Rifampin Dosage

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Usual Adult Dose for Tuberculosis - Active

The manufacturer recommends: 10 mg/kg (not to exceed 600 mg) orally or IV once a day

The American Thoracic Society (ATS), Centers for Disease Control and Prevention (CDC), and Infectious Diseases Society of America (IDSA) recommend:
Daily regimen: 10 mg/kg (up to 600 mg/day) orally or IV once a day
Intermittent regimen: 10 mg/kg (up to 600 mg/dose) orally or IV 2 or 3 times a week

A three-drug regimen consisting of isoniazid, rifampin, and pyrazinamide is recommended in the initial phase of short-course therapy which is usually continued for 2 months. Treatment should then be continued with isoniazid and rifampin for at least 4 months. Treatment duration should be extended if the patient's sputum or culture remains positive, if resistant organisms are present, or if the patient is HIV positive.

The Advisory Council for the Elimination of Tuberculosis, the ATS, and the CDC recommend adding streptomycin or ethambutol as a fourth drug in a regimen including isoniazid, pyrazinamide, and rifampin for initial treatment of tuberculosis unless the probability of isoniazid or rifampin resistance is very low. The need for a fourth drug should be reevaluated when susceptibility test results are known. If current community rates of isoniazid resistance are less than 4%, initial treatment with less than 4 drugs may be considered.

Usual Adult Dose for Tuberculosis - Latent

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.

Usual Adult Dose for Meningococcal Meningitis Prophylaxis

Treatment of asymptomatic carriers of Neisseria meningitidis to eliminate meningococci from the nasopharynx: 600 mg orally or IV twice a day for 2 days

Usual Adult Dose for Haemophilus influenzae Prophylaxis

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

Usual Adult Dose for Endocarditis

300 mg orally or IV every 8 hours for 6 weeks

Used concomitantly with nafcillin or vancomycin for the treatment of endocarditis in the presence of prosthetic material. Gentamicin is often added for the first 2 weeks of therapy.

Usual Adult Dose for Legionella Pneumonia

600 mg orally or IV once a day for 14 days

May be added to erythromycin therapy

Usual Adult Dose for Nasal Carriage of Staphylococcus aureus

600 mg orally or IV twice a day for 5 days for the treatment of chronic carriage of Staphylococcus aureus

Rifampin monotherapy or rifampin plus penicillin has been shown to eradicate staphylococci and Streptococcus pyogenes nasal colonization in nearly all cases.

Usual Adult Dose for Meningitis

Caused by Streptococcus pneumoniae: 600 mg orally or IV once a day for 10 to 14 days, in patients with severe penicillin allergy needing empiric or specific coverage

Sometimes used as adjunctive therapy for penicillin-resistant (MIC greater than or equal to 2.0 mcg/mL) meningitis. Regimen consists of vancomycin IV and rifampin. In addition, rifampin is sometimes used as adjunctive therapy to vancomycin in patients with infected CSF shunts.

Usual Adult Dose for Leprosy - Tuberculoid

Paucibacillary (tuberculid or indeterminate): 600 mg orally once a month, plus dapsone 100 mg daily, for a total of 6 months of therapy

Usual Adult Dose for Leprosy - Borderline

Multibacillary (lepromatous or borderline): 600 mg orally once a month along with clofazimine, plus daily dapsone and clofazimine, for a total of 12 months of therapy

Usual Pediatric Dose for Meningococcal Meningitis Prophylaxis

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

Usual Pediatric Dose for Tuberculosis - Active

For pediatric patients, the manufacturer recommends: 10 to 20 mg/kg/day (not to exceed 600 mg/day) orally or IV

For patients less than 15 years, the ATS, CDC, IDSA, and American Academy of Pediatrics (AAP) recommend:
Daily regimen: 10 to 20 mg/kg/day (up to 600 mg/day) orally or IV
Intermittent regimen: 10 to 20 mg/kg (up to 600 mg/dose) orally or IV twice a week

For patients 15 years or older, the ATS, CDC, and IDSA recommend:
Daily regimen: 10 mg/kg (up to 600 mg/day) orally or IV once a day
Intermittent regimen: 10 mg/kg (up to 600 mg/dose) orally or IV 2 or 3 times a week

A three-drug regimen consisting of isoniazid, rifampin, and pyrazinamide is recommended in the initial phase of short-course therapy which is usually continued for 2 months. Treatment should then be continued with isoniazid and rifampin for at least 4 months. Treatment duration should be extended if the patient's sputum or culture remains positive, if resistant organisms are present, or if the patient is HIV positive.

The Advisory Council for the Elimination of Tuberculosis, the ATS, and the CDC recommend adding streptomycin or ethambutol as a fourth drug in a regimen including isoniazid, pyrazinamide, and rifampin for initial treatment of tuberculosis unless the probability of isoniazid or rifampin resistance is very low. The need for a fourth drug should be reevaluated when susceptibility test results are known. If current community rates of isoniazid resistance are less than 4%, initial treatment with less than 4 drugs may be considered.

Study (n=175)
Directly Observed Therapy (DOT) - Two weeks daily therapy:
Greater than 1 month:
Weeks 1 and 2: Daily dosing of rifampin 10 to 20 mg/kg/day, isoniazid 10 to 15 mg/kg/day, and pyrazinamide 20 to 40 mg/kg/day
Weeks 3 to 8: Twice weekly rifampin 10 to 20 mg/kg/dose, isoniazid 20 to 40 mg/kg/dose, and pyrazinamide 50 to 70 mg/kg/dose
Weeks 9 to 24: Twice weekly rifampin 10 to 20 mg/kg/dose and isoniazid 20 to 40 mg/kg/dose

Usual Pediatric Dose for Tuberculosis - Latent

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

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Patients with impaired liver function should only be given rifampin in cases of necessity and then with caution and under strict medical supervision.

Dose Adjustments

Based on considerable clinical experience, 5 days/week administration by directly observed therapy is considered equivalent to 7 days/week administration; therefore, either may be considered "daily" for the treatment of tuberculosis.

There are four recommended regimens for treating patients with tuberculosis caused by drug-susceptible organisms. Each regimen has an initial phase of 2 months followed by a choice of several options for the continuation phase of either 4 or 7 months.

If pyrazinamide can not be used, due to organism resistance or if patient has severe liver disease, gout, or pregnancy, the initial phase for patients receiving daily therapy should consist of isoniazid, rifampin, and ethambutol until drug susceptibility determines that the isolate is fully susceptible to isoniazid and rifampin.

In children where visual acuity cannot be monitored, ethambutol is usually not recommended except when there is the likelihood of the disease being caused by isoniazid-resistant organisms or when the child has "adult-type" (upper lobe infiltrate, cavity formation) tuberculosis.

The continuation phase of treatment is given for 4 or 7 months. The vast majority of patients will use the 4-month continuation phase. The 7-month continuation phase is recommended for the following 3 groups: patients with cavitary pulmonary tuberculosis caused by drug-susceptible organisms and with positive sputum culture at the end of the 2-month initial treatment phase; patients whose initial phase of treatment did not include pyrazinamide; and patients with positive sputum cultures at the end of the initial phase and are treated with isoniazid and rifapentine once weekly for the continuation phase.

Most cases of pulmonary and extrapulmonary tuberculosis (except disseminated infections and tuberculous meningitis) usually require 6 to 9 months of treatment. In general, a treatment duration of 9 to 12 months is recommended for tuberculous meningitis; however, the optimal duration of therapy has not been established.

Precautions

Rifampin is contraindicated in patients receiving ritonavir-boosted saquinavir due to an increased risk of severe hepatocellular toxicity. Rifampin is contraindicated in patients receiving atazanavir, darunavir, fosamprenavir, saquinavir, or tipranavir due to the potential of rifampin to substantially decrease plasma concentrations of these antiviral drugs, which may result in loss of antiviral efficacy and/or development of viral resistance.

Rifampin has been shown to produce hepatotoxicity in patients with preexisting liver dysfunction and in patients with normal liver function who are also taking other hepatotoxic agents. Some cases have been fatal. Patients with impaired liver function should only be given rifampin in cases of necessity and then with caution and under strict medical supervision. In these patients, careful monitoring of liver function, especially SGPT/ALT and SGOT/AST should be carried out prior to therapy and then every 2 to 4 weeks during therapy. If signs of hepatocellular damage occur, rifampin should be withdrawn.

In some cases, hyperbilirubinemia resulting from competition between rifampin and bilirubin for excretory pathways of the liver at the cell level have been observed in the early days of treatment. An isolated report showing a moderate rise in bilirubin and/or transaminase level is not in itself an indication for interrupting therapy; rather, the decision should be made after repeating the laboratory tests, noting trends in the levels, and considering them in conjunction with the patient's clinical condition.

Rifampin possesses enzyme-inducing properties, including induction of delta amino levulinic acid synthetase. Isolated reports have associated porphyria exacerbation with rifampin use. The possibility of rapid emergence of resistant meningococci restricts the administration of rifampin to short-term treatment of the asymptomatic carrier state. Due to the rapid emergence of resistant organisms, rifampin should not be used in the treatment of meningococcal infection.

Administering rifampin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

For the treatment of tuberculosis, rifampin is usually given on a daily basis. Doses of rifampin greater than 600 mg administered once or twice weekly have resulted in a higher incidence of adverse reactions, including the "flu syndrome" (fever, chills, and malaise), hematopoietic reactions (leucopenia, thrombocytopenia, or acute hemolytic anemia), cutaneous, gastrointestinal, and hepatic reactions, shortness of breath, shock, anaphylaxis, and renal failure. Recent studies indicate that regimens using twice-weekly doses of rifampin 600 mg plus isoniazid 15 mg/kg are much better tolerated.

Intermittent rifampin therapy is not recommended by the manufacturer. Patients should be cautioned against intentional or accidental interruption of the daily dosage regimen since rare renal hypersensitivity reactions have been reported when therapy was resumed in such cases.

Rifampin IV is for intravenous infusion only. It must not be given by intramuscular or subcutaneous route. Extravasation must be avoided during injection. Local irritation and inflammation due to extravascular infiltration of the infusion have been reported. If these occur, the infusion should be discontinued and restarted at an alternate site.

Adults treated for tuberculosis with rifampin therapy should have baseline measurements of hepatic enzymes, bilirubin, serum creatinine, a complete blood count, and a platelet count (or estimate). Baseline tests are not required in pediatric patients unless a complicating condition is known or clinically suspected. Patients should be seen at least monthly during rifampin therapy and should be specifically questioned concerning symptoms associated with adverse reactions. All patients with abnormalities should have follow-up, including laboratory testing, if necessary. Routine laboratory monitoring for toxicity in people with normal baseline measurements is generally not required.

Rifampin should be used with caution in patients with a history of diabetes mellitus as diabetes management may be more difficult.

Because of the numerous drug interactions which may occur with rifampin therapy, the use and effectiveness of all medications in a patient's drug regimen should be reconsidered when rifampin is added to or deleted from that regimen.

Caution should be exercised when using rifampin and pyrazinamide for the treatment of latent tuberculosis infection because of the potential for severe liver injury with fatal outcome. Close monitoring for any signs of hepatitis and laboratory testing for elevated liver enzymes is recommended on these patients.

Clinical studies of rifampin did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experiences have not identified differences in responses between the elderly and younger patients. Caution should be exercised when used in the elderly.

Dialysis

Rifampin is not significantly removed via hemodialysis or peritoneal dialysis, but it is recommended to administer the dose after the dialysis session on the day of hemodialysis.

Other Comments

In general, rifampin is administered orally. Rifampin may be given via IV infusion when oral therapy is not possible.

Oral rifampin should be given on an empty stomach (1 hour before or 2 hours after a meal) with a full glass of water. Once-daily administration of oral rifampin is recommended for the treatment of tuberculosis.

A liquid suspension, rifampin 1% w/v (10 mg/mL), may be prepared using the capsules. Empty the contents of four rifampin 300 mg capsules onto a piece of weighing paper. If necessary, gently crush the capsule contents with a spatula to produce a fine powder. Transfer the rifampin powder to a 4-ounce amber glass or plastic prescription bottle. Rinse the paper and spatula with 20 mL of syrup (syrup NF, simple syrup, Syrpalta (R) syrup, or raspberry syrup), and add the rinse to the bottle. Shake vigorously. Add 100 mL of syrup to the bottle and shake vigorously. The final suspension may be stored at room temperature or refrigerated for 4 weeks. Shake well prior to use.

Patients should be informed that rifampin may cause a brownish-red or orange discoloration of urine, tears, feces, saliva, sputum, and sweat. Permanent discoloration of contact lens may occur.

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