Rifampin

Rifampin is an antibiotic that fights bacteria and prevents it from spreading in your body.

Rifampin is used to treat or prevent tuberculosis (TB).

Rifampin may also be used to reduce certain bacteria in your nose and throat that could cause meningitis or other infections. Rifampin prevents you from spreading these bacteria to other people, but this medicine will not treat an active meningitis infection.

Rifampin may also be used for purposes not listed in this medication guide.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Contraindications

• Known hypersensitivity to rifampin or other rifamycins (rifabutin, rifapentine).161

Warnings/Precautions

Warnings

Hepatic dysfunction reported.161 Fatalities associated with jaundice reported in patients with preexisting liver disease or receiving other hepatotoxic agents.161 Discontinue if signs of hepatocellular damage occur.161 (See Hepatic Impairment under Cautions.)

Hyperbilirubinemia (resulting from competition between rifampin and bilirubin for excretory pathways in the liver) can occur shortly after initiation of rifampin therapy.161 An isolated report of a moderate increase in bilirubin and/or transaminase concentrations is not an indication to interrupt rifampin therapy; the decision to discontinue the drug should be made after repeating the tests, noting trends in the concentrations, and considering the patient’s clinical condition.161

Transient abnormalities in liver function tests (e.g., elevated serum bilirubin, alkaline phosphatase, serum transaminases) and reduced biliary excretion of contrast media used for visualization of the gallbladder reported; the gallbladder test should be performed prior to the morning dose of rifampin.161

Severe liver injuries, including some fatalities, have been reported in patients receiving a 2-drug regimen of pyrazinamide and rifampin (once daily for 2 months) for the treatment of LTBI.177 222 225 257 A 2-drug regimen of rifampin and pyrazinamide should be considered for treatment of LTBI only in carefully selected patients with close monitoring and only if potential benefits outweigh the risk of hepatotoxicity and death.257 If a rifampin and pyrazinamide regimen is used, monitor serum aminotransferases and bilirubin concentrations at baseline and at 2, 4, 6, and 8 weeks; assess patient at 2, 4, 6 and 8 weeks for adherence, tolerance, and adverse effects.257 Permanently discontinue in asymptomatic patients with an aminotransferase concentration >5 times the ULN, in patients with symptoms of hepatitis who have an aminotransferase concentration >ULN, and in patients who have serum bilirubin concentrations >ULN (regardless of the presence or absence of symptoms).257

There have been isolated reports of exacerbation of porphyria in patients receiving rifampin; rifampin has enzyme-inducing properties, including induction of delta amino levulinic acid synthetase.161

Sensitivity Reactions

Hypersensitivity reactions characterized by flu-like syndrome with episodes of fever, chills, and sometimes with headache, dizziness, and bone pain reported.115 Edema of the face and extremities, decrease in blood pressure, shock, or dyspnea (sometimes accompanied by wheezing) also reported.115 161

Pruritus, urticaria, acneiform eruptions,154 155 rash, pemphigoid reactions, erythema multiforme including Stevens-Johnson syndrome,154 156 161 toxic epidermal necrolysis,161 vasculitis,161 eosinophilia, sore mouth, sore tongue,154 exfoliative dermatitis,153 and exudative conjunctivitis reported.a Anaphylaxis reported rarely.154 161

Some cutaneous reactions, including flushing and pruritus (with or without rash), are mild and self-limiting and do not appear to be hypersensitivity reactions.161 More serious cutaneous reactions occur less frequently and do appear to be hypersensitivity reactions.161

Rifampin sterile powder for injection contains sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.a

General Precautions

Possible enhanced metabolism of endogenous substrates (e.g., cortisol, thyroid hormones, vitamin D) secondary to hepatic microsomal enzyme induction.108 161

Decreased plasma concentrations of 25-hydroxy vitamin D (the major circulating metabolite of vitamin D) and/or 1α,25-dihydroxy vitamin D accompanied by decreased plasma calcium and phosphate concentrations and increased parathyroid hormone concentrations reported.161 223 b

Urine, sputum, sweat, or tears may have a reddish coloration.161 172 258 259 b Soft contact lenses may become permanently stained.161 172 258 b

Obtain baseline measurements of liver function (hepatic enzymes, bilirubin) and hematologic status (CBC, platelet count) in adults receiving rifampin for treatment of TB; baseline tests not considered necessary in pediatric patients unless a complicating condition is known or suspected.161

Evaluate patient at least monthly during therapy; question patient about adverse effects.161 Follow up all abnormalities, including laboratory monitoring, if indicated.161 Routine laboratory monitoring for drug-induced toxicity generally not necessary in patients with normal baseline test results.161

When the fixed-combination preparations (Rifamate containing rifampin, isoniazid, and pyrazinamide or Rifater containing rifampin and isoniazid) are used, observe the usual precautions and contraindications associated with all drugs in the preparation.172 259 Use these preparations only when all drugs contained in the fixed combination are indicated.258

To reduce development of drug-resistant bacteria and maintain effectiveness of rifampin and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.161

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.161 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.161

If used to eliminate nasopharyngeal carriage of N. meningitidis or for postexposure prophylaxis to prevent meningococcal disease, a short-term rifampin regimen (e.g., 2-day regimen) should be used since resistant strains of N. meningitidis may rapidly emerge during prolonged rifampin treatment.161 Rifampin should be used only when the risk of meningococcal disease is high.161 Appropriate diagnostic laboratory procedures (e.g., serotyping, in vitro susceptibility testing) should be performed.161

When used for treatment of TB, there is some evidence that rifampin dosage >600 mg once daily or twice weekly is associated with a higher incidence of adverse reactions, including flu syndrome (fever, chills, malaise), hematopoietic reactions (leukopenia, thrombocytopenia, acute hemolytic anemia), cutaneous, GI, and hepatic reactions, shortness of breath, shock, anaphylaxis, and renal failure.161 Regimens using rifampin 600 mg twice weekly (in conjunction with isoniazid 15 mg/kg) are better tolerated.161

Should not be used alone for the treatment of active TB; must be used in conjunction with other antituberculosis agents.258

Clinical specimens for microscopic examination and mycobacterial cultures and in vitro susceptibility testing should be obtained prior to initiation of antituberculosis therapy and periodically during treatment to monitor therapeutic response.258 The antituberculosis regimen should be modified as needed.258 Patients with positive cultures after 4 months of treatment should be considered to have failed treatment (usually as the result of noncompliance or drug-resistant TB).258

Compliance with the full course of antituberculosis therapy and all drugs included in the multiple-drug regimen is critical.258 Missed doses increase the risk of treatment failure and increase the risk that M. tuberculosis will develop resistance to the antituberculosis regimen.258

To ensure compliance, ATS, CDC, IDSA, and AAP recommend that directly observed (supervised) therapy (DOT) be used for treatment of active (clinical) TB and for treatment of LTBI whenever possible, especially when intermittent regimens are used, when the patient is immunocompromised or infected with HIV, or when drug-resistant M. tuberculosis is involved.176 215 269 r s u v

When used for the treatment of active (clinical) TB in HIV-infected individuals with CD4+ T-cell counts <100/mm3, once- or twice-weekly rifampin regimens are associated with an increased risk of emergence of resistant M. tuberculosis.r CDC and others recommend these patients receive once-daily or 3-times weekly rifampin regimens.100 r

Specific Populations

Category C.161

A regimen of isoniazid, rifampin, and ethambutol is recommended by ATS, CDC, IDSA, and AAP for treatment of active TB in pregnant women.176 258 r

Rifampin administration during the last few weeks of pregnancy can cause postnatal hemorrhages in the mother and infant; treat such hemorrhages with vitamin K.161 Some experts recommend prophylactic administration of vitamin K (10 mg) to neonates born to women who received rifampin during pregnancy.r

Distributed into milk.176 Discontinue nursing or the drug.161

Used in pediatric patients for the treatment of active (clinical) TB and treatment of LTBI,167 169 171 176 to eliminate nasopharyngeal carriage of N. meningitidis,161 163 176 179 187 for chemoprophylaxis against meningococcal disease†176 179 187 or H. influenzae type b (Hib) infection†,102 103 104 134 135 136 137 138 144 145 176 and for treatment of leprosy†.198 204 206

Rifater: Safety and efficacy not established in children <15 years of age; the ratio of rifampin and isoniazid in this preparation may not be appropriate for this age group.172

Rifamate: Safety and efficacy not established in pediatric patients.259

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.161 Clinical experience has not identified differences in response relative to younger adults.161

Use caution.161

Use in patients with impaired liver function only when clearly necessary and only under strict medical supervision; fatalities associated with jaundice reported in patients with liver disease.161

Monitor liver function (ALT and AST) before initiating therapy and every 2–4 weeks during therapy in patients with impaired hepatic function.161 Discontinue if signs of hepatocellular damage occur.161

Exacerbation of porphyria reported.161

Common Adverse Effects

GI effects (heartburn, epigastric distress, nausea, vomiting, anorexia, abdominal cramps, flatulence, diarrhea).161 a

• A rifamycin structurally and pharmacologically similar to other rifamycins (rifabutin, rifapentine).

• Usually bactericidal.161

• Suppresses initiation of chain formation for RNA synthesis in susceptible bacteria by inhibiting DNA-dependent RNA polymerase.161 a

• Spectrum of activity includes some gram-positive and -negative bacteria and some Mycobacterium.161

• Mycobacterium: Active in vitro against M. tuberculosis,a M. bovis,a M. marinum,a dd M. kansasii,a and some strains of M. fortuituma and M. avium complex.a Also active against M. leprae.a

• Gram-positive bacteria: Active against S. aureus, S. epidermidis, and Bacillus anthracis.161 252

• Gram-negative bacteria: Active against N. meningitidis,161 H. influenzae, Brucella melitensis, and L. pneumophila.161 230 241 Also active against Ehrlichia canis, E. chaffeensis, and Anaplasma phagocytophilum.l

• Natural and acquired resistance to rifampin observed in vitro and in vivo in M. tuberculosis, M. kansasii,165 and N. meningitidis.189 190 Strains of M. leprae resistant to rifampin reported rarely.128 133 jj β-lactamase production has no effect on rifampin activity.161

• Cross-resistance occurs between rifampin and other rifamycin derivatives (rifabutin, rifapentine).161 258 a M. tuberculosis resistant to rifampin usually are resistant to both rifabutin and rifapentine; only rarely are rifampin-resistant strains susceptible to rifabutin.258

• M. tuberculosis resistant to both isoniazid and rifampin (MDR TB) occurs.w x y z There also have been recent reports of extensively drug-resistant (XDR) TB in various parts of the world, including the US.w x z XDR TB is caused by M. tuberculosis resistant to rifampin and isoniazid (multiple-drug resistant strains) that also are resistant to a fluoroquinolone and at least one parenteral second-line antimycobacterial (capreomycin, kanamycin, amikacin).w x z

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)

• Antitubercular Agent
• Rifamycin

≤24 hours

Half-Life Elimination

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

Protein Binding

80%

Refer to adult dosing.

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]).

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]).

Patients with a positive tuberculin test without evidence of disease: 10 mg/kg (not to exceed 600 mg) orally or IV once a day for 4 months

While isoniazid monotherapy is usually sufficient for treatment with a positive tuberculin skin test and no signs of disease, rifampin may be used if isoniazid resistance is suspected or if isoniazid is not tolerated.

600 mg orally or IV once a day for 4 consecutive days

600 mg orally or IV once a day for 14 days

May be added to erythromycin therapy

Treatment of asymptomatic carriers of Neisseria meningitidis to eliminate meningococci from the nasopharynx:
Less than 1 month: 5 mg/kg orally or IV every 12 hours for 2 days
1 month or older: 10 mg/kg (not to exceed 600 mg/dose) orally or IV every 12 hours for 2 days

Infants, children, and adolescents:
The ATS, CDC, and AAP recommend: 10 to 20 mg/kg/day (up to 600 mg/day) orally or IV for 4 to 6 months