for the elimination of tuberculosis, the american thoracic society, and centers for disease control and prevention recommend that either streptomycin or ethambutol be added as a fourth drug in a regimen containing isoniazid (inh), rifampin, and pyrazinamide for initial treatment of tuberculosis unless the likelihood of inh resistance is very low. the need for a fourth drug should be reassessed when the results of susceptibility testing are known. if community rates of inh resistance are currently less than 4%, an initial treatment regimen with less than four drugs may be considered. following the initial phase, treatment should be continued with rifampin and isoniazid for at least 4 months. treatment should be continued for longer if the patient is still sputum or culture positive, if resistant organisms are present, or if the patient is hiv positive. rifampin iv is indicated for the initial treatment and retreatment of tuberculosis when the drug cannot be taken by mouth. meningococcal carriers rifampin is indicated for the treatment of asymptomatic carriers of neisseria meningitidis to eliminate meningococci from the nasopharynx. rifampin is not indicated for the treatment of meningococcal infection because of the possibility of the rapid emergence of resistant organisms (see warnings .) rifampin should not be used indiscriminately, and, therefore, diagnostic laboratory procedures, including serotyping and susceptibility testing, should be performed for establishment of the carrier state and the correct treatment. so that the usefulness of rifampin in the treatment of asymptomatic meningococcal carriers is preserved, the drug should be used only when the risk of meningococcal disease is high. to reduce the development of drug-resistant bacteria and maintain the effectiveness of rifampin and other antibacterial drugs, rifampin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. when culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. in the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

ta amino levulinic acid synthetase. isolated reports have associated porphyria exacerbation with rifampin administration. the possibility of rapid emergence of resistant meningococci restricts the use of rifampin capsules to short-term treatment of the asymptomatic carrier state. rifampin capsules are not to be used for the treatment of meningococcal disease. systemic hypersensitivity reactions were reported with rifampin capsules administration. signs and symptoms of hypersensitivity reactions may include fever, rash, urticaria, angioedema, hypotension, acute bronchospasm, conjunctivitis, thrombocytopenia, neutropenia, elevated liver transaminases or flu-like syndrome (weakness, fatigue, muscle pain, nausea, vomiting, headache, chills, aches, itching, sweats, dizziness, shortness of breath, chest pain, cough, syncope, palpitations). manifestations of hypersensitivity, such as fever, lymphadenopathy or laboratory abnormalities (including eosinophilia, liver abnormalities) may be present even though rash is not evident. monitor patients receiving rifampin capsules for signs and/or symptoms of hypersensitivity reactions. if these signs or symptoms occur, discontinue rifampin capsules and administer supportive measures. 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) syndrome have been reported with rifampin. if symptoms or signs of severe cutaneous adverse reactions develop, discontinue rifampin capsules immediately and institute appropriate therapy. rifampin may cause vitamin k–dependent coagulation disorders and bleeding (see adverse reactions ). monitor coagulation tests during rifampin treatment (prothrombin time and other coagulation tests) in patients at risk of vitamin k deficiency (such as those with chronic liver disease, poor nutritional status, on prolonged antibacterial drugs or anticoagulants). consider discontinuation of rifampin capsules if abnormal coagulation tests and/or bleeding occur. supplemental vitamin k administration should be considered when appropriate. pulmonary toxicity manifested as interstitial lung disease (including, but not limited to, pneumonitis, hypersensitivity pneumonitis, eosinophilic pneumonia, pulmonary infiltrates, and organizing pneumonia) has been reported with rifampin treatment. pulmonary toxicity could be fatal. if symptoms or signs of severe pulmonary toxicity (including respiratory failure, pulmonary fibrosis, and acute respiratory distress syndrome) develop, discontinue rifampin capsules immediately and initiate appropriate treatment. postmarketing reports suggest that concomitant administration of high doses of cefazolin and rifampin may prolong the prothrombin time, leading to severe vitamin k–dependent coagulation disorders that may be life-threatening or fatal. avoid concomitant use of cefazolin and rifampin in patients at increased risk for bleeding. if no alternative treatment options are available, closely monitor prothrombin time and other coagulation tests, and administer vitamin k as indicated. 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 capsules (see adverse reactions ). 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.

zinamide for initial treatment of tuberculosis unless the likelihood of inh resistance is very low. the need for a fourth drug should be reassessed when the results of susceptibility testing are known. if community rates of inh resistance are currently less than 4%, an initial treatment regimen with less than four drugs may be considered. following the initial phase, treatment should be continued with rifampin and isoniazid for at least 4 months. treatment should be continued for longer if the patient is still sputum or culture positive, if resistant organisms are present, or if the patient is hiv positive. meningococcal carriers adults: for adults, it is recommended that 600 mg rifampin be administered twice daily for two days. pediatric patients: pediatric patients 1 month of age or older: 10 mg/kg (not to exceed 600 mg per dose) every 12 hours for two days. pediatric patients under 1 month of age: 5 mg/kg every 12 hours for two days. preparation of extemporaneous oral suspension for pediatric and adult patients in whom capsule swallowing is difficult or where lower doses are needed, a liquid suspension may be prepared as follows: rifampin 1% w/v suspension (10 mg/ml) can be compounded using one of four syrups–simple syrup (syrup nf), simple syrup (humco laboratories), syrpalta ®+ syrup (emerson laboratories), or raspberry syrup (humco laboratories). empty the contents of four rifampin capsules 300 mg or eight rifampin capsules 150 mg 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 blend to a 4-ounce amber glass or plastic (high density polyethylene [hdpe], polypropylene, or polycarbonate) prescription bottle. rinse the paper and spatula with 20 ml of one of the above-mentioned syrups, and add the rinse to the bottle. shake vigorously. add 100 ml of syrup to the bottle and shake vigorously. this compounding procedure results in a 1% w/v suspension containing 10 mg rifampin/ml. stability studies indicate that the suspension is stable when stored at room temperature (25 ± 3°c) or in a refrigerator (2 to 8°c) for four weeks. this extemporaneously prepared suspension must be shaken well prior to administration.

esumption of interrupted treatment. it rarely occurs during well-supervised daily therapy. this effect is reversible if the drug is discontinued as soon as purpura occurs. cerebral hemorrhage and fatalities have been reported when rifampin administration has been continued or resumed after the appearance of purpura. rare reports of disseminated intravascular coagulation have been observed. leukopenia, hemolytic anemia, decreased hemoglobin, bleeding, and vitamin k–dependent coagulation disorders (abnormal prolongation of prothrombin time or low vitamin k–dependent coagulation factors) have been observed. agranulocytosis has been reported very rarely. central nervous system headache, fever, drowsiness, fatigue, ataxia, dizziness, inability to concentrate, mental confusion, behavioral changes, muscular weakness, pains in extremities, and generalized numbness have been observed. psychoses have been rarely reported. rare reports of myopathy have also been observed. ocular visual disturbances have been observed. endocrine menstrual disturbances have been observed. rare reports of adrenal insufficiency in patients with compromised adrenal function have been observed. renal elevations in bun and serum uric acid have been reported. rarely, hemolysis, hemoglobinuria, hematuria, interstitial nephritis, acute tubular necrosis, renal insufficiency, and acute renal failure have been noted. these are generally considered to be hypersensitivity reactions. they usually occur during intermittent therapy or when treatment is resumed following intentional or accidental interruption of a daily dosage regimen, and are reversible when rifampin is discontinued and appropriate therapy instituted. dermatologic cutaneous reactions are mild and self-limiting and do not appear to be hypersensitivity reactions. typically, they consist of flushing and itching with or without a rash. more serious cutaneous reactions which may be due to hypersensitivity occur but are uncommon. hypersensitivity reactions occasionally, pruritus, urticaria, rash, pemphigoid reaction, erythema multiforme, acute generalized exanthematous pustulosis, stevens-johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms syndrome (see warnings), vasculitis, eosinophilia, sore mouth, sore tongue, and conjunctivitis have been observed. anaphylaxis has been reported rarely. respiratory, thoracic and mediastinal disorders pulmonary toxicity (including, but not limited to, interstitial lung disease, pneumonitis, hypersensitivity pneumonitis, eosinophilic pneumonia, pulmonary infiltrates, organizing pneumonia, respiratory failure, pulmonary fibrosis, and acute respiratory distress syndrome) has been observed (see warnings ). miscellaneous paradoxical drug reaction has been reported with rifampin (see warnings ). edema of the face and extremities has been reported. other reactions which have occurred with intermittent dosage regimens include "flu syndrome" (such as episodes of fever, chills, headache, dizziness, and bone pain), shortness of breath, wheezing, decrease in blood pressure and shock. the "flu syndrome" may also appear if rifampin is taken irregularly by the patient or if daily administration is resumed after a drug-free interval.

rage values of approximately 2 to 3 hours. the half-life does not differ in patients with renal failure at doses not exceeding 600 mg daily, and consequently, no dosage adjustment is required. the half-life of rifampin at a dose of 720 mg daily has not been established in patients with renal failure. following a single 900 mg oral dose of rifampin in patients with varying degrees of renal insufficiency, the mean half-life increased from 3.6 hours in healthy adults to 5.0, 7.3, and 11.0 hours in patients with glomerular filtration rates of 30 to 50 ml/min, less than 30 ml/min, and in anuric patients, respectively. refer to the warnings section for information regarding patients with hepatic insufficiency. after absorption, rifampin is rapidly eliminated in the bile, and an enterohepatic circulation ensues. during this process, rifampin undergoes progressive deacetylation so that nearly all the drug in the bile is in this form in about 6 hours. this metabolite has antibacterial activity. intestinal reabsorption is reduced by deacetylation, and elimination is facilitated. up to 30% of a dose is excreted in the urine, with about half of this being unchanged drug. pediatrics oral administration in one study, pediatric patients 6 to 58 months old were given rifampin suspended in simple syrup or as dry powder mixed with applesauce at a dose of 10 mg/kg body weight. peak serum concentrations of 10.7 ± 3.7 and 11.5 ± 5.1 mcg/ml were obtained 1 hour after preprandial ingestion of the drug suspension and the applesauce mixture, respectively. after the administration of either preparation, the t 1/2 of rifampin averaged 2.9 hours. it should be noted that in other studies in pediatric populations, at doses of 10 mg/kg body weight, mean peak serum concentrations of 3.5 mcg/ml to 15 mcg/ml have been reported. microbiology mechanism of action rifampin inhibits dna-dependent rna polymerase activity in susceptible mycobacterium tuberculosis organisms. specifically, it interacts with bacterial rna polymerase but does not inhibit the mammalian enzyme. resistance organisms resistant to rifampin are likely to be resistant to other rifamycins. in the treatment of both tuberculosis and the meningococcal carrier state (see indications and usage ), the small number of resistant cells present within large populations of susceptible cells can rapidly become predominant. in addition, resistance to rifampin has been determined to occur as single-step mutations of the dna-dependent rna polymerase. since resistance can emerge rapidly, appropriate susceptibility tests should be performed in the event of persistent positive cultures. activity in vitro and in vivo rifampin has bactericidal activity in vitro against slow and intermittently growing m tuberculosis organisms. rifampin has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections (see indications and usage ) . aerobic gram-negative microorganisms: neisseria meningitidis "other" microorganisms: mycobacterium tuberculosis the following in vitro data are available, but their clinical significance is unknown . at least 90% of the following bacteria exhibit an in vitro minimum inhibitory concentration (mic) less than or equal to the susceptible breakpoint for rifampin against isolates of similar genus or organism group. however, the efficacy of rifampin in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials. aerobic gram-positive microorganisms: staphylococcus aureus (including methicillin-resistant s aureus /mrsa) staphylococcus epidermidis aerobic gram-negative microorganisms: haemophilus influenzae "other" microorganisms: mycobacterium leprae ß-lactamase production should have no effect on rifampin activity. susceptibility testing for specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by fda for this drug, please see: https://www.fda.gov/stic.