Rifabutin

(BAN, USAN, rINN)
Rifabutin Chemical formula
Synonyms: Ansamicin; Ansamycin; Ansamycinum; Ansamysiini; LM-427; Rifabutiini; Rifabutina; Rifabutinas; Rifabutine; Rifabutinum. (9S,12E,14S,15R,16S,17R,18R,19R,20S,21S,22E,24Z)-6,16,18,20Te tr a hy d rox y -1 ′-isobutyl-14-methoxy7,9,15,17,19,21,25-heptamethylspiro[9,4-(epoxypentadeca[1,11,13]trienimino)-2Hfuro-[2′,3′:7,8]naphth[1,2d]imidazole-2,4′-piperidine]-5,10,26(3H,9H)-trione-16-acetate.
Cyrillic synonym: Рифабутин.

💊 Chemical information

Chemical formula: C46H62N4O11 = 847.0.
CAS — 72559-06-9.
ATC — J04AB04.
ATC Vet — QJ04AB04.

Pharmacopoeias.

In Eur. and US.

Ph. Eur. 6.2

(Rifabutin). A reddish-violet amorphous powder. Slightly soluble in water and in alcohol; soluble in methyl alcohol.

USP 31

(Rifabutin). An amorphous red-violet powder. Very slightly soluble in water; sparingly soluble in alcohol; soluble in chloroform and in methyl alcohol. Store at a temperature not exceeding 40°. Protect from light.

Stability.

Study of the stability of two extemporaneous oral liquid preparations of rifabutin. 1 1. Haslam JL, et al. Stability of rifabutin in two extemporaneously compounded oral liquids. Am J Health-Syst Pharm 1999; 56: 333–6.

💊 Adverse Effects and Precautions

As for Rifampicin. Rifabutin is usually well tolerated. The most common adverse effects include rash, gastrointestinal disturbances, and neutropenia. It produces a syndrome of polyarthralgia-arthritis at doses greater than 1 g daily. Uveitis has been reported, especially in patients also receiving clarithromycin or other macrolides and possibly also with fluconazole. Asymptomatic corneal opacities have been reported after long-term use. Rifabutin should be used with caution in patients with severe hepatic or renal impairment.
Urine may be discoloured.2 A flu-like syndrome has been reported in 2 of 12 patients given 300 mg daily for Crohn’s disease,3 in 1 of 16 HIV-infected patients on continuous rifabutin,1 and in 8 of 15 HIV-infected patients receiving increasing doses of rifabutin.2 Other reported adverse effects include hepatitis,1 leucopenia2 (including neutropenia4), epigastric pain,3 rash,3 erythema,2 and ageusia.5 Rash, fever, and vomiting occurred in 1 of 2 children receiving 6.5 mg/kg daily.6
1. Siegal FP, et al. Dose-limiting toxicity of rifabutin in AIDS-related complex: syndrome of arthralgia/arthritis. AIDS 1990; 4: 433–41
2. Torseth J, et al. Evaluation of the antiviral effect of rifabutin in AIDS-related complex. J Infect Dis 1989; 159: 1115–18
3. Basilisco G, et al. Controlled trial of rifabutin in Crohn’s disease. Curr Ther Res 1989; 46: 245–50
4. Apseloff G, et al. Severe neutropenia caused by recommended prophylactic doses of rifabutin. Lancet 1996; 348: 685
5. Morris JT, Kelly JW. Rifabutin-induced ageusia. Ann Intern Med 1993; 119: 171–2
6. Levin RH, Bolinger AM. Treatment of nontuberculous mycobacterial infections in pediatric patients. Clin Pharm 1988; 7: 545–51.

Effects on the eyes.

Uveitis may occur a few weeks or months after starting rifabutin, and generally necessitates withdrawal of the drug and treatment with topical or systemic corticosteroids and cycloplegics.1 In 1994, the UK CSM was aware of 48 reports of uveitis in patients taking rifabutin.2 Most patients were also receiving clarithromycin for treatment of AIDS-related Mycobacterium avium complex (MAC) infection and many were also receiving fluconazole (see Interactions, below). A dosage reduction to 300 mg rifabutin daily is now recommended in patients also receiving macrolides or triazole antifungals2,3 and is reported to produce a satisfactory response in MAC infections.4 Panuveitis and retinal vasculitis has been reported5 in 4 patients with active tuberculosis given rifabutin, and was thought to be a result of activation of the immune system by Mycobacterium tuberculosis and the very low weight of the patients. Rifabutin-associated uveitis in children is less commonly reported probably because they may not notice or complain about visual changes, therefore monitoring of their vision while on treatment is advised.6
1. Tseng AL, Walmsley SL. Rifabutin-associated uveitis. Ann Pharmacother 1995; 29: 1149–55
2. Committee on Safety of Medicines. Rifabutin (Mycobutin)— uveitis. Current Problems 1994; 20: 4. Also available at: http:// www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE& dDocName=CON2024457&RevisionSelectionMethod= LatestReleased (accessed 05/10/07
3. Committee on Safety of Medicines. Revised indications and drug interactions of rifabutin. Current Problems 1997; 23: 14. Also available at: http://www.mhra.gov.uk/home/ idcplg?IdcService=GET_FILE&dDocName=CON2023238& RevisionSelectionMethod=LatestReleased (accessed 05/10/07
4. Shafran SD, et al. A comparison of two regimens for the treatment of Mycobacterium avium complex bacteremia in AIDS; rifabutin, ethambutol, and clarithromycin versus rifampin, ethambutol, clofazimine, and ciprofloxacin. N Engl J Med 1996; 335: 377–83
5. Skolik S, et al. Rifabutin-associated panuveitis with retinal vasculitis in pulmonary tuberculosis. Ocul Immunol Inflamm 2005; 13: 483–5
6. Olesen HH, Krag S. Rifabutin-associated uveitis in a child. Pediatr Infect Dis J 2005; 24: 1023–5.

Effects on the joints.

A polyarthralgia-arthritis syndrome was reported in an initial dose finding study1 in 9 of 10 patients receiving rifabutin, as monotherapy, at doses greater than 1 g. The syndrome did not occur in patients receiving less than 1 g daily and disappeared on drug withdrawal. Two patients with polyarthralgia-arthritis symptoms developed uveitis (see also under Effects on the Eyes, above) and aphthous stomatitis at doses of about 1.8 g daily. However, a later study2 and case reports3 have reported polyarthralgia-arthritis syndrome when rifabutin was given at doses of 300 to 600 mg daily as part of a multidrug regimen, including a macrolide (azithromycin or clarithromycin), for the treatment of Mycobacterium avium complex infection. Concentrations of rifabutin were increased as a result of inhibition of cytochrome P450 isoenzymes by the macrolide and some have suggested a maximum dose of rifabutin of 300 mg daily when used with a macrolide.2 Higher doses of 450 to 600 mg daily may be considered for patients of large body mass or those who have failed to respond to initial treatment with a lower dose.
1. Siegal FP, et al. Dose-limiting toxicity of rifabutin in AIDS-related complex: syndrome of arthralgia/arthritis. AIDS 1990; 4: 433–41
2. Griffith DE, et al. Adverse events associated with high-dose rifabutin in macrolide-containing regimens for the treatment of Mycobacterium avium complex lung disease. Clin Infect Dis 1995; 21: 594–8
3. Le Gars L, et al. Polyarthralgia-arthritis syndrome induced by low doses of rifabutin. J Rheumatol 1999; 26: 1201–2.

💊 Interactions

As for Rifampicin. Rifabutin accelerates the metabolism of many drugs by inducing microsomal liver enzymes (in particular the cytochrome P450 isoenzyme CYP3A4). It is a less potent inducer of cytochrome P450 isoenzymes than rifampicin, but similar interactions should nevertheless be anticipated. Use with other drugs that induce or inhibit these isoenzymes may result in changes in plasma concentrations of rifabutin, and possibly adverse effects. Plasma concentrations of rifabutin are increased by clarithromycin (and possibly other macrolides) or fluconazole, resulting in increased rifabutin toxicity, in particular uveitis, (see Effects on the Eyes, above), neutropenia, and polyarthralgia-arthritis syndrome (see Effects on the Joints, above). Some other interactions affecting the activity of rifabutin are discussed below.

Antiretroviral drugs.

Rifabutin may be used as a substitute for rifampicin in the treatment of tuberculosis.1,2 It has little effect on the serum concentrations of unboosted HIV-protease inhibitors (except saquinavir) and ritonavir-boosted HIV-protease inhibitors. However, HIV-protease inhibitors, particularly if boosted with ritonavir, significantly increase serum concentrations and toxicity of rifabutin. The dose of rifabutin is therefore usually substantially decreased when given with HIV-protease inhibitors (see Tuberculosis and HIV infection under Uses, below). Rifabutin should not be given with unboosted saquinavir; but saquinavir may be given with rifabutin if boosted with ritonavir.2 Increases in the dose of indinavir are also required.2 Serum concentrations of rifabutin may be increased or decreased in those taking NNRTIs. However, rifabutin may usually be given to patients taking etravirine or nevirapine without the need for any dose modifications. Rifabutin is, however, not recommended in patients taking delavirdine or in those taking etravirine with ritonavir-boosted darunavir or ritonavir-boosted saquinavir. In patients taking efavirenz, the dose of rifabutin should be increased by at least 50% (see Tuberculosis and HIV infection under Uses, below). No clinically significant interactions are expected with the integrase inhibitor raltegravir or the CCR-5 receptor antagonist maraviroc.2 Although rifabutin is reported to reduce the plasma concentrations of zidovudine, studies have shown that the effect is not marked, and licensed product information for rifabutin suggests that the reduction may not be clinically relevant.
1. Pozniak AL, et al. British HIV Association. BHIVA treatment guidelines for TB/HIV infection, February 2005. Available at: http://www.bhiva.org/files/file1001577.pdf (accessed 28/07/08
2. CDC. Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis (issued December 2007). Available at: http:// www.cdc.gov/tb/TB_HIV_Drugs/PDF/tbhiv.pdf (accessed 28/07/08)

Azole antifungals.

Rifabutin concentrations are increased by triazole antifungals and patients are at increased risk of rifabutin toxicity, specifically uveitis (see under Effects on the Eyes, above). Rifabutin also markedly reduces the plasma concentrations of itraconazole, posaconazole, and voriconazole, but does not affect the metabolism of fluconazole. The area under the concentration-time curve (AUC) for rifabutin and its active 25-deacetyl metabolite were increased by 82% and 216% respectively when fluconazole was given to 12 HIV-infected patients.1 Another study2 in 10 patients with HIV infection, found that fluconazole increased the AUC of rifabutin by 76% and by 152% when the patients were also given clarithromycin. Raised plasma-rifabutin concentrations were reported in a patient who developed uveitis while also receiving itraconazole.3 The mechanism of the interaction remains uncertain but could involve microsomal cytochrome P450 isoenzyme CYP3A4 (see Metabolism under Pharmacokinetics, below).
1. Trapnell CB, et al. Increased plasma rifabutin levels with concomitant fluconazole therapy in HIV-infected patients. Ann Intern Med 1996; 124: 573–6
2. Jordan MK, et al. Effects of fluconazole and clarithromycin on rifabutin and 25-O-desacetylrifabutin pharmacokinetics. Antimicrob Agents Chemother 2000; 44: 2170–2
3. Lefort A, et al. Uveitis associated with rifabutin prophylaxis and itraconazole therapy. Ann Intern Med 1996; 125: 939–40.

Macrolides.

As discussed under Effects on the Eyes, above, most patients developing uveitis during rifabutin treatment are also receiving clarithromycin and it may also be implicated in the polyarthralgia-arthritis syndrome (see Effects on the Joints, above). In a study1 of the treatment of Mycobacterium avium complex infection in AIDS patients, uveitis or pseudojaundice or both were noted in those receiving rifabutin, ethambutol, and clarithromycin, but not in those receiving rifabutin, ethambutol, ciprofloxacin, and clofazimine. A retrospective study2 after an outbreak of uveitis in a similar patient population also found clarithromycin to be a risk factor, with a trend towards greater risk at higher rifabutin doses, although patient numbers were small. In 26 patients taking rifabutin with either clarithromycin or azithromycin,3 the incidence and severity of adverse effects in general was similar, although the 2 patients who developed uveitis were both receiving clarithromycin. Pharmacokinetic studies have found increased rifabutin concentrations when clarithromycin is also used. A study in healthy subjects4 was terminated prematurely because of the high incidence of adverse effects, including neutropenia, fevers, and myalgia, particularly in subjects receiving rifabutin with azithromycin or clarithromycin. Mean serum concentrations of rifabutin and its 25-O-deacetyl metabolite in subjects also receiving clarithromycin were more than 4 times and 37 times those in subjects receiving rifabutin alone. Plasma concentrations were unaffected by azithromycin. Similar effects on rifabutin concentrations were found in HIV-infected subjects receiving clarithromycin5and reductions in clarithromycin concentrations were also noted. A study6 to determine the tolerance and pharmacokinetic interactions of rifabutin and azithromycin in subjects with or without HIV infection found no significant drug interaction; however, the combination was poorly tolerated, mainly because of a high incidence of gastrointestinal symptoms and neutropenia.
1. Shafran SD, et al. Uveitis and pseudojaundice during a regimen of clarithromycin, rifabutin, and ethambutol. N Engl J Med 1994; 330: 438–9
2. Kelleher P, et al. Uveitis associated with rifabutin and macrolide therapy for Mycobacterium avium intracellulare infection in AIDS patients. Genitourin Med 1996; 72: 419–21
3. Griffith DE, et al. Adverse events associated with high-dose rifabutin in macrolide-containing regimens for the treatment of Mycobacterium avium complex lung disease. Clin Infect Dis 1995; 21: 594–8
4. Apseloff G, et al. Comparison of azithromycin and clarithromycin in their interactions with rifabutin in healthy volunteers. J Clin Pharmacol 1998; 38: 830–5
5. Hafner R, et al. Tolerance and pharmacokinetic interactions of rifabutin and clarithromycin in human immunodeficiency virusinfected volunteers. Antimicrob Agents Chemother 1998; 42: 631–9
6. Hafner R, et al. Tolerance and pharmacokinetic interactions of rifabutin and azithromycin. Antimicrob Agents Chemother 2001; 45: 1572–7.

💊 Antimicrobial Action

Rifabutin possesses a spectrum of antibacterial activity similar to that of rifampicin. However, most investigations have concentrated on its action against mycobacteria. Cross-resistance with rifampicin is common.

Antimycobacterial action.

Rifabutin possesses activity against most species of mycobacteria. It may be more active in vivo than in vitro studies suggest, as a result of its favourable pharmacokinetic profile and prolonged postantibiotic effect.1 Rifabutin has been reported to be active in animal assays against Mycobacterium leprae,2 including a rifampicin-resistant strain.3Synergistic activity against M. leprae has been reported4 in vitro for rifabutin with sparfloxacin.
1. Kunin CM. Antimicrobial activity of rifabutin. Clin Infect Dis 1996; 22 (suppl 1): S3–S14
2. Hastings RC, Jacobson RR. Activity of ansamycin against Mycobacterium leprae in mice. Lancet 1983; ii: 1079–80. Correction. ibid.; 1210
3. Hastings RC, et al. Ansamycin activity against rifampicin-resistant Mycobacterium leprae. Lancet 1984; i: 1130
4. Dhople AM, Ibanez MA. In-vitro activity of three new fluoroquinolones and synergy with ansamycins against Mycobacterium leprae. J Antimicrob Chemother 1993; 32: 445–51.

Resistance.

Rifampicin-resistant strains of Mycobacterium tuberculosis have been identified in 2 patients receiving rifabutin alone as prophylaxis against M. avium complex.1,2 It is therefore important to exclude M. tuberculosis infection before beginning rifabutin prophylaxis. Rifampicin-resistant M. kansasii has also been reported in a patient receiving rifabutin.3 Acquired resistance has been reported in HIV-infected persons receiving highly intermittent regimens (once- or twice-weekly) of rifabutin for the treatment of active tuberculosis,4,5 and the CDC has advised that such patients receive daily treatment during the intensive phase of therapy and daily or 3 times-weekly treatment during the continuation phase.
1. Weltman AC, et al. Rifampicin-resistant Mycobacterium tuberculosis. Lancet 1995; 345: 1513
2. Bishai WR, et al. Brief report: rifampin-resistant tuberculosis in a patient receiving rifabutin prophylaxis. N Engl J Med 1996; 334: 1573–6
3. Meynard JL, et al. Rifampin-resistant Mycobacterium kansasii infection in a patient with AIDS who was receiving rifabutin. Clin Infect Dis 1997; 24: 1262–3
4. CDC. Notice to readers: acquired rifamycin resistance in persons with advanced HIV disease being treated for active tuberculosis with intermittent rifamycin-based regimens. MMWR 2002; 51: 214–15
5. Burman W, et al.Acquired rifamycin resistance with twiceweekly treatment of HIV-related tuberculosis. Am J Respir Crit Care Med 2006; 173: 350–6.

💊 Pharmacokinetics

Rifabutin is readily but incompletely absorbed from the gastrointestinal tract and peak plasma concentrations of about 0.25 to 0.6 micrograms/mL have been reported 2 to 4 hours after an oral dose of 300 mg; doubling the dose increases the peak plasma concentration. Food may delay absorption but does not affect the extent of absorption. Rifabutin is about 70% bound to plasma proteins. Rifabutin is lipophilic and therefore is widely distributed in body tissues and fluids. Rifabutin is rapidly metabolised in the liver by the cytochrome P450 isoenzyme CYP3A4 mainly to active 25-O-deacetyl and 31-hydroxy metabolites. Rifabutin induces its own metabolism resulting in a lower area under the curve after 4 weeks of continuous treatment than after the first few doses. About 53% of a dose is found in the urine, mainly as metabolites and about 30% of a dose is excreted in the faeces. The mean half-life for rifabutin is reported to be about 40 hours, with a range of 16 to 69 hours.
1. Skinner MH, et al. Pharmacokinetics of rifabutin. Antimicrob Agents Chemother 1989; 33: 1237–41.

HIV-infected patients.

Malabsorption of rifabutin and other antituberculous drugs may occur in patients with HIV infection and tuberculosis, and may contribute to acquired drug resistance and reduced efficacy of tuberculosis treatment. For further information on the absorption of antituberculous drugs in HIV-infected patients see Pharmacokinetics, under Rifampicin. The pharmacokinetics of rifabutin were studied in HIV-infected patients with normal renal and hepatic function.1 A two-compartment open pharmacokinetic model was proposed. Rifabutin was rapidly but incompletely absorbed from the gastrointestinal tract and bioavailability was poor, being 20% on day 1 of the study and 12% on day 28. Mean peak plasma concentrations occurred 2 to 3 hours after oral doses and were about 350, 500, and 900 nanograms/mL after doses of 300, 600, and 900 mg respectively. The peak and trough concentrations after 600 mg twice daily were about 900 and 200 nanograms/mL respectively. Rifabutin was about 70% bound to plasma proteins. The area under the curve showed a decrease on repeated dosage which might be explained by the induction of drug-metabolising liver enzymes. A large volume of distribution of 8 to 9 litres/kg, indicative of extensive tissue distribution, and a mean terminal half-life of 32 to 38 hours were reported. This study1 also showed that the peak plasma concentration of the major metabolite, 25-deacetylrifabutin, was 10% of the parent compound. Only 4% of unchanged rifabutin was excreted in the urine after oral use and between 6 to 14% after intravenous use. Total urinary excretion of rifabutin and metabolite 72 hours after intravenous use was 44%; total faecal excretion was between 30 and 49%. Peak and trough concentrations at steady state were reported as 900 and 200 nanograms/mL respectively in a patient with tuberculosis given rifabutin 450 mg daily.2 While these figures were the same as those previously reported with 600 mg twice daily,1the earlier study showed that there was considerable interpatient variability. CSF concentrations in 5 patients with AIDS on rifabutin 450 mg daily ranged from 36 to 70% of serum concentrations.3
1. Skinner MH, et al. Pharmacokinetics of rifabutin. Antimicrob Agents Chemother 1989; 33: 1237–41
2. Gillespie SH, et al. The serum rifabutin concentrations in a patient successfully treated for multi-resistant mycobacterium tuberculosis infection. J Antimicrob Chemother 1990; 25: 490–1. Correction. ibid. 1991; 27: 877
3. Siegal FP, et al. Dose-limiting toxicity of rifabutin in AIDS-related complex: syndrome of arthralgia/arthritis. AIDS 1990; 4: 433–41.

Metabolism.

Five metabolites of rifabutin were identified in an in-vitro study1 using human hepatic and enterocyte microsomes. Cytochrome P450 isoenzyme CYP3A4 was involved in the formation of all metabolites except 25-O-deacetylrifabutin. Deacetylation of rifabutin was apparently mediated by microsomal cholinesterase,1 although another study2 showed that further metabolism of 25-O-deacetylrifabutin is dependent on CYP3A4. The results1 also suggested that metabolism by intestinal CYP3A4 contributes significantly to presystemic metabolism of rifabutin (and consequently its low bioavailability) and to drug interactions with azole antifungals and with macrolides (see above).
1. Iatsimirskaia E, et al. Metabolism of rifabutin in human enterocyte and liver microsomes: kinetic parameters, identification of enzyme systems, and drug interactions with macrolides and antifungal agents. Clin Pharmacol Ther 1997; 61: 554–62
2. Trapnell CB, et al. Metabolism of rifabutin and its 25-desacetyl metabolite, LM565, by human liver microsomes and recombinant human cytochrome P-450 3A4: relevance to clinical interaction with fluconazole. Antimicrob Agents Chemother 1997; 41: 924–6.

💊 Uses and Administration

Rifabutin is a rifamycin antibacterial used as an alternative to the macrolides for the prophylaxis of Mycobacterium avium complex (MAC) infection in immunocompromised patients. It is also used for the treatment of other nontuberculous mycobacterial infections (including those due to MAC) and tuberculosis. When used for treatment rifabutin, like rifampicin, should be used with other antibacterials to prevent the emergence of resistant organisms. Rifabutin is given as a single oral daily dose. The dose for the prophylaxis of MAC infection is 300 mg daily. For the treatment of nontuberculous mycobacterial infections the dose is 450 to 600 mg daily in a multidrug regimen for up to 6 months after negative cultures are obtained. For pulmonary tuberculosis the usual dose is 300 mg daily for at least 6 months as part of a multidrug regimen; it can also be given intermittently (usually 3 times each week) as an alternative to daily use. For details of doses in infants, children, and adolescents, see below. Doses should be reduced to 300 mg daily in patients also receiving macrolides or azole antifungals (see under Adverse Effects, Effects on the Eyes, above). Dosage alterations may also be necessary in patients receiving HIV-protease inhibitors (see under Tuberculosis, below) and in those with severe renal impairment (see below).
1. Brogden RN, Fitton A. Rifabutin: a review of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1994; 47: 983–1009.

Administration in children.

For the prophylaxis of MAC in HIV-infected infants and children with low CD4+ counts, the American Academy of Pediatrics (AAP) suggests an oral dose of rifabutin 5 mg/kg daily in those older than 6 years; the BNFC suggest the same dose may be given from 1 year of age and those 12 years of age and older may be given the usual adult dose. For the treatment of nontuberculous mycobacterial disease in children aged 1 month to 12 years the BNFC suggests a dose of 5 mg/kg once daily for at least 6 months as part of a multidrug regimen; those 12 years of age and older may be given the usual adult dose. For the treatment of tuberculosis in those 12 years of age and older the BNFC suggests a dose of 150 to 450 mg once daily for at least 6 months as part of a multidrug regimen.

Administration in renal impairment.

Dosage of rifabutin should be reduced by 50% in patients with severe renal impairment (creatinine clearance less than 30 mL/minute).

Cryptosporidiosis.

Rifabutin may have a potential prophylactic effect against cryptosporidiosis.

Mycobacterium avium complex infections.

Alterations in rifabutin dosage may be necessary in patients receiving antiretrovirals for the management of HIV infection; further details are given under Tuberculosis, below.

Peptic ulcer disease.

For mention of the use of rifabutin in eradication regimens for Helicobacter pylori.
1. Borody TJ, et al. Efficacy and safety of rifabutin-containing ‘rescue therapy’ for resistant Helicobacter pylori infection. Aliment Pharmacol Ther 2006; 23: 481–8. Correction. ibid.; 24: 439
2. Miehlke S, et al. Randomized trial of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin. Aliment Pharmacol Ther 2006; 24: 395–403
3. González Carro P, et al. Efficacy of rifabutin-based triple therapy in Helicobacter pylori infected patients after two standard treatments. J Gastroenterol Hepatol 2007; 22: 60–3
4. Navarro-Jarabo JM, et al. Efficacy of rifabutin-based triple therapy as second-line treatment to eradicate helicobacter pylori infection. BMC Gastroenterol 2007; 7: 31. Available at: http:// www.biomedcentral.com/1471-230X/7/31 (accessed 12/11/07).
To x o p l a s m o s i s . A beneficial response to rifabutin used with pyrimethamine was reported in a patient with AIDS-related To xoplasma gondii encephalitis.1 The patient was allergic to sulfonamides and clindamycin, which are commonly used.
1. Schürmann D, et al. Rifabutin appears to be a promising agent for combination treatment of AIDS-related toxoplasma encephalitis. J Infect 1998; 36: 352–3.

Tuberculosis and HIV infection.

Rifabutin may be used in place of rifampicin in short-course therapy for tuberculosis in patients given antiretroviral drugs for HIV infection and may be preferred for patients unable to take efavirenz.1,2 However, dose modifications are often necessary; additionally, some combinations, notably rifabutin with delavirdine, or saquinavir alone, should not be used, although rifabutin may be given with saquinavir if ritonavir is also given.
In patients taking ritonavir-boosted HIV-protease inhibitors the dose of rifabutin should be substantially reduced from 300 mg daily or intermittently to 150 mg every other day or three times each week
In patients taking unboosted atazanavir the dose of rifabutin should be substantially reduced from 300 mg daily or intermittently to 150 mg every other day or three times each week
In those taking unboosted amprenavir, fosamprenavir, indinavir, or nelfinavir the daily dose of rifabutin should be decreased from 300 mg to 150 mg, and the dose for intermittent therapy should be 300 mg three times weekly. The dose of indinavir may need to be increased
In patients taking efavirenz, the dose of rifabutin should be increased from 300 mg daily or intermittently to 450 to 600 mg daily or three times each week
In patients taking nevirapine or etravirine, the usual dose of rifabutin is given (300 mg daily or 300 mg three times each week); rifabutin should not be used in patients taking etravirine plus ritonavir-boosted darunavir or saquinavir
1. CDC. Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis (issued December 2007). Available at: http:// www.cdc.gov/tb/TB_HIV_Drugs/PDF/tbhiv.pdf (accessed 28/07/08
2. Pozniak AL, et al. British HIV Association. BHIVA treatment guidelines for TB/HIV infection, February 2005. Available at: http://www.bhiva.org/files/file1001577.pdf (accessed 28/07/08)

💊 Preparations

USP 31: Rifabutin Capsules.

Proprietary Preparations

Austral.: Mycobutin; Austria: Mycobutin; Belg.: Mycobutin; Canad.: Mycobutin; Cz.: Mycobutin; Fin.: Ansatipin; Fr.: Ansatipine; Ger.: Alfacid; Mycobutin†; Gr.: Ansatipin†; Mycobutin; Hong Kong: Mycobutin; Israel: Mycobutin; Ital.: Mycobutin; Neth.: Mycobutin; NZ: Mycobutin; Port.: Mycobutin; Rus.: Mycobutin (Микобутин); S.Afr.: Mycobutin; Spain: Ansatipin; Swed.: Ansatipin; Switz.: Mycobutin; Turk.: Mycobutin; UK: Mycobutin; USA: Mycobutin.
Published May 08, 2019.