus is a CYP3A and P-gp substrate and rifampin is a strong CYP3A and P-gp inducer. Concomitant use decreased sirolimus overall exposure by 82%.
    Naproxen; Esomeprazole: (Major) Avoid coadministration of esomeprazole with rifampin due to the risk of decreased esomeprazole plasma concentrations which may decrease efficacy. Esomeprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Nateglinide: (Major) Rifampin is expected to reduce the plasma concentrations and possibly the efficacy of nateglinide. If these drugs must be used together, closely monitor blood glucose concentrations and for glycemic control. In some patients, a dosage adjustment of nateglinide may be necessary. Rifampin is a potent inducer of CYP2C9. Nateglinide is a CYP2C9 substrate.
    Nebivolol: (Major) Avoid the concomitant use of nebivolol and rifampin. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inducers, such as rifampin, could potentially decrease nebivolol plasma concentrations via CYP2D6 induction; the clinical significance of this potential interaction is unknown, but a decrease in therapeutic effect is possible. If these drugs are coadministered, patients should be monitored for therapeutic response.
    Nebivolol; Valsartan: (Major) Avoid the concomitant use of nebivolol and rifampin. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inducers, such as rifampin, could potentially decrease nebivolol plasma concentrations via CYP2D6 induction; the clinical significance of this potential interaction is unknown, but a decrease in therapeutic effect is possible. If these drugs are coadministered, patients should be monitored for therapeutic response. (Minor) Coadministration may increase systemic exposure to valsartan. Valsartan is a substrate of the hepatic uptake transporter OATP1B1 and rifampin is an inhibitor of OATP. Patients should be monitored for adverse effects of valsartan.
    Nefazodone: (Moderate) Monitor for decreased efficacy of nefazodone if coadministration with rifampin is necessary. Concomitant use may decrease nefazodone exposure. Nefazodone is a primary CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased nefazodone and hydroxynefazodone exposure by almost 95%.
    Nelfinavir: (Contraindicated) Coadministration of rifampin and nelfinavir is contraindicated due to the potential for subtherapeutic antiretroviral activity and development of resistant HIV mutations. Nelfinavir is metabolized by CYP3A4 and 2C19, rifampin is an inducer of these isoenzymes. Administering these drugs together causes a decrease in the nelfinavir plasma AUC, Cmax, and Cmin of 83%, 76%, and 92%, respectively.
    Neratinib: (Major) Avoid concomitant use of rifampin with neratinib due to decreased efficacy of neratinib. Neratinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased neratinib exposure by 87%, while exposure to active metabolites M6 and M7 were reduced by 37% to 49%.
    Netupitant, Fosnetupitant; Palonosetron: (Major) Netupitant is mainly metabolized by CYP3A4. Avoid coadministration of netupitant in patients who are chronically using a strong CYP3A4 inducer, such as rifampin. A strong CYP3A inducer can decrease the efficacy of netupitant by substantially reducing plasma concentrations of netupitant. A Single dose of netupitant; palonosetron was administered with rifampicin, following once daily administration of 600 mg rifampicin for 17 days. Pharmacokinetics of netupitant and palonosetron were compared to that after administration of netupitant; palonosetron alone. Coadministration of rifampicin decreased the mean Cmax and AUC of netupitant by 62% and 82%, respectively, compared to those after netupitant; palonosetron alone. Coadministration of rifampicin decreased the mean Cmax and AUC for palonosetron by 15% and 19%, respectively.
    Nevirapine: (Contraindicated) The CDC recommends using nevirapine and rifampin in combination only if clearly indicated, if no other options exist, and when careful clinical and virologic monitoring are possible. When coadministered, the AUC and Cmin of nevirapine decreases by 20-58% and 68%, respectively. While the virologic consequences of coadministration are uncertain, the potential for additive hepatotoxicity exists; use of this combination is not recommended. If rifampin and nevirapine are used together, more frequent monitoring of HIV viral load, CD4+ counts, and hepatic function should take place.
    Niacin; Simvastatin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of simvastatin. Monitor for potential reduced cholesterol-lowering and hypotensive efficacy when these drugs are coadministered.
    Nicardipine: (Major) Rifampin is a potent hepatic enzyme inducer and has been shown to exert a substantial reduction of the oral bioavailability of some calcium channel blockers. Patients should be monitored for loss of antihypertensive effect if rifampin is added to nicardipine therapy.
    Nifedipine: (Major) Avoid coadministration of nifedipine with rifampin, and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and rifampin is a strong CYP3A4 inducer. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
    Nilotinib: (Major) Avoid the concomitant use of nilotinib and rifampin; significantly decreased nilotinib exposure was observed in a drug interaction study. Coadministration of these drugs may lead to reduced nilotinib efficacy. Nilotinib is a CYPA4 substrate and rifampin is a strong CYP3A4 inducer. In a drug interaction study, the AUC value of nilotinib was decreased by about 80% following the addition of rifampicin/rifampin 600 mg once daily for 12 days.
    Nimodipine: (Major) Rifampin is a potent hepatic enzyme inducer and has been shown to reduce the oral bioavailability of some calcium channel blockers. Patients should be monitored for loss of therapeutic effect if rifampin is added to nimodipine therapy.
    Nintedanib: (Major) Avoid the use of rifampin with nintedanib, as rifampin significantly decreases the exposure of nintedanib and is expected to compromise the efficacy of nintedanib. Rifampin is a potent CYP3A4 inducer a moderate P-glycoprotein (P-gp) inducer; nintedanib is a P-gp substrate and a minor substrate of CYP3A4. In a drug interaction study, the use of nintedanib with oral doses of rifampin decreased the nintedanib AUC to 50.3% and the Cmax to 60.3% compared with administration of nintedanib alone.
    Nirmatrelvir; Ritonavir: (Contraindicated) Coadministration of rifampin and ritonavir results in markedly decreased ritonavir concentrations; HIV treatment failure and virologic resistance would be expected. Rifampin (300 or 600 mg daily for 10 days) decreases the AUC and Cmax of ritonavir (500 mg every 12 hours for 20 days) by 35% and 25%, respectively. Coadministration may lead to loss of virologic response if ritonavir is the sole protease inhibitor and increase the risk of hepatotoxicity. The DHHS/NIH HIV Treatment Guidelines recommend ritonavir and rifampin should not be coadministered and suggest the consideration of alternative antimycobacterial agents, such as rifabutin. However, CDC guidelines suggest no change in ritonavir or rifampin dose when the drugs are coadministered, but this appears to only be in the setting of low-dose ritonavir (i.e., 100 mg or 200 mg twice daily) used to 'boost' concentrations of other protease inhibitors. In this setting it would be less likely to produce adverse events than higher ritonavir doses; however, a net CYP3A4 induction still results when used with rifampin. (Contraindicated) Concomitant use of ritonavir-boosted nirmatrelvir and rifampin is contraindicated; consider an alternative COVID-19 therapy. Coadministration may decrease nirmatrelvir exposure resulting in reduced virologic response. The risk for reduced efficacy may persist following rifampin discontinuation. Nirmatrelvir is a CYP3A substrate and rifampin is a strong CYP3A inducer.
    Nisoldipine: (Major) Avoid coadministration of nisoldipine with rifampin due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Norethindrone: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Norethindrone; Ethinyl Estradiol: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Norfloxacin: (Minor) Rifampin has been reported to inhibit the bactericidal action of norfloxacin.
    Norgestimate; Ethinyl Estradiol: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Norgestrel: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Nortriptyline: (Moderate) It may be necessary to adjust the dosage of tricyclic antidepressants if given concurrently with rifampin. Rifampin may induce the metabolism of tricyclic antidepressants; coadministration may result in decreased tricyclic antidepressant plasma concentrations.
    Olanzapine: (Moderate) Monitor for reduced olanzapine efficacy if rifampin coadministration is medically necessary; in some patients, dosage adjustments may be needed. Olanzapine is metabolized by the CYP1A2 hepatic microsomal isoenzyme, and potent inducers of this enzyme increase olanzapine clearance. While rifampin is a CYP3A inducer, it is likely its induction of CYP1A2 is responsible for the increased olanzapine clearance, and roughly 48% decrease in olanzapine AUC (exposure) seen when rifampin is used with olanzapine.
    Olanzapine; Fluoxetine: (Moderate) Monitor for reduced olanzapine efficacy if rifampin coadministration is medically necessary; in some patients, dosage adjustments may be needed. Olanzapine is metabolized by the CYP1A2 hepatic microsomal isoenzyme, and potent inducers of this enzyme increase olanzapine clearance. While rifampin is a CYP3A inducer, it is likely its induction of CYP1A2 is responsible for the increased olanzapine clearance, and roughly 48% decrease in olanzapine AUC (exposure) seen when rifampin is used with olanzapine.
    Olanzapine; Samidorphan: (Major) Avoid the concurrent use of samidorphan and rifampin; decreased samidorphan exposure and loss of efficacy may occur. Samidorphan is a CYP3A substrate and rifampin is a strong CYP3A inducer. Concomitant use of rifampin reduced samidorphan exposure by 73%. (Moderate) Monitor for reduced olanzapine efficacy if rifampin coadministration is medically necessary; in some patients, dosage adjustments may be needed. Olanzapine is metabolized by the CYP1A2 hepatic microsomal isoenzyme, and potent inducers of this enzyme increase olanzapine clearance. While rifampin is a CYP3A inducer, it is likely its induction of CYP1A2 is responsible for the increased olanzapine clearance, and roughly 48% decrease in olanzapine AUC (exposure) seen when rifampin is used with olanzapine.
    Olaparib: (Major) Avoid coadministration of olaparib with rifampin due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and rifampin is a strong CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with rifampin decreased the olaparib Cmax by 71% and the AUC by 87%.
    Oliceridine: (Moderate) Monitor for reduced efficacy of oliceridine and signs of opioid withdrawal if coadministration with rifampin is necessary; consider increasing the dose of oliceridine as needed. If rifampin is discontinued, consider a dose reduction of oliceridine and frequently monitor for signs of respiratory depression and sedation. Oliceridine is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease the plasma concentrations of oliceridine; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Ombitasvir; Paritaprevir; Ritonavir: (Contraindicated) Coadministration of rifampin and ritonavir results in markedly decreased ritonavir concentrations; HIV treatment failure and virologic resistance would be expected. Rifampin (300 or 600 mg daily for 10 days) decreases the AUC and Cmax of ritonavir (500 mg every 12 hours for 20 days) by 35% and 25%, respectively. Coadministration may lead to loss of virologic response if ritonavir is the sole protease inhibitor and increase the risk of hepatotoxicity. The DHHS/NIH HIV Treatment Guidelines recommend ritonavir and rifampin should not be coadministered and suggest the consideration of alternative antimycobacterial agents, such as rifabutin. However, CDC guidelines suggest no change in ritonavir or rifampin dose when the drugs are coadministered, but this appears to only be in the setting of low-dose ritonavir (i.e., 100 mg or 200 mg twice daily) used to 'boost' concentrations of other protease inhibitors. In this setting it would be less likely to produce adverse events than higher ritonavir doses; however, a net CYP3A4 induction still results when used with rifampin. (Contraindicated) Concomitant use of dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir with rifampin is contraindicated due to the potential for hepatitis C treatment failure. Coadministration may result in reduced systemic exposes to dasabuvir, ombitasvir, paritaprevir and ritonavir. Rifampin is a potent inducer of the hepatic isoenzyme CYP3A4; dasabuvir (minor), paritaprevir and ritonavir are substrates of this isoenzyme. Rifampin also induces CYP2D6 and CYP2C8, enzymes partially responsible for the metabolism of ritonavir and dasabuvir, respectively. In addition, rifampin induces the drug transporter proteins P-glycoprotein (P-gp) and UGT; dasabuvir, ombitasvir, paritaprevir and ritonavir are substrates for P-gp, while dasabuvir, ombitasvir and paritaprevir are also substrates of UGT.
    Omeprazole: (Major) Avoid coadministration of omeprazole with rifampin due to the risk of decreased omeprazole plasma concentrations which may decrease efficacy. Omeprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid coadministration of omeprazole with rifampin due to the risk of decreased omeprazole plasma concentrations which may decrease efficacy. Omeprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Omeprazole; Sodium Bicarbonate: (Major) Avoid coadministration of omeprazole with rifampin due to the risk of decreased omeprazole plasma concentrations which may decrease efficacy. Omeprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Moderate) Concomitant use of sodium bicarbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of sodium bicarbonate.
    Ondansetron: (Minor) Rifampin may reduce the efficacy of ondansetron by decreasing its systemic exposure; however, based on available data, no ondansetron dosage adjustment is recommended. If used together, monitor patients for antiemetic efficacy. In a pharmacokinetic study of 10 healthy subjects receiving a single-dose intravenous dose of ondansetron 8 mg after 600 mg rifampin once daily for 5 days, the AUC and the half-life of ondansetron were reduced by 48% and 46%, respectively. The proposed mechanism is rifampin-related induction of ondansetron metabolism through cytochrome P450 3A4. These changes in ondansetron exposure with CYP3A4 inducers are not thought to be clinically relevant.
    Osilodrostat: (Major) Monitor cortisol concentration and patient's signs and symptoms during coadministration of osilodrostat and rifampin. Concurrent use may decrease osilodrostat exposure and reduce its efficacy; an increase in osilodrostat dose may be necessary. After discontinuation of rifampin, monitor cortisol concentration and patient's signs and symptoms; a reduction in osilodrostat dose may be needed. Osilodrostat is a CYP3A4 and CYP2B6 substrate and rifampin is a strong CYP3A4 and strong CYP2B6 inducer.
    Osimertinib: (Major) Avoid coadministration of rifampin with osimertinib due to decreased plasma concentrations of osimertinib which may lead to reduced efficacy. If concomitant use is unavoidable, increase the dose of osimertinib to 160 mg once daily. If rifampin is discontinued, reduce the dose of osimertinib to 80 mg once daily after a washout period of 3 weeks. Osimertinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased osimertinib exposure by 78%.
    Ospemifene: (Major) Avoid the use of rifampin with ospemifene if possible. Rifampin, a strong CYP3A4 / moderate CYP2C9 / moderate CYP2C19 inducer, decreases the systemic exposure of ospemifene by 58%. Therefore, coadministration of ospemifene with rifampin would be expected to decrease the systemic exposure of ospemifene, which may decrease the clinical effect.
    Oxcarbazepine: (Moderate) Monitor MHD, the active metabolite of oxcarbazepine, concentrations during oxcarbazepine dosage titration if oxcarbazepine and rifampin are used concurrently. A dose adjustment of oxcarbazepine may be required after initiation, dosage modification, or discontinuation of rifampin. Rifampin is a strong CYP3A4 inducer and a UGT inducer. Coadministration with other strong CYP3A4 inducers and/or UGT inducers decreased MHD concentrations by 25% to 40%.
    Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with rifampin is necessary; consider increasing the dose of oxycodone as needed. If rifampin is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Ozanimod: (Major) Coadministration of ozanimod with rifampin is not recommended. Coadministration may decrease the exposure of the active metabolites of ozanimod, which may reduce its efficacy. Ozanimod is a CYP2C8 substrate. Coadministration with rifampin (a strong inducer of CYP3A and P-gp, and a moderate inducer of CYP2C8) reduced the exposure for ozanimod, CC112273, and CC1084037 by approximately 24%, 60%, and 55%, respectively. The effect on CC112273 and CC1084037 is primarily caused by induction of CYP2C8.
    Paclitaxel: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Closely monitor patients for possibly decreased efficacy when administering paclitaxel with any agent that induces CYP2C8 or CYP3A4 isoenzymes, such as rifampin.
    Pacritinib: (Contraindicated) Concurrent use of pacritinib with rifampin is contraindicated due to decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased pacritinib exposure by 87%.
    Palbociclib: (Major) Avoid coadministration of rifampin with palbociclib due to decreased plasma concentrations of palbociclib, which may result in decreased efficacy. Palbociclib is primarily metabolized by CYP3A4 and rifampin is a strong CYP3A4 inducer. In a drug interaction trial, coadministration with rifampin decreased the AUC and Cmax of palbociclib by 85% and 70%, respectively.
    Paliperidone: (Major) It may be necessary to increase the dose of oral paliperidone during coadministration of a strong inducer of both CYP3A4 and P-gp, such as rifampin. Conversely, a reduction in oral paliperidone dose may be needed upon discontinuation of the inducer. Avoid using a strong inducer of CYP3A4 and/or P-gp if possible during the 1-month injectable dosing interval of Invega Sustenna or the 3-month injectable dosing interval of Invega Trinza. If use of a strong inducer is required in patients receiving injectable paliperidone, consider management with oral paliperidone. Paliperidone is a P-gp substrate, with minor contributions in metabolism by CYP3A4 and CYP2D6.
    Pazopanib: (Major) Avoid administering pazopanib in patients who require chronic treatment with a strong CYP3A4 inducer, such as rifampin. The concomitant use of pazopanib, a substrate for CYP3A4 and P-glycoprotein (P-gp), and rifampin, a strong CYP3A4 inducer and a P-gp inducer, may result in decreased pazopanib concentrations.
    Pemigatinib: (Major) Avoid coadministration of pemigatinib and rifampin due to the risk of decreased pemigatinib exposure which may reduce its efficacy. Pemigatinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased pemigatinib exposure by 85%.
    Pentobarbital: (Moderate) It may be necessary to adjust the dosage of pentobarbital if given concurrently with rifampin. Rifampin may induce the metabolism of pentobarbital; coadministration may result in decreased pentobarbital plasma concentrations.
    Perampanel: (Major) Start perampanel at a higher initial dose of 4 mg once daily at bedtime when using concurrently with rifampin due to a potential reduction in perampanel plasma concentration. If introduction or withdrawal of rifampin occurs during perampanel therapy, closely monitor patient response; a dosage adjustment may be necessary. Rifampin is a strong CYP3A4 inducer, and perampanel is a CYP3A4 substrate.
    Perindopril; Amlodipine: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Perphenazine; Amitriptyline: (Moderate) It may be necessary to adjust the dosage of tricyclic antidepressants if given concurrently with rifampin. Rifampin may induce the metabolism of tricyclic antidepressants; coadministration may result in decreased tricyclic antidepressant plasma concentrations.
    Pexidartinib: (Major) Avoid coadministration of pexidartinib with rifampin as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. Additionally, both pexidartinib and rifampin may cause hepatotoxicity and should be avoided in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease. Pexidartinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration of rifampin decreased pexidartinib exposure by 65%.
    Phenobarbital: (Moderate) It may be necessary to adjust the dosage of phenobarbital if given concurrently with rifampin. Rifampin may induce the metabolism of phenobarbital; coadministration may result in decreased phenobarbital plasma concentrations. Phenobarbital is a CYP29 and CYP2C19 substrate, and rifampin is an inducer of these enzymes.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) It may be necessary to adjust the dosage of phenobarbital if given concurrently with rifampin. Rifampin may induce the metabolism of phenobarbital; coadministration may result in decreased phenobarbital plasma concentrations. Phenobarbital is a CYP29 and CYP2C19 substrate, and rifampin is an inducer of these enzymes.
    Phenothiazines: (Major) Rifamycins can increase the metabolism or reduce the bioavailability of phenothiazines. Dosage increases of phenothiazines may be necessary following the addition of rifampin or another rifamycin.
    Phenytoin: (Major) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of the phenytoin.
    Pimavanserin: (Major) Avoid use of rifampin with pimavanserin due to decreased pimavanserin exposure. Rifampin is a strong CYP3A4 inducer; pimavanserin is a CYP3A4 substrate. Monitor for reduced pimavanserin efficacy if concurrent use is required. Rifampin decreased the AUC by 91% when it was coadministered with pimavanserin during drug interaction studies.
    Pioglitazone: (Minor) Concomitant administration of rifampin with pioglitazone resulted in a decrease in the AUC of pioglitazone. Patients receiving rifampin with pioglitazone should be monitored for changes in glycemic control; dosage adjustments may be necessary.
    Pioglitazone; Glimepiride: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers. (Minor) Concomitant administration of rifampin with pioglitazone resulted in a decrease in the AUC of pioglitazone. Patients receiving rifampin with pioglitazone should be monitored for changes in glycemic control; dosage adjustments may be necessary.
    Pioglitazone; Metformin: (Minor) Concomitant administration of rifampin with pioglitazone resulted in a decrease in the AUC of pioglitazone. Patients receiving rifampin with pioglitazone should be monitored for changes in glycemic control; dosage adjustments may be necessary.
    Pitavastatin: (Major) Do not exceed a daily dose of 2 mg PO for pitavastatin if used concomitantly with rifampin due to increased pitavastatin exposure and risk for myopathy or rhabdomyolysis. When coadministered with rifampin 600 mg daily for 5 days, the pitavastatin AUC increased by 29% and the Cmax increased by 2-fold.
    Pitolisant: (Major) Monitor for loss of pitolisant efficacy after initiation of rifampin. Increase to double the original daily dose of pitolisant over 7 days in patients stable on 8.9 mg or 17.8 mg once daily (i.e., 17.8 mg or 35.6 mg, respectively). Decrease the pitolisant dose by half if rifampin is discontinued. Pitolisant is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration of rifampin decreased pitolisant exposure by 50%.
    Polatuzumab Vedotin: (Moderate) Monitor for decreased polatuzumab vedotin efficacy during coadministration of rifampin due to the risk of decreased exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; rifampin is a strong CYP3A4 inducer. Rifampin is predicted to decrease the exposure of MMAE by 63%.
    Pomalidomide: (Moderate) Use pomalidomide and rifampin together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and rifampin is a CYP1A2 inducer.
    Ponatinib: (Major) Avoid coadministration of ponatinib with rifampin due to decreased plasma concentrations of ponatinib. If concomitant use is unavoidable, monitor for reduced efficacy of ponatinib. Ponatinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased ponatinib exposure by 62%.
    Ponesimod: (Major) Avoid concurrent use of ponesimod and rifampin and monitor for decreased ponesimod efficacy if use is necessary. Ponesimod is a CYP3A and an UGT1A1 substrate and rifampin is a strong CYP3A inducer and an UGT1A1 inducer that may decrease ponesimod exposure.
    Posaconazole: (Major) Do not administer rifampin with posaconazole when treating an invasive fungal infection. If treating non-invasive fungal infection, these drugs may be administered together with monitoring of posaconazole concentration and appropriate dose modifications. Taking these drugs together is expected to significantly reduce posaconazole plasma concentrations. Rifampin is an inducer and substrate of the drug efflux protein, P-glycoprotein, for which posaconazole is an inhibitor and also a substrate.
    Pralsetinib: (Major) Avoid coadministration of rifampin with pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is unavoidable, double the current dose of pralsetinib starting on day 7 of coadministration. After rifampin has been discontinued for at least 14 days, resume the pralsetinib dose taken prior to initiating rifampin. Pralsetinib is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased the pralsetinib AUC by 68%.
    Pravastatin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of atorvastatin, simvastatin and fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors (Statins). To evaluate this interaction, monitor serum lipid concentrations during coadministration of rifamycins with HMG-CoA reductase inhibitors.
    Praziquantel: (Contraindicated) The concomitant use of rifampin with praziquantel is contraindicated due to decreased exposure and efficacy of praziquantel. If treatment with praziquantel is necessary, treatment with rifampin should be discontinued 4 weeks before administration of praziquantel. Treatment with rifampin can then be restarted 1 day after completion of praziquantel treatment. Rifampin is a strong CYP3A4 inducer and praziquantel is a CYP3A4 substrate. In a crossover study with a 2-week washout period, administration of praziquantel followed by rifampin resulted in undetectable plasma concentrations of praziquantel in 7 out of 10 subjects. When praziquantel was administered two weeks after discontinuation of rifampin, the mean praziquantel AUC and Cmax were 23% and 35% lower, respectively, than when praziquantel was given alone.
    Prednisolone: (Moderate) Monitor for decreased corticosteroid efficacy if prednisolone is used with rifampin; a dosage increase may be necessary. Concurrent use may decrease the exposure of prednisolone. Prednisolone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Prednisone: (Moderate) Monitor for decreased corticosteroid efficacy if prednisone is used with rifampin; a dosage increase may be necessary. Concurrent use may decrease the exposure of prednisone. Prednisone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Primidone: (Moderate) It may be necessary to adjust the dosage of primidone if given concurrently with rifampin. Primidone is metabolized to phenobarbital. Rifampin may induce the metabolism of phenobarbital; coadministration may result in decreased phenobarbital plasma concentrations. Phenobarbital is a CYP29 and CYP2C19 substrate, and rifampin is an inducer of these enzymes.
    Probenecid: (Moderate) Concomitant use of rifampin and probenecid may result in increased serum concentrations of rifampin. Monitor for increased rifampin toxicity during coadministration.
    Probenecid; Colchicine: (Moderate) Concomitant use of rifampin and probenecid may result in increased serum concentrations of rifampin. Monitor for increased rifampin toxicity during coadministration.
    Progesterone: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Progestins: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Propafenone: (Major) Rifampin may reduce the bioavailability of oral propafenone via induction of propafenone metabolism. Rifampin induces Phase I and Phase II metabolism of propafenone, increasing drug clearance via N-dealkylation and glucuronidation pathways by over 4-fold, but does not appear to induce hydroxylation of propafenone. The extent of reduction in propafenone mean bioavailability is greater in extensive metabolizers of propafenone (reduced from 30% to 10%), although bioavailability is also significantly reduced in poor metabolizers (81% to 48%). The manufacturer reports that concomitant administration of rifampin and propafenone in extensive metabolizers decreases the plasma concentrations of propafenone by 67%, with a corresponding decrease of 5OH-propafenone by 65%. The concentrations of norpropafenone is increased by 30%. In poor metabolizers, there is 50% decrease in propafenone plasma concentrations, and increased the AUC and Cmax of norpropafenone by 74 and 20%, respectively. Urinary excretion of propafenone and its metabolites decreased significantly. Similar results were noted in elderly patients; both the AUC and Cmax propafenone decreased by 84%, with a corresponding decrease in AUC and Cmax of 5OH-propafenone by 69 and 57%. When propafenone is coadministered with rifamycins which induce hepatic metabolism (e.g., rifampin, rifabutin, rifapentine), monitor therapeutic response and adjust dosage as needed to attain antiarrhythmic efficacy endpoints.
    Propranolol: (Moderate) Rifamycins are inducers of hepatic enzymes, and may alter the pharmacokinetics of beta-blockers including propranolol. Patients should be monitored for loss of propranolol effects if rifamycins are added.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Rifamycins are inducers of hepatic enzymes, and may alter the pharmacokinetics of beta-blockers including propranolol. Patients should be monitored for loss of propranolol effects if rifamycins are added.
    Protriptyline: (Moderate) It may be necessary to adjust the dosage of tricyclic antidepressants if given concurrently with rifampin. Rifampin may induce the metabolism of tricyclic antidepressants; coadministration may result in decreased tricyclic antidepressant plasma concentrations.
    Pyrazinamide, PZA: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of rifampin and pyrazinamide, PZA. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. The use of the 2-month rifampin plus pyrazinamide latent tuberculosis infection (LTBI) regimen should no longer be offered due to the known increased risk of severe liver injury and death. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
    Quazepam: (Major) Rifampin is a hepatic inducer and can theoretically increase the clearance of benzodiazpines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations.
    Quetiapine: (Major) Coadministration of rifampin, a potent CYP3A4 inducer, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks.
    Quinidine: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Inducers of CYP3A4 may increase hepatic elimination of quinidine. Rifampin is a potent inducer of this isoenzyme. Quinidine concentrations should be monitored closely after rifampin is added to the treatment regimen. No special precautions appear necessary if rifampin is begun several weeks before quinidine is added but quinidine doses may require adjustment if it is added or discontinued during quinidine therapy.
    Quinine: (Major) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of quinine. Dosages of quinine may need to be adjusted while the patient is receiving rifampin.
    Raltegravir: (Major) Coadministration of rifampin with raltegravir administered as a once daily dose (high dose regimen) is not recommended. Increase the raltegravir dose to 800 mg PO twice daily when administered as the twice daily regimen in adults. Concurrent use of raltegravir with rifampin has not been studied in pediatric patients. Raltegravir is a substrate of uridine diphosphate glucuronosyltransferase (UGT) 1A1; rifampin is a strong UGT1A1 inducer. Coadministration may result in decreased plasma raltegravir concentrations, which could lead to HIV treatment failure or to the development of viral resistance. In a drug interaction study, the AUC for raltegravir 400 mg was reduced by 40% when coadministered with rifampin. The effects of rifampin on the pharmacokinetics of raltegravir administered once daily are not known.
    Ramelteon: (Moderate) Administration of rifampin, a potent CYP1A2 enzyme inducer, may result in a decrease in total exposure to ramelteon. Efficacy may be reduced when ramelteon is used in combination with strong CYP1A2 enzyme inducers such as rifampin.
    Ranolazine: (Contraindicated) Ranolazine is contraindicated in patients receiving drugs known to be CYP3A inducers including rifampin. Ranolazine also is a substrate for CYP2D6 and P-glycoprotein. Rifampin potently induces cytochrome P450 enzymes, including CYP3A isoenzymes, and is also an inducer of P-glycoprotein transport. Rifampin (600 mg daily) decreases the plasma concentration of ranolazine (1000 mg twice daily) by approximately 95%, likely due to induction of CYP3A and P-glycoprotein.
    Red Yeast Rice: (Moderate) Since certain red yeast rice products (i.e., pre-2005 Cholestin formulations) contain lovastatin, clinicians should use red yeast rice cautiously in combination with drugs known to interact with lovastatin. CYP3A4 inducers can theoretically reduce the effectiveness of HMG-CoA reductase activity via induction of CYP3A4 metabolism. Examples of CYP3A4 inducers include rifampin.
    Regorafenib: (Major) Avoid coadministration of regorafenib with rifampin due to decreased plasma concentrations of regorafenib and increased plasma concentrations of the M-5 active metabolite, which may lead to decreased efficacy. Regorafenib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the mean AUC of regorafenib by 50% and increased the mean AUC of M-5 by 264%; no change in the mean AUC of M-2 was observed.
    Relugolix: (Major) Avoid concurrent use of relugolix and rifampin. Concurrent use may decrease relugolix exposure and compromise the efficacy of relugolix therapy. If concurrent use is unavoidable, increase the relugolix maintenance dose to 240 mg once daily. If rifampin is discontinued resume the recommended relugolix treatment dose of 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) and CYP3A substrate and rifampin is a P-gp and strong CYP3A inducer. Concurrent use of another P-gp and strong CYP3A inducer decreased relugolix overall exposure by 55%.
    Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concurrent use of relugolix and rifampin. Concurrent use may decrease relugolix exposure and compromise the efficacy of relugolix therapy. If concurrent use is unavoidable, increase the relugolix maintenance dose to 240 mg once daily. If rifampin is discontinued resume the recommended relugolix treatment dose of 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) and CYP3A substrate and rifampin is a P-gp and strong CYP3A inducer. Concurrent use of another P-gp and strong CYP3A inducer decreased relugolix overall exposure by 55%. (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Repaglinide: (Major) Coadministration of rifampin and repaglinide decreases the AUC and Cmax of repaglinide; if coadministration is necessary, a dose increase of repaglinide may be necessary and an increased frequency of glucose monitoring is recommended. Rifampin is a potent CYP3A4 inducer and also a moderate inducer of CYP2C8. Repaglinide is a CYP3A4 substrate and an in vitro sensitive CYP2C8 substrate. Monitor for the possibility of reduced effectiveness of repaglinide and possible symptoms indicating hyperglycemia.
    Revefenacin: (Major) Coadministration of revefenacin with rifampin is not recommended because it could lead to an increase in systemic exposure of the active metabolite of revefenacin and an increased potential for anticholinergic adverse effects. The active metabolite of revefenacin is a substrate of OATP1B1 and OATP1B3; rifampin is an inhibitor of OATP1B1/1B3 when given as a single dose; when rifampin is given chronically, the hepatic enzyme induction effects of rifampin may supercede the OATP effects.
    Ribociclib: (Major) Avoid coadministration of rifampin with ribociclib due to decreased ribociclib exposure resulting decreased efficacy. Ribociclib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased ribociclib exposure in healthy subjects by 89%.
    Ribociclib; Letrozole: (Major) Avoid coadministration of rifampin with ribociclib due to decreased ribociclib exposure resulting decreased efficacy. Ribociclib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased ribociclib exposure in healthy subjects by 89%.
    Rilpivirine: (Contraindicated) Concurrent use of rifampin and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Rifampin is a potent inducer of CYP3A4, which is primarily responsible for the metabolism of rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine.
    Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury and decreased riluzole efficacy during coadministration of riluzole and rifampin. Concomitant use may increase the risk for hepatotoxicity and may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and rifampin is a CYP1A2 inducer.
    Rimegepant: (Major) Avoid coadministration of rimegepant with rifampin; concurrent use may significantly decrease rimegepant exposure which may result in loss of efficacy. Rimegepant is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration of rimegepant with rifampin decreased rimegepant exposure by 80%.
    Riociguat: (Major) Strong inducers of CYP3A (e.g., rifampin, phenytoin, carbamazepine, phenobarbital or St. John's Wort) may significantly reduce riociguat exposure. Dosage adjustment recommendations are not available when strong CYP3A inducers are co-administered with riociguat.
    Ripretinib: (Major) Avoid coadministration of ripretinib with rifampin. Coadministration may decrease the exposure of ripretinib and its active metabolite (DP-5439), which may decrease ripretinib anti-tumor activity. Ripretinib and DP-5439 are metabolized by CYP3A4 and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased ripretinib exposure by 61% and decreased DP-5439 exposure by 57%.
    Risperidone: (Major) The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp like rifampin. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting an inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating rifampin in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of rifampin in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
    Ritonavir: (Contraindicated) Coadministration of rifampin and ritonavir results in markedly decreased ritonavir concentrations; HIV treatment failure and virologic resistance would be expected. Rifampin (300 or 600 mg daily for 10 days) decreases the AUC and Cmax of ritonavir (500 mg every 12 hours for 20 days) by 35% and 25%, respectively. Coadministration may lead to loss of virologic response if ritonavir is the sole protease inhibitor and increase the risk of hepatotoxicity. The DHHS/NIH HIV Treatment Guidelines recommend ritonavir and rifampin should not be coadministered and suggest the consideration of alternative antimycobacterial agents, such as rifabutin. However, CDC guidelines suggest no change in ritonavir or rifampin dose when the drugs are coadministered, but this appears to only be in the setting of low-dose ritonavir (i.e., 100 mg or 200 mg twice daily) used to 'boost' concentrations of other protease inhibitors. In this setting it would be less likely to produce adverse events than higher ritonavir doses; however, a net CYP3A4 induction still results when used with rifampin.
    Rivaroxaban: (Major) Avoid concomitant use of rivaroxaban with drugs that are combined P-glycoprotein and strong CYP3A4 inducers such as rifampin. Consider increasing the rivaroxaban dose if rifampin must be coadministered. In a drug interaction study, coadministration of rivaroxaban 20 mg single dose with food with a drug that is a combined P-glycoprotein and strong CYP3A4 inducer (rifampicin titrated up to 600 mg once daily) led to an approximate decrease of 50% in AUC and an approximate decrease of 22% in Cmax. Similar decreases in pharmacodynamic effects were also observed. These decreases in exposure to rivaroxaban may decrease efficacy.
    Rofecoxib: (Major) Co-administration of rofecoxib with rifampin, a potent, non-specific inducer of hepatic metabolism, produces a decrease in rofecoxib plasma concentrations. When rofecoxib is coadministered with rifampin, the patient should be monitored for potential loss of rofecoxib efficacy and need for a higher dosage requirement.
    Roflumilast: (Major) Coadministration of rifampin and roflumilast is not recommended, as significantly reduced systemic exposure to roflumilast has been demonstrated in pharmacokinetic study. Rifampin, known as rifampicin internationally, is a strong CYP3A4 inducer; roflumilast is a CYP3A4 substrate. In an open-label, three-period, fixed-sequence study in 15 healthy volunteers, coadministration of rifampin (600 mg once daily for 11 days) with a single oral dose of roflumilast 500 mcg resulted in reduction of roflumilast Cmax and AUC by 68% and 79%, respectively. The pharmacokinetics of the active metabolite roflumilast N-oxide were also affected; roflumilast N-oxide Cmax was increased by 30% and AUC was decreased by 56%.
    Rolapitant: (Major) Avoid the use of rolapitant with chronic administration of rifampin. Rolapitant is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. When rifampin (600 mg once daily) was administered for 7 days before and 7 days after a single dose of rolapitant (180 mg), the mean Cmax and AUC of rolapitant were decreased by 30% and 85%, respectively; additionally, the mean half-life decreased from 176 hours to 41 hours. Significantly reduced plasma concentrations and decreased half-life can decrease the efficacy of rolapitant.
    Romidepsin: (Major) The concomitant use of romidepsin, a CYP3A4 substrate and a P-glycoprotein (P-gp) substrate, and rifampin, a strong CYP3A4 inducer and a P-gp inhibitor and substrate, increased the romidepsin plasma exposure in a drug interaction trial in patients with advanced cancer. Avoid using romidepsin with potent CYP3A4 inducers if possible. Following a 4-hour infusion of romidepsin 14mg/m2 IV administered with multiple oral doses of rifampin, the AUC and Cmax values of romidepsin were increased by 80% and 60%, respectively, compared with romidepsin alone; these increases were statistically significant. Co-administration of rifampin decreased the romidepsin clearance and volume of distribution by 44% and 52%, respectively. Typically, administering a CYP3A4 substrate with a strong CYP3A4 inducer would decrease the substrate exposure; this interaction may be due to the P-gp inhibitor effect of rifampin or because of another undetermined hepatic uptake process that rifampin inhibits. If these agents are used together, monitor patients for signs and symptoms of romidepsin toxicity including hematologic toxicity, infection, and electrocardiogram changes; therapy interruption or discontinuation or a dosage reduction may be required if toxicity develops.
    Ropinirole: (Major) Ropinirole is primarily metabolized by cytochrome P450 1A2. Ropinirole clearance may be altered by coadministration of substrates or inhibitors of CYP1A2. Therefore, if therapy with a drug known to be a potent inducer of CYP1A2, such as rifampin, is initiated or discontinued during treatment with ropinirole, adjustment of ropinirole dose may be required.
    Rosiglitazone: (Minor) The coadministration of rifampin and rosiglitazone may decrease the concentration of rosiglitazone. This interaction is most likely due to rifampin's inhibition of the CYP2C8 and, to a lesser extent, CYP2C9 isozymes. Use caution if rifampin and rosiglitazone are to be coadministered, as decreased rosiglitazone efficacy may be seen. Blood glucose concentrations should be monitored and possible dose adjustments of rosiglitazone may need to be made.
    Ruxolitinib: (Moderate) Monitor patients frequently and adjust the ruxolitinib dose based on safety and efficacy if coadministered with rifampin; decreased ruxolitinib exposure is possible. Ruxolitinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration of rifampin decreased ruxolitinib Cmax and AUC by 32% and 61%, respectively. The relative exposure to ruxolitinib's active metabolites increased approximately 100%.
    Sacubitril; Valsartan: (Minor) Coadministration may increase systemic exposure to valsartan. Valsartan is a substrate of the hepatic uptake transporter OATP1B1 and rifampin is an inhibitor of OATP. Patients should be monitored for adverse effects of valsartan.
    Saquinavir: (Contraindicated) Coadministration of rifampin and saquinavir is contraindicated. Coadministration results in markedly decreased saquinavir concentrations; HIV treatment failure and virologic resistance would be expected. Coadministration of rifampin with saquinavir reduced the steady-state AUC and Cmax of saquinavir by about 80%. In addition, saquinavir, alone or 'boosted' with ritonavir, is contraindicated in combination with rifampin due to inceased risk of severe hepatocellular toxicity. In a 28 day phase I, randomized, open-label, multiple-dose study, significant drug-induced hepatitis with marked transaminase levels occurred in 11 of 17 healthy volunteers receiving saquinavir (1000 mg twice daily) with ritonavir (100 mg twice daily) and rifampin (600 mg once daily).
    Saxagliptin: (Minor) Coadministration of saxagliptin and rifampin decreased the maximum serum saxagliptin concentration by 53% and the systemic exposure by 76%. As expected, the maximum serum concentration of the saxagliptin active metabolite was increased by 39%; no significant change in the systemic exposure was noted. Saxagliptin dose adjustment is not advised when coadministered with rifampin, as the plasma dipeptidyl peptidase-4 activity over a 24-hour period was unaffected.
    Segesterone Acetate; Ethinyl Estradiol: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Selegiline: (Moderate) Use caution if selegiline and rifampin are used concomitantly. Although rifampin is a strong CYP3A4 inducer and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate its effect, if any, on the effectiveness of selegiline.
    Selexipag: (Major) Increase the dose of selexipag up to twice when coadministering with rifampin. Reduce the selexipag dose when rifampin is stopped. Coadministration of selexipag and rifampin resulted in halved exposure to the selexipag active metabolite. Selexipag is a substrate of CYP2C8, UGT1A3, and UGT2B7; rifampin is an inducer of CYP2C8, UGT1A3, and UGT2B7.
    Selpercatinib: (Major) Avoid coadministration of selpercatinib and rifampin due to the risk of decreased selpercatinib exposure which may reduce its efficacy. Selpercatinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased selpercatinib exposure by 87%.
    Selumetinib: (Major) Avoid coadministration of selumetinib and rifampin due to the risk of decreased selumetinib exposure which may reduce its efficacy. Selumetinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased selumetinib exposure by 51%.
    Sertraline: (Minor) Concurrent use of rifampin and sertraline can decrease sertraline exposure which may result in decreased sertraline efficacy and symptoms suggestive of antidepressant discontinuation syndrome in some patients. Sertraline is a substrate of CYP2B6, CYP2C9, CYP2C19, and CYP3A; rifampin is an inducer of CYP2B6, a moderate inducer of CYP2C9, and a strong inducer of both CYP2C19 and CYP3A. Data regarding the clinical relevance of this interaction are limited to postmarketing case reports and case series, but the possibility of an interaction cannot be dismissed.
    Sevoflurane: (Moderate) Caution is advised with the concomitant use of sevoflurane and rifampin as concurrent use may increase the risk of hepatotoxicity.
    Sildenafil: (Minor) Sildenafil is metabolized principally by cytochrome P450 3A4 and 2C9 enzymes. It can be expected that concomitant administration of CYP3A4 enzyme-inducers, such as rifampin, will decrease plasma levels of sildenafil, however, no interaction studies have been performed.
    Simeprevir: (Major) Avoid concurrent use of simeprevir and rifampin, rifabutin, and rifapentine. Induction of CYP3A4 by the rifamycins may significantly reduce the plasma concentrations of simeprevir, resulting in treatment failure. When administered with rifampin, the Cmin and AUC of simeprevir decrease by 92% and 48%, respectively.
    Simvastatin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of simvastatin. Monitor for potential reduced cholesterol-lowering and hypotensive efficacy when these drugs are coadministered.
    Simvastatin; Sitagliptin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of simvastatin. Monitor for potential reduced cholesterol-lowering and hypotensive efficacy when these drugs are coadministered.
    Siponimod: (Major) Concomitant use of siponimod and rifampin is not recommended due to a significant decrease in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; rifampin is a moderate CYP2C9/strong CYP3A4 dual inducer. Coadministration with rifampin decreased siponimod exposure by 57%. Across different CYP2C9 genotypes, rifampin decreased the exposure of siponimod by up to 78%.
    Sirolimus: (Major) Avoid concomitant use of sirolimus and rifampin due to the risk of decreased sirolimus exposure which may reduce its efficacy. Sirolimus is a CYP3A and P-gp substrate and rifampin is a strong CYP3A and P-gp inducer. Concomitant use decreased sirolimus overall exposure by 82%.
    Sodium Bicarbonate: (Moderate) Concomitant use of sodium bicarbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of sodium bicarbonate.
    Sofosbuvir: (Major) Avoid coadministration of sofosbuvir, a P-glycoprotein (P-gp) substrate, with inducers of P-gp, such as rifampin. Taking these drugs together may significantly decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. In a single-dose study, coadministration reduced the sofosbuvir Cmax and AUC to 23% and 28% of normal concentrations, respectively.
    Sofosbuvir; Velpatasvir: (Major) Avoid coadministration of sofosbuvir, a P-glycoprotein (P-gp) substrate, with inducers of P-gp, such as rifampin. Taking these drugs together may significantly decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. In a single-dose study, coadministration reduced the sofosbuvir Cmax and AUC to 23% and 28% of normal concentrations, respectively. (Major) Avoid coadministration of velpatasvir with inducers of P-glycoprotein (P-gp), CYP3A4, CYP2B6, and CYP2C8, such as rifampin. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. In a single-dose study, coadministration reduced the velpatasvir Cmax and AUC to 29% and 18% or normal concentrations, respectively. Velpatasvir is a substrate of P-gp, CYP3A4, CYP2B6, and CYP2C8.
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Contraindicated) Concurrent administration of voxilaprevir and rifampin is contraindicated. Taking these drugs together significantly decreases voxilaprevir plasma concentrations, potentially resulting in loss of antiviral efficacy. Voxilaprevir is metabolized by P-glycoprotein (P-gp) and CYP3A4; rifampin is an inducer of P-gp and a potent inducer of CYP3A4. (Major) Avoid coadministration of sofosbuvir, a P-glycoprotein (P-gp) substrate, with inducers of P-gp, such as rifampin. Taking these drugs together may significantly decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. In a single-dose study, coadministration reduced the sofosbuvir Cmax and AUC to 23% and 28% of normal concentrations, respectively. (Major) Avoid coadministration of velpatasvir with inducers of P-glycoprotein (P-gp), CYP3A4, CYP2B6, and CYP2C8, such as rifampin. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. In a single-dose study, coadministration reduced the velpatasvir Cmax and AUC to 29% and 18% or normal concentrations, respectively. Velpatasvir is a substrate of P-gp, CYP3A4, CYP2B6, and CYP2C8.
    Sonidegib: (Major) Avoid the concomitant use of sonidegib and rifampin; sonidegib exposure was significantly decreased in healthy subjects who received rifampin and sonidegib compared with sonidegib only. Therefore, the efficacy of sonidegib may be reduced if these agents are administered together. Sonidegib is a CYP3A substrate and rifampin is a strong CYP3A4 inducer. The sonidegib geometric mean Cmax and AUC were decreased by 54% and 72%, respectively when coadministered with rifampin in a drug interaction study.
    Sorafenib: (Major) Avoid coadministration of sorafenib with rifampin due to decreased plasma concentrations of sorafenib. Sorafenib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with rifampin decreased sorafenib exposure by 37%.
    Sotorasib: (Major) Avoid concurrent use of sotorasib and rifampin. Coadministration may decrease sotorasib exposure resulting in decreased efficacy. Sotorasib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the AUC of sotorasib by 51%.
    Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if rifampin must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with rifampin is necessary; consider increasing the dose of sufentanil injection as needed. If rifampin is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. 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.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Rifampin is a potent enzyme inducer. Rifampin can increase the metabolism of sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. A pharmacokinetic effect on the combination has been reported with another rifamycin. Concomitant administration of rifabutin and sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole (double-strength) in 12 HIV-infected patients decreased the AUC of SMX-TMP by about 15 to 20%. Rifabutin decreased the AUC and Cmax of trimethoprim by 14% and 6%, respectively, when rifabutin was given with trimethoprim alone. The drugs are often given clinically together with certain patient populations, so the ultimate clinical significance of a possible pharmacokinetic interaction is not clear. Monitor for therapeutic response to therapy. (Moderate) Rifampin is a potent enzyme inducer. Rifampin can increase the metabolism of sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. A pharmacokinetic effect on the combination has been reported with another rifamycin. Concomitant administration of rifabutin and sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole (double-strength) in 12 HIV-infected patients decreased the AUC of SMX-TMP by about 15% to 20%. Rifabutin decreased the AUC and Cmax of trimethoprim by 14% and 6%, respectively, when rifabutin was given with trimethoprim alone. Additionally, sulfamethoxazole; trimethoprim may increase the serum concentration of rifampin. The drugs are often given together for certain patient populations, so the ultimate clinical significance of a possible pharmacokinetic interaction is not clear. Monitor for therapeutic response to therapy and increased rifampin toxicity
    Sulfasalazine: (Moderate) A decrease in sulfasalazines therapeutic efficacy could be seen when rifampin is coadministered; monitor the patient for response to therapy. Sulfasalazine is metabolized to its active components, sulfapyridine and mesalamine, by bacteria in the colon. Concomitant use of rifampin may alter the colonic bacteria.
    Sulfonylureas: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
    Sunitinib: (Major) Avoid coadministration of rifampin with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the daily dose of sunitinib to a maximum of 87.5 mg for patients with GIST or RCC, and to a maximum of 62.5 mg for patients with pNET; monitor carefully for toxicity. Sunitinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased exposure to sunitinib and its primary active metabolite by 46%.
    Suvorexant: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with rifampin is necessary. Suvorexant is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased suvorexant exposure by 77% to 88%.
    Tacrolimus: (Major) Coadministration with strong CYP3A4-inducers such as rifampin is not recommended without adjustments in the dosing regimen of tacrolimus and subsequent close monitoring of tacrolimus whole blood trough concentrations and tacrolimus-associated adverse reactions. Strong CYP3A4-inducers can decrease whole blood concentrations of tacrolimus. In a study of 6 normal volunteers, a significant decrease in tacrolimus oral bioavailability (14 +/- 6% vs. 7 +/- 3%) was observed with concomitant rifampin administration (600 mg). In addition, there was a significant increase in tacrolimus clearance with concomitant rifampin administration.
    Tadalafil: (Major) Avoid coadministration of tadalafil with rifampin in patients with pulmonary hypertension due to decreased plasma concentrations of tadalafil. In patients with erectile dysfunction and/or benign prostatic hyperplasia, consider the potential for loss of efficacy of tadalafil during concurrent administration of rifampin due to reduced tadalafil exposure. Tadalafil is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased tadalafil exposure by 88%.
    Tamoxifen: (Major) Avoid coadministration of rifampin with tamoxifen due to decreased exposure to tamoxifen which may affect efficacy. Tamoxifen is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the AUC and Cmax of tamoxifen by 86% and 55%, respectively.
    Tasimelteon: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as rifampin, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of rifampin 600 mg/day for 11 days, the exposure of tasimelteon decreased by about 90%. Rifampin also induces CYP1A2, a secondary metabolic pathway of tasimelteon.
    Tazemetostat: (Major) Avoid coadministration of tazemetostat with rifampin as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Telaprevir: (Contraindicated) There is a potential for telaprevir treatment failure when telaprevir is administered with rifampin; concurrent use is contraindicated. Rifampin is a potent inducer of CYP3A4, which is responsible for telaprevir metabolism. Coadministration may result in decreased telaprevir serum concentrations and impaired virologic response.
    Telithromycin: (Contraindicated) Concomitant use of telithromycin and rifampin, a potent CYP3A4 inducer, should be avoided. During administration in repeated doses, the Cmax and AUC of telithromycin were decreased by 79% and 86%, respectively. This is expected to cause subtherapeutic concentrations of telithromycin and loss of efficacy.
    Telmisartan; Amlodipine: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Temsirolimus: (Major) Avoid coadministration of temsirolimus with rifampin due to the risk of decreased plasma concentrations of the primary active metabolite of temsirolimus (sirolimus). If concomitant use is unavoidable, consider increasing the dose of temsirolimus from 25 mg per week up to 50 mg per week. If rifampin is discontinued, decrease the dose of temsirolimus to the dose used before initiation of rifampin. Temsirolimus is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin did not significantly affect temsirolimus exposure, but decreased the AUC and Cmax of sirolimus by 56% and 65%, respectively.
    Teniposide: (Moderate) Monitor patients for reduced efficacy of teniposide if coadministration with rifampin is necessary. Teniposide is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers reduced plasma concentrations of teniposide.
    Tenofovir Alafenamide: (Major) Administering tenofovir alafenamide with rifampin is not recommended. Taking these drugs together is expected to decrease tenofovir plasma concentrations, which may increase the potential for resistance and HIV treatment failure.
    Tepotinib: (Major) Avoid concomitant use of tepotinib and rifampin due to decreased plasma concentrations of tepotinib, which may reduce its efficacy. Tepotinib is a CYP3A substrate and rifampin is a strong CYP3A inducer.
    Terbinafine: (Moderate) According to the manufacturer, rifampin doubles terbinafine's clearance systemically. Studies were performed in normal volunteers. It is unknown if this interaction would be clinically significant; the exact mechanisms are not known. When terbinafine is administered to patients who are prescribed rifampin, patients should be monitored for decreased responses to terbinafine therapy.
    Teriflunomide: (Moderate) Concurrent use of teriflunomide, an inhibitor of the hepatic uptake organic anion transporting polypeptides OATP1B1/1B3, with rifampin, an OATP substrate, may increase exposure to rifampin. Consider reducing the dosage of rifampin as necessary and clinically appropriate, and monitor patients closely. Additive hepatotoxicity or hematologic toxicity may occur. The potential for additive adverse effects should also be considered when such medications would be prescribed after teriflunomide administration has ceased, if the patient has not received the teriflunomide elimination procedure.
    Tezacaftor; Ivacaftor: (Major) Coadministration of ivacaftor with rifampin is not recommended due to decreased plasma concentrations of ivacaftor. Ivacaftor is a sensitive CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin significantly decreased ivacaftor exposure by approximately 9-fold. (Major) Do not administer tezacaftor; ivacaftor and rifampin together; coadministration may reduce the efficacy of tezacaftor; ivacaftor. Exposure to ivacaftor is significantly decreased and exposure to tezacaftor may be reduced by the concomitant use of rifampin, a strong CYP3A inducer; both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate). Coadministration of ivacaftor with rifampin decreased ivacaftor exposure 89%.
    Theophylline, Aminophylline: (Major) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of aminophylline. Dosages of aminophylline may need to be adjusted while the patient is receiving rifampin. (Major) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of theophylline. Dosages of theophylline may need to be adjusted while the patient is receiving rifampin.
    Thiotepa: (Major) Avoid the concomitant use of thiotepa and rifampin if possible; increased metabolism to the active thiotepa metabolite may result in increased thiotepa toxicity (e.g., infection, bleeding, skin toxicity). Consider an alternative agent with no or minimal potential to induce CYP3A4. If coadministration is necessary, monitor patients for signs and symptoms of thiotepa toxicity. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; rifampin is a strong CYP3A4 inducer.
    Thiothixene: (Major) Limited data suggest that rifampin can increase the metabolism or reduce the bioavailability of thiothixene. Dosage adjustments of thiothixene may be necessary following the addition of rifampin or another rifamycin (e.g., rifabutin, rifapentine).
    Thyroid hormones: (Moderate) Rifampin increases thyroid hormone metabolism by inducing uridine 5-diphospho-glucuronosyltransferase (UGT) and leads to lower T4 serum levels. Clinicians should be alert for a decreased response to thyroid hormones if rifampin is used during thyroid hormone therapy.
    Ticagrelor: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inducers, such as rifampin. Ticagrelor is a substrate of CYP3A4/5 and concomitant use with rifampin substantially decreases ticagrelor exposure which may decrease the efficacy of ticagrelor.
    Tinidazole: (Moderate) Monitor for decreased efficacy of tinidazole if coadministration with rifampin is necessary. Concomitant use may accelerate the elimination of tinidazole, decreasing plasma concentrations. Tinidazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Tipranavir: (Contraindicated) The coadministration of tipranavir and rifampin is contraindicated. Rifampin induces CYP isoenzymes, thereby decreasing the plasma concentrations and AUC of most protease inhibitors by roughly 90%. Loss of antiretroviral efficacy and the potential for viral resistance is expected during concurrent use.
    Tivozanib: (Major) Avoid concomitant use of tivozanib with rifampin due to decreased plasma concentrations of tivozanib, which may reduce its efficacy. Tivozanib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the overall exposure of tivozanib by 52%.
    Tocainide: (Major) Rifampin is a potent inducer of hepatic metabolic enzymes. Rifampin has been shown to accelerate the hepatic metabolism of tocainide, reducing tocainide serum concentrations. Patients should be observed for loss of tocainide antiarrhythmic effectiveness if rifampin is added. Conversely, if rifampin is discontinued during tocainide therapy, tocainide dosage may need to be decreased.
    Tofacitinib: (Major) Coadministration of tofacitinib and rifampin is not recommended due to the potential for a loss of response or reduced clinical response to tofacitinib. Tofacitinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Tofacitinib exposure is decreased when coadministered with strong CYP3A4 inducers. In one study, the mean AUC and Cmax of tofacitinib were decreased by 84% and 74%, respectively when administered with rifampin.
    Tolazamide: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
    Tolbutamide: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
    Tolvaptan: (Major) Avoid concurrent use of tolvaptan and rifampin due to the risk for decreased tolvaptan plasma concentrations and reduced efficacy. Tolvaptan is a sensitive CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased tolvaptan exposure by 85%.
    Toremifene: (Major) Avoid coadministration of rifampin with toremifene due to decreased plasma concentrations of toremifene which may result in decreased efficacy. Toremifene is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with strong CYP3A4 inducers lowers steady-state serum concentrations of toremifene.
    Torsemide: (Moderate) Monitor the diuretic effect and blood pressure if torsemide and rifampin are administered together. The torsemide dose may need to be increased. Concomitant use of torsemide and rifampin can increase torsemide clearance and decrease torsemide plasma concentrations. Torsemide is a substrate of CYP2C9; rifampin induces CYP2C9.
    Trabectedin: (Major) Avoid the concomitant use of trabectedin with rifampin; coadministration resulted in decreased trabectedin exposure. Trabectedin is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with multiple doses of rifampin (600 mg PO daily for 6 days) decreased the systemic exposure of a single dose of trabectedin by 31% compared to a single dose of trabectedin given alone.
    Tramadol: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with rifampin is necessary; consider increasing the dose of tramadol as needed. If rifampin is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Tramadol; Acetaminophen: (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with rifampin is necessary; consider increasing the dose of tramadol as needed. If rifampin is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Trandolapril; Verapamil: (Major) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of verapamil. Dosages of verapamil may need to be adjusted while the patient is receiving rifampin.
    Trazodone: (Moderate) Consider increasing the trazodone dose based on therapeutic response when coadministered with rifampin. Concurrent use may decrease trazodone exposure. Trazodone is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers decreased the exposure of trazodone compared to the use of trazodone alone.
    Treprostinil: (Minor) Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diethanolamine) indicated that coadministration of rifampin, a cytochrome P450 (CYP) 2C8 enzyme inducer, decreased exposure to treprostinil. The clinical significance of this interaction with orally inhaled treprostinil and other CYP2C8 inducers is unknown.
    Tretinoin, ATRA: (Moderate) Rifampin may increase the CYP450 metabolism of tretinoin, ATRA, potentially resulting in decreased plasma concentrations of tretinoin, ATRA. No specific studies have been done with oral tretinoin and rifampin, however, patients should be closely monitored for decreased clinical effects of tretinoin, ATRA while receiving concomitant therapy.
    Triazolam: (Moderate) Monitor for withdrawal symptoms or lack of triazolam efficacy if coadministration with rifampin is necessary. Consider appropriate dose adjustment of triazolam if clinically indicated. Triazolam is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Tricyclic antidepressants: (Moderate) It may be necessary to adjust the dosage of tricyclic antidepressants if given concurrently with rifampin. Rifampin may induce the metabolism of tricyclic antidepressants; coadministration may result in decreased tricyclic antidepressant plasma concentrations.
    Trimethoprim: (Moderate) Rifampin is a potent enzyme inducer. Rifampin can increase the metabolism of sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. A pharmacokinetic effect on the combination has been reported with another rifamycin. Concomitant administration of rifabutin and sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole (double-strength) in 12 HIV-infected patients decreased the AUC of SMX-TMP by about 15 to 20%. Rifabutin decreased the AUC and Cmax of trimethoprim by 14% and 6%, respectively, when rifabutin was given with trimethoprim alone. The drugs are often given clinically together with certain patient populations, so the ultimate clinical significance of a possible pharmacokinetic interaction is not clear. Monitor for therapeutic response to therapy.
    Trimetrexate: (Minor) Drugs such as rifabutin, rifampin, and rifapentine can increase the metabolism of trimetrexate by induction of the cytochrome P-450 system. This can lead to lower plasma concentrations of trimetrexate.
    Trimipramine: (Moderate) It may be necessary to adjust the dosage of tricyclic antidepressants if given concurrently with rifampin. Rifampin may induce the metabolism of tricyclic antidepressants; coadministration may result in decreased tricyclic antidepressant plasma concentrations.
    Tucatinib: (Major) Avoid coadministration of tucatinib and rifampin due to the risk of decreased tucatinib exposure which may reduce its efficacy. Tucatinib is a CYP3A4 and CYP2C8 substrate and rifampin is a strong CYP3A4/moderate CYP2C8 inducer. Coadministration with rifampin decreased tucatinib exposure by 50%.
    Ubrogepant: (Major) Avoid the coadministration of ubrogepant and rifampin as concurrent use may decrease ubrogepant exposure and reduce the efficacy. Ubrogepant is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration with rifampin resulted in an 80% reduction in ubrogepant exposure.
    Ulipristal: (Major) Avoid use of rifampin with ulipristal. Ulipristal is a substrate of CYP3A4 and rifampin is a strong CYP3A4 inducer. Concomitant use decreases the plasma concentration of ulipristal significantly and may decrease its effectiveness. When a single 30-mg dose of ulipristal acetate was administered following administration of rifampin 600 mg/day for 9 days, the Cmax and AUC of ulipristal acetate decreased by 90% and 93% respectively. The Cmax and AUC of monodemethyl-ulipristal acetate decreased by 84% and 90% respectively.
    Upadacitinib: (Major) Coadministration of upadacitinib with rifampin is not recommended as upadacitinib exposure may be decreased leading to reduced therapeutic effect. Upadacitinib is CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Concurrent use of upadacitinib with rifampin 600 mg once daily for 9 days decreased upadacitinib exposure by 61%.
    Valbenazine: (Major) Co-administration of strong CYP3A4 inducers, such as Rifampin, and valbenazine, a CYP3A4 substrate, is not recommended. Strong CYP3A4 inducers can decrease systemic exposure of valbenazine and its active metabolite compared to the use of valbenazine alone. Reduced exposure of valbenazine and its active metabolite may reduce efficacy.
    Valproic Acid, Divalproex Sodium: (Major) The oral clearance of valproate may be increased in patients receiving valproic acid and rifampin concurrently. Valproate dosage adjustments may be necessary.
    Valsartan: (Minor) Coadministration may increase systemic exposure to valsartan. Valsartan is a substrate of the hepatic uptake transporter OATP1B1 and rifampin is an inhibitor of OATP. Patients should be monitored for adverse effects of valsartan.
    Valsartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration may increase systemic exposure to valsartan. Valsartan is a substrate of the hepatic uptake transporter OATP1B1 and rifampin is an inhibitor of OATP. Patients should be monitored for adverse effects of valsartan.
    Vandetanib: (Major) Avoid coadministration of vandetanib with rifampin due to decreased plasma concentrations of vandetanib and increased concentrations of the active metabolite. Vandetanib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with rifampin decreased the geometric mean AUC of vandetanib by 40%; the geometric mean AUC and Cmax of N-desmethylvandetanib increased by 266% and 414%, respectively.
    Vemurafenib: (Major) Avoid the concomitant use of vemurafenib and rifampin; significantly decreased vemurafenib exposure has been reported. Consider the use of an alternative agent. If use with rifampin cannot be avoided, increase the vemurafenib dose by 240 mg (as tolerated). If rifampin is discontinued, the previous (lower) vemurafenib dose may be resumed 2 weeks after the last rifampin dose. Vemurafenib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. In a drug interaction study, the vemurafenib AUC value decreased by 40% (90% CI, 24% to 53%) when a single 960-mg vemurafenib dose was administered with rifampin 600 mg/day; the vemurafenib Cmax was not changed.
    Venetoclax: (Major) Avoid the concomitant use of venetoclax and rifampin due to the potential for decreased venetoclax exposure and efficacy. Consider alternative agents. Venetoclax is a substrate of CYP3A4 and P-glycoprotein (P-gp) and rifampin is a strong inducer of CYP3A4 and an inducer of P-gp. Coadministration of rifampin decreased the venetoclax Cmax and AUC values by 42% and 71%, respectively.
    Verapamil: (Major) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of verapamil. Dosages of verapamil may need to be adjusted while the patient is receiving rifampin.
    Vilazodone: (Moderate) Consider increasing the dose of vilazodone up to 2-fold over 1 to 2 weeks (maximum, 80 mg per day) based on clinical response if coadministration with rifampin is necessary for more than 14 days. After discontinuation of rifampin, resume the previous vilazodone dose over 1 to 2 weeks. Vilazodone is primarily metabolized by CYP3A4 and rifampin is a strong CYP3A4 inducer. Decreased plasma concentrations of vilazodone are expected if vilazodone is used concomitantly with strong CYP3A4 inducers.
    Vincristine Liposomal: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of the drug, including rifampin. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
    Vincristine: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of the drug, including rifampin. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
    Vitamin D: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can decrease the plasma concentrations and possibly the efficacy of cholecalciferol, Vitamin D3. In some cases, reduced concentrations of circulating vitamin D and 1,25-dihydoxy vitamin D have been accompanied by decreased serum calcium and phosphate, and elevated parathyroid hormone. Dosage adjustments of cholecalciferol, Vitamin D3 may be required. (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can decrease the plasma concentrations and possibly the efficacy of ergocalciferol, Vitamin D2. In some cases, reduced concentrations of circulating vitamin D and 1,25-dihydoxy vitamin D have been accompanied by decreased serum calcium and phosphate, and elevated parathyroid hormone. Dosage adjustments of ergocalciferol, Vitamin D2 may be required.
    Voclosporin: (Major) Avoid coadministration of voclosporin with rifampin. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased voclosporin exposure by 87%.
    Vorapaxar: (Major) Avoid coadministration of vorapaxar and rifampin. Decreased serum concentrations of vorapaxar and thus decreased efficacy are possible when vorapaxar, a CYP3A4 substrate, is coadministered with rifampin, a strong CYP3A inducer.
    Voriconazole: (Contraindicated) Use of rifampin with voriconazole is contraindicated. Induction of CYP3A4, CYP2C9 and CYP2C19 by rifampin could result in increased voriconazole clearance and impaired antifungal activity. Voriconazole AUC and Cmax may be reduced by roughly 95%. Doubling the dose of voriconazole to 400 mg every 12 hours does not restore adequate exposure to voriconazole during rifampin coadministration.
    Vortioxetine: (Major) Vortioxetine is extensively metabolized by CYP isoenzymes, primarily CYP2D6 and by CYP3A4 and other isoenzymes to a lesser extent. Therefore, the manufacturer recommends that the practitioner consider an increase in dose of vortioxetine when a strong CYP inducer, such as rifampin, is co-administered for more than 14 days. In such cases, the maximum recommended dose of vortioxetine should not exceed three times the original dose. When the inducer is discontinued, the dose of vortioxetine should be reduced to the original level within 14 days.
    Voxelotor: (Major) Avoid coadministration of voxelotor and rifampin 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 in patients 12 years and older. In patients 4 to 11 years old, weight-based dosage adjustments are recommended; consult product labeling for specific recommendations. Voxelotor is a substrate of CYP3A; rifampin is a strong CYP3A inducer. Coadministration of voxelotor with a strong CYP3A inducer is predicted to decrease voxelotor exposure by up to 40%.
    Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with rifamycins is necessary as concurrent use may decrease the exposure of warfarin leading to reduced efficacy. Rifamycins may induce the hepatic metabolism of warfarin through induction of CYP3A4, CYP2C9, and CYP1A2. A 2- to 3-fold increase in the daily dose of warfarin may be needed within a week of starting rifamycins to maintain appropriate anticoagulation. Once the rifamycin is discontinued, the dose of warfarin will need to be decreased.
    Zaleplon: (Moderate) Monitor for decreased efficacy of zaleplon if coadministration with rifampin is necessary. Zaleplon is a partial CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Although CYP3A4 is normally a minor metabolizing enzyme of zaleplon, multiple-dose administration of rifampin (600 mg every 24 hours for 14 days) reduced zaleplon Cmax and AUC by approximately 80%.
    Zanubrutinib: (Major) Avoid the concomitant use of zanubrutinib and rifampin. Coadministration may result in decreased zanubrutinib exposure and reduced efficacy. Zanubrutinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. The AUC of zanubrutinib was decreased by 93% when coadministered with rifampin.
    Zidovudine, ZDV: (Minor) Rifampin can accelerate the metabolism of zidovudine, causing a decrease in AUC of approximately 50%. However the effectiveness of zidovudine against HIV does not appear to be altered and no dosage adjustments are required.
    Ziprasidone: (Moderate) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4, such as rifampin. The concurrent use of ziprasidone with carbamazepine, a potent CYP3A4 inducer, causes a 35% decrease in the AUC of ziprasidone.
    Zolpidem: (Major) Concurrent use of zolpidem with potent CYP3A4 inducers, such as rifampin, is not recommended. CYP3A4 is the primary isoenzyme responsible for zolpidem metabolism, and there is evidence of a significant decrease in systemic exposure and pharmacodynamic effects of zolpidem during co-administration of rifampin. During one small drug interaction study of healthy females, a single 10 mg dose of zolpidem co-administered with rifampin at steady state levels resulted in a 73%, 58%, and 36% decrease in the AUC, Cmax, and half-life, respectively, of zolpidem; this decrease in exposure resulted in significant reductions in the pharmacodynamic effects of zolpidem.
    Zonisamide: (Major) Zonisamide is metabolized by hepatic cytochrome P450 enzyme 3A4 (CYP3A4). Inducers of CYP3A4, such as rifampin, can reduce the systemic exposure to zonisamide by increasing the metabolism of the drug. Coadminister these drugs with caution.

    PREGNANCY AND LACTATION

    Pregnancy

    Use rifampin during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies of rifampin in pregnant women. Rifampin does cross the placenta. When given during the last few weeks of pregnancy, rifampin can cause postnatal hemorrhages in the mother and infant; vitamin K therapy may be indicated. Rifampin has been shown to be teratogenic in rodents. Congenital malformations, including spina bifida and cleft palate, were increased in the offspring of pregnant rats. Imperfect osteogenesis and embryotoxicity were also observed in pregnant rabbits given oral doses up to about 3-times the maximum recommended human dose based on body surface area.[30314] Rifampin does not appear to be teratogenic in humans. Tuberculosis guidelines support treatment initiation in pregnancy whenever the probability of maternal disease is moderate to high due to the risk of untreated tuberculosis to a pregnant woman and her fetus.[61094]

    Because of the potential for tumorigenicity demonstrated for rifampin in animal studies, the FDA-approved labeling recommends discontinuing breast-feeding or rifampin, taking into consideration the importance of the drug to the mother.[30314] However, previous American Academy of Pediatrics (AAP) recommendations considered rifampin to be compatible with breast-feeding.[27500] Guidelines encourage breast-feeding for women who are noninfectious and taking first-line tuberculosis agents, such as rifampin, as the small concentrations of these drugs measured in breast milk have not been reported to produce toxic effects in the nursing infant.[61094]

    MECHANISM OF ACTION

    Rifampin inhibits bacterial and mycobacterial RNA synthesis. It binds to the beta-subunit of DNA-dependent RNA polymerase, thereby inhibiting the binding of the enzyme to DNA and blocking RNA transcription. Rifampin does not bind to RNA polymerase in eukaryotic cells, so RNA synthesis in human cells is not affected. Rifampin is bactericidal or bacteriostatic, depending on the concentration reached within an infected site and the susceptibility of the organism. Rifampin is effective against bacilli that are rapidly dividing in extracellular cavitary lesions, as well as against slowly or intermittently dividing organisms such as those found in closed caseous lesions and macrophages.
     
    Susceptibility is delineated by pathogen. The MICs for N. meningitidis are defined as susceptible at concentrations of 0.5 mcg/mL or less, intermediate at a concentration of 1 mcg/mL, and resistant at concentrations of 2 mcg/mL or more. The MICs for S. pneumoniae, Enterococcus sp., Staphylococcus sp., H. influenzae, and H. parainfluenzae are defined as susceptible at concentrations of 1 mcg/mL or less, intermediate at a concentration of 2 mcg/mL, and resistant at concentrations of 4 mcg/mL or more. These breakpoints do not apply to therapy of patients with invasive H. influenzae disease and may only be appropriate for prophylaxis of case contacts.
     
    Rifampin has been used for the treatment of pruritus secondary to cholestasis associated with primary biliary cirrhosis. Rifampin induces microsomal enzyme activity increasing the metabolism and urinary excretion of bile acids. Rifampin may also increase the metabolism of nonbile pruritogenic substances.

    PHARMACOKINETICS

    Rifampin is administered orally and intravenously. High interpatient variability, particularly with peak serum concentrations, has been noted with rifampin in children and adults in clinical studies. Rifampin is widely distributed into most body tissues and fluids including lungs, liver, bone, saliva, and peritoneal and pleural fluids. Cerebrospinal fluid (CSF) concentrations are roughly 10% to 20% of concurrent systemic drug concentrations. In a study in 9 patients undergoing CSF shunt placement, CSF concentrations exceeded the MIC of rifampin against staphylococci by at least 150-fold. Protein binding of rifampin is approximately 80%. The volume of distribution of rifampin at steady state is 0.52 to 0.8 L/kg. Rifampin is metabolized in the liver to an active metabolite, desacetyl-rifampicin, via deacetylation. Rifampin undergoes enterohepatic circulation with significant reabsorption. Competition between rifampin and bilirubin for excretory pathways of the liver at the cellular level can occur and result in hyperbilirubinemia in the early days of treatment. The parent compound and its metabolite are primarily excreted (30% to 40%) in feces via biliary elimination. Up to 30% of a dose is excreted in the urine, with approximately half of this as unchanged drug. The elimination half-life in adults is 3 to 5 hours, but it decreases with prolonged use due to auto-induction of hepatic metabolism.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, P-gp
    Rifampin is a significant inducer of many hepatic CYP450 isoenzymes. Rifampin is most potently an inducer of CYP3A4, but also potently induces the CYP2B6 isoenzyme in vitro. Comparatively, rifampin is a relatively weak inducer of CYP1A2. Rifampin also induces the CYP2C8 isoenzyme in vitro. Both in vitro and in vivo studies have shown that rifampin induces the CYP2C9 and CYP2C19 isoenzyme. While no specific in vitro or in vivo studies have shown that rifampin induces the CYP2D6 isoenzyme, some pharmacokinetic studies suggest that rifampin may be a modest inducer. Rifampin is also an inducer of P-glycoprotein (P-gp).

    Oral Route

    Rifampin is absorbed rapidly from the GI tract after oral administration. Peak serum concentrations in healthy populations vary widely from individual to individual. After a single 600 mg oral dose of rifampin in healthy adults, the peak serum concentration averages 7 mcg/mL but varies from 4 to 32 mcg/mL. Peak serum concentrations are attained within 2 to 4 hours. Food decreases rifampin absorption by approximately 30%; therefore, rifampin is recommended to be administered 1 hour before or 2 hours after a meal. Highly variable absorption has been noted with oral rifampin suspension in clinical studies.

    Intravenous Route

    Peak concentrations are reached at the end of infusion. After intravenous administration of a 300 or 600 mg dose of rifampin infused over 30 minutes to healthy male volunteers (n = 12), mean peak plasma concentrations were 9 +/- 3 mcg/mL and 17.5 +/- 5 mcg/mL, respectively. Plasma concentrations after the 600 mg dose, which were disproportionately higher (up to 30% more than expected) than those found after the 300 mg dose, indicated that the elimination of larger doses was not as rapid. After repeated daily administration of 600 mg IV infusions over 3 hours for 7 days (n = 5), concentrations of rifampin decreased from 5.81 +/- 3.38 mcg/mL at 8 hours after the infusion on day 1 to 2.6 +/- 1.88 mcg/mL at 8 hours after the infusion on day 7.