Version July 2025
INTRODUCTION —
The rifamycins include rifampin, rifapentine, and rifabutin. Of these, rifampin is most commonly used, either as first-line therapy (in combination with other agents) for treatment of mycobacterial disease (including tuberculosis) or for select invasive staphylococcal infections (as part of combination therapy) [1-4].
Rifamycins (most notably rifampin) are moderate to potent inducers of drugs undergoing metabolism by the cytochrome P450 enzyme system (notably CYP3A4), which can lead to reduced bioavailability and enhanced clearance of some coadministered medications. Such interactions may be delayed in onset but persist beyond rifamycin coadministration. Rifampin may also induce P-glycoprotein (P-gp) multidrug efflux transporters. Therefore, patients receiving any rifamycin should have their medication regimen analyzed carefully for drug interactions. This may be done by use of the drug interaction program included within UpToDate.
Issues related to pharmacology of rifampin, rifabutin, and rifapentine will be reviewed here. Issues related to clinical use of these agents are discussed separately. (See related topics.)
NITROSAMINE IMPURITIES —
In August 2020, the US Food and Drug Administration (FDA) announced detection of nitrosamine impurities in samples of rifampin and rifapentine [5].
Nitrosamines are commonly found as contaminants in processed foods and beverages as well as some medications. They also are produced endogenously following ingestion of some foods, drinks, or medications. Some nitrosamines have been implicated as possible human carcinogens based largely on long-term animal studies, with toxicity largely related to cumulative exposure. The risk of cancer (if any) among individuals who complete a 4-month course of RIF or a 12-dose course of RPT with current levels of contamination by these compounds is unknown. Regulatory agencies worldwide have set upper acceptable intake limits for these compounds [6].
In the United States, to preserve the supply of these important drugs, the FDA increased the upper acceptable daily intake limits for RIF and RPT and is working with manufacturers to reduce nitrosamine levels in these products [7].
Because the risks from TB appear to be greater than those from cancer, and the risks for serious toxicity such as INH-induced hepatitis may be substantial with alternative regimens, we favor continued use of rifampin or rifapentine if acceptable to the patient, as the risk of not taking rifampin or rifapentine for treatment of TB infection or disease likely outweighs any potential risk from nitrosamine impurities; this approach is consistent with the United States Centers for Disease Control and Prevention (CDC) guidance issued in September 2020 [8]. Precise levels of contamination for a given drug lot are not provided to the consumer and a discussion with the patient should reflect informed decision making if either of these drugs is recommended for treatment of tuberculosis infection or disease.
RIFAMPIN —
Rifampin is the most commonly used rifamycin for treatment of nontuberculous mycobacterial (NTM) diseases, in combination with other agents [2,9]. It is also used for treatment of tuberculosis (active disease and latent infection), for prophylaxis following exposure to Neisseria meningitidis or Haemophilus influenzae, and as an adjunctive agent for treatment of select deep-seated staphylococcal infections. (See related topics.)
Mechanism of action — Rifampin is thought to inhibit bacterial DNA-dependent RNA polymerase, which appears to occur as a result of drug binding in the polymerase subunit deep within the DNA/RNA channel, facilitating direct blocking of the elongating RNA [10]. This effect is thought to be concentration related [11].
Resistance — Resistance to rifampin arises due to missense mutations in the rpoB gene and occurs in a variety of bacteria including Mycobacterium tuberculosis, Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA]), Streptococcus pneumoniae, and Rickettsiae [12-16].
Phenotypic (culture-based) cross-resistance between rifampin and the other rifamycins (rifabutin and rifapentine) depends on the mutation type; it is extensive but not complete [17,18]. Molecular drug susceptibility testing (specifically nucleic acid amplification testing [NAAT]) is providing new insights into the potential significance of these mutations in the clinical management of tuberculosis. Since cross-resistance to other rifamycins is incomplete, it may be appropriate (in select cases, notably in patients with multidrug-resistant strains of M. tuberculosis) to perform rifabutin susceptibility testing when rifampin resistance is observed [19].
The rate of spontaneous resistance of M. tuberculosis via single-step mutation to rifampin is 1 in 108 bacilli [20]. The rate of resistance in other types of bacteria (eg, Escherichia coli, S. aureus, Streptococcus spp, and N. meningitidis) is much higher [21]. Since the rate of development of resistance is both high and predictable, rifampin should be used as monotherapy only for prophylaxis against N. meningitidis or H. influenzae, or for latent infection with tuberculosis where the organism burden is relatively low.
Spectrum of in vitro activity — Rifampin is useful for treatment of intracellular pathogens due to high intracellular penetration. It demonstrates bactericidal activity in vitro against most strains of tuberculosis. Rifampin also demonstrates activity in vitro against NTM, including Mycobacterium kansasii. Activity against Mycobacterium avium complex (MAC) organisms is variable. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection" and "Treatment of Mycobacterium avium complex pulmonary infection in adults".)
Rifampin demonstrates in vitro activity against a broad spectrum of bacteria other than Mycobacteria spp. Susceptible gram-positive organisms include S. aureus, coagulase-negative staphylococci, Streptococcus pyogenes, Streptococcus pneumoniae, viridans streptococci, and Listeria monocytogenes. Rifampin also has activity against Chlamydia spp and diverse gram-negative pathogens, including Legionella spp, Brucella spp, H. influenzae, Haemophilus ducreyi, Neisseria gonorrhoeae, and N. meningitidis.
Pharmacokinetics and pharmacodynamics
●Pharmacokinetics – Rifampin undergoes rapid and complete absorption after oral administration. Absorption may be formulation dependent and is improved when the oral dose is taken on an empty stomach but may be delayed or reduced if taken with food and in patients with diabetes and/or HIV infection [22-25]. Oral doses exceeding 10 mg/kg may result in a disproportionately high increase in dose-exposure relationship [26-28]. Rifampin undergoes wide distribution into most body tissues and fluids, including penetration into the cerebrospinal fluid (in patients with inflamed meninges). It concentrates intracellularly up to five times that of extracellular concentrations, primarily in polymorphonuclear leukocytes [29]. The protein binding of rifampin is approximately 80 percent.
Rifampin undergoes extensive hepatic metabolism to less active metabolites, with a half-life of three hours. After multiple doses, exposure may decline after steady state is achieved, which may be due (at least in part) to autoinduction leading to enhanced clearance [26,27,30].
Renal elimination of unchanged drug is minimal (<30 percent). Caution should be exercised when rifampin is administered to patients with significant hepatic disease, especially when used in combination with other hepatotoxins (such as isoniazid). (See "Isoniazid hepatotoxicity".)
●Pharmacodynamics – Concentration-dependent activity has been described in animal models of tuberculosis.
The AUC/MIC relationship is thought to best reflect activity of rifampin; however, clinical targets for nonmycobacterial infections have not been established.
Dosing and administration — Doses and treatment durations for rifampin vary by indication. Oral doses should be administered one hour before or two hours after meals. Intravenous doses are generally comparable to the oral dose.
●Tuberculosis – Rifampin dosing for treatment of tuberculosis is presented separately:
•(See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection".)
•(See "Tuberculosis disease in children: Treatment and prevention".)
Based on pharmacokinetic/pharmacodynamic studies (noting concentration-dependent activity and the variability in kinetic parameters) and the desire to use shorter courses of therapy, there is interest in use of higher rifampin doses (up to 35 mg/kg or fixed dosing in adults of 1200 or 1800 mg/d] than those routinely recommended for pulmonary tuberculosis treatment [11,26-28,31-38]. However, findings of both efficacy and safety with such increases have been mixed. In one trial, high-dose rifampin for four months did not exhibit dose-limiting side effects but failed to meet noninferiority criteria compared with the standard 6-month control regimen [35]. Others reported that hepatotoxicity, clinical jaundice, and treatment interruptions occurred more frequently in patients receiving 30 to 35mg/kg daily than those receiving 10mg/kg [36,38]. In these trials, rifampin 20 to 25mg/kg was as safe as the 10mg/kg dose.
●Staphylococcal infection – Rifampin dosing for treatment of staphylococcal infection is presented separately:
•(See "Prosthetic joint infection: Treatment".)
●Nontuberculous mycobacterial infection – Rifampin dosing for treatment of nontuberculous mycobacterial infection is presented separately:
•(See "Treatment of Mycobacterium avium complex pulmonary infection in adults".)
•(See "Rapidly growing mycobacterial infections: Mycobacteria abscessus, chelonae, and fortuitum".)
●Postexposure prophylaxis (N. meningitidis and H. influenzae) – Rifampin dosing for postexposure prophylaxis is presented separately:
•(See "Prevention of Haemophilus influenzae type b infection".)
•(See "Treatment and prevention of meningococcal infection".)
Special populations — Rifampin has been safely administered during pregnancy. Teratogenicity has been demonstrated in laboratory animals; therefore, it should be used only if potential benefits outweigh risks. Concentrations of rifampin in breast milk are reported to be insufficient to produce toxicity in the nursing newborn. Rifampin can cause orange discoloration to breast milk, which is considered harmless [39].
No dose adjustments are needed for rifampin in patients with renal dysfunction or those undergoing dialysis.
Rifampin metabolism may be altered in patients with hepatic impairment. Caution should be exercised in administering rifampin to patients with underlying hepatic dysfunction; no formal guidelines are available to guide dosing in this population.
Adverse effects — Patients should be advised that rifampin typically causes an orange or red-orange discoloration of body fluids (including urine, sweat, saliva, and tears).
Adverse effects associated with the administration of rifampin include gastrointestinal effects (nausea, vomiting, diarrhea), central nervous system effects (headache, fever), dermatologic effects (rash, itching, flushing), hematologic effects (thrombocytopenia, neutropenia, and acute hemolytic anemia), and pulmonary toxicity [40]. Pruritus (with or without rash) can occur but may not represent a true hypersensitivity reaction; therefore, continued use may be possible in some patients.
Hepatitis is infrequently associated with rifampin but is more commonly observed in patients with predisposing factors, including administration of concomitant hepatotoxins (such as isoniazid), HIV coinfection, history of liver disease, regular alcohol consumption, pregnancy, or postpartum patients. For unclear reasons, a high incidence of hepatotoxicity has been observed in patients treated with a two-month regimen of rifampin and pyrazinamide for latent tuberculosis infection [41]. For this reason, subsequent guidelines have advised against use of this regimen.
Rifampin can cause a flu-like syndrome beginning one to two hours after administration and resolving six to eight hours later [42]. Typically, this syndrome occurs more commonly with intermittent rather than daily therapy, particularly at higher doses. Most patients are able to tolerate rifampin if the interval is changed from intermittent to daily.
Reactions associated with rifampin that should prompt discontinuation of the drug include moderate-severe hepatotoxicity, anaphylaxis, cutaneous vasculitis, red cell aplasia, leukopenia and agranulocytosis, thrombocytopenia, disseminated intravascular coagulation, hemolytic anemia, pulmonary infiltrates, lupoid reactions, and acute renal failure.
Monitoring
●Clinical monitoring – All patients must be educated about possible symptoms of hepatic toxicity, including unexplained anorexia, nausea, vomiting, dark urine, icterus, rash, pruritus, persistent fatigue, weakness or fever lasting three or more days, abdominal discomfort (particularly right upper quadrant discomfort), or easy bruising or bleeding. Arthralgias also can occur. Patients should be directly questioned at visits for these symptoms. In addition, they should immediately report any signs or symptoms that occur between visits and stop the medication treatment pending further evaluation. All patients with such complaints should be fully evaluated clinically, including serum testing for hepatic injury.
●Therapeutic drug monitoring – Serum concentration monitoring of rifampin therapy is not routinely performed, but may be considered in patients failing therapy or in whom impaired absorption is suspected. Based on available data, the therapeutic serum concentration for rifampin against M. tuberculosis is a two-hour post-dose concentration of 8 to 24 microgram/mL (see "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection"). Such sample timing, however, may underestimate peak concentrations in a subset of patients with tuberculosis and delayed drug absorption [43].
Issues related to laboratory monitoring for patients on antituberculous drugs are discussed separately. (See "Antituberculous drugs: An overview", section on 'Clinical and laboratory monitoring'.)
Drug interactions — Rifampin is a potent inducer of several drug-metabolizing enzymes as well as P-glycoprotein (P-gp) multidrug efflux transporters, which can lead to significant reductions in concentrations and (in some cases) therapeutic failure of other drugs. Drug interactions result from the ability of rifampin to induce cytochrome P450 CYP3A metabolism (and to a lesser extent CYP2B6, CYP2C8, CYP2C9, and CYP2C) and glucuronidation, thereby accelerating drug excretion. Rifampin also increases intestinal P-gp mediated drug efflux, thereby reducing gastrointestinal absorption of drugs that are P-gp substrates [44-48]. Such interactions include (but are not limited to) oral or other hormonal contraceptives, glucocorticoids, cyclosporine, HMG-CoA reductase inhibitors ("statins"), macrolide antibiotics, tacrolimus, warfarin, direct oral anticoagulants (eg, dabigatran), phenytoin, levothyroxine, azole antifungal agents, oral sulfonylurea hypoglycemics, several antimalarials, quinidine, verapamil, methadone, and beta-blockers.
There are a number of drug interactions between rifampin and antiretrovirals including integrase inhibitors (bictegravir, dolutegravir, elvitegravir-containing formulations), protease inhibitors (lopinavir, darunavir or atazanavir with or without cobicistat or ritonavir), non-nucleoside reverse-transcriptase inhibitors (etravirine and rilpivirine), and fostemsavir. Use of rifampin with protease inhibitors is contraindicated [49].
Information regarding the interactions between rifampin (as a treatment for tuberculosis) and antiretrovirals is dynamic. The United States Centers for Disease Control and Prevention maintains guidelines for management of such interactions [3]. Details about specific interactions may be obtained by using the drug interactions program included within UpToDate.
The impact of rifampin dose on the degree of drug interactions has been assessed [50]. Higher doses demonstrated mild additional induction of CYP2C9, CYP2C19, CYP2D6, and CYP3A, and marginal inhibition of P-gp. No additional effect was observed on CYP1A2.
While the onset of effect of enzyme induction (resulting in reductions in coadministered medication[s]) can be observed within hours following oral administration of rifampin, the full effect can require up to two weeks. After rifampin discontinuation, the effect can persist while slowly abating over two weeks [51-54]. As a result of such interaction, substantial increase in dosage of the coadministered drug may be needed when taken either concomitant or immediately following rifampin administration. In clinical scenarios where serum concentration monitoring is available for the interacting drug (eg, tacrolimus, warfarin) more frequent measurements are needed when starting or stopping rifampin.
RIFABUTIN —
Rifabutin has reduced potential for drug interactions (relative to rifampin) [55]. Therefore, it is most commonly used for treatment of select mycobacterial infections in patients receiving concomitant medications exhibiting significant interactions with rifampin (such as select antiretroviral therapies) [56]. Rifabutin is approved by the US Food and Drug Administration for the prevention of disseminated M. avium complex (MAC) disease in patients with advanced HIV infection.
Mechanism of action — Rifabutin inhibits DNA-dependent RNA polymerase at the beta subunit, thus preventing chain initiation [57].
Resistance — Rifampin-resistant isolates generally have been considered resistant to all rifamycins (including rifabutin). However, phenotypic cross-resistance is not universal [17,18]. In some studies, about 20 to 30 percent of rifampin-resistant multidrug-resistant tuberculosis strains demonstrate in vitro susceptibility to rifabutin [58]. It has been suggested that rifabutin susceptibility testing should be done in select cases when rifampin resistance is observed [19].
Pharmacokinetics — Following a single 300 mg oral dose, mean (±standard deviation) peak plasma rifabutin concentrations of 375 (±267) ng/mL have been reported [57]. In a healthy volunteer study, absolute oral bioavailability is approximately 20 percent, with the capsules achieving approximately 85 percent of the oral solution [57]. High-fat meals slow the rate (but not the extent) of absorption from the capsule dosage form. Rifabutin has extensive distribution and intracellular uptake. About 85 percent of the drug is bound to plasma proteins. Approximately 53 percent and 30 percent of the oral dose is excreted in the urine (primarily as metabolites) and stool, respectively. Less than 10 percent is excreted in urine as unchanged drug. A mean terminal half-life of 45 (±17) hours was reported in healthy volunteers.
Dosing — Rifabutin dosing is presented separately:
●(See "Mycobacterium avium complex (MAC) infections in persons with HIV".)
●(See "Treatment of Helicobacter pylori infection in adults".)
Rifabutin serum concentrations can be impacted by coadministration of agents that inhibit or induce CYA-3A4. In patients with HIV infection, coadministration of protease inhibitors (specifically atazanavir with or without booster [cobicistat], darunavir and lopinavir with or without booster [ritonavir]) can significantly increase the area under the time-concentration curve for rifabutin. In such situations, rifabutin dosing for the treatment of tuberculosis should be reduced to 150 mg daily [59]. Subsequent rifabutin dose increases would be necessary if the interacting drugs were discontinued. In contrast, efavirenz coadministration may significantly reduce concentrations of rifabutin (see 'Drug interactions' below). Rifabutin should not be used with elvitegravir/cobicistat or bictegravir.
In patients with significant renal impairment (creatinine clearance [CrCl] of <30 ml/min), the manufacturer’s labeling recommends consideration of 50 percent dose reduction if toxicity is suspected. However, area under the curve values reported in patients with CrCl <30 have been similar to those found in healthy volunteers, suggesting that no dose reduction is needed [60,61]. If available, therapeutic drug monitoring in these patients may be helpful, particularly if drug toxicity is suspected.
Special populations — Limited data are available for the use of rifabutin in children with tuberculosis and the appropriate dose is unknown. In such settings, 5 mg/kg mg/kg (maximum dose 300 mg) may be administered once daily [3].
Rifabutin should not be administered as MAC prophylaxis to patients with active tuberculosis.
Adverse effects — Similar to other rifamycins, hematologic toxicity (most notably neutropenia) and hepatotoxicity have been reported in patients receiving rifabutin. Similar to rifampin, the risks of hepatotoxicity would be greatest in patients with predisposing factors, including administration of concomitant hepatotoxins (such as isoniazid), HIV coinfection, history of liver disease, regular alcohol consumption, pregnancy, or postpartum patients.
Rifabutin-induced uveitis has also been reported [62]. It is generally considered a rare, dose-related event. Concomitant administration of drugs that may increase serum concentrations of rifabutin (notably clarithromycin or fluconazole) significantly increase the risk of this reaction.
Similar to other rifamycins, rifabutin administration may result in orange or red-orange discoloration of body fluids (including urine, sweat, saliva, and tears).
There have been reports of severe cutaneous adverse reactions due to rifabutin; these include Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis.
Monitoring — Routine monitoring of rifabutin serum concentrations is not performed. Therapeutic concentration monitoring could assist in minimizing the risk of rifabutin-related toxicities, especially in the setting of coadministration of interacting agents (such as protease inhibitors).
Drug interactions — Rifabutin is a potent inhibitor of P-glycoprotein. Rifabutin shares the property of uridine diphosphate gluconyltransferase 1A1 and CYP enzyme induction with other rifamycins (predominately CYP-3A4) but is generally considered less potent [63]. However, significant interactions with rifabutin and CYP substrates do occur. As an example, coadministration of rifabutin (300 mg/day) and clarithromycin (500 mg every 12 hours) decreased the area under the curve of clarithromycin by about 50 percent [57]. Trough raltegravir concentrations are reduced by coadministration with rifabutin by about 20 percent, although standard-dose raltegravir (400 mg twice daily) is recommended with concomitant rifabutin. In contrast, coadministration of elvitegravir (with or without cobicistat) with rifabutin is not recommended due to reductions of elvitegravir trough concentrations (67 percent) when cobicistat-boosted elvitegravir is given together with rifabutin [64].
Because rifabutin is also a substrate of CYP-3A4, its concentrations may be impacted by concomitant administration of agents inhibiting or inducing this enzyme. Protease inhibitors such as ritonavir (a potent CYP-3A4 inhibitor) may increase rifabutin serum concentrations by up to fourfold and its major metabolite by up to 35-fold [64]. Other protease inhibitors (such as nelfinavir and amprenavir) are also known to significantly increase rifabutin concentrations and often require dose reductions of rifabutin (see 'Dosing' above).
Coadministration of CYP-3A4 inducers may decrease serum concentrations of rifabutin. As an example, efavirenz (a potent CYP-3A4 inducer) decreases rifabutin serum concentrations by one-third. Therefore, the CDC recommends that rifampin be used as the rifamycin of choice for patients taking efavirenz-based antiretroviral therapy [64].
Two-way interactions are also observed with agents coadministered with rifabutin. As an example, administration of rifabutin with etravirine may reduce etravirine concentrations while increasing rifabutin concentrations (35 percent and 17 percent, respectively) [65]; however, the CDC does not recommend dosing modifications in such situations [64].
Information regarding the interactions between protease inhibitors, rifabutin (as a treatment for tuberculosis), and antiretrovirals is dynamic. The CDC maintains guidelines as to the management of such interactions [3].
Specific interactions of rifabutin with other medications may be determined by using the drug interaction program included within UpToDate.
RIFAPENTINE —
Rifapentine has a longer half-life than rifampin [66].
Rifapentine (administered in combination with isoniazid, once weekly for three months) an accepted regimen for the treatment of latent tuberculosis [4]. Issues related to use of this regimen are discussed separately. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection".)
Mechanism of action — Rifapentine inhibits DNA-dependent RNA polymerase in susceptible strains of M. tuberculosis. Rifapentine is bactericidal against both intracellular and extracellular M. tuberculosis organisms.
Resistance — Strains of M. tuberculosis resistant to other rifamycins (including rifampin) are likely to be resistant to rifapentine, although drug susceptibility testing to rifapentine may be considered when rifampin resistance is observed and treatment options are limited.
Pharmacokinetics — Rifapentine absorption is increased in the presence of high-fat meals and divided doses [67]. Rifapentine has high protein binding (97 percent) [68]. The active metabolite is 25-desacetlyl rifapentine. Pharmacokinetic studies suggest that higher doses of the drug may be associated with higher concentrations of both free drug and metabolites [69]. Most of the drug is eliminated in the feces (approximately 70 percent).
Dosing — Rifapentine dosing is presented separately:
●(See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection".)
●(See "Tuberculosis disease in children: Treatment and prevention".)
●(See "Tuberculosis infection (latent tuberculosis) in children".)
Special populations — Among pregnant women, clearance of rifapentine in the setting of HIV infection is more rapid than among those without HIV infection [70].
Adverse effects — Adverse effects of rifapentine include nausea/vomiting and hepatotoxicity. Hyperuricemia and elevations in liver function tests have been reported [71].
Rifapentine, like other rifamycins, may produce an orange-red discoloration of body fluids (urine, tears, sputum, feces, and cerebrospinal fluid). Contact lenses and dentures can become permanently stained [72].
Severe adverse cutaneous reactions such as Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS) have been described [73]. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis" and "Drug reaction with eosinophilia and systemic symptoms (DRESS)".)
When given once weekly with isoniazid for treatment of latent tuberculosis infection, reported reactions include a flu-like syndrome as well as more serious reactions including hypotension and syncope [74,75]. Questioning about side effects with a previous dose may prevent a more serious event; prodromal symptoms require holding the next dose until a clinical evaluation is performed.
Monitoring — Issues related to laboratory monitoring for patients on antituberculous drugs are discussed separately. (See "Antituberculous drugs: An overview", section on 'Clinical and laboratory monitoring'.)
Drug interactions — Rifapentine, like other rifamycins, is a strong inducer of the cytochrome P450 (CYP) system. Use of rifapentine in patients on antiretroviral therapy is discussed further separately. (See "Treatment of tuberculosis infection (latent tuberculosis) in nonpregnant adults with HIV infection".)
Information regarding the interactions between rifapentine (as a treatment for tuberculosis) and antiretrovirals is dynamic. The CDC maintains guidelines as to the management of such interactions [64].
Specific interactions of rifapentine with other medications may be determined by using the drug interaction program included within UpToDate.
SUMMARY
●Rifamycin indications – The rifamycins include rifampin, rifabutin, and rifapentine. Of these, rifampin is most commonly used as first-line therapy (in combination with other agents) for treatment of mycobacterial infections including tuberculosis and in select invasive staphylococcal infections. The rate of development of resistance to rifamycins is high; for this reason, these agents are not used as monotherapy except for rifampin prophylaxis against Neisseria meningitidis or Haemophilus influenzae. (See 'Introduction' above and 'Resistance' above.)
●Adverse effects – Adverse effects associated with the administration of rifamycins include gastrointestinal, central nervous system, and dermatologic and hematologic effects. Rifamycins may produce an orange-red discoloration of body fluids (urine, tears, sputum, feces, and spinal fluid). Hepatitis is infrequently associated with rifampin but is more commonly observed in patients with predisposing factors, including administration of concomitant hepatotoxins such as isoniazid. Uveitis, a rare complication in patients receiving rifabutin, is most likely a consequence of elevated rifabutin serum concentrations due to interacting drugs. (See 'Adverse effects' above.)
●Monitoring (See 'Monitoring' above.)
•Patients receiving rifampin as part of combination antituberculous therapy should undergo baseline evaluations of hepatic enzymes (aspartate aminotransferase, bilirubin, alkaline phosphatase), platelet count, and serum creatinine prior to the initiation of therapy.
•All patients must be educated about possible symptoms of hepatic toxicity. Patients should be questioned regarding these symptoms at visits and should report any signs or symptoms that occur between visits. All patients should be fully evaluated clinically, including serum testing for hepatic injury.
●Drug interactions – Drug interactions result from the ability of rifamycins to induce the cytochrome P450 isoenzyme CYP3A4 (and to lesser extent CYP2C8 and CYP2C9) and uridine diphosphate gluconyltransferase 1A1 enzymes, potentially decreasing serum concentrations of coadministered drugs. In addition, serum concentrations of rifabutin (a substrate of CYP-3A4) may be altered by inducers or inhibitors of this enzyme. (See 'Drug interactions' above.)
