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Rifampin

Pronunciation

(rif AM pin)

Index Terms

  • Rifampicin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

Rifadin: 150 mg

Rifadin: 300 mg [DSC] [contains brilliant blue fcf (fd&c blue #1), fd&c red #40]

Generic: 150 mg, 300 mg

Solution Reconstituted, Intravenous:

Rifadin: 600 mg (1 ea) [contains sodium formaldehyde sulfoxylate]

Generic: 600 mg (1 ea)

Suspension, Oral:

RifAMPin+SyrSpend SF PH4: 25 mg/mL (120 mL)

Brand Names: U.S.

  • Rifadin
  • RifAMPin+SyrSpend SF PH4

Pharmacologic Category

  • Antitubercular Agent
  • Rifamycin

Pharmacology

Inhibits bacterial RNA synthesis by binding to the beta subunit of DNA-dependent RNA polymerase, blocking RNA transcription

Absorption

Oral: Well absorbed; food may delay or slightly reduce peak

Distribution

Crosses the blood-brain barrier well

Relative diffusion of antimicrobial agents from blood into cerebrospinal fluid (CSF): Adequate with or without inflammation (exceeds usual MICs)

Ratio of CSF to blood level (%): Inflamed meninges: 25

Metabolism

Hepatic; undergoes enterohepatic recirculation

Excretion

Feces (60% to 65%) and urine (~30%) as unchanged drug

Time to Peak

Serum: Oral: 2-4 hours

Duration of Action

≤24 hours

Half-Life Elimination

3-4 hours, prolonged with hepatic impairment; End-stage renal disease: 1.8-11 hours

Protein Binding

80%

Special Populations: Children

After oral administration, the Cmax ranged from 3.5 to 15 mcg/mL, Tmax was 1 hour, and half-life was approximately 2.9 hours. After IV administration, the Cmax after the initial infusion was approximately 25.9 mcg/mL and half-life ranged from 1.04 to 3.81 hours.

Use: Labeled Indications

Meningococcal prophylaxis: Treatment of asymptomatic carriers of Neisseria meningitidis to eliminate meningococci from the nasopharynx

Tuberculosis: Treatment of tuberculosis in combination with other agents

Off Label Uses

Anaplasmosis

Based on the IDSA guidelines for the clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis (HGA) and babesiosis and the Centers for Disease Control and Prevention (CDC) guideline for the Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis, rifampin may be considered as an alternative therapy to doxycycline for the treatment of mild cases of human anaplasmosis (also known as human granulocytic anaplasmosis [HGA]) in patients who are pregnant or who have a severe drug allergy to doxycycline. Due to similar symptoms, Rocky Mountain spotted fever (RMSF) should be ruled out before considering rifampin treatment for human anaplasmosis; rifampin is not an acceptable treatment of RMSF. In addition, rifampin does not treat coinfection with Lyme disease (B. burgdorferi).

Brain abscess, empyema, and epidural abscess (MRSA)

According to Infectious Diseases Society of America (IDSA) guidelines regarding the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections, rifampin can be considered as adjunctive therapy to vancomycin in the treatment of brain abscess, empyema, or spinal epidural abscess. The use of rifampin warrants increased awareness of possible drug interactions caused by liver enzyme induction. Rifampin should only be used in combination with other antibiotics for S. aureus infections because resistance can develop rapidly with monotherapy.

Brucellosis

Data from randomized studies support the use of rifampin, in combination with doxycycline, as an alternative regimen for the treatment of brucellosis [Hashemi 2012], [Solera 1995]. Additional trials may be necessary to further define the role of rifampin in this condition.

Based on the World Health Organization (WHO) guidelines for brucellosis, rifampin, in combination with doxycycline, is an effective and recommended alternative agent in the management of uncomplicated brucellosis.

Cholestatic pruritus (adults)

Data from a meta-analysis of randomized controlled trials support the use of rifampin in the treatment of cholestatic pruritus.

American Association for the Study of Liver Diseases practice guidelines for primary biliary cirrhosis recommend the use of rifampin for cholestatic pruritus refractory to bile acid sequestrants.

Device-related osteoarticular infection (MRSA) (adults)

According to IDSA guidelines, rifampin is recommended as part of the treatment regimen for MRSA in device-related osteoarticular infection. Initial therapy should include a parenteral therapy regimen for osteomyelitis followed by rifampin and another antibiotic (a fluoroquinolone, sulfamethoxazole/trimethoprim, a tetracycline, or clindamycin). At this time, treatment of device-related osteoarticular infection with rifampin alone or without initial parenteral antibiotic therapy is not recommended.

Group A streptococci (GAS) chronic carrier (treatment)

Based on the IDSA Clinical Practice Guideline for the Diagnosis and Management of Group A Streptococcal Pharyngitis, rifampin (in combination with oral penicillin V or intramuscular benzathine penicillin G) is an effective and recommended treatment option in chronic carriers of GAS.

Haemophilus influenzae type B, chemoprophylaxis

Based on the Advisory Committee on Immunization Practices (ACIP) recommendations for prevention and control of H. influenzae type b disease, rifampin is effective and recommended as chemoprophylaxis in index patients with invasive Hib disease (unless treated with cefotaxime or ceftriaxone); all household contacts in households with members aged <4 years who are not fully vaccinated or members aged <18 years who are immunocompromised, regardless of their vaccination status; and child care settings when two or more cases of invasive Hib disease occurred within 60 days and unimmunized or underimmunized children attend the facility.

Infective endocarditis (prosthetic valve), treatment (adults)

Based on the American Heart Association (AHA) Scientific Statement for Infective Endocarditis in Adults, rifampin (in combination with other antibiotics) is an effective and recommended treatment regimen for infective endocarditis due to staphylococci (methicillin-susceptible or methicillin-resistant) involving a prosthetic valve.

Leprosy

Based on the National Hansen’s Disease Program (NHDP) treatment recommendations and World Health Organization (WHO) Expert Committee on Leprosy, rifampin, in combination with other agents, is an effective and recommended treatment for lepromatous (multibacillary) and tuberculoid (paucibacillary) leprosy.

Meningitis due to Streptococcus pneumoniae or staphylococci

Based on the IDSA guidelines for management of bacterial meningitis, rifampin is an effective and recommended adjunctive agent in the treatment of bacterial meningitis caused by S. pneumoniae (when used in combination with a third-generation cephalosporin with or without vancomycin) when there is a delay in the expected clinical or bacteriologic response, and in patients with CSF shunt infections caused by staphylococci (in combination with vancomycin), especially in cases where the shunt cannot be removed.

Nasal decolonization of S. aureus

Based on the IDSA guidelines for the Treatment of Methicillin-Resistant S. aureus Infections, rifampin, in combination with another antistaphylococcal antibiotic (eg, trimethoprim and sulfamethoxazole, doxycycline), is an effective and recommended alternative option for nasal decolonization of S. aureus in patients who continue to experience infections in spite of other decolonization measures.

Nontuberculous mycobacterial disease, pulmonary

Based on the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) Guideline for the Diagnosis, Treatment, and Prevention of Nontuberculosis Mycobacterial Disease, rifampin (in combination with other antimicrobials) is effective and recommended for the treatment of Mycobacterium avium complex (MAC) and Mycobacterium kansasii pulmonary disease.

Osteomyelitis (MRSA)

IDSA, SIMIT, and BSAC guidelines recommend the use of rifampin as a therapeutic option for MRSA and MSSA osteomyelitis. Evidence for the use of rifampin is based largely on clinical experience and observational studies. The use of rifampin warrants increased awareness of possible drug interactions caused by liver enzyme induction. Rifampin should only be used in combination with other antibiotics for S. aureus infections because resistance can develop rapidly with monotherapy.

Prosthetic joint infection

Based on the Infectious Diseases Society of America (IDSA) guidelines for the management of prosthetic joint infection, rifampin is an effective and recommended adjunctive agent for the treatment of prosthetic joint infection with Staphylococci (oxacillin-susceptible or -resistant) infection.

Septic thrombosis of cavernous or dural venous sinus (MRSA)

According to IDSA guidelines regarding the treatment of MRSA infections, rifampin can be considered as add-on therapy to vancomycin in septic thrombosis of cavernous or dural venous sinus. The use of rifampin warrants increased awareness of possible drug interactions caused by liver enzyme induction. Rifampin should only be used in combination with other antibiotics for S. aureus infections because resistance can develop rapidly with monotherapy.

Contraindications

Hypersensitivity to rifampin, any rifamycins, or any component of the formulation; concurrent use of atazanavir, darunavir, fosamprenavir, ritonavir/saquinavir, saquinavir, or tipranavir

Canadian labeling: Additional contraindications (not in US labeling): Jaundice associated with reduced bilirubin excretion; premature and newborn infants; breastfeeding women.

Dosing: Adult

Meningococcal prophylaxis: Oral, IV: 600 mg twice daily for 2 days

Tuberculosis, active (drug-susceptible): Oral, IV: Note: Always administer in combination with other antitubercular drugs (Nahid 2016).

Dosing:

Manufacturer’s labeling: 10 mg/kg/day once daily (maximum: 600 mg/day)

Alternate recommendations: ATS/CDC/IDSA Drug-susceptible tuberculosis guideline recommendations (Nahid 2016):

Once-daily therapy: 10 mg/kg/day once daily (usual dose: 600 mg). Note: The preferred frequency of administration is once daily during the intensive and continuation phases; however, 5-days-per-week administration by directly observed therapy (DOT) is an acceptable alternative.

Twice-weekly or three-times-weekly DOT: 10 mg/kg/dose (usual dose: 600 mg) administered 2 or 3 times weekly (Nahid 2016)

Regimens: Treatment regimens for pulmonary tuberculosis and tuberculous meningitis consist of an initial 2-month phase of a 4-drug regimen, followed by a continuation phase of an additional 4 to 7 months of rifampin and isoniazid for pulmonary tuberculosis and a continuation phase of an additional 7 to 10 months of rifampin and isoniazid for tuberculous meningitis (optimal duration is not defined although continuation phase must continue for a minimum of 7 additional months). Adjunctive corticosteroid therapy (eg, dexamethasone, prednisolone) tapered over 6 to 8 weeks is also recommended for tuberculous meningitis. Rifampin frequency and dosing differs depending on treatment regimen selected; consult current Drug-sensitive TB guidelines (Nahid 2016).

Tuberculosis, latent infection (LTBI): As an alternative to isoniazid: Oral, IV: 10 mg/kg/day (maximum: 600 mg/day) for 4 months. Note: Combination with pyrazinamide should not generally be offered (MMWR, Aug 8, 2003).

Anaplasmosis, mild cases (patients with severe allergy to doxycycline) (off-label use): Oral: 300 mg twice daily for 7 to 10 days. Note: Rifampin is not an effective agent for Rocky Mountain spotted fever (RMSF); ensure that RMSF has been ruled out prior to use. Rifampin is also not effective for Lyme disease; if co-infection with B. burgdorferi is suspected, treat with an additional appropriate antimicrobial agent (CDC [Biggs 2016]; IDSA [Wormser 2006]).

Brain abscess, empyema, and epidural abscess (MRSA) (off-label use): Oral, IV: 600 mg once daily or 300 to 450 mg twice daily with concomitant vancomycin for 4 to 6 weeks (IDSA [Liu 2011])

Brucellosis (off-label use): Oral: 600 to 900 mg once daily for 6 weeks; use in combination with doxycycline (WHO 2006). Additional data may be necessary to further define the role of rifampin in this condition.

Cholestatic pruritus (off-label use) (Lindor 2009): Oral: Dose based on bilirubin value:

Bilirubin < 3 mg/dL: 150 mg daily

Bilirubin ≥3 mg/dL: 150 mg twice daily

Device-related osteoarticular infection (MRSA) (off-label use): Oral: 600 mg once daily or 300 to 450 mg twice daily in combination with another antistaphylococcal antibiotic (IDSA [Liu 2011])

Endocarditis, treatment (prosthetic valve) (off-label use): Oral, IV:

MRSA: 300 mg every 8 hours for at least 6 weeks (combine with vancomycin for the entire duration of therapy and gentamicin for the first 2 weeks) (IDSA [Liu 2011]; AHA [Baddour 2015])

MSSA: 300 mg every 8 hours for at least 6 weeks (combine with nafcillin or oxacillin for the entire duration of therapy and gentamicin for the first 2 weeks) (AHA [Baddour 2015])

Group A streptococci (GAS) chronic carrier, treatment (off-label use): Oral: 20 mg/kg/day once daily (maximum: 600 mg daily) for the last 4 days of treatment when combined with oral penicillin V or 20 mg/kg/day in 2 divided doses (maximum: 600 mg daily) for 4 days when combined with intramuscular benzathine penicillin G (IDSA [Shulman 2012])

H. influenzae type B, chemoprophylaxis (off-label use): Oral: 600 mg once daily for 4 days (Red Book [AAP] 2015)

Leprosy (off-label use): Oral:

Lepromatous (multibacillary):

National Hansen Disease Program: 600 mg once daily for 24 months in combination with clofazimine and dapsone (NHDP [HRSA 2016])

World Health Organization: 600 mg once monthly for 12 months in combination with clofazimine and dapsone (WHO 2012)

Tuberculoid (paucibacillary):

National Hansen Disease Program: 600 mg once daily for 12 months in combination with dapsone (NHDP [HRSA 2016])

World Health Organization: 600 mg once monthly for 6 months in combination with dapsone (WHO 2012)

Meningitis due to S. pneumoniae or staphylococci (off-label use): Oral, IV: 600 mg once daily; use in combination with other antimicrobials (IDSA [Tunkel 2004])

Nasal decolonization of Staphylococcus aureus (off-label use): Oral, IV: 600 mg/day for 5 to 10 days; Note: Must use in combination with at least one other systemic antistaphylococcal antibiotic. Not recommended as first-line drug for decolonization; evidence is weak for use in patients with recurrent infections (IDSA [Liu 2011]).

Nontuberculous mycobacterial disease, pulmonary (off-label use): Oral, IV:

M. avium complex (nodular/bronchiectatic disease) (ATS/IDSA [Griffith 2007]): 600 mg 3 times weekly in combination with a 3-times-weekly regimen of a macrolide (azithromycin or clarithromycin) and ethambutol; continue treatment until patient is culture negative on therapy for 1 year.

M. avium complex (severe nodular/bronchiectatic or cavitary disease) (ATS/IDSA [Griffith 2007]): 600 mg (450 mg in patients weighing <50 kg) once daily in combination with daily macrolide (azithromycin or clarithromycin) and ethambutol therapy; continue treatment until patient is culture negative on therapy for 1 year. May also consider addition of 3 times weekly amikacin or streptomycin early in therapy.

M. avium complex (cystic fibrosis patients) (Floto 2016):

<50 kg: 450 mg once daily in combination with daily macrolide (azithromycin [preferred] or clarithromycin) and ethambutol therapy

>50 kg: 600 mg once daily in combination with daily macrolide (azithromycin [preferred] or clarithromycin) and ethambutol therapy

M. kansasii (ATS/IDSA [Griffith 2007]): 600 mg once daily in combination with daily ethambutol and isoniazid therapy; continue treatment until patient is culture negative on therapy for 1 year.

Osteomyelitis (MRSA) (off-label use): Oral, IV: 600 mg once daily or 300 to 450 mg twice daily for at least 8 weeks with concomitant trimethoprim/sulfamethoxazole, linezolid or clindamycin (IDSA [Liu 2011])

Prosthetic joint infection (off-label use): Staphylococci (oxacillin-susceptible or oxacillin-resistant): Oral:

Debridement and prosthesis retention or following 1-stage exchange, acute treatment: 300 to 450 mg every 12 hours in combination with an IV antistaphylococcal antibiotic for 2 to 6 weeks (IDSA [Osmon 2013])

Debridement and prosthesis retention or following 1-stage exchange, chronic treatment:

Total ankle, elbow, hip, or shoulder arthroplasty: 300 to 450 mg every 12 hours in combination with an oral antistaphylococcal antibiotic for 3 months (IDSA [Osmon 2013])

Total knee arthroplasty: 300 to 450 mg every 12 hours in combination with an oral antistaphylococcal antibiotic for 6 months (IDSA [Osmon 2013])

Septic thrombosis of cavernous or dural venous sinus (MRSA) (off-label use): Oral, IV: 600 mg once daily or 300 to 450 mg twice daily with concomitant vancomycin for 4 to 6 weeks (IDSA [Liu 2011])

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Tuberculosis, active (drug-susceptible) (excludes meningitis): Oral, IV: Use as part of a multidrug regimen:

Manufacturer’s labeling: Infants, Children, and Adolescents: 10 to 20 mg/kg/day once daily (maximum: 600 mg/day)

Alternate dosing: ATS/CDC/IDSA Drug-susceptible tuberculosis guideline recommendations (Nahid 2016):

Dosing:

Once-daily therapy: Note: The preferred frequency of administration is once daily during the intensive and continuation phases; however, 5-days-per-week administration by directly observed therapy (DOT) is an acceptable alternative.

Infants, Children, and Adolescents <15 years and ≤40 kg: 10 to 20 mg/kg/dose once daily; maximum dose: 600 mg/dose

Children and Adolescents <15 years and >40 kg and Adolescents ≥15 years: 10 mg/kg/dose once daily (usual dose: 600 mg)

Three-times-weekly directly observed therapy (DOT): Note: Although suggested dosing based on experience with twice-weekly regimen; experts suggest three-times-weekly regimens are more effective than twice-weekly DOT regimens; three-times-weekly DOT may be used as part of an intensive phase and/or continuation phase dosing regimen; consult guidelines for specific information.

Infants, Children, and Adolescents <15 years and ≤40 kg: 10 to 20 mg/kg/dose administered three times weekly; maximum dose: 600 mg/dose.

Children and Adolescents <15 years and >40 kg and Adolescents ≥15 years: 10 mg/kg/dose (usual dose: 600 mg) administered 3 times weekly

Regimens: Treatment regimens for pulmonary tuberculosis consist of an initial 2-month phase of a 4-drug regimen, followed by a continuation phase of an additional 4 to 7 months of rifampin and isoniazid. Rifampin frequency and dosing differs depending on treatment regimen selected; consult current Drug-sensitive TB guidelines (Nahid 2016).

Tuberculosis, latent infection (LTBI): As an alternative to isoniazid: Children: 10 to 20 mg/kg/day (maximum: 600 mg/day) for 6 months

Group A streptococci (GAS) chronic carrier, treatment (off-label use): Children and Adolescents: Refer to adult dosing.

Anaplasmosis, mild cases (patients with severe allergy to doxycycline) (off-label use): Children and Adolescents: Oral: 20 mg/kg/day in 2 divided doses, not to exceed 300 mg/dose. Note: Rifampin is not an effective agent for Rocky Mountain spotted fever (RMSF); ensure that RMSF has been ruled out prior to use. Rifampin is also not effective for Lyme disease; if co-infection with B. burgdorferi is suspected, treat with an additional appropriate antimicrobial agent (CDC [Biggs 2016]; IDSA [Wormser 2006]).

H. influenzae prophylaxis (off-label use): Oral, IV: Infants and Children: 20 mg/kg/day every 24 hours for 4 days, not to exceed 600 mg/dose

Leprosy (off-label use): Oral:

Lepromatous (multibacillary):

National Hansen Disease Program: Children and Adolescents: 10 to 20 mg/kg/dose once daily (maximum dose: 600 mg/dose) for 24 months in combination with clofazimine and dapsone (NHDP [HRSA 2016])

World Health Organization (WHO 2012):

Children <10 years: 10 mg/kg/dose once monthly for 12 months in combination with clofazimine and dapsone

Children ≥10 years and Adolescents: 450 mg once monthly for 12 months in combination with clofazimine and dapsone

Tuberculoid (paucibacillary):

National Hansen Disease Program: Children and Adolescents: 10 to 20 mg/kg/dose once daily (maximum dose: 600 mg/dose) for 12 months in combination with dapsone (NHDP [HRSA 2016])

World Health Organization (WHO 2012):

Children <10 years: 10 mg/kg/dose once monthly for 6 months in combination with dapsone

Children ≥10 years and Adolescents: 450 mg once monthly for 6 months in combination with dapsone

Meningococcal prophylaxis: Oral:

<1 month: 10 mg/kg/day in divided doses every 12 hours for 2 days

Infants, Children, and Adolescents: 20 mg/kg/day in divided doses every 12 hours for 2 days (maximum: 600 mg/dose)

Nasal carriers of Staphylococcus aureus (off-label use): Oral, IV: 15 mg/kg/day divided every 12 hours for 5 to 10 days; Note: Must use in combination with at least one other systemic antistaphylococcal antibiotic. Not recommended as first-line drug for decolonization; evidence is weak for use in patients with recurrent infections (IDSA [Liu 2011]).

Dosing: Renal Impairment

Treatment of drug-susceptible TB: Adults:

CrCl <30 mL/minute: 600 mg once daily or 600 mg administered 3 times weekly (Nahid 2016)

Intermittent hemodialysis: 600 mg once daily or 600 mg administered 3 times weekly; administer after hemodialysis on the day of dialysis (Nahid 2016).

Dosing: Hepatic Impairment

There are no dosage adjustments provided in manufacturer’s labeling; use with caution.

Reconstitution

Reconstitute vial with 10 mL SWFI. Prior to injection, dilute in appropriate volume of a compatible solution (eg, 100 mL D5W).

Extemporaneously Prepared

A rifampin 1% w/v suspension (10 mg/mL) may be made with capsules and one of four syrups (Syrup NF, simple syrup, Syrpalta® syrup, or raspberry syrup). Empty the contents of four 300 mg capsules or eight 150 mg capsules onto a piece of weighing paper. If necessary, crush contents to produce a fine powder. Transfer powder to a 4-ounce amber glass or plastic prescription bottle. Rinse paper and spatula with 20 mL of chosen syrup and add the rinse to bottle; shake vigorously. Add 100 mL syrup to the bottle and shake vigorously. Label "shake well". Stable for 4 weeks at room temperature or refrigerated.

A 25 mg/mL oral suspension may be made with capsules and cherry syrup concentrate diluted 1:4 with simple syrup, NF. Empty the contents of ten 300 mg capsules into a mortar and reduce to a fine powder. Add 20 mL of the vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label "shake well" and "refrigerate". Stable for 28 days refrigerated (preferred) or at room temperature.

Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.

Administration

IV: Administer IV preparation by slow IV infusion over 30 minutes to 3 hours at a final concentration not to exceed 6 mg/mL. Do not administer IM or SubQ. Avoid extravasation.

Oral: Administer on an empty stomach (ie, 1 hour prior to, or 2 hours after meals or antacids) to increase total absorption. The compounded oral suspension must be shaken well before using. May mix contents of capsule with applesauce or jelly.

Storage

Store capsules and intact vials at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); avoid excessive heat (>40°C [104°F]). Protect the intact vials from light. Reconstituted vials are stable for 24 hours at room temperature.

Stability of parenteral admixture at room temperature (25°C [77°F]) is 4 hours for D5W or 24 hours for NS.

Drug Interactions

Abemaciclib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Abemaciclib. Avoid combination

Abiraterone Acetate: CYP3A4 Inducers (Strong) may decrease the serum concentration of Abiraterone Acetate. Management: Avoid whenever possible. If such a combination cannot be avoided, increase abiraterone acetate dosing frequency from once daily to twice daily during concomitant use. Avoid combination

Afatinib: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Afatinib. Management: Per US labeling: if requiring chronic use of P-gp inducers, increase afatinib dose by 10mg as tolerated; reduce to original afatinib dose 2-3 days after stopping P-gp inducers. Per Canadian labeling: avoid combination if possible. Consider therapy modification

Alfentanil: Rifamycin Derivatives may decrease the serum concentration of Alfentanil. Management: Monitor closely for decreased alfentanil effectiveness. Increased alfentanil doses will likely be needed. Alternatively, changing from alfentanil to a different opioid anesthetic (e.g., sufentanil) may also be considered. Consider therapy modification

Amifampridine: May enhance the QTc-prolonging effect of RifAMPin. Avoid combination

Amiodarone: RifAMPin may decrease serum concentrations of the active metabolite(s) of Amiodarone. Specifically, desethylamiodarone concentrations may decrease. RifAMPin may decrease the serum concentration of Amiodarone. Management: Seek alternatives. When used together, monitor closely for decreased amiodarone concentrations/effects. Dose adjustment may be needed. Consider therapy modification

Antifungal Agents (Azole Derivatives, Systemic): May increase the serum concentration of Rifamycin Derivatives. Only rifabutin appears to be affected. Rifamycin Derivatives may decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Management: Avoid these combinations when possible. Voriconazole and isavuconazonium are considered contraindicated. Consider therapy modification

Antihepaciviral Combination Products: CYP3A4 Inducers (Strong) may decrease the serum concentration of Antihepaciviral Combination Products. Avoid combination

Apixaban: CYP3A4 Inducers (Strong) may decrease the serum concentration of Apixaban. Avoid combination

Apremilast: CYP3A4 Inducers (Strong) may decrease the serum concentration of Apremilast. Avoid combination

Aprepitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Aprepitant. Avoid combination

ARIPiprazole: CYP3A4 Inducers (Strong) may decrease the serum concentration of ARIPiprazole. Management: Double the oral aripiprazole dose and closely monitor. Reduce oral aripiprazole dose to 10-15 mg/day (for adults) if the inducer is discontinued. Avoid use of strong CYP3A4 inducers for more than 14 days with extended-release injectable aripiprazole. Consider therapy modification

ARIPiprazole Lauroxil: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Patients taking the 441 mg dose of aripiprazole lauroxil increase their dose to 662 mg if used with a strong CYP3A4 inducer for more than 14 days. No dose adjustment is necessary for patients using the higher doses of aripiprazole lauroxil. Consider therapy modification

Artemether: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Artemether. Specifically, dihydroartemisinin concentrations may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Artemether. Avoid combination

Asunaprevir: RifAMPin may decrease the serum concentration of Asunaprevir. This effect is most likely with longer-term coadministration; single-dose rifampin may increase asunaprevir concentrations. RifAMPin may increase the serum concentration of Asunaprevir. This effect is likely following only single-dose or short-term rifampin administration. Longer-term coadministration is likely to result in decreased asunaprevir concentrations. Avoid combination

Ataluren: RifAMPin may decrease the serum concentration of Ataluren. Monitor therapy

Atazanavir: RifAMPin may decrease the serum concentration of Atazanavir. Avoid combination

Atovaquone: Rifamycin Derivatives may decrease the serum concentration of Atovaquone. Avoid combination

Axitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib. Avoid combination

Barbiturates: Rifamycin Derivatives may increase the metabolism of Barbiturates. Monitor therapy

Bazedoxifene: RifAMPin may decrease the serum concentration of Bazedoxifene. This may lead to loss of efficacy or, if bazedoxifene is combined with estrogen therapy, an increased risk of endometrial hyperplasia. Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Bedaquiline: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bedaquiline. Avoid combination

Benperidol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Benperidol. Monitor therapy

Beta-Blockers: Rifamycin Derivatives may decrease the serum concentration of Beta-Blockers. Exceptions: Atenolol; Carteolol (Ophthalmic); Levobunolol; Metipranolol; Nadolol. Monitor therapy

Boceprevir: RifAMPin may decrease the serum concentration of Boceprevir. Avoid combination

Bortezomib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bortezomib. Avoid combination

Bosentan: RifAMPin may decrease the serum concentration of Bosentan. Following the initial several weeks of concurrent rifampin, this effect is most likely. RifAMPin may increase the serum concentration of Bosentan. This effect is most likely to be observed within the initial few weeks of concurrent therapy (and may be greatest immediately following initiation of the combination). Management: Weekly monitoring of liver function tests during the first 4 weeks of concurrent therapy is recommended, with a return to normal recommended monitoring thereafter as appropriate. Monitor therapy

Bosutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bosutinib. Avoid combination

Brentuximab Vedotin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Monitor therapy

Brentuximab Vedotin: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Monitor therapy

Brexpiprazole: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brexpiprazole. Management: If brexpiprazole is used together with a strong CYP3A4 inducer, the brexpiprazole dose should gradually be doubled over the course of 1 to 2 weeks. Consider therapy modification

Brigatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brigatinib. Avoid combination

Brivaracetam: RifAMPin may decrease the serum concentration of Brivaracetam. Management: Increase the brivaracetam dose by up to 100% (ie, double the dose) if used together with rifampin. Consider therapy modification

Buprenorphine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Buprenorphine. Monitor therapy

BusPIRone: Rifamycin Derivatives may decrease the serum concentration of BusPIRone. Management: The degree to which rifampin alters buspirone concentrations warrants the consideration of an alternative to buspirone that is not metabolized by CYP3A4. If these agents are used together, buspirone dose adjustments may be needed. Consider therapy modification

Cabozantinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cabozantinib. Management: Avoid use of strong CYP3A4 inducers with cabozantinib if possible. If combined, cabozantinib dose adjustments are recommended and vary based on the cabozantinib product used and the indication for use. See monograph for details. Consider therapy modification

Calcifediol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Calcifediol. Monitor therapy

Calcium Channel Blockers: Rifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Management: The labeling for some US and Canadian calcium channel blockers contraindicate use with rifampin, however recommendations vary. Consult appropriate labeling. Exceptions: Clevidipine. Consider therapy modification

Canagliflozin: RifAMPin may decrease the serum concentration of Canagliflozin. Management: Consider increasing canagliflozin dose to 300 mg/day in patients with estimated GFR >60 mL/min/1.73 m2 who tolerate canagliflozin 100 mg/day and require greater glycemic control. Consider alternatives in patients with estimated GFR 45-60 mL/min/1.73 m2. Consider therapy modification

Cannabidiol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabidiol. Monitor therapy

Cannabis: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Monitor therapy

Cariprazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cariprazine. Avoid combination

Caspofungin: RifAMPin may decrease the serum concentration of Caspofungin. Management: Caspofungin prescribing information recommends using a dose of 70 mg daily in adults (or 70 mg/m2, up to a maximum of 70 mg, daily in pediatric patients) who are also receiving rifampin. Consider therapy modification

Celiprolol: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Celiprolol. Monitor therapy

Ceritinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ceritinib. Avoid combination

Chloramphenicol: RifAMPin may increase the metabolism of Chloramphenicol. Consider therapy modification

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination

Citalopram: RifAMPin may decrease the serum concentration of Citalopram. Monitor therapy

Clarithromycin: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Clarithromycin. Clarithromycin may increase the serum concentration of CYP3A4 Inducers (Strong). CYP3A4 Inducers (Strong) may decrease the serum concentration of Clarithromycin. Management: Consider alternative antimicrobial therapy for patients receiving a CYP3A inducer. Drugs that enhance the metabolism of clarithromycin into 14-hydroxyclarithromycin may alter the clinical activity of clarithromycin and may impair clarithromycin efficacy. Consider therapy modification

Clopidogrel: Rifamycin Derivatives may enhance the adverse/toxic effect of Clopidogrel. Specifically,clopidogrel antiplatelet effects may be enhanced. Monitor therapy

CloZAPine: CYP3A4 Inducers (Strong) may decrease the serum concentration of CloZAPine. Avoid combination

Cobicistat: RifAMPin may decrease the serum concentration of Cobicistat. Avoid combination

Cobimetinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cobimetinib. Avoid combination

Copanlisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Copanlisib. Avoid combination

Corticosteroids (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Corticosteroids (Systemic). Exceptions: Hydrocortisone (Systemic); PrednisoLONE (Systemic); PredniSONE. Monitor therapy

Crizotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Crizotinib. Avoid combination

CycloSPORINE (Systemic): Rifamycin Derivatives may increase the metabolism of CycloSPORINE (Systemic). Consider therapy modification

CYP2A6 Substrates (High risk with Inducers): CYP2A6 Inducers (Strong) may increase the metabolism of CYP2A6 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP2B6 Substrates (High risk with Inducers): CYP2B6 Inducers (Moderate) may decrease the serum concentration of CYP2B6 Substrates (High risk with Inducers). Monitor therapy

CYP2C19 Substrates (High risk with Inducers): CYP2C19 Inducers (Strong) may increase the metabolism of CYP2C19 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP2C8 Substrates (High risk with Inducers): CYP2C8 Inducers (Strong) may increase the metabolism of CYP2C8 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP2C9 Substrates (High risk with Inducers): CYP2C9 Inducers (Strong) may increase the metabolism of CYP2C9 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Substrates (High risk with Inducers): CYP3A4 Inducers (Strong) may increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Exceptions: Buprenorphine; Etizolam; HYDROcodone; Zolpidem. Consider therapy modification

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Dabigatran Etexilate. Management: Avoid concurrent use of dabigatran with p-glycoprotein inducers when possible. Closely monitor for decreased levels/effects of dabigatran if concomitantly administering P-glycoprotein inducers, particularly strong inducers. Avoid combination

Daclatasvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Daclatasvir. Avoid combination

Darunavir: RifAMPin may decrease the serum concentration of Darunavir. Avoid combination

Dasabuvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dasabuvir. Avoid combination

Dasabuvir: CYP2C8 Inducers (Strong) may decrease the serum concentration of Dasabuvir. Avoid combination

Dasatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dasatinib. Management: Avoid when possible. If such a combination cannot be avoided, consider increasing dasatinib dose and monitor clinical response and toxicity closely. Consider therapy modification

Deferasirox: RifAMPin may decrease the serum concentration of Deferasirox. Management: Avoid combination when possible; if the combination must be used, consider a 50% increase in initial deferasirox dose, with monitoring of serum ferritin concentrations and clinical responses to guide further dosing. Consider therapy modification

Deflazacort: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Deflazacort. Avoid combination

Delamanid: CYP3A4 Inducers (Strong) may decrease the serum concentration of Delamanid. Avoid combination

Delavirdine: Rifamycin Derivatives may increase the metabolism of Delavirdine. Delavirdine may increase the serum concentration of Rifamycin Derivatives. Specifically, Rifabutin serum concentration may be increased. Avoid combination

Dexamethasone (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Dexamethasone (Systemic). Management: Consider dexamethasone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced steroid efficacy. Consider therapy modification

Diclofenac (Systemic): CYP2C9 Inducers (Strong) may decrease the serum concentration of Diclofenac (Systemic). Monitor therapy

Dienogest: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dienogest. Management: Avoid use of dienogest for contraception when using medications that induce CYP3A4 and for at least 28 days after discontinuation of a CYP3A4 inducer. An alternative form of contraception should be used during this time. Avoid combination

Diethylstilbestrol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Diethylstilbestrol. Monitor therapy

DilTIAZem: RifAMPin may decrease the serum concentration of DilTIAZem. Avoid combination

Disopyramide: RifAMPin may decrease the serum concentration of Disopyramide. Monitor therapy

Dolutegravir: RifAMPin may decrease the serum concentration of Dolutegravir. Management: Increase dolutegravir dose to 50 mg twice daily in adults or children. Consider alternatives to rifampin for INSTI experienced patients with clinically suspected INSTI resistance or certain INSTI associated resistance substitutions. Consider therapy modification

Doxercalciferol: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Doxercalciferol. Monitor therapy

DOXOrubicin (Conventional): CYP3A4 Inducers (Strong) may decrease the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to strong CYP3A4 inducers in patients treated with doxorubicin. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inducers in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification

Doxycycline: RifAMPin may decrease the serum concentration of Doxycycline. Monitor therapy

Dronabinol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronabinol. Monitor therapy

Dronedarone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronedarone. Avoid combination

Edoxaban: RifAMPin may decrease the serum concentration of Edoxaban. Avoid combination

Efavirenz: RifAMPin may decrease the serum concentration of Efavirenz. Management: Increase efavirenz adult dose to 800 mg daily in patients weighing over 50 kg. Consider therapy modification

Eliglustat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Eliglustat. Avoid combination

Eltrombopag: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Monitor therapy

Eluxadoline: RifAMPin may increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with rifampin and monitor patients for increased eluxadoline effects/toxicities. Consider therapy modification

Elvitegravir: RifAMPin may decrease the serum concentration of Elvitegravir. Avoid combination

Enzalutamide: CYP2C8 Inducers (Strong) may decrease the serum concentration of Enzalutamide. Avoid combination

Enzalutamide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Enzalutamide. Management: Consider using an alternative agent that has no or minimal CYP3A4 induction potential when possible. If this combination cannot be avoided, increase the dose of enzalutamide from 160 mg daily to 240 mg daily. Avoid combination

Erlotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Erlotinib. Management: Avoid combination if possible. If combination must be used, increase erlotinib dose by 50 mg increments every 2 weeks as tolerated, to a maximum of 450 mg/day. Consider therapy modification

Esomeprazole: RifAMPin may decrease the serum concentration of Esomeprazole. Avoid combination

Estriol (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Estriol (Systemic). Monitor therapy

Estriol (Topical): CYP3A4 Inducers (Strong) may decrease the serum concentration of Estriol (Topical). Monitor therapy

Estrogen Derivatives (Contraceptive): Rifamycin Derivatives may decrease the serum concentration of Estrogen Derivatives (Contraceptive). Contraceptive failure is possible. Management: Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification

Etoposide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etoposide. Management: When possible, seek alternatives to strong CYP3A4-inducing medications in patients receiving etoposide. If these combinations cannot be avoided, monitor patients closely for diminished etoposide response. Consider therapy modification

Etoposide Phosphate: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etoposide Phosphate. Management: When possible, seek alternatives to strong CYP3A4-inducing medications in patients receiving etoposide phosphate. If these combinations cannot be avoided, monitor patients closely for diminished etoposide phosphate response. Consider therapy modification

Etravirine: Rifamycin Derivatives may decrease the serum concentration of Etravirine. Avoid combination

Everolimus: CYP3A4 Inducers (Strong) may decrease the serum concentration of Everolimus. Management: Avoid concurrent use of strong CYP3A4 inducers, but if strong CYP3A4 inducers cannot be avoided, consider gradually (in 5 mg increments) increasing the everolimus dose from 10 mg/day to 20 mg/day (adult doses). Avoid combination

Evogliptin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Evogliptin. Monitor therapy

Exemestane: CYP3A4 Inducers (Strong) may decrease the serum concentration of Exemestane. Management: Exemestane U.S. product labeling recommends using an increased dose (50 mg/day) in patients receiving concurrent strong CYP3A4 inducers. The Canadian product labeling does not recommend a dose adjustment with concurrent use of strong CYP3A4 inducers. Consider therapy modification

FentaNYL: CYP3A4 Inducers (Strong) may decrease the serum concentration of FentaNYL. Monitor therapy

Fexofenadine: RifAMPin may decrease the serum concentration of Fexofenadine. RifAMPin may increase the serum concentration of Fexofenadine. Monitor therapy

Fimasartan: RifAMPin may increase the serum concentration of Fimasartan. Avoid combination

Flibanserin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Flibanserin. Avoid combination

Fosamprenavir: RifAMPin may decrease the serum concentration of Fosamprenavir. Specifically, concentrations of amprenavir (active metabolite) may be decreased. Avoid combination

Fosaprepitant: RifAMPin may decrease the serum concentration of Fosaprepitant. More specifically, rifampin may decrease concentrations of the active metabolite aprepitant. Monitor therapy

Fosphenytoin: RifAMPin may decrease the serum concentration of Fosphenytoin. Management: Seek alternatives when possible. If used together, monitor closely for decreased serum phenytoin concentrations following rifampin initiation/dose increase, or increased concentrations and toxic effects following rifampin discontinuation/dose decrease. Consider therapy modification

Gefitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Gefitinib. Management: In the absence of severe adverse reactions, increase gefitinib dose to 500 mg daily in patients receiving strong CYP3A4 inducers; resume 250 mg dose 7 days after discontinuation of the strong inducer. Carefully monitor clinical response. Consider therapy modification

Gemfibrozil: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. See separate drug interaction monographs for agents listed as exceptions. Monitor therapy

Gemigliptin: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Gemigliptin. CYP3A4 Inducers (Strong) may decrease the serum concentration of Gemigliptin. Avoid combination

Gestrinone: RifAMPin may decrease the serum concentration of Gestrinone. Monitor therapy

Glecaprevir and Pibrentasvir: RifAMPin may decrease the serum concentration of Glecaprevir and Pibrentasvir. RifAMPin may increase the serum concentration of Glecaprevir and Pibrentasvir. Specifically, a single dose of rifampin may increase glecaprevir/pibrentasvir concentrations, while chronic daily use of rifampin may decrease glecaprevir/pibrentasvir concentrations. Avoid combination

Grazoprevir: RifAMPin may decrease the serum concentration of Grazoprevir. Conversely, single doses of Rifampin may increase Grazoprevir concentrations. Avoid combination

GuanFACINE: CYP3A4 Inducers (Strong) may decrease the serum concentration of GuanFACINE. Management: Increase the guanfacine dose by up to double when initiating concomitant therapy with strong CYP3A4 inducers. Increase guanfacine dose gradually over 1-2 weeks if strong CYP3A4 inducer therapy is just beginning. Consider therapy modification

HMG-CoA Reductase Inhibitors (Statins): Rifamycin Derivatives may decrease the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Consider use of noninteracting antilipemic agents (note: pitavastatin concentrations may increase with rifamycin treatment). Monitor for altered HMG-CoA reductase inhibitor effects. Rifabutin and fluvastatin, or possibly pravastatin, may pose lower risk. Exceptions: Pitavastatin; Rosuvastatin. Consider therapy modification

HYDROcodone: CYP3A4 Inducers (Strong) may decrease the serum concentration of HYDROcodone. Monitor therapy

Hydrocortisone (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Hydrocortisone (Systemic). Monitor therapy

Ibrutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ibrutinib. Avoid combination

Idelalisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Idelalisib. Avoid combination

Ifosfamide: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Ifosfamide. CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Monitor therapy

Imatinib: Rifamycin Derivatives may decrease the serum concentration of Imatinib. Management: Avoid concurrent use of imatinib with the rifamycin derivatives when possible. If such a combination must be used, increase imatinib dose by at least 50% and monitor the patient's clinical response closely. Consider therapy modification

Imatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Imatinib. Management: Avoid concurrent use of imatinib with strong CYP3A4 inducers when possible. If such a combination must be used, increase imatinib dose by at least 50% and monitor the patient's clinical response closely. Consider therapy modification

Indinavir: RifAMPin may decrease the serum concentration of Indinavir. Avoid combination

Irinotecan Products: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Irinotecan Products. Avoid combination

Isavuconazonium Sulfate: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Strong) may decrease isavuconazole serum concentrations. Avoid combination

Isoniazid: Rifamycin Derivatives may enhance the hepatotoxic effect of Isoniazid. Even so, this is a frequently employed combination regimen. Monitor therapy

Itraconazole: CYP3A4 Inducers (Strong) may decrease the serum concentration of Itraconazole. Avoid combination

Ivabradine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivabradine. Avoid combination

Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivacaftor. Avoid combination

Ixabepilone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ixabepilone. Management: Avoid this combination whenever possible. If this combination must be used, a gradual increase in ixabepilone dose from 40 mg/m2 to 60 mg/m2 (given as a 4-hour infusion), as tolerated, should be considered. Consider therapy modification

Ixazomib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ixazomib. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

LamoTRIgine: RifAMPin may increase the metabolism of LamoTRIgine. Monitor therapy

Lapatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lapatinib. Management: If therapy overlap cannot be avoided, consider titrating lapatinib gradually from 1,250 mg/day up to 4,500 mg/day (HER2 positive metastatic breast cancer) or 1,500 mg/day up to 5,500 mg/day (hormone receptor/HER2 positive breast cancer) as tolerated. Avoid combination

Ledipasvir: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Ledipasvir. Avoid combination

Leflunomide: RifAMPin may increase serum concentrations of the active metabolite(s) of Leflunomide. Monitor therapy

Linagliptin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Linagliptin. Management: Strongly consider using an alternative to any strong CYP3A4 inducer in patients who are being treated with linagliptin. If this combination is used, monitor patients closely for evidence of reduced linagliptin effectiveness. Consider therapy modification

Linagliptin: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Linagliptin. Management: Strongly consider using an alternative to any strong P-glycoprotein inducer in patients who are being treated with linagliptin. If this combination is used, monitor patients closely for evidence of reduced linagliptin effectiveness. Consider therapy modification

Lopinavir: RifAMPin may enhance the adverse/toxic effect of Lopinavir. Specifically, the risk of hepatocellular toxicity may be increased. RifAMPin may decrease the serum concentration of Lopinavir. Avoid combination

Losartan: RifAMPin may decrease the serum concentration of Losartan. Monitor therapy

Lumacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Lumefantrine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lumefantrine. Avoid combination

Lurasidone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lurasidone. Avoid combination

Macitentan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Macitentan. Avoid combination

Macrolide Antibiotics: May decrease the metabolism of Rifamycin Derivatives. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. Consider therapy modification

Manidipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Manidipine. Management: Consider avoiding concomitant use of manidipine and strong CYP3A4 inducers. If combined, monitor closely for decreased manidipine effects and loss of efficacy. Increased manidipine doses may be required. Consider therapy modification

Maraviroc: CYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice daily when used with strong CYP3A4 inducers. This does not apply to patients also receiving strong CYP3A4 inhibitors. Do not use maraviroc with strong CYP3A4 inducers in patients with CrCl less than 30 mL/min. Consider therapy modification

Methadone: Rifamycin Derivatives may decrease the serum concentration of Methadone. Management: Seek alternatives when possible. If used concomitantly, monitor closely for symptoms of methadone withdrawal upon rifamycin derivative initiation, and for excess sedation upon rifamycin derivative discontinuation. Consider therapy modification

MethylPREDNISolone: CYP3A4 Inducers (Strong) may decrease the serum concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced steroid efficacy. Consider therapy modification

Midostaurin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Midostaurin. Avoid combination

MiFEPRIStone: CYP3A4 Inducers (Strong) may decrease the serum concentration of MiFEPRIStone. Avoid combination

Mirabegron: RifAMPin may decrease the serum concentration of Mirabegron. Monitor therapy

Mirodenafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Mirodenafil. Management: Consider avoiding the concomitant use of mirodenafil and strong CYP3A4 inducers. If combined, monitor for decreased mirodenafil effects. Mirodenafil dose increases may be required to achieve desired effects. Consider therapy modification

Morphine (Systemic): RifAMPin may decrease the serum concentration of Morphine (Systemic). Monitor therapy

Mycophenolate: Rifamycin Derivatives may decrease the serum concentration of Mycophenolate. Specifically, rifamycin derivatives may decrease the concentration of the active metabolite mycophenolic acid. Avoid combination

Naldemedine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Naldemedine. Avoid combination

Nalmefene: RifAMPin may decrease the serum concentration of Nalmefene. Monitor therapy

Naloxegol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Naloxegol. Avoid combination

Nelfinavir: RifAMPin may decrease the serum concentration of Nelfinavir. Avoid combination

Neratinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Neratinib. Avoid combination

Netupitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Netupitant. Avoid combination

Nevirapine: RifAMPin may decrease the serum concentration of Nevirapine. Management: Avoid whenever possible. When this combination is necessary, use immediate-release nevirapine (avoid extended-release nevirapine) at a dose of 200 mg twice daily with no lead-in (per adult/adolescent HIV guidelines). Monitor nevirapine response closely. Consider therapy modification

NIFEdipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of NIFEdipine. Avoid combination

Nilotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib. Avoid combination

NiMODipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of NiMODipine. Avoid combination

Nintedanib: Combined Inducers of CYP3A4 and P-glycoprotein may decrease the serum concentration of Nintedanib. Avoid combination

Nisoldipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nisoldipine. Avoid combination

Nitrazepam: RifAMPin may decrease the serum concentration of Nitrazepam. Management: Monitor closely for reduced effects of nitrazepam. When possible, consider alternatives to one of these drugs, or increases in initial nitrazepam doses. Consider therapy modification

Olaparib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Olaparib. Avoid combination

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: CYP2C8 Inducers (Strong) may decrease the serum concentration of Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir. Specifically, the serum concentrations of dasabuvir may decrease significantly. Avoid combination

Omeprazole: RifAMPin may decrease the serum concentration of Omeprazole. Avoid combination

Osimertinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Osimertinib. Consider therapy modification

OXcarbazepine: RifAMPin may decrease serum concentrations of the active metabolite(s) of OXcarbazepine. Specifically, concentrations of the major active 10-monohydroxy metabolite may be reduced. Monitor therapy

OxyCODONE: RifAMPin may decrease the serum concentration of OxyCODONE. Monitor therapy

Palbociclib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Palbociclib. Avoid combination

Paliperidone: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease the serum concentration of Paliperidone. Management: Avoid using the 3-month extended-release injectable suspension (Invega Trinza) with inducers of both CYP3A4 and P-glycoprotein during the 3-month dosing interval if possible. If combination is necessary, consider using extended-release tablets. Consider therapy modification

Panobinostat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Panobinostat. Avoid combination

PAZOPanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of PAZOPanib. Avoid combination

Perampanel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used concurrently with moderate and strong CYP3A4 inducers. Consider therapy modification

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Phenytoin: RifAMPin may decrease the serum concentration of Phenytoin. Management: Seek alternatives when possible. If used together, monitor closely for decreased serum phenytoin concentrations following rifampin initiation/dose increase, or increased concentrations and toxic effects following rifampin discontinuation/dose decrease. Consider therapy modification

Pimavanserin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pimavanserin. Monitor therapy

Pitavastatin: Rifamycin Derivatives may increase the serum concentration of Pitavastatin. Management: Limit pitavastatin dose to a maximum of 2 mg/day with concurrent rifampin. Consider therapy modification

Pitolisant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pitolisant. Monitor therapy

PONATinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of PONATinib. Avoid combination

Prasugrel: RifAMPin may diminish the antiplatelet effect of Prasugrel. Monitor therapy

Praziquantel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Praziquantel. Management: Avoid concomitant use of praziquantel with strong CYP3A4 inducers. Discontinue rifampin 4 weeks prior to initiation of praziquantel therapy. Rifampin may be resumed the day following praziquantel completion. Avoid combination

PrednisoLONE (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of PrednisoLONE (Systemic). Monitor therapy

PredniSONE: CYP3A4 Inducers (Strong) may decrease the serum concentration of PredniSONE. Monitor therapy

Progestins (Contraceptive): Rifamycin Derivatives may decrease the serum concentration of Progestins (Contraceptive). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification

Propacetamol: RifAMPin may increase the metabolism of Propacetamol. . This may 1) diminish the desired effects of propacetamol; and 2) increase the risk of liver damage. Monitor therapy

Propafenone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Propafenone. Monitor therapy

Propofol: RifAMPin may enhance the hypotensive effect of Propofol. Management: Note that use of propofol in a patient who has been taking rifampin may result in clinically significant hypotension. If possible, avoid use of this combination. Consider therapy modification

Prothionamide: RifAMPin may enhance the hepatotoxic effect of Prothionamide. Management: Avoid concomitant use of prothionamide and rifampin if possible. If combined use is considered necessary, monitor patients closely for signs and symptoms of hepatotoxicity (eg, jaundice, elevations in liver function tests). Consider therapy modification

Pyrazinamide: May enhance the hepatotoxic effect of RifAMPin. Severe (even fatal) liver injury has been reported in patients receiving these 2 drugs as a 2-month treatment regimen for latent TB infection. Consider therapy modification

QUEtiapine: CYP3A4 Inducers (Strong) may decrease the serum concentration of QUEtiapine. Management: An increase in quetiapine dose (as much as 5 times the regular dose) may be required to maintain therapeutic benefit. Reduce the quetiapine dose back to the previous/regular dose within 7-14 days of discontinuing the inducer. Consider therapy modification

QuiNIDine: Rifamycin Derivatives may decrease the serum concentration of QuiNIDine. Management: Consider alternatives to combination treatment with quinidine and rifampin due to large potential decreases in quinidine concentrations. Monitor for decreased quinidine concentrations/effects with initiation/dose increase of any rifamycin derivative. Consider therapy modification

QuiNINE: RifAMPin may decrease the serum concentration of QuiNINE. Avoid combination

Radotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Radotinib. Management: Consider alternatives to this combination when possible as the risk of radotinib treatment failure may be increased. Consider therapy modification

Raltegravir: RifAMPin may decrease the serum concentration of Raltegravir. Management: Increase raltegravir dose to 800 mg twice daily (adult dose) when used concomitantly with rifampin. Concurrent use of rifampin with once-daily raltegravir (Isentress HD) is not recommended. Consider therapy modification

Ramelteon: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ramelteon. Monitor therapy

Ranolazine: RifAMPin may decrease the serum concentration of Ranolazine. Avoid combination

Reboxetine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Reboxetine. Monitor therapy

Regorafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Regorafenib. Avoid combination

Repaglinide: RifAMPin may decrease the serum concentration of Repaglinide. Management: Consider alternatives to this combination. Dose timing may substantially affect this interaction; in clinical studies, the lowest magnitude of interaction was seen when repaglinide was given 1 h after rifampin (compared to 0, 12, or 24 h). Consider therapy modification

Ribociclib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ribociclib. Avoid combination

Rilpivirine: Rifamycin Derivatives may decrease the serum concentration of Rilpivirine. Avoid combination

Ritonavir: RifAMPin may decrease the serum concentration of Ritonavir. Avoid combination

Rivaroxaban: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rivaroxaban. Avoid combination

Roflumilast: RifAMPin may decrease the serum concentration of Roflumilast. Management: Roflumilast U.S. prescribing information recommends against combining rifampin with roflumilast. The Canadian product monograph makes no such recommendation but notes that rifampin may reduce roflumilast therapeutic effects. Avoid combination

Rolapitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rolapitant. Management: Avoid rolapitant use in patients requiring chronic administration of strong CYP3A4 inducers. Monitor for reduced rolapitant response and the need for alternative or additional antiemetic therapy even with shorter-term use of such inducers. Consider therapy modification

RomiDEPsin: RifAMPin may increase the serum concentration of RomiDEPsin. Avoid combination

Saquinavir: RifAMPin may enhance the adverse/toxic effect of Saquinavir. Specifically, the risk of hepatocellular toxicity may be increased. RifAMPin may decrease the serum concentration of Saquinavir. Avoid combination

SAXagliptin: CYP3A4 Inducers (Strong) may decrease the serum concentration of SAXagliptin. Monitor therapy

Selexipag: RifAMPin may decrease serum concentrations of the active metabolite(s) of Selexipag. Consider therapy modification

Sertraline: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sertraline. Monitor therapy

Simeprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Simeprevir. Avoid combination

Sirolimus: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sirolimus. Management: Avoid concomitant use of strong CYP3A4 inducers and sirolimus if possible. If combined, monitor for reduced serum sirolimus concentrations. Sirolimus dose increases will likely be necessary to prevent subtherapeutic sirolimus levels. Consider therapy modification

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Sofosbuvir: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Sofosbuvir. Avoid combination

Sonidegib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sonidegib. Avoid combination

SORAfenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of SORAfenib. Avoid combination

SUFentanil: CYP3A4 Inducers (Strong) may decrease the serum concentration of SUFentanil. Monitor therapy

Sulfonylureas: RifAMPin may decrease the serum concentration of Sulfonylureas. Management: Seek alternatives to these combinations when possible. Monitor closely for diminished therapeutic effects of sulfonylureas if rifampin is initiated/dose increased, or enhanced effects if rifampin is discontinued/dose decreased. Consider therapy modification

SUNItinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of SUNItinib. Management: Avoid when possible. If such a combination cannot be avoided, consider increasing sunitinib dose and monitor clinical response and toxicity closely. Consider therapy modification

Suvorexant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Suvorexant. Avoid combination

Tacrolimus (Systemic): Rifamycin Derivatives may decrease the serum concentration of Tacrolimus (Systemic). Management: Consider alternatives when possible. If these combination are used, monitor for reduced tacrolimus concentrations/effects following rifamycin initiation/dose increase, or increased concentrations/effects following rifamycin discontinuation/dose decrease. Consider therapy modification

Tadalafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tadalafil. Management: Erectile dysfunction: monitor for decreased effectiveness - no standard dose adjustments recommended. Avoid use of tadalafil for pulmonary arterial hypertension in patients receiving a strong CYP3A4 inducer. Consider therapy modification

Tamoxifen: Rifamycin Derivatives may increase the metabolism of Tamoxifen. Consider therapy modification

Tasimelteon: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tasimelteon. Avoid combination

Telaprevir: RifAMPin may decrease the serum concentration of Telaprevir. Avoid combination

Temsirolimus: Rifamycin Derivatives may decrease the serum concentration of Temsirolimus. Rifamycins will likely cause an even greater decrease in the concentration of the active metabolite sirolimus. Management: Temsirolimus prescribing information recommends against coadministration with strong CYP3A4 inducers such as rifampin; however, if concurrent therapy is necessary, an increase in temsirolimus adult dose to 50 mg/week should be considered. Consider therapy modification

Temsirolimus: CYP3A4 Inducers (Strong) may decrease the serum concentration of Temsirolimus. Management: Consider increasing the dose of temsirolimus to 50 mg IV/week (from 25 mg IV/week) if a concomitant CYP3A4 strong inducer is necessary. Consider therapy modification

Tenofovir Alafenamide: RifAMPin may decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Terbinafine (Systemic): RifAMPin may decrease the serum concentration of Terbinafine (Systemic). Monitor therapy

Teriflunomide: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Monitor therapy

Tetrahydrocannabinol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tetrahydrocannabinol. Monitor therapy

Thiazolidinediones: RifAMPin may increase the metabolism of Thiazolidinediones. Management: Consider alternatives to the concomitant use of rifampin with thiazolidinedione antidiabetic agents. Monitor patients receiving these combinations for decreased effects of the thiazolidinedione derivative. Consider therapy modification

Thyroid Products: RifAMPin may decrease the serum concentration of Thyroid Products. Monitor therapy

TiaGABine: CYP3A4 Inducers (Strong) may decrease the serum concentration of TiaGABine. Management: Approximately 2-fold higher tiagabine doses and a more rapid dose titration will likely be required in patients concomitantly taking a strong CYP3A4 inducer. Consider therapy modification

Ticagrelor: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Strong) may decrease the serum concentration of Ticagrelor. Avoid combination

Tipranavir: RifAMPin may decrease the serum concentration of Tipranavir. Avoid combination

Tofacitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tofacitinib. Avoid combination

Tolvaptan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tolvaptan. Management: If concurrent use is necessary, increased doses of tolvaptan (with close monitoring for toxicity and clinical response) may be needed. Avoid combination

Toremifene: CYP3A4 Inducers (Strong) may decrease the serum concentration of Toremifene. Avoid combination

Trabectedin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Trabectedin. Avoid combination

Treprostinil: CYP2C8 Inducers (Strong) may decrease the serum concentration of Treprostinil. Monitor therapy

Tropisetron: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tropisetron. Monitor therapy

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Udenafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Udenafil. Monitor therapy

Ulipristal: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ulipristal. Avoid combination

Valbenazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Valbenazine. Avoid combination

Valproate Products: RifAMPin may decrease the serum concentration of Valproate Products. Consider therapy modification

Vandetanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vandetanib. Avoid combination

Velpatasvir: CYP2B6 Inducers (Moderate) may decrease the serum concentration of Velpatasvir. Avoid combination

Velpatasvir: CYP2C8 Inducers (Strong) may decrease the serum concentration of Velpatasvir. Avoid combination

Velpatasvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Velpatasvir. Avoid combination

Velpatasvir: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Velpatasvir. Avoid combination

Vemurafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vemurafenib. Management: Avoid concurrent use of vemurafenib with a strong CYP3A4 inducer and replace with another agent when possible. If a strong CYP3A4 inducer is indicated and unavoidable, the dose of vemurafenib may be increased by 240 mg (1 tablet) as tolerated. Consider therapy modification

Venetoclax: CYP3A4 Inducers (Strong) may decrease the serum concentration of Venetoclax. Avoid combination

Vilazodone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vilazodone. Management: Consider increasing vilazodone dose by as much as 2-fold (do not exceed 80 mg/day), based on response, in patients receiving strong CYP3A4 inducers for > 14 days. Reduce to the original vilazodone dose over 1-2 weeks after inducer discontinuation. Consider therapy modification

VinCRIStine (Liposomal): CYP3A4 Inducers (Strong) may decrease the serum concentration of VinCRIStine (Liposomal). Avoid combination

VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of VinCRIStine (Liposomal). Avoid combination

Vinflunine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vinflunine. Avoid combination

Vitamin K Antagonists (eg, warfarin): Rifamycin Derivatives may increase the metabolism of Vitamin K Antagonists. Monitor therapy

Vorapaxar: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vorapaxar. Avoid combination

Voriconazole: May increase the serum concentration of Rifamycin Derivatives. Rifamycin Derivatives may decrease the serum concentration of Voriconazole. Avoid combination

Vortioxetine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vortioxetine. Management: Consider increasing the vortioxetine dose to no more than 3 times the original dose when used with a strong drug metabolism inducer for more than 14 days. The vortioxetine dose should be returned to normal within 14 days of stopping the strong inducer. Consider therapy modification

Voxilaprevir: RifAMPin may increase the serum concentration of Voxilaprevir. Specifically, a single dose of rifampin may increase voxilaprevir concentrations, while chronic daily use of rifampin may decrease voxilaprevir concentrations. RifAMPin may decrease the serum concentration of Voxilaprevir. Avoid combination

Zaleplon: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zaleplon. Management: Consider the use of an alternative hypnotic that is not metabolized by CYP3A4 in patients receiving strong CYP3A4 inducers. If zalephon is combined with a strong CYP3A4 inducer, monitor for decreased effectiveness of zaleplon. Consider therapy modification

Zidovudine: Rifamycin Derivatives may decrease the serum concentration of Zidovudine. Monitor therapy

Zolpidem: RifAMPin may decrease the serum concentration of Zolpidem. Avoid combination

Zuclopenthixol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zuclopenthixol. Monitor therapy

Test Interactions

May interfere with urine detection of opioids (false-positive); positive Coombs' reaction [direct], rifampin inhibits standard assay's ability to measure serum folate and B12; transient increase in LFTs and decreased biliary excretion of contrast media

Adverse Reactions

>10%: Hepatic: Increased liver enzymes (≤14%)

1% to 10%:

Dermatologic: Skin rash (1% to 5%)

Gastrointestinal: Abdominal cramps (1% to 2%), anorexia (1% to 2%), diarrhea (1% to 2%), epigastric distress (1% to 2%), flatulence (1% to 2%), heartburn (1% to 2%), nausea (1% to 2%), pseudomembranous colitis (1% to 2%), pancreatitis (1% to 2%), vomiting (1% to 2%)

Frequency not defined:

Cardiovascular: Edema, flushing

Central nervous system: Ataxia, behavioral changes, confusion, dizziness, drowsiness, fatigue, headache, lack of concentration, numbness, psychosis, sore mouth

Dermatologic: Erythema multiforme, pemphigoid reaction, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, vasculitis

Endocrine & metabolic: Adrenocortical insufficiency, increased uric acid, menstrual disease

Gastrointestinal: Glossalgia

Genitourinary: Hemoglobinuria, hematuria

Hematologic & oncologic: Decreased hemoglobin, disseminated intravascular coagulation, eosinophilia, hemolysis, hemolytic anemia, leukopenia, thrombocytopenia (especially with high-dose therapy)

Hepatic: Jaundice

Immunologic: DRESS Syndrome

Neuromuscular & skeletal: Myalgia, osteomalacia, weakness

Ophthalmic: Conjunctivitis (exudative), visual disturbance

Renal: Acute renal failure, increased blood urea nitrogen, interstitial nephritis

Respiratory: Flu-like symptoms

Miscellaneous: Fever

<1%, postmarketing, and/or case reports: Agranulocytosis, anaphylaxis, hepatitis

Warnings/Precautions

Concerns related to adverse effects:

• Flu-like syndrome: Regimens of >600 mg once or twice weekly in adults have been associated with a high incidence of adverse reactions including a flu-like syndrome.

• Hematologic effects: May cause thrombocytopenia, leukopenia, or anemia with regimens >600 mg once or twice weekly in adults.

• Hepatotoxicity: May cause hepatic dysfunction; fatal cases have occurred in patients with hepatic disease taking rifampin with other hepatotoxic agents. Closely monitor hepatic function and discontinue use if hepatocellular damage occurs.

• Hyperbilirubinemia: Hyperbilirubinemia may occur early in therapy as a result of competition between rifampin and bilirubin for excretory pathways in the liver. Discontinue therapy if hyperbilirubinemia occurs in conjunction with clinical symptoms or any signs of significant hepatocellular damage develop.

• Hypersensitivity: Hypersensitivity reactions, including severe and potentially fatal reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, have occurred with anti-tuberculosis therapy. Signs and symptoms of hypersensitivity reactions may include fever, rash, urticaria, angioedema, hypotension, acute bronchospasm, conjunctivitis, thrombocytopenia, neutropenia, elevated liver transaminases, or flu-like syndrome. Monitor patients for signs/symptoms of hypersensitivity; discontinue therapy if signs/symptoms suggestive of hypersensitivity (eg, fever, lymphadenopathy, eosinophilia, liver abnormalities) occur, even if rash is not evident.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Alcoholism: Use with caution in patients with a history of alcoholism (even if ethanol consumption is discontinued during therapy).

• Diabetes mellitus: Use with caution in patients with diabetes mellitus; management of diabetes may be more difficult in patients taking rifampin.

• Hepatic impairment: Use with caution and close monitoring in patients with hepatic impairment.

• Meningococcal disease: Do not use for treatment of meningococcal disease, only for short-term treatment of asymptomatic carrier states.

• Porphyria: Use with caution in patients with porphyria; exacerbations have been reported due to enzyme-inducing properties.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate administration: Do not administer IV form via IM or SubQ routes; restart infusion at another site if extravasation occurs.

• Compliance: Monitor for compliance in patients on intermittent therapy.

• Contact lenses: Remove soft contact lenses during therapy since permanent staining may occur.

• Red/orange discoloration: Urine, feces, saliva, sweat, tears, and CSF may be discolored to red/orange.

Monitoring Parameters

Periodic (baseline and every 2 to 4 weeks during therapy) monitoring of liver function (AST, ALT, bilirubin), CBC, mental status, sputum culture, chest x-ray 2 to 3 months into treatment

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Rifampin crosses the human placenta. Postnatal hemorrhages have been reported in the infant and mother with administration during the last few weeks of pregnancy.

Maternal treatment of tuberculosis is recommended when the probability of maternal disease is moderate to high due to the risk of infection to the fetus (ATC/CDC 2003). Rifampin may be considered for use as an alternative agent in pregnant women for the treatment of mild illness due to human anaplasmosis (also known as human granulocytic anaplasmosis [HGA]); case reports have shown favorable maternal and pregnancy outcomes in small numbers of rifampin-treated pregnant women (CDC [Biggs 2016]).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience diarrhea, dizziness, fatigue, flatulence, headache, nausea, vomiting, lack of appetite, heartburn, abdominal cramps, or body fluid discoloration. Have patient report immediately to prescriber signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), severe loss of strength and energy, confusion, flu-like symptoms, chills, pharyngitis, joint pain, joint edema, muscle pain, muscle weakness, shortness of breath, swelling of arms or legs, bruising, bleeding, change in balance, difficulty focusing, behavioral changes, menstrual changes, vision changes, severe injection site redness, pain, edema, or irritation, or signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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