RIFADIN (Brand for RIFAMPIN)

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Tuberculosis patients
-Directly observed therapy (DOT) is recommended for all children, adolescents with living HIV, and any regimen consisting of intermittent therapy.

Route-Specific Administration

Oral Administration
-To ensure maximum absorption, administer at least 1 hour before or 2 hours after a meal with a full glass of water.
-Concurrent antacid administration may decrease the absorption of rifampin; administer rifampin at least 1 hour before ingestion of antacids.
-For patients unable to take the capsules, the contents of the capsules may be mixed with applesauce.
Oral Liquid Formulations
-Shake well before each use. Use a calibrated device to measure the appropriate oral dosage.

Extemporaneous Compounding-Oral
Extemporaneous 10 mg/mL oral suspension

-A 1% suspension (10 mg/mL) may be made by combining the contents of four 300-mg or eight 150-mg rifampin capsules with 20 mL of Simple Syrup, Simple Syrup NF, Raspberry syrup, or Syrpalta and shaking vigorously or, alternatively, mixing via trituration (preferred).
-Further dilute this suspension with 100 mL of the chosen diluent.
-Storage: The suspension is stable for 4 weeks when stored in a light-resistant container at room temperature or under refrigeration.
-Shake well before each administration.

Extemporaneous 25 mg/mL oral suspension*
-A 25 mg/mL suspension may be made by combining the contents of ten 300 mg capsules with 20 mL of a 1:1 mixture of Ora-Plus and Ora-Sweet (or Ora-Sweet NF) or cherry syrup in a mortar and mixing into a uniform paste.
-Add the vehicle in geometric proportions and mix thoroughly after each addition.
-Transfer the contents to a bottle and further dilute to a final volume of 120 mL.
-Storage: The suspension is stable for 28 days when stored in a light-resistant container at room temperature or under refrigeration.
-Shake well before each administration.

Extemporaneous 10 mg/mL oral suspension using IV rifampin*
-A 10 mg/mL suspension may be made by mixing 10 mL of IV rifampin solution (60 mg/mL) with 50 mL of Simple Syrup (60 mL total volume).
-Storage: The suspension is stable for 56 days under refrigeration (4 degrees C).



Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Reconstitution
-Reconstitute each 600 mg vial with 10 mL of Sterile Water for Injection to give a concentration of 60 mg/mL. Swirl gently to dissolve.
-Storage: Reconstituted solution is stable for up to 30 hours at room temperature.

Dilution
-Dilute appropriate dose in 5% Dextrose Injection or 0.9% Sodium Chloride Injection to a maximum concentration of 6 mg/mL. Other infusion solutions are not recommended.
-Storage: Solutions diluted in 5% Dextrose Injection are stable for up to 8 hours at room temperature. Solutions diluted in 0.9% Sodium Chloride Injection are stable for up to 6 hours at room temperature. However, a compatibility study showed that rifampin 0.1 mg/mL in 0.9% Sodium Chloride Injection underwent up to 7% loss in 8 hours and up to 13% loss in 24 hours at room temperature. Under refrigeration, about 7% loss occurred in 3 days. In 5% Dextrose Injection, rifampin exhibited 5% loss in 8 hours and up to 17% loss in 24 hours at room temperature. Under refrigeration, about 8% loss occurred in 3 days.

Intermittent IV Infusion
-Infuse IV over 30 minutes to 3 hours.

Gastrointestinal (GI) disturbances reported in patients receiving rifampin include epigastric distress, nausea, vomiting, anorexia, flatulence, cramps, diarrhea, and pyrosis (heartburn). A higher incidence of adverse events has been reported in tuberculosis patients treated more often than twice weekly.

Systemic hypersensitivity and cutaneous reactions have been observed with rifampin therapy. Cases of severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with rifampin. Signs and symptoms of hypersensitivity reactions may include fever, rash, urticaria, angioedema, hypotension, acute bronchospasm, conjunctivitis, decreased platelet count, neutropenia, elevated liver transaminases, or flu-like illness (tiredness, myalgia, bone pain, nausea, vomiting, head pain, chills, aches, itching, sweats, lightheadedness, dyspnea, chest pain (unspecified), cough, syncope, palpitations). The "flu syndrome" may also occur if rifampin is taken irregularly or if daily administration is resumed after a drug-free interval. Shortness of breath, wheezing, decrease in blood pressure, and shock have also been noted with intermittent rifampin dosage regimens. Occasionally, pruritus, pemphigoid reaction (pemphigus), erythema multiforme, vasculitis, sore mouth, and sore tongue have been observed. Anaphylactoid reactions (i.e., anaphylaxis) have been reported rarely. Manifestations of hypersensitivity, such as fever, lymphadenopathy, or laboratory abnormalities (including eosinophilia, hepatic abnormalities) may be present even though a rash is not evident. Mild and self-limiting dermatologic reactions that do not appear to be associated with a hypersensitivity reaction have been reported with rifampin use and include flushing and itching with or without a rash. In a study of 157 adolescent patients receiving rifampin for latent tuberculosis infection, rash was reported in 9 patients (6%). Monitor patients receiving rifampin for signs and symptoms of hypersensitivity or cutaneous reactions; discontinue treatment, and institute appropriate therapy if a reaction occurs. A higher incidence of adverse events has been reported in tuberculosis patients treated more often than twice weekly.

Rifampin has been reported to cause adverse renal effects, including elevations in BUN and uric acid (e.g., hyperuricemia). Hemolysis, hemoglobinuria, hematuria, interstitial nephritis, acute renal tubular necrosis, renal insufficiency, and acute renal failure (unspecified) have been rarely reported and are generally considered to be hypersensitivity reactions. These reactions usually occur during intermittent therapy or when treatment is resumed after an interruption of a daily regimen and are reversible when rifampin is discontinued and appropriate therapy instituted. A higher incidence of adverse events has been reported in tuberculosis patients treated more often than twice weekly. Over 100 cases of acute renal failure have been reported in adult patients treated with rifampin, and the renal failure appears to be immune related. Acute renal failure has been rarely reported in pediatric patients.

Rifampin can cause a discoloration (i.e., yellow, orange, red, brown) of the teeth, urine (urine discoloration), sweat, tears, and sputum. Soft contact lens discoloration and tooth discoloration may be permanent.

Monitor for signs and symptoms of hepatic injury, especially if rifampin treatment is prolonged or given with other hepatotoxic drugs. Discontinue rifampin if signs or symptoms of hepatic damage occur or worsen. Hepatotoxicity of hepatocellular, cholestatic, and mixed patterns has been reported in patients treated with rifampin. Severity ranged from asymptomatic elevated hepatic enzymes, isolated jaundice/hyperbilirubinemia, symptomatic self-limited hepatitis to fulminant hepatic failure and death. Cases of drug-induced liver injury, including fatal cases (especially when used in combination with other anti-tuberculosis drugs), hepatotoxicity including transient abnormalities in liver function tests (e.g., elevations in serum bilirubin, alkaline phosphatase, serum transaminases, gamma-glutamyl transferase), hepatitis, shock-like syndrome with hepatic involvement and abnormal liver function tests, and cholestasis have been reported in patients treated with rifampin, with an onset of a few days to a few months after treatment initiation. Signs and symptoms include elevated serum hepatic enzymes, cholestatic jaundice, hepatitis, hepatotoxicity, hepatocellular injury, and mixed liver injury. Most patients recovered on discontinuation of rifampin treatment; nevertheless, progression to acute liver failure requiring liver transplantation can occur. The mechanism of rifampin-induced liver injury is not clearly elucidated, but data indicate either an immuno-allergic mechanism or direct toxicity of metabolic products. Do not reintroduce rifampin in patients with an episode of hepatic injury during treatment with rifampin for which no other cause of liver injury has been determined. Most combination therapy for active tuberculosis disease includes more than 1 agent that may contribute to hepatotoxicity.

Possible adverse central nervous system effects due to rifampin use include headache, pyrexia, drowsiness, fatigue, ataxia, dizziness, inability to concentrate, mental confusion, behavioral changes, muscular weakness, pain in the extremities, and generalized numbness. In rare instances, myopathy and psychosis have been observed. Visual impairment/disturbances of unknown characterization have been reported.

Although thrombocytopenia predominantly occurs with high-dose intermittent rifampin treatment, it has also been reported after rifampin was discontinued and reinitiated. It has occurred rarely during well supervised daily therapy. Thrombocytopenia is reversible if the drug is discontinued as soon as purpura occurs. Intracranial bleeding and fatalities have resulted from continuing or resuming rifampin after purpura has developed. Additionally, rifampin may cause vitamin K-dependent coagulation disorders (i.e., abnormal prolongation of the prothrombin time or low vitamin K-dependent coagulation factors) and bleeding. Monitor coagulation tests during rifampin treatment (e.g., prothrombin time and other coagulation tests) in patients at risk of vitamin K deficiency, such as patients with chronic hepatic disease or malnutrition or those on prolonged antibacterial drugs or anticoagulant therapy. Consider supplementation with vitamin K when appropriate and discontinuation of rifampin if abnormal coagulation tests and/or bleeding occur. Disseminated intravascular coagulation (DIC) and agranulocytosis have been reported rarely. Hemolytic anemia has been reported, including cases in children. Leukopenia and decreased hemoglobin (anemia) have also been noted. A higher incidence of adverse events has been reported in tuberculosis patients treated more often than twice weekly.

Menstrual disturbances (menstrual irregularity) have been reported with rifampin use. In addition, rarely, there have been reports of adrenal insufficiency in patients with compromised adrenal function receiving rifampin.

Peripheral edema has been reported with rifampin.

Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with rifampin. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Also, postmarketing cases of paradoxical drug reaction (recurrence or appearance of new symptoms, physical and radiological signs in a patient who had previously shown improvement with appropriate antimycobacterial treatment, in the absence of disease relapse, poor treatment compliance, drug resistance, side effects of treatment, or secondary infection/diagnosis) have been reported with rifampin. Paradoxical drug reactions are often transient and should not be misinterpreted as failure to respond to treatment. If worsening of symptoms or signs occurs during antimycobacterial treatment, consider paradoxical drug reaction in the differential diagnosis, monitor, or treat accordingly.

Rifampin is a pyridoxine antagonist and may cause vitamin B6 deficiency. Supplementation with vitamin B6 is recommended in patients taking rifampin. Additionally, vitamin D deficiency has been reported in patients taking long-term rifampin therapy (i.e., greater than 1 month). Monitoring of vitamin D concentrations and supplementation when necessary is recommended.

Isolated reports of porphyria exacerbation have been associated with rifampin administration. Rifampin has enzyme-inducing properties, including induction of delta amino levulinic acid synthetase.

Interstitial lung disease or pneumonitis has been reported in patients receiving rifampin for the treatment of tuberculosis. Interstitial lung disease/pneumonitis is a potentially fatal disorder. Carefully assess all patients with an acute onset and/or unexplained worsening of pulmonary symptoms (e.g., dyspnea with a dry cough) and fever to confirm the diagnosis of interstitial lung disease/pneumonitis. If interstitial lung disease/pneumonitis is diagnosed, permanently discontinue rifampin due to the risk for severe manifestations (i.e., respiratory failure and acute respiratory distress syndrome) and initiate appropriate treatment as necessary.

Cases of thrombotic microangiopathy (TMA), manifested as thrombotic thrombocytopenic purpura (TTP) or hemolytic-uremic syndrome (HUS), including fatal cases, have been reported with rifampin use. If laboratory or clinical findings associated with TMA occur in a patient receiving rifampin, discontinue rifampin and evaluate for TMA, including platelet concentrations, renal function, serum lactate dehydrogenase (LDH), and a blood film for schistocytes (erythrocyte fragmentation). ADAMTS13 activity and anti-ADAMTS13-antibody determination should be completed. If anti-ADMASTS13-antibody is elevated in conjunction with low ADAMTS13 activity, do not resume rifampin therapy and treat patients accordingly (i.e., consider plasma exchange).

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

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

Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including rifampin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

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

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

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

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

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

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

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

Description: Rifampin (rifampicin), a semisynthetic rifamycin antibiotic, is primarily used as part of first-line, combination therapy in the treatment of tuberculosis. Rifampin is also used to treat asymptomatic carriers of Neisseria meningitidis; as prophylaxis against Haemophilus influenzae type b in high-risk contacts; and in the treatment of rare diseases such as Hansen's disease (leprosy), bartonellosis, and brucellosis. Rifampin has been used in combination with vancomycin for synergy in staphylococcal infections; however, data are insufficient to support its routine use. Significant drug interactions are associated with rifampin use. Rifampin is a potent inducer of hepatic microsomal enzymes, which results in decreased serum concentrations of many concomitant drugs. This may limit its use in certain pediatric patients, particularly HIV-infected children receiving protease inhibitors. Rifampin is FDA-approved for use in pediatric patients as young as neonates.

Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Mycobacterium leprae, Mycobacterium tuberculosis, Neisseria meningitidis, Staphylococcus aureus (MRSA), Staphylococcus aureus (MSSA), Staphylococcus epidermidis
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.

For the treatment of drug-susceptible tuberculosis infection as part of combination therapy:
-for the treatment of drug-susceptible tuberculosis infection in persons without HIV as part of combination therapy:
Oral dosage:
Neonates*: 10 to 20 mg/kg/dose PO once daily. Although tuberculosis is rare in neonates, congenital and postnatal cases have been successfully treated with antitubercular agents. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.
Infants and Children: 10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily or 5 days/week, or alternatively, 3 days/week or twice weekly. 20 to 30 mg/kg/dose PO once daily may be considered for infants and toddlers or for disseminated disease. Daily dosing is preferred and is defined as 5- or 7 days/week. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.
Adolescents: 10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily or 5 days/week, or alternatively, 3 days/week or twice weekly. 20 to 30 mg/kg/dose PO once daily may be considered for disseminated disease. Daily dosing is preferred and is defined as 5- or 7 days/week. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.
Intravenous dosage:
Neonates*: 10 to 20 mg/kg/dose IV once daily. Although tuberculosis is rare in neonates, congenital and postnatal cases have been successfully treated with antitubercular agents. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.
Infants and Children: 10 to 20 mg/kg/dose (Max: 600 mg/dose) IV once daily or 5 days/week, or alternatively, 3 days/week or twice weekly. 20 to 30 mg/kg/dose IV once daily may be considered for infants and toddlers or for disseminated disease. Daily dosing is preferred and is defined as 5- or 7 days/week. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.
Adolescents: 10 to 20 mg/kg/dose (Max: 600 mg/dose) IV once daily or 5 days/week, or alternatively, 3 days/week or twice weekly. 20 to 30 mg/kg/dose IV once daily may be considered for disseminated disease. Daily dosing is preferred and is defined as 5- or 7 days/week. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.
-for the treatment of drug-susceptible tuberculosis infection in persons living with HIV as part of combination therapy:
Oral dosage:
Neonates*: 10 to 20 mg/kg/dose PO once daily. Although tuberculosis is rare in neonates, congenital and postnatal cases have been successfully treated with antitubercular agents. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.
Infants and Children: 10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily or 5 days/week. 20 to 30 mg/kg/dose PO once daily may be considered for infants and toddlers or for disseminated disease. Daily dosing is defined as 5- or 7 days/week. Alternatively, 15 to 20 mg/kg/dose (Max: 600 mg/dose) PO 3 days/week may be considered during the continuation phase with good adherence and treatment response. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.
Adolescents: 10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily or 5 days/week. 20 to 30 mg/kg/dose PO once daily may be considered for disseminated disease. Daily dosing is defined as 5- or 7 days/week. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.
Intravenous dosage:
Neonates*: 10 to 20 mg/kg/dose IV once daily. Although tuberculosis is rare in neonates, congenital and postnatal cases have been successfully treated with antitubercular agents. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.
Infants and Children: 10 to 20 mg/kg/dose (Max: 600 mg/dose) IV once daily or 5 days/week. 20 to 30 mg/kg/dose IV once daily may be considered for infants and toddlers or for disseminated disease. Daily dosing is defined as 5- or 7 days/week. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.
Adolescents: 10 to 20 mg/kg/dose (Max: 600 mg/dose) IV once daily or 5 days/week. 20 to 30 mg/kg/dose IV once daily may be considered for disseminated disease. Daily dosing is defined as 5- or 7 days/week. Rifampin is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.
-for the treatment of CNS-related tuberculosis as part of combination therapy*:
Oral dosage:
Infants, Children, and Adolescents: 20 to 35 mg/kg/dose PO once daily during the intensive phase, which may be considered for the duration of therapy, or alternatively 20 to 30 mg/kg/dose PO once daily for the duration of therapy. Rifampin may be considered as part of shortened intensive combination therapy.
Intravenous dosage:
Infants, Children, and Adolescents: 20 to 30 mg/kg/dose IV once daily. Rifampin may be considered as part of shortened intensive combination therapy.

For the treatment of drug-resistant tuberculosis infection as part of combination therapy:
Oral dosage:
Infants and Children: 10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily. 20 to 30 mg/kg/dose PO once daily may be considered for infants and toddlers or meningitis and/or disseminated disease.
Adolescents: 10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily. 20 to 30 mg/kg/dose PO once daily may be considered for meningitis and/or disseminated disease.
Intravenous dosage:
Infants and Children: 10 to 20 mg/kg/dose (Max: 600 mg/dose) IV once daily. 20 to 30 mg/kg/dose IV once daily may be considered for infants and toddlers or meningitis and/or disseminated disease.
Adolescents: 10 to 20 mg/kg/dose (Max: 600 mg/dose) IV once daily. 20 to 30 mg/kg/dose IV once daily may be considered for meningitis and/or disseminated disease.

For tuberculosis prophylaxis* or latent tuberculosis infection* (LTBI):
-for tuberculosis prophylaxis* or LTBI* in combination with isoniazid:
Oral dosage:
Infants, Children, and Adolescents: 10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily for 3 to 4 months.
-for tuberculosis prophylaxis* or LTBI* as monotherapy in persons without HIV:
Oral dosage:
Infants, Children, and Adolescents: 10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily for 3 to 4 months.
-for tuberculosis prophylaxis* or LTBI* as monotherapy in persons living with HIV:
Oral dosage:
Infants, Children, and Adolescents: 10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily for 4 months.

For post-exposure meningococcal infection prophylaxis*:
Oral dosage:
Neonates: 5 mg/kg/dose PO every 12 hours for 2 days. Initiate prophylaxis as soon as possible after exposure (ideally less than 24 hours after identification of index patient); prophylaxis initiated more than 14 days after onset of illness in the index patient has very limited or no value.
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 600 mg/dose) PO every 12 hours for 2 days. Initiate prophylaxis as soon as possible after exposure (ideally less than 24 hours after identification of index patient); prophylaxis initiated more than 14 days after onset of illness in the index patient has very limited or no value.

For Haemophilus influenzae type b prophylaxis* in carriers who are at high risk of transmitting the disease to children ages 4 years and less:
Oral dosage:
Neonates: 10 mg/kg/dose PO once daily for 4 days.
Infants, Children, and Adolescents: 20 mg/kg/dose (Max: 600 mg/dose) PO once daily for 4 days.

For the treatment of leprosy (Hansen's disease)*:
NOTE: Treatment that is more intensive and of longer duration is preferable.
-for the daily treatment of paucibacillary disease:
Oral dosage:
Infants, Children, and Adolescents: 10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily with dapsone for 12 months.
-for the monthly treatment of paucibacillary disease:
Oral dosage:
Infants and Children 1 to 9 years or weighing less than 20 kg: 10 mg/kg/dose PO once monthly with dapsone for 12 months or dapsone and clofazimine for 6 months. Monthly treatment is recommended for those receiving prednisone and those receiving treatment through the WHO's Global Leprosy Program. The WHO's Global Leprosy Program also allows for shorter treatment durations.
Children and Adolescents 10 to 14 years weighing 20 to 40 kg: 10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once monthly with dapsone for 12 months or 300 mg PO once monthly with dapsone and clofazimine for 6 months. Monthly treatment is recommended for those receiving prednisone and those receiving treatment through the WHO's Global Leprosy Program. The WHO's Global Leprosy Program also allows for shorter treatment durations.
Children and Adolescents 10 to 14 years weighing more than 40 kg: 10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once monthly with dapsone for 12 months or 450 mg PO once monthly with dapsone and clofazimine for 6 months. Monthly treatment is recommended for those receiving prednisone and those receiving treatment through the WHO's Global Leprosy Program. The WHO's Global Leprosy Program also allows for shorter treatment durations.
Adolescents 15 to 17 years: 600 mg PO once monthly with dapsone for 12 months or dapsone and clofazimine for 6 months. Monthly treatment is recommended for those receiving prednisone and those receiving treatment through the WHO's Global Leprosy Program. The WHO's Global Leprosy Program also allows for shorter treatment durations.
-for the daily treatment of multibacillary disease:
Oral dosage:
Infants, Children, and Adolescents: 10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily with dapsone and clofazimine for 24 months.
-for the monthly treatment of multibacillary disease:
Oral dosage:
Infants and Children 1 to 9 years or weighing less than 20 kg: 10 mg/kg/dose PO once monthly with dapsone and clofazimine for 12 or 24 months. Monthly treatment is recommended for those receiving prednisone and those receiving treatment through the WHO's Global Leprosy Program. The WHO's Global Leprosy Program also allows for shorter treatment durations.
Children and Adolescents 10 to 14 years weighing 20 to 40 kg: 10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once monthly with dapsone and clofazimine for 24 months or 300 mg PO once monthly with dapsone and clofazimine for 12 months. Monthly treatment is recommended for those receiving prednisone and those receiving treatment through the WHO's Global Leprosy Program. The WHO's Global Leprosy Program also allows for shorter treatment durations.
Children and Adolescents 10 to 14 years weighing more than 40 kg: 10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once monthly with dapsone and clofazimine for 24 months or 450 mg PO once monthly with dapsone and clofazimine for 12 months. Monthly treatment is recommended for those receiving prednisone and those receiving treatment through the WHO's Global Leprosy Program. The WHO's Global Leprosy Program also allows for shorter treatment durations.
Adolescents 15 to 17 years: 600 mg PO once monthly with dapsone and clofazimine for 12 or 24 months. Monthly treatment is recommended for those receiving prednisone and those receiving treatment through the WHO's Global Leprosy Program. The WHO's Global Leprosy Program also allows for shorter treatment durations.

For the treatment of infective endocarditis*:
-for the treatment of prosthetic valve endocarditis due to Staphylococcus sp.*:
Oral dosage:
Neonates: 10 mg/kg/dose PO every 24 hours plus penicillin G, nafcillin/oxacillin, vancomycin, or daptomycin for at least 6 weeks and gentamicin for 2 weeks.
Infants, Children, and Adolescents: 15 to 20 mg/kg/day PO divided every 8 hours (Max: 900 mg/day) plus penicillin G, nafcillin/oxacillin, vancomycin, or daptomycin for at least 6 weeks and gentamicin for 2 weeks.
Intravenous dosage:
Neonates: 10 mg/kg/dose IV every 24 hours plus penicillin G, nafcillin/oxacillin, vancomycin, or daptomycin for at least 6 weeks and gentamicin for 2 weeks.
Infants, Children, and Adolescents: 15 to 20 mg/kg/day IV divided every 8 hours (Max: 900 mg/day) plus penicillin G, nafcillin/oxacillin, vancomycin, or daptomycin for at least 6 weeks and gentamicin for 2 weeks.
-for the treatment of culture-negative prosthetic valve endocarditis*:
Oral dosage:
Neonates: 10 mg/kg/dose PO every 24 hours plus vancomycin and cefepime/ceftazidime for 6 weeks and gentamicin for 2 weeks for early (1 year or less after surgery) infection or plus ampicillin; sulbactam with or without vancomycin for at least 6 weeks and gentamicin for 2 weeks for late (more than 1 year after surgery) infection.
Infants, Children, and Adolescents: 15 to 20 mg/kg/day PO divided every 8 hours (Max: 900 mg/day) plus vancomycin and cefepime/ceftazidime for 6 weeks and gentamicin for 2 weeks for early (1 year or less after surgery) infection or plus ampicillin; sulbactam with or without vancomycin for at least 6 weeks and gentamicin for 2 weeks for late (more than 1 year after surgery) infection.
Intravenous dosage:
Neonates: 10 mg/kg/dose IV every 24 hours plus vancomycin and cefepime/ceftazidime for 6 weeks and gentamicin for 2 weeks for early (1 year or less after surgery) infection or plus ampicillin; sulbactam with or without vancomycin for at least 6 weeks and gentamicin for 2 weeks for late (more than 1 year after surgery) infection.
Infants, Children, and Adolescents: 15 to 20 mg/kg/day IV divided every 8 hours (Max: 900 mg/day) plus vancomycin and cefepime/ceftazidime for 6 weeks and gentamicin for 2 weeks for early (1 year or less after surgery) infection or plus ampicillin; sulbactam with or without vancomycin for at least 6 weeks and gentamicin for 2 weeks for late (more than 1 year after surgery) infection.
-for the treatment of documented Bartonella endocarditis*:
Oral dosage:
Children and Adolescents: 20 mg/kg/day PO divided every 12 hours (Max: 600 mg/day) for 6 weeks plus doxycycline.
Intravenous dosage:
Children and Adolescents: 20 mg/kg/day IV divided every 12 hours (Max: 600 mg/day) for 6 weeks plus doxycycline.

For the treatment of bartonellosis*, including atypical cat scratch disease, neuroretinitis*, CNS infections*, and chronic verruga peruana*:
NOTE: See endocarditis for treatment of endocarditis.
-for the treatment of atypical hepatosplenic or bony cat scratch disease in immunocompetent patients*:
Oral dosage:
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 300 mg/dose) PO every 12 hours for 4 to 6 weeks plus azithromycin as first-line therapy.
Intravenous dosage:
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 300 mg/dose) IV every 12 hours for 4 to 6 weeks plus azithromycin as first-line therapy.
-for the treatment of Bartonella-related neuroretinitis in immunocompetent patients*:
Oral dosage:
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 300 mg/dose) PO every 12 hours for 4 to 6 weeks plus azithromycin with or without corticosteroids as first-line therapy.
Intravenous dosage:
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 300 mg/dose) IV every 12 hours for 4 to 6 weeks plus azithromycin with or without corticosteroids as first-line therapy.
-for the treatment of severe Bartonella infections, including multifocal disease or with clinical decompensation, in immunocompromised patients*:
Oral dosage:
Adolescents: 300 PO every 12 hours for at least 3 months plus doxycycline or erythromycin as first-line therapy or azithromycin or clarithromycin as an alternative.
Intravenous dosage:
Adolescents: 300 IV every 12 hours for at least 3 months plus doxycycline or erythromycin as first-line therapy or azithromycin or clarithromycin as an alternative.
-for the treatment of Bartonella infections involving the central nervous system in immunocompromised patients*:
Oral dosage:
Adolescents: 300 mg PO every 12 hours for at least 3 months plus doxycyline as first-line therapy.
Intravenous dosage:
Adolescents: 300 mg IV every 12 hours for at least 3 months plus doxycyline for at least 3 months as first-line therapy.
-for the treatment of chronic verruga peruana*:
Oral dosage:
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 600 mg/dose) PO once daily for 14 to 28 days as second-line therapy.

For the treatment of pruritus* secondary to cholestasis:
Oral dosage:
Infants, Children, and Adolescents: 5 mg/kg/dose (Max: 150 to 300 mg/dose) PO twice daily. For older or bigger children, may consider initiating with a maximum dose of 150 mg and titrating up to a maximum dose of 300 mg. Response rates of more than 90% have been noted with rifampin in clinical studies of children unresponsive to other treatments.

For the treatment of central nervous system infections*, including meningitis*, ventriculitis*, cerebrospinal fluid (CSF) shunt infections, brain abscess*, subdural empyema*, spinal epidural abscess*, or septic thrombosis of the cavernous or dural venus sinus*:
Intravenous dosage:
Neonates: Data not available in neonates 7 days and younger; however, 10 to 20 mg/kg/day IV in 2 divided doses is recommended in older neonates. The Infectious Diseases Society of America (IDSA) recommends consideration of the addition of rifampin to vancomycin for meningitis due to S. epidermidis or methicillin-resistant S. aureus or vancomycin plus a third-generation cephalosporin for meningitis due to penicillin-resistant S. pneumoniae. For pneumococcal meningitis, the addition of rifampin should be considered for ceftriaxone/cefotaxime MIC of more than 2 mcg/mL. Although rifampin in combination with vancomycin has been used successfully for staphylococcal CNS infections in neonates, current clinical guidelines for methicillin-resistant Staphylococcus aureus (MRSA) infections do not recommend the addition of rifampin to vancomycin in neonates with CNS infections due to limited data of a clinical benefit. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.
Infants, Children, and Adolescents: 10 to 20 mg/kg/day IV in 1 to 2 divided doses (Max: 600 mg/day). The Infectious Diseases Society of America (IDSA) recommends consideration of the addition of rifampin to vancomycin for meningitis due to S. epidermidis or methicillin-resistant S. aureus or vancomycin plus a third-generation cephalosporin for meningitis due to penicillin-resistant S. pneumoniae. For pneumococcal meningitis, the addition of rifampin should be considered for ceftriaxone/cefotaxime MIC of more than 2 mcg/mL. Although rifampin in combination with vancomycin has been used successfully for staphylococcal CNS infections in children, current clinical guidelines for methicillin-resistant Staphylococcus aureus (MRSA) infections do not recommend the addition of rifampin to vancomycin in children with CNS infections due to limited data of a clinical benefit. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.
Oral dosage:
Neonates: Data not available in neonates 7 days and younger; however, 10 to 20 mg/kg/day PO in 2 divided doses is recommended in older neonates. The Infectious Diseases Society of America (IDSA) recommends consideration of the addition of rifampin to vancomycin for meningitis due to S. epidermidis or methicillin-resistant S. aureus or vancomycin plus a third-generation cephalosporin for meningitis due to penicillin-resistant S. pneumoniae. For pneumococcal meningitis, the addition of rifampin should be considered for ceftriaxone/cefotaxime MIC of more than 2 mcg/mL. Although rifampin in combination with vancomycin has been used successfully for staphylococcal CNS infections in neonates, current clinical guidelines for methicillin-resistant Staphylococcus aureus (MRSA) infections do not recommend the addition of rifampin to vancomycin in neonates with CNS infections due to limited data of a clinical benefit. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.
Infants, Children, and Adolescents: 10 to 20 mg/kg/day PO in 1 to 2 divided doses (Max: 600 mg/day). The Infectious Diseases Society of America (IDSA) recommends consideration of the addition of rifampin to vancomycin for meningitis due to S. epidermidis or methicillin-resistant S. aureus or vancomycin plus a third-generation cephalosporin for meningitis due to penicillin-resistant S. pneumoniae. For pneumococcal meningitis, the addition of rifampin should be considered for ceftriaxone/cefotaxime MIC of more than 2 mcg/mL. Although rifampin in combination with vancomycin has been used successfully for staphylococcal CNS infections in children, current clinical guidelines for methicillin-resistant Staphylococcus aureus (MRSA) infections do not recommend the addition of rifampin to vancomycin in children with CNS infections due to limited data of a clinical benefit. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

For the treatment of staphylococcal bacteremia* as an adjunct to vancomycin:
Oral dosage:
Neonates: 10 to 20 mg/kg/day PO in 1 to 2 divided doses in combination with vancomycin. Small studies in neonates with persistent bacteremia despite vancomycin therapy have demonstrated a benefit to the addition of rifampin to vancomycin. In one study in 10 neonates (mean gestational age (GA) 27 weeks; range, 23 to 32 weeks) with persistent staphylococcal bacteremia, 8 out of 10 infants had sterile blood culture within 24 hours of the addition of rifampin to vancomycin therapy. There are limited data available and routine use of combination therapy with vancomycin and rifampin for MRSA bacteremia is not recommended in neonates by the Infectious Diseases Society of America (IDSA).
Infants, Children, and Adolescents: 10 to 20 mg/kg/day PO in 1 to 2 divided doses (Max: 600 mg/dose) in combination with vancomycin. Although rifampin has been used successfully for synergy in combination with vancomycin for staphylococcal infections, there are limited data available and routine use of combination therapy with vancomycin and rifampin for MRSA bacteremia is not recommended in children by the Infectious Diseases Society of America (IDSA).
Intravenous dosage:
Neonates: 10 to 20 mg/kg/day IV in 1 to 2 divided doses in combination with vancomycin. Small studies in neonates with persistent bacteremia despite vancomycin therapy have demonstrated a benefit to the addition of rifampin to vancomycin. In one study in 10 neonates (mean gestational age (GA) 27 weeks; range, 23 to 32 weeks) with persistent staphylococcal bacteremia, 8 out of 10 infants had sterile blood culture within 24 hours of the addition of rifampin to vancomycin therapy. There are limited data available, and routine use of combination therapy with vancomycin and rifampin for MRSA bacteremia is not recommended in neonates by the Infectious Diseases Society of America (IDSA).
Infants, Children, and Adolescents: 10 to 20 mg/kg/day IV in 1 to 2 divided doses (Max: 600 mg/dose) in combination with vancomycin. Although rifampin has been used successfully for synergy in combination with vancomycin for staphylococcal infections, there are limited data available and routine use of combination therapy with vancomycin and rifampin for MRSA bacteremia is not recommended in children by the Infectious Diseases Society of America (IDSA).

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

For the treatment of brucellosis*:
Oral dosage:
Infants and Children 1 month to 7 years: 15 to 20 mg/kg/day PO in 1 or 2 divided doses for 6 to 8 weeks; a max dose of 600 mg/day has been suggested. Rifampin in combination with trimethoprim; sulfamethoxazole is the preferred regimen. In a clinical study of 140 children (younger than 16 years) with brucellosis who received rifampin (15 mg/kg/day) in combination with trimethoprim; sulfamethoxazole (8 mg/kg/day trimethoprim), relapse and failure of therapy was reported in 10.9% and 4.5% of patients who received 6 or 8 weeks of therapy, respectively (p = 0.204). Cure rates were 89.1% and 95.5%, respectively.
Children and Adolescents 8 to 17 years: 15 to 20 mg/kg/day PO in 1 or 2 divided doses or 600 to 900 mg/day PO for 6 to 8 weeks. Rifampin should be used in combination with a tetracycline, such as doxycycline. In a clinical study of 140 children (younger than 16 years) with brucellosis who received rifampin (15 mg/kg/day) in combination with trimethoprim; sulfamethoxazole (8 mg/kg/day trimethoprim), relapse and failure of therapy was reported in 10.9% and 4.5% of patients who received 6 or 8 weeks of therapy, respectively (p = 0.204). Cure rates were 89.1% and 95.5%, respectively.
Intravenous dosage:
Infants and Children 1 month to 7 years: 15 to 20 mg/kg/day IV in 1 or 2 divided doses for 6 to 8 weeks; a max dose of 600 mg/day has been suggested. Rifampin in combination with trimethoprim; sulfamethoxazole is the preferred regimen. In a clinical study of 140 children (younger than 16 years) with brucellosis who received rifampin (15 mg/kg/day) in combination with trimethoprim; sulfamethoxazole (8 mg/kg/day trimethoprim), relapse and failure of therapy was reported in 10.9% and 4.5% of patients who received 6 or 8 weeks of therapy, respectively (p = 0.204). Cure rates were 89.1% and 95.5%, respectively.
Children and Adolescents 8 to 17 years: 15 to 20 mg/kg/day IV in 1 or 2 divided doses or 600 to 900 mg/day IV for 6 to 8 weeks. Rifampin should be used in combination with a tetracycline, such as doxycycline. In a clinical study of 140 children (younger than 16 years) with brucellosis who received rifampin (15 mg/kg/day) in combination with trimethoprim; sulfamethoxazole (8 mg/kg/day trimethoprim), relapse and failure of therapy was reported in 10.9% and 4.5% of patients who received 6 or 8 weeks of therapy, respectively (p = 0.204). Cure rates were 89.1% and 95.5%, respectively.

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

For the treatment of anthrax*:
-for the treatment of systemic anthrax* without aerosol exposure, including those with signs and symptoms of meningitis, as part of combination therapy:
Intravenous dosage:
Neonates 32 weeks gestation and older: 10 mg/kg/dose IV every 24 hours for at least 14 days; may consider step-down to oral therapy.
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 300 mg/dose) IV every 12 hours for at least 14 days; may consider step-down to oral therapy.
-for the treatment of systemic anthrax* with aerosol exposure, including those with signs and symptoms of meningitis, as part of combination therapy:
Intravenous dosage:
Neonates 32 weeks gestation and older: 10 mg/kg/dose IV every 24 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.
Infants, Children and Adolescents: 10 mg/kg/dose (Max: 300 mg/dose) IV every 12 hours for at least 14 days; may consider step-down to oral therapy.
Immunocompromised Infants, Children and Adolescents: 10 mg/kg/dose (Max: 300 mg/dose) IV every 12 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.

For meningococcal carriage eradication in asymptomatic carriers:
Oral dosage:
Neonates: 5 mg/kg/dose PO every 12 hours for 2 days.
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 600 mg/dose) PO every 12 hours for 2 days.
Intravenous dosage:
Neonates: 5 mg/kg/dose IV every 12 hours for 2 days.
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 600 mg/dose) IV every 12 hours for 2 days.

For the treatment of staphylococcal peritoneal dialysis-related peritonitis* and peritoneal dialysis catheter-related infection*:
-for the treatment of peritoneal dialysis-related peritonitis*:
Oral dosage:
Infants, Children, and Adolescents: 5 to 10 mg/kg/dose (Max: 300 mg/dose) PO every 12 hours as adjuvant therapy.
-for the treatment of peritoneal dialysis catheter-related infection*:
Oral dosage:
Infants, Children, and Adolescents: 5 to 10 mg/kg/dose (Max: 300 mg/dose) PO every 12 hours as adjuvant therapy.

For the treatment of bone and joint infections*, including osteomyelitis* and infectious arthritis*:
-for the treatment of osteomyelitis* due to methicillin-resistant S. aureus:
Intravenous dosage:
Neonates: 10 mg/kg/dose IV every 24 hours as adjunctive therapy. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 10 mg/kg/dose IV every 12 hours as adjunctive therapy. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 10 mg/kg/dose (Max: 300 mg/dose) IV every 12 hours as adjunctive therapy. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
Oral dosage:
Neonates: 10 mg/kg/dose PO every 24 hours as adjunctive therapy. Treat for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 10 mg/kg/dose PO every 12 hours as adjunctive therapy. Treat for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 10 mg/kg/dose (Max: 300 mg/dose) PO every 12 hours as adjunctive therapy. Treat for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
-for the treatment of infectious arthritis* due to methicillin-resistant S. aureus:
Intravenous dosage:
Neonates: 10 mg/kg/dose IV every 24 hours as adjunctive therapy. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 10 mg/kg/dose IV every 12 hours as adjunctive therapy. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 10 mg/kg/dose (Max: 300 mg/dose) IV every 12 hours as adjunctive therapy. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
Oral dosage:
Neonates: 10 mg/kg/dose PO every 24 hours as adjunctive therapy. Treat for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 10 mg/kg/dose PO every 12 hours as adjunctive therapy. Treat for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 10 mg/kg/dose (Max: 300 mg/dose) PO every 12 hours as adjunctive therapy. Treat for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.

For the treatment of acute exacerbations of bronchiectasis*:
Oral dosage:
Infants, Children, and Adolescents: 15 to 20 mg/kg/day (Max: 600 mg/day) divided every 12 to 24 hours for 14 days.

Maximum Dosage Limits:
-Neonates
20 mg/kg/day PO/IV for tuberculosis treatment has been used off-label; 10 mg/kg/day PO/IV for meningococcal prophylaxis.
-Infants
20 mg/kg/day PO/IV.
-Children
20 mg/kg/day PO/IV (Max: 600 mg/day PO/IV for tuberculosis treatment; 1,200 mg/day PO/IV for meningococcal prophylaxis).
-Adolescents
20 mg/kg/day PO/IV (Max: 600 mg/day PO/IV for tuberculosis treatment; 1,200 mg/day PO/IV for meningococcal prophylaxis).

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

Patients with Renal Impairment Dosing
No dosage adjustment needed.

Intermittent hemodialysis
Rifampin is not cleared by hemodialysis; no dosage adjustment needed.

Peritoneal dialysis*
No dosage adjustment needed.

Continuous renal replacement therapy (CRRT)*
NOTE: Various CRRT modalities include continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous high-flux hemodialysis (CVVHFD), continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVHD), and continuous arteriovenous hemodiafiltration (CAVHDF). Dosing should take into consideration patient-specific factors (e.g., intrinsic renal function), type of infection, the duration of renal replacement therapy, the effluent flow rate, and the replacement solution administered.

No dosage adjustment needed.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Rifampin inhibits bacterial and mycobacterial RNA synthesis. It binds to the beta-subunit of DNA-dependent RNA polymerase, thereby inhibiting the binding of the enzyme to DNA and blocking RNA transcription. Rifampin does not bind to RNA polymerase in eukaryotic cells, so RNA synthesis in human cells is not affected. Rifampin is bactericidal or bacteriostatic, depending on the concentration reached within an infected site and the susceptibility of the organism. Rifampin is effective against bacilli that are rapidly dividing in extracellular cavitary lesions, as well as against slowly or intermittently dividing organisms such as those found in closed caseous lesions and macrophages.

The susceptibility interpretive criteria for rifampin are delineated by pathogen. The MICs for N. meningitidis are defined as susceptible at concentrations of 0.5 mcg/mL or less, intermediate at a concentration of 1 mcg/mL, and resistant at concentrations of 2 mcg/mL or more. MICs for S. pneumoniae, Enterococcus sp., Staphylococcus sp., H. influenzae, H. parainfluenzae, Bacillus sp. (excluding B. anthracis), Corynebacterium sp., Aggregatibacter sp., Cardiobacterium sp., E. corrodens, Kingella sp., and M. catarrhalis are defined as susceptible at concentrations of 1 mcg/mL or less, intermediate at a concentration of 2 mcg/mL, and resistant at concentrations of 4 mcg/mL or more. These breakpoints do not apply to therapy of patients with invasive H. influenzae disease and may only be appropriate for prophylaxis of case contacts.

Rifampin has been used for the treatment of pruritus secondary to cholestasis associated with primary biliary cirrhosis. Rifampin induces microsomal enzyme activity increasing the metabolism and urinary excretion of bile acids. Rifampin may also increase the metabolism of nonbile pruritogenic substances.

Pharmacokinetics: Rifampin is administered orally and intravenously. High interpatient variability, particularly with peak serum concentrations, has been noted with rifampin in children and adults in clinical studies. Rifampin is widely distributed into most body tissues and fluids including lungs, liver, bone, saliva, and peritoneal and pleural fluids. Cerebrospinal fluid (CSF) concentrations are roughly 10% to 20% of concurrent systemic drug concentrations. In a pharmacokinetic study in 9 patients (1 day to 18 years) undergoing CSF shunt placement, the mean CSF concentration of rifampin was 1.4 mcg/mL (range, 0.12 to 3 mcg/mL) after a 20 mg/kg IV dose. CSF concentrations exceeded the MIC of rifampin against staphylococci by at least 150-fold. Protein binding of rifampin is approximately 80%. Rifampin is metabolized in the liver to an active metabolite, desacetyl-rifampicin, via deacetylation. Rifampin undergoes enterohepatic circulation with significant reabsorption. The parent compound and its metabolite are primarily excreted (30% to 40%) in feces via biliary elimination. Up to 30% of a dose is excreted in urine, with approximately half of this as unchanged drug. The elimination half-life in adults is 3 to 5 hours, but it decreases with prolonged use due to auto-induction of hepatic metabolism.

Affected cytochrome P450 enzymes and drug transporters: CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, P-gp
Rifampin is a significant inducer of many hepatic CYP450 isoenzymes. Rifampin is most potently an inducer of CYP3A4, but also potently induces the CYP2B6 isoenzyme in vitro. Comparatively, rifampin is a relatively weak inducer of CYP1A2. Rifampin also induces the CYP2C8 isoenzyme in vitro. Both in vitro and in vivo studies have shown that rifampin induces the CYP2C9 and CYP2C19 isoenzyme. While no specific in vitro or in vivo studies have shown that rifampin induces the CYP2D6 isoenzyme, some pharmacokinetic studies suggest that rifampin may be a modest inducer. Rifampin is also an inducer of P-glycoprotein (P-gp).


-Route-Specific Pharmacokinetics
Oral Route
Rifampin (capsules) is well absorbed after oral administration. Peak concentrations are reached approximately 1 to 2 hours after oral administration in infants and children. Similar peak concentrations (10.7 vs. 11.5 mcg/mL) were observed when rifampin was administered as an oral suspension compared to administration of rifampin powder in applesauce in a pharmacokinetic study in 38 children (6 to 58 months old). Food decreases rifampin absorption by approximately 30%; therefore, rifampin is recommended to be administered 1 hour before or 2 hours after a meal. Highly variable absorption has been noted with oral rifampin suspension in clinical studies. In a study in 20 children who received oral rifampin suspension, a mean bioavailability of 0.5 was observed with a range of 0.28 to more than 1.

Intravenous Route
Peak concentrations are reached at the end of infusion.


-Special Populations
Pediatrics
Neonates
The clearance of rifampin in neonates is similar to that seen in adults. In a pharmacokinetic study in 21 neonates (mean gestational age (GA) 29.9 weeks [range, 26 to 41.3 weeks]) who received IV rifampin (5 to 10 mg/kg/day), mean clearance, volume of distribution, and elimination half-life were 0.28 L/kg/hour, 1.84 L/kg, and 4.9 hours, respectively. As is seen in adults, the clearance of rifampin increased with continuing therapy in neonates. After 2 weeks of rifampin therapy in 8 neonates, mean clearance increased from 0.22 to 0.36 L/kg/hour and elimination half-life decreased from 6.1 to 4.4 hours.

Infants, Children, and Adolescents
The pharmacokinetics of rifampin in infants and children are similar to those seen in adults. Total clearance, volume of distribution, and elimination half-life of rifampin in children ranges from approximately 0.2 to 0.41 L/kg/hour, 0.7 to 1.9 L/kg, and 2 to 4 hours, respectively. In a pharmacokinetic study of 20 children (range, 3 months to 14 years), a mean elimination half-life of 2.25 and 2.66 hours was reported for IV and oral rifampin, respectively. In another study in 12 children (3 months to 12.8 years) who received multiple IV rifampin doses, a mean clearance and elimination half-life of 3.99 L/m2/hour and 1.9 hours, respectively, were reported. As is seen in adults, the clearance of rifampin increased with continuing therapy in children. Compared with the first 2 days of therapy, clearance increased by approximately 52% (3.1 to 4.72 L/m2/hour) and elimination half-life decreased by approximately 27% (2.38 to 1.73 hours) after at least 8 days of therapy. No correlation was noted between rifampin clearance and age or rifampin dose.

Hepatic Impairment
Rifampin is substantially eliminated by the liver and the clearance of rifampin would be expected to be decreased in patients with liver impairment.

Renal Impairment
In adult patients with renal failure, the elimination half-life of rifampin was not significantly different at doses up to 600 mg daily. In patients receiving a single 900 mg oral dose, the mean elimination half-life increased from 3.6 hours in healthy adults to 5, 7.3, and 11 hours in patients with a CrCl of 30 to 50 mL/minute, less than 30 mL/minute, and anuric patients, respectively. Dosage adjustment is not necessary in patients with renal impairment.