Rifampin Dosage

Drug Detail:Rifampin (monograph) (Rifadin)

Drug Class:

Usual Adult Dose for Tuberculosis - Active

10 mg/kg IV OR orally once a day
Maximum dose: 600 mg/day
Duration of therapy:

Initial phase: 2 months (with isoniazid, pyrazinamide, with/without streptomycin or ethambutol)
Continued phase: At least 4 months (with isoniazid)

Comments:

IV formulations should be used during initiation treatment and retreatment when the drug cannot be taken orally.
The Advisory Council for the Elimination of Tuberculosis, American Thoracic Society (ATS), and US Centers for Disease Control and Prevention (US CDC) recommend that either streptomycin or ethambutol be added to initial treatment unless the likelihood of isoniazid resistance is very low; treatment with less than 4 drugs may be considered if resistance is less than 4%.
Treatment may be continued in patients who remain sputum/culture positive, have resistant organisms, or are HIV positive.

Use: Treatment of all forms of tuberculosis

ATS, US CDC, and Infectious Diseases Society of America (IDSA) Recommend:
Up to 40 kg:

Daily regimen: 10 to 20 mg/kg IV or orally once a day
Intermittent regiment: 10 to 20 mg IV or orally 2 to 3 times a week

Over 40 kg:

Daily regimen: 10 mg/kg (usually 600 mg/day) orally or IV once a day
Intermittent regimen: 10 mg/kg (up to 600 mg/dose) orally or IV 2 to 3 times a week

Comment: Doses up to 35 mg/kg are being studied in clinical trials.

Use: Treatment of drug-susceptible tuberculosis

Usual Adult Dose for Meningococcal Meningitis Prophylaxis

600 mg IV OR orally 2 times a day

Duration of therapy: 2 days

Comments:

This drug should not be used to treat meningococcal infections due to the potential for rapid resistance.
Use should be restricted to high-risk of meningococcal disease situations.

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

Usual Adult Dose for Tuberculosis - Latent

US CDC Recommendations:
10 mg/kg IV OR orally once a day with/without isoniazid
Maximum dose: 600 mg/day
Duration of therapy: 4 months

10 mg/kg IV OR orally once a day with pyrazinamide
Maximum dose: 600 mg/day
Duration of therapy: 2 months

Comments:

Compared to single treatment with isoniazid, studies noted that dual treatment with this drug and isoniazid showed cost savings; there were greater cost savings as the prevalence of resistance to isoniazid increased.
Pyrazinamide treatments should be reserved for patients who are not likely to complete a longer course of treatment, can be closely monitored, and do not have contraindications to the regimen.

Use: Treatment of latent tuberculosis in patients with abnormal chest radiographs consistent with prior tuberculosis

Usual Adult Dose for Endocarditis

IDSA Recommendations:
300 mg IV or orally every 8 hours with vancomycin and/or gentamicin

Duration of therapy: At least 6 weeks

Comment: Early evaluation for valve replacement surgery should be considered.

Use: Treatment of prosthetic valve endocarditis

Usual Adult Dose for Nasal Carriage of Staphylococcus aureus

US CDC Recommendations:
600 mg IV OR orally once a day and another antibiotic agent
Duration of therapy: 5 to 10 days

Comments:

Oral decontamination should be limited to patients with active infections with susceptible strains.
Symptomatic household contacts should be treated.

Use: Treatment of recurrent skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA) despite using appropriate wound care and hygiene measures

Usual Adult Dose for Meningitis

IDSA Recommendations:
Streptococcal meningitis: 600 mg IV or orally once a day
Encephalitis and MRSA infections: 300 to 450 mg IV or orally 2 times a day or 600 mg orally once a day
Duration of therapy:

MRSA meningitis: 2 weeks
Brain abscess, subdural empyema, spinal epidural abscess, or septic thrombosis of cavernous/dural venous sinus: 4 to 6 weeks

Comments:

This drug is recommended for use in patients with intracranial/spinal hardware (e.g., cerebrospinal fluid shunt/drain.
Where possible, surgical evaluation for incision and drainage of contiguous sites of infection or abscess should be considered.

Uses:

Treatment of streptococcal ventriculitis and meningitis in combination with other antimicrobial agents
Management of MRSA meningitis in combination with vancomycin

Usual Adult Dose for CNS Infection

MRSA meningitis: 2 weeks
Brain abscess, subdural empyema, spinal epidural abscess, or septic thrombosis of cavernous/dural venous sinus: 4 to 6 weeks

Comments:

This drug is recommended for use in patients with intracranial/spinal hardware (e.g., cerebrospinal fluid shunt/drain.
Where possible, surgical evaluation for incision and drainage of contiguous sites of infection or abscess should be considered.

Uses:

Treatment of streptococcal ventriculitis and meningitis in combination with other antimicrobial agents
Management of MRSA meningitis in combination with vancomycin

Usual Adult Dose for Leprosy - Borderline

National Hansen's Disease (Leprosy) Program (NHDP) Recommendations:
Paucibacillary (PB)/Tuberculoid (TT and BT): 600 mg orally once a day PLUS dapsone
Duration of therapy: 12 months, then discontinue

Multibacillary (MB)/Lepromatous (LL, BL, BB): 600 mg orally once a day PLUS dapsone and clofazimine
Duration of therapy: 24 months, then discontinue

Comments:

A CBC with platelets should be monitored prior to treatment, then after 1 to 2 months, 3 months, 6 months, 12 months, 18 months, and 24 months.
In some areas, clofazimine is considered an investigational new drug (IND) that must be prescribed by a registered investigator; providers are encouraged to request investigator status by calling the NDHP at 1-800-642-2477.
Ofloxacin 400 mg/day may be substituted for clofazimine; clarithromycin 500 mg/day may be substituted for any of the drugs. Minocycline 100 mg/day may be substituted for dapsone in patients intolerant of the drug, and may also be used to substitute clofazimine; however, anti-inflammatory activity is not as substantial as clofazimine.

Use: Treatment of Hansen's disease (leprosy)

Usual Adult Dose for Leprosy - Tuberculoid

A CBC with platelets should be monitored prior to treatment, then after 1 to 2 months, 3 months, 6 months, 12 months, 18 months, and 24 months.
In some areas, clofazimine is considered an investigational new drug (IND) that must be prescribed by a registered investigator; providers are encouraged to request investigator status by calling the NDHP at 1-800-642-2477.
Ofloxacin 400 mg/day may be substituted for clofazimine; clarithromycin 500 mg/day may be substituted for any of the drugs. Minocycline 100 mg/day may be substituted for dapsone in patients intolerant of the drug, and may also be used to substitute clofazimine; however, anti-inflammatory activity is not as substantial as clofazimine.

Use: Treatment of Hansen's disease (leprosy)

Usual Adult Dose for Leprosy

A CBC with platelets should be monitored prior to treatment, then after 1 to 2 months, 3 months, 6 months, 12 months, 18 months, and 24 months.
In some areas, clofazimine is considered an investigational new drug (IND) that must be prescribed by a registered investigator; providers are encouraged to request investigator status by calling the NDHP at 1-800-642-2477.
Ofloxacin 400 mg/day may be substituted for clofazimine; clarithromycin 500 mg/day may be substituted for any of the drugs. Minocycline 100 mg/day may be substituted for dapsone in patients intolerant of the drug, and may also be used to substitute clofazimine; however, anti-inflammatory activity is not as substantial as clofazimine.

Use: Treatment of Hansen's disease (leprosy)

Usual Adult Dose for Joint Infection

IDSA Recommendations:
300 to 450 mg IV or orally 2 times a day OR 600 mg IV or orally once a day
Duration of treatment:

Debridement and total ankle, elbow, hip, or shoulder arthroplasty OR after 1-stage exchange: 3 months
Debridement and total knee arthroplasty: 6 months
Osteomyelitis: At least 8 weeks; some experts recommend an additional 1 to 3 months (e.g., for chronic infection or in cases where debridement is not performed)

Comments:

Pathogen-specific antimicrobial therapy should be given via IV for the first 2 to 6 weeks.
Surgical debridement and abscess drainage should be performed whenever possible.
This drug should be used after bacteremia is cleared (if present).

Use: Treatment of staphylococcal prosthetic joint infections, in combination with pathogen-specific antimicrobial therapy

Usual Adult Dose for Osteomyelitis

IDSA Recommendations:
300 to 450 mg IV or orally 2 times a day OR 600 mg IV or orally once a day
Duration of treatment:

Debridement and total ankle, elbow, hip, or shoulder arthroplasty OR after 1-stage exchange: 3 months
Debridement and total knee arthroplasty: 6 months
Osteomyelitis: At least 8 weeks; some experts recommend an additional 1 to 3 months (e.g., for chronic infection or in cases where debridement is not performed)

Comments:

Pathogen-specific antimicrobial therapy should be given via IV for the first 2 to 6 weeks.
Surgical debridement and abscess drainage should be performed whenever possible.
This drug should be used after bacteremia is cleared (if present).

Use: Treatment of staphylococcal prosthetic joint infections, in combination with pathogen-specific antimicrobial therapy

Usual Adult Dose for Bacteremia

IDSA Recommendations:
300 to 450 mg IV or orally 2 times a day OR 600 mg IV or orally once a day

Comments:

Search for and removal of foci of infection, drainage, or surgical debridement should be performed.
This drug should be given with high-dose daptomycin.

Use: Management of persistent MRSA bacteremia and vancomycin treatment failures

Usual Pediatric Dose for Tuberculosis - Active

10 to 20 mg/kg IV OR orally once a day
Maximum dose: 600 mg/day
Duration of therapy:

Initial phase: 2 months (with isoniazid, pyrazinamide, with/without streptomycin or ethambutol)
Continued phase: At least 4 months (with isoniazid)

Comments:

IV formulations should be used during initiation treatment and retreatment when the drug cannot be taken orally.
The Advisory Council for the Elimination of Tuberculosis, ATS, and US CDC recommend that either streptomycin or ethambutol be added to initial treatment unless the likelihood of isoniazid resistance is very low; treatment with less than 4 drugs may be considered if resistance is less than 4%.
Treatment may be continued in patients who remain sputum/culture positive, have resistant organisms, or are HIV positive.

Use: Treatment of all forms of tuberculosis

ATS, US CDC, and IDSA Recommendations:
Less than 15 years OR up to 40 kg:

Daily regimen: 10 to 20 mg/kg IV or orally once a day
Intermittent regiment: 10 to 20 mg IV or orally 2 to 3 times a week

15 years and older AND/OR over 40 kg:

Daily regimen: 10 mg/kg (usually 600 mg/day) orally or IV once a day
Intermittent regimen: 10 mg/kg (up to 600 mg/dose) orally or IV 2 to 3 times a week

Comment: Doses up to 35 mg/kg are being studied in clinical trials.

Use: Treatment of drug-susceptible tuberculosis

Usual Pediatric Dose for Meningococcal Meningitis Prophylaxis

Less than 1 month: 5 mg/kg IV OR orally every 12 hours
1 month and older: 10 mg/kg IV OR orally every 12 hours
Maximum dose: 600 mg/dose
Duration of therapy: 2 days

Comments:

This drug should not be used to treat meningococcal infections due to the potential for rapid resistance.
Use should be restricted to high-risk of meningococcal disease situations.

Use: Treatment of asymptomatic carriers of N meningitidis to eliminate meningococci from the nasopharynx

Usual Pediatric Dose for Tuberculosis - Latent

US CDC Recommendations:
Children:
10 to 20 mg/kg IV OR orally once a day with/without isoniazid
Maximum dose: 600 mg/day
Duration of therapy: 4 months

10 to 20 mg/kg IV OR orally once a day with pyrazinamide
Maximum dose: 600 mg/day
Duration of therapy: 2 months

15 years and older
10 mg/kg IV OR orally once a day with/without isoniazid
Maximum dose: 600 mg/day
Duration of therapy: 4 months

10 mg/kg IV OR orally once a day with pyrazinamide
Maximum dose: 600 mg/day
Duration of therapy: 2 months

Comments:

Compared to single treatment with isoniazid, studies noted that dual treatment with this drug and isoniazid showed cost savings; there were greater cost savings as the prevalence of resistance to isoniazid increased.
Pyrazinamide treatments should be reserved for patients who are not likely to complete a longer course of treatment, can be closely monitored, and do not have contraindications to the regimen.

Use: Treatment of latent tuberculosis in patients with abnormal chest radiographs consistent with prior tuberculosis

Usual Pediatric Dose for Meningitis

American Academy of Pediatrics (AAP) Recommendations:
20 mg/kg IV every 12 hours

Maximum dose: 600 mg/dose

Use: Treatment of meningitis caused by invasive pneumococcal infections

IDSA Recommendations:
20 mg/kg IV OR orally once a day

Comment: This drug is recommended for use in patients with intracranial/spinal hardware (e.g., cerebrospinal fluid shunt/drain.

Use: Treatment of ventriculitis and meningitis in combination with other antimicrobial agents

Usual Pediatric Dose for Meningitis - Pneumococcal

American Academy of Pediatrics (AAP) Recommendations:
20 mg/kg IV every 12 hours

Maximum dose: 600 mg/dose

Usual Pediatric Dose for Leprosy - Borderline

NHDP Recommendations:
Paucibacillary (PB)/Tuberculoid (TT and BT): 10 to 20 mg/kg orally once a day PLUS dapsone
Maximum dose: 600 mg/day
Duration of therapy: 12 months, then discontinue

Multibacillary (MB)/Lepromatous (LL, BL, BB): 10 to 20 mg/kg orally once a day PLUS dapsone and clofazimine
Maximum dose: 600 mg/day
Duration of therapy: 24 months, then discontinue

Comments:

A CBC with platelets should be monitored prior to treatment, then after 1 to 2 months, 3 months, 6 months, 12 months, 18 months, and 24 months.
In some areas, clofazimine is considered an IND that must be prescribed by a registered investigator; providers are encouraged to request investigator status by calling the NDHP at 1-800-642-2477.
Ofloxacin 400 mg/day may be substituted for clofazimine; clarithromycin 500 mg/day may be substituted for any of the drugs. Minocycline 100 mg/day may be substituted for dapsone in patients intolerant of the drug, and may also be used to substitute clofazimine; however, anti-inflammatory activity is not as substantial as clofazimine.

Use: Treatment of Hansen's disease (leprosy)

Usual Pediatric Dose for Leprosy - Tuberculoid

A CBC with platelets should be monitored prior to treatment, then after 1 to 2 months, 3 months, 6 months, 12 months, 18 months, and 24 months.
In some areas, clofazimine is considered an IND that must be prescribed by a registered investigator; providers are encouraged to request investigator status by calling the NDHP at 1-800-642-2477.
Ofloxacin 400 mg/day may be substituted for clofazimine; clarithromycin 500 mg/day may be substituted for any of the drugs. Minocycline 100 mg/day may be substituted for dapsone in patients intolerant of the drug, and may also be used to substitute clofazimine; however, anti-inflammatory activity is not as substantial as clofazimine.

Use: Treatment of Hansen's disease (leprosy)

Usual Pediatric Dose for Leprosy

A CBC with platelets should be monitored prior to treatment, then after 1 to 2 months, 3 months, 6 months, 12 months, 18 months, and 24 months.
In some areas, clofazimine is considered an IND that must be prescribed by a registered investigator; providers are encouraged to request investigator status by calling the NDHP at 1-800-642-2477.
Ofloxacin 400 mg/day may be substituted for clofazimine; clarithromycin 500 mg/day may be substituted for any of the drugs. Minocycline 100 mg/day may be substituted for dapsone in patients intolerant of the drug, and may also be used to substitute clofazimine; however, anti-inflammatory activity is not as substantial as clofazimine.

Use: Treatment of Hansen's disease (leprosy)

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

Liver dysfunction: Use with caution; frequent monitoring recommended.

Dose Adjustments

Resistant organism development AND no response to treatment: Treatment should be modified.

Patients with tuberculosis: Continue treatment in patients with positive sputum/cultures, in the presence of resistant organisms, or in HIV-positive patients.

Precautions

CONTRAINDICATIONS:

Hypersensitivity to the active component, any of the rifamycins, or any of the ingredients
Patients receiving ritonavir-boosted saquinavir concomitantly
Patients who are also receiving atazanavir, darunavir, fosamprenavir, saquinavir, or tipranavir

NARROW THERAPEUTIC INDEX:

This drug should be considered a narrow therapeutic index (NTI) drug as small differences in dose or blood concentrations may lead to serious therapeutic failures or adverse drug reactions.

Recommendations:

Generic substitution should be done cautiously, if at all, as current bioequivalence standards are generally insufficient for NTI drugs.
Additional and/or more frequent monitoring should be done to ensure receipt of an effective dose while avoiding unnecessary toxicities.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

Oral: Take 30 to 60 minutes before OR 2 hours after meals with a full glass of water.
Oral suspension: Shake well before use.
IV: IV formulations may be administered over 0.5 to 3 hours.

Storage requirements:

Protect from light

Reconstitution/preparation techniques:

Oral suspension: A 1% w/v oral suspension may be compounded. The manufacturer product information should be consulted.

IV compatibility:

The manufacturer product information should be consulted.

General:

IV formulations may be used by patients who are acutely ill or are unable to tolerate oral treatment (e.g. postoperative, comatose, impaired gastrointestinal absorption).
Directly observed treatment, short-course (DOTS) should be considered in all patients.

Monitoring:

General: Signs/symptoms of adverse reactions at least monthly
Hematologic: Complete blood count and platelet count (or estimate) at baseline for adults with tuberculosis and pediatric patients with a known/suspected compelling condition
Hepatic: Bilirubin and hepatic enzymes at baseline for adults with tuberculosis and pediatric patients with a known/suspected compelling condition; liver function tests every 2 to 4 weeks in patients with liver dysfunction or receiving hepatotoxic agents
Immunologic: Susceptibility tests to confirm susceptibility to this drug prior to initiation, and repeated throughout treatment; repeat tests for persistent positive cultures
Local: Signs/symptoms of localized infusion reactions
Renal: Serum creatinine at baseline for adults with tuberculosis and pediatric patients with a known/suspected compelling condition

Patient advice:

Patients should be advised to avoid missing doses and to complete the entire course of therapy.
Patients should be warned that treatment may produce a discoloration of sputum, sweat, tears, teeth, and urine; soft contact lenses may be permanently stained.
Patients should be told to immediately contact their healthcare provider if any of the following signs/symptoms occur: cough, darkened urine, fever, loss of appetite, malaise, nausea and vomiting, pain/swelling of the joints, rash, shortness of breath, swollen lymph nodes, wheezing, yellowish discoloration of the skin and eyes.
Patients should be instructed to report signs/symptoms of Clostridium difficile (e.g., watery/bloody stools, stomach cramps, fever), for up to 2 months after stopping treatment.
Advise patients to speak to their healthcare provider if they become pregnant, intend to become pregnant, or are breastfeeding.

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