Rifampin dosing

Oral rifampin dose and AUC changes abstracted from alfentanil (205), buspirone (208), gefitinib (209), L-a-acetylmethadol (210), midazolam (77) nifedipine (62), simvastatin (211), tamoxifen (212), toremifene (212), triazolam (213), and verapamil (60). 

Recently, bioavailability and clearance data obtained from a crossover study of cyclosporine kinetics before and after rifampin dosing revealed a new understanding of drug metabolism and disposition of the compound (9). Healthy volunteers were given cyclosporine, intravenously and orally, before and after CYP3A (P450 3A) enzymes were introduced by rifampin. As expected, the blood clearance and cyclosporine increased from 0.31 to 0.42 L... 

Ruslami R, Nijland HM, AUsjahbana B, Parwati 1, van Crevel R, Aamoutse RE. Pharmacokinetics and tolerability of a higher rifampin dose versus the standard dose in pulmonary tuberculosis patients. Antimicrob Agents Chemother 2007 51(7) 2546-51. 

Maintenance doses widely vary among patients (e.g., from 1 to 20 mg/day for warfarin), and are influenced by diet (variable vitamin K intake) and medications that affect coumarin metabolism (decreased drug clearance e.g., cotrimoxazole, amiodarone, erythromycin increased clearance e.g., barbiturates, carbamaze-pine, rifampin). Thus, regular monitoring is needed... 

Acetaminophen may alter blood glucose test results, causing falsely lower blood glucose values. Use with the barbiturates, hydantoins, isoniazid, and rifampin may increase the toxic effects and possibly decrease the therapeutic effects of acetaminophen. The effects of the loop diuretics may be decreased when administered with acetaminophen. Hepatotoxicity has occurred in chronic alcoholics who are taking moderate doses of acetaminophen. 

Doses of hydrocortisone may need to be increased or decreased in patients taking CYP450 3A4 inducers (e.g., phenytoin, rifampin, barbiturates) or inhibitors (e.g., protease inhibitors), respectively. 

Empirical therapy for postoperative infections in neurosurgical patients (including patients with CSF shunts) should include vancomycin in combination with either cefepime, ceftazidime, or meropenem. Linezolid has been reported to reach adequate CSF concentrations and resolve cases of meningitis refractory to vancomycin.35 However, data with linezolid are limited. The addition of rifampin should be considered for treatment of shunt infections. When culture and sensitivity data are available, pathogen-directed antibiotic therapy should be administered. Removal of infected devices is desirable aggressive antibiotic therapy (including high-dose intravenous antibiotic therapy plus intraventricular vancomycin and/or tobramycin) may be effective for patients in whom hardware removal is not possible.36... 

Isoniazid is used for treating LTBI.2,6,12,28 Typically, isoniazid 300 mg daily (5-10 mg/kg of body weight) is given alone for 9 months. Lower doses usually are less effective.2,31 The treatment of LTBI reduces a person s lifetime risk of active TB from about 10% to about 1%20 (Table 72-2). Rifampin 600 mg... 

Because they are hepatically cleared, isoniazid and rifampin do not require dose modification in renal failure.31,36,39 Pyrazinamide and ethambutol typically are reduced to three times weekly to avoid accumulation of the parent drug (ethambutol) or metabolites (pyrazinamide).28,31 Renally cleared TB drugs include the aminoglycosides (e.g., amikacin, kanamycin, and streptomycin), capreomycin, ethambutol, cycloserine, and lev-ofloxacin.28,31,33,39 Dosing intervals need to be extended for... 

Rifabutin Adults0 5 mg/kg (300 mg) Children Appropriate dosing unknown Hematologic toxicity, uveitis, gastrointestinal symptoms, polyarthralgias, hepatotoxicity, pseudojaundice (skin discoloration with normal bilirubin), rash, flulike syndrome, orange discoloration of bodily fluids (sputum, urine, sweat, tears) Drug interactions are less problematic than rifampin... 

Oral azoles are associated with significant interactions, particularly due to cytochrome P-450 isoenzymes. Medications that interact with azoles include warfarin, phenytoin, theophylline, rifampin, cyclosporine, and zidovudine. For patients receiving only a few doses, these interactions do not pose a significant risk. These interactions may pose a risk for patients receiving long-term suppressive therapy for recurrent infections. 

Adult patients should receive 600 mg of rifampin orally every 12 hours for four doses. Children 1 month to 12 years of age should receive 10 mg/kg of rifampin orally every 12 hours for four doses, and children younger than 1 month should receive 5 mg/kg orally every 12 hours for four doses. 

Concurrent administration of rifampin is recommended at doses of 10 to 20 mg/kg/day (maximum 600 mg/day) for children and 600 mg/day for adults. The addition ofpyrazinamide (children and adults, 15 to 30 mg/kg/ day maximum in both, 2 g/day) to the regimen of isoniazid and rifampin is now recommended. The duration of concomitant pyrazinamide therapy should be limited to 2 months to avoid hepatotoxicity. 

Rifampin 900 mg per 24 hours IV/orally in three equally divided doses >6 ... 

Isoniazid, rifampin, pyra- Seven days per week for 56 doses (8 weeks) la Isoniazid/rifampin Seven days per week for 126 doses (18 182-130(26 A(l) A (II)... 

The drug can likely be used safely in older children but should be used with caution in children less than 5 years of age, in whom visual acuity cannot be monitored. In younger children, ethambutol at the dose of 15 mg/kg per day can be used if there is suspected or proven resistance to isoniazid or rifampin. 

The long-term (more than several weeks) use of levofloxacin in children and adolescents has not been approved because of concerns about effects on bone and cartilage growth. However, most experts agree that the drug should be considered for children with tuberculosis caused by organisms resistant to both isoniazid and rifampin. The optimal dose is not known. 

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