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Rifabutin

Medically reviewed by Drugs.com. Last updated on Aug 4, 2019.

Pronunciation

(rif a BYOO tin)

Index Terms

  • Ansamycin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Mycobutin: 150 mg

Generic: 150 mg

Brand Names: U.S.

  • Mycobutin

Pharmacologic Category

  • Antitubercular Agent
  • Rifamycin

Pharmacology

Inhibits DNA-dependent RNA polymerase at the beta subunit which prevents chain initiation

Absorption

Readily, 53%

Distribution

Vd: Adults: 9.3 ± 1.5 L/kg

Metabolism

To 5 metabolites; predominantly 25-O-desacetyl-rifabutin (antimicrobial activity equivalent to parent drug; contributes ≤10% of antimicrobial activity) and 31-hydroxy-rifabutin

Excretion

Urine (53% as metabolites); feces (30%)

Time to Peak

Serum: 2 to 4 hours

Half-Life Elimination

Terminal: 45 hours (range: 16 to 69 hours)

Protein Binding

85%

Special Populations: Renal Function Impairment

AUC is increased 71% in patients with CrCl <30 mL/minute.

Use: Labeled Indications

Mycobacterium avium complex (MAC), prophylaxis: Prevention of disseminated MAC disease in patients with advanced human immunodeficiency virus (HIV) infection

Off Label Uses

Mycobacterium avium complex disease (disseminated) treatment in HIV-infected patients

Based on the US Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, rifabutin is an effective and recommended optional adjunctive agent in the treatment of disseminated Mycobacterium avium complex (MAC) in HIV-infected patients.

Tuberculosis, treatment (drug-susceptible) (excludes meningitis)

Based on the ATS, CDC, and IDSA joint guidelines on the treatment of drug-susceptible tuberculosis, rifabutin is recommended as a substitute for rifampin in patients who are currently receiving medications that have unacceptable interactions with rifampin or who have intolerance to rifampin.

Tuberculosis, treatment in HIV-infected patients

Based on the US Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, rifabutin as part of a multidrug regimen is an effective and recommended alternative to rifampin in the treatment of tuberculosis in HIV-infected patients.

Latent tuberculosis (LTBI) in HIV-infected patients

Based on the US Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, rifabutin is an effective and recommended alternative to rifampin in the treatment of LTBI to prevent TB in HIV-infected patients.

Contraindications

Clinically significant hypersensitivity to rifabutin, other rifamycins, or any component of the formulation

Dosing: Adult

Mycobacterium avium complex (MAC) disease (disseminated) in HIV-infected patients:

Note: Rule out active tuberculosis before initiating rifabutin (HHS [OI adult] 2019).

Primary prophylaxis (patients with CD4 count <50 cells/mm3 who are not initiated on fully suppressive antiretroviral therapy [ART]) (alternative agent): Oral: 300 mg once daily; may discontinue prophylaxis when patient is initiated on effective ART (HHS [OI adult] 2019; IAS-USA [Saag 2018]).

Treatment (off-label use): Oral: 300 mg once daily as optional adjunct therapy with clarithromycin or azithromycin (plus ethambutol) (HHS [OI adult] 2019).

Secondary prophylaxis: Oral: 300 mg once daily as optional adjunct therapy with clarithromycin or azithromycin (plus ethambutol); may discontinue when patient has completed ≥12 months of therapy, has no signs/symptoms of MAC disease, and has sustained (>6 months) CD4 count >100 cells/mm3 in response to ART (HHS [OI adult] 2019).

Tuberculosis (off-label use): Oral:

Latent tuberculosis (LTBI) treatment (to prevent TB) in HIV-infected patients: Daily dose based on concomitant ART for 4 months; refer to current guidelines for more information (HHS [OI adult] 2019). Note: LTBI treatment is recommended in HIV-infected patients testing positive for LTBI (but have no evidence of TB disease or no prior history of treatment for active or LTBI) or in HIV-infected close contacts of anyone who has infectious TB (regardless of screening tests for LTBI) (HHS [OI adult] 2019]).

Treatment of drug-susceptible TB (excludes meningitis) (as an alternative/substitute for rifampin):

Non-HIV-infected patients: 5 mg/kg/dose (usual dose: 300 mg) once daily as part of a multidrug regimen (CDC [Nahid 2016]).

HIV-infected patients (and not receiving protease inhibitors, efavirenz, rilpivirine, tenofovir alafenamide, or an elvitegravir/cobicistat containing regimen): 5 mg/kg/dose (usual dose: 300 mg) once daily for 5 to 7 days/week as part of a multidrug regimen (HHS [OI adult] 2019).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Tuberculosis; active TB, treatment of drug-susceptible (excluding meningitis): Limited data available; optimal dose not established (ATS/CDC/IDSA [Nahid 2016]); Note: Recommendations often change due to epidemiology (resistance) and emerging information; consult CDC and WHO for current recommendations, as appropriate (ATS/CDC/IDSA [Nahid 2016]; WHO 2010; WHO 2014). Always use as part of a multidrug regimen. Regimens using less than 5 times weekly dosing should administer dosing as directly observed therapy (DOT). Treatment regimens for pulmonary tuberculosis consist of an initial 2-month intensive phase of a 4-drug regimen, followed by a continuation phase of an additional 4 to 7 months of isoniazid and rifampin (or rifabutin). Rifabutin duration differs depending on treatment regimen selected; it is generally not recommended for use in 3-times- or twice-weekly regimens; consult current drug-sensitive TB guidelines for detailed information (ATS/CDC/IDSA [Nahid 2016]).

Non-HIV-exposed/-positive: Infants, Children, and Adolescents: Oral: 5 mg/kg/dose once daily or 5-times-weekly (DOT); maximum dose: 300 mg/dose (ATS/CDC/IDSA [Nahid 2016])

HIV-exposed/-positive: Note: Not appropriate for all HIV patients due to drug-drug interactions with some anti-retrovirals, refer to specific guidelines for guidance on drug interaction management with antiretroviral therapy (see Drug-Drug Interactions). Infants and Children: Oral: 10 to 20 mg/kg/dose once daily or 3-times-weekly (DOT); maximum dose: 300 mg/dose (HHS [pediatric 2016])

Mycobacterium avium complex infection (MAC):

Treatment, add-on therapy for severe infection:

Infants and Children: Oral: 10 to 20 mg/kg/dose once daily; maximum dose: 300 mg/dose; in combination with a macrolide (clarithromycin or azithromycin) and ethambutol (Bradley 2016; HHS [pediatric OI 2016])

Adolescents: Oral: 300 mg once daily in combination with a macrolide (clarithromycin or azithromycin) and ethambutol (HHS [adult OI 2016])

Primary prophylaxis:

Non-HIV-exposed/-positive: Infants, Children, and Adolescents: Oral: 5 mg/kg/dose once daily; maximum dose: 300 mg/dose (Bradley 2016)

HIV-exposed/-positive: Children ≥6 years and Adolescents: Oral: 300 mg once daily; active TB should be ruled out prior to initiation (HHS [adult OI 2016]; HHS [pediatric OI 2016])

Chronic suppressive therapy in HIV-exposed/-positive:

Children ≥6 years: Oral: 5 mg/kg/dose once daily; maximum dose: 300 mg/dose; for patients who received rifabutin as part of initial MAC treatment regimen (HHS [pediatric OI 2016)

Adolescents: Oral: 300 mg once daily; for patients who received rifabutin as part of initial MAC treatment regimen (HHS [adult OI 2016])

Extemporaneously Prepared

A 20 mg/mL rifabutin oral suspension may be made with capsules and a 1:1 mixture of Ora-Sweet® and Ora-Plus®. Empty the the powder from eight 150 mg rifabutin capsules into a glass mortar; add 20 mL of vehicle and mix to a uniform paste. Mix while adding vehicle in incremental proportions to almost 60 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 60 mL. Label "shake well". Stable for 12 weeks at 4°C, 25°C, 30°C, and 40°C.

Haslam JL, Egodage KL, Chen Y, et al, "Stability of Rifabutin in Two Extemporaneously Compounded Oral Liquids," Am J Health Syst Pharm, 1999, 56(4):333-6.10690216

Administration

May be administered with meals to minimize nausea or vomiting.

Dietary Considerations

May be taken with meals.

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

Abemaciclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Abemaciclib. Avoid combination

Abiraterone Acetate: Rifabutin may decrease the serum concentration of Abiraterone Acetate. Monitor therapy

Alfentanil: Rifamycin Derivatives may decrease the serum concentration of Alfentanil. Management: Monitor closely for decreased alfentanil effectiveness. Increased alfentanil doses will likely be needed. Alternatively, changing from alfentanil to a different opioid anesthetic (e.g., sufentanil) may also be considered. Consider therapy modification

Antifungal Agents (Azole Derivatives, Systemic): May increase the serum concentration of Rifamycin Derivatives. Only rifabutin appears to be affected. Rifamycin Derivatives may decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Management: Avoid these combinations when possible. Voriconazole and isavuconazonium are considered contraindicated. Consider therapy modification

Antihepaciviral Combination Products: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Antihepaciviral Combination Products. Avoid combination

Asunaprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Asunaprevir. Avoid combination

Atazanavir: May increase serum concentrations of the active metabolite(s) of Rifabutin. Atazanavir may increase the serum concentration of Rifabutin. Management: Reduce rifabutin doses. Clinical guidelines recommend 150 mg daily or 300 mg 3 times per week with atazanavir/ritonavir. Atazanavir labeling recommends a decrease of at least 75%, to 150 mg every other day or 150 mg 3 times per week for adults. Consider therapy modification

Atovaquone: Rifamycin Derivatives may decrease the serum concentration of Atovaquone. Avoid combination

Axitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib. Avoid combination

Barbiturates: Rifamycin Derivatives may increase the metabolism of Barbiturates. Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Bedaquiline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bedaquiline. Avoid combination

Benzhydrocodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Monitor therapy

Bictegravir: Rifabutin may decrease the serum concentration of Bictegravir. Avoid combination

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Bosutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bosutinib. Avoid combination

Brigatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inducers when possible. If combined, increase the daily dose of brigatinib in 30 mg increments after 7 days of treatment with the current brigatinib dose, up to maximum of twice the dose. Consider therapy modification

Cabozantinib: Rifabutin may decrease the serum concentration of Cabozantinib. Monitor therapy

Calcium Channel Blockers: Rifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Management: The labeling for some US and Canadian calcium channel blockers contraindicate use with rifampin, however recommendations vary. Consult appropriate labeling. Exceptions: Clevidipine. Consider therapy modification

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination

Clarithromycin: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Clarithromycin. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Clarithromycin. Management: Consider alternative antimicrobial therapy for patients receiving a CYP3A inducer. Drugs that enhance the metabolism of clarithromycin into 14-hydroxyclarithromycin may alter the clinical activity of clarithromycin and impair its efficacy. Consider therapy modification

CloZAPine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of CloZAPine. Monitor therapy

Cobicistat: May increase the serum concentration of Rifabutin. Management: Reduce rifabutin dose. Clinical guidelines recommend administering rifabutin 150 mg daily or 300 mg 3 times per week when used with cobicistat. Cobicistat labeling recommends decreasing the rifabutin dose to 150 mg every other day. Consider therapy modification

Cobimetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cobimetinib. Avoid combination

Codeine: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Codeine. Monitor therapy

Crizotinib: Rifabutin may decrease the serum concentration of Crizotinib. Monitor therapy

CycloSPORINE (Systemic): Rifamycin Derivatives may increase the metabolism of CycloSPORINE (Systemic). Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Substrates (High risk with Inducers): CYP3A4 Inducers (Moderate) may decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Exceptions: Apixaban; Rivaroxaban. Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Daclatasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Daclatasvir. Management: Increase the daclatasvir dose to 90 mg once daily if used with a moderate CYP3A4 inducer. Consider therapy modification

Dapsone (Systemic): Rifabutin may decrease the serum concentration of Dapsone (Systemic). Monitor therapy

Darunavir: May increase serum concentrations of the active metabolite(s) of Rifabutin. Rifabutin may increase the serum concentration of Darunavir. Darunavir may increase the serum concentration of Rifabutin. Management: Reduce rifabutin doses. Darunavir US labeling recommends a decrease of at least 75%, to 150 mg every other day or 3 times per week for adults. Clinical guidelines recommend 150 mg/day or 300 mg 3 times per week when used with darunavir/ritonavir. Consider therapy modification

Dasabuvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dasabuvir. Avoid combination

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Deflazacort: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Deflazacort. Avoid combination

Delavirdine: Rifamycin Derivatives may increase the metabolism of Delavirdine. Delavirdine may increase the serum concentration of Rifamycin Derivatives. Specifically, Rifabutin serum concentration may be increased. Avoid combination

Doravirine: Rifabutin may decrease the serum concentration of Doravirine. Management: Increase doravirine dose to 1 tablet (100 mg) twice daily when combined with rifabutin. If taking the combination product doravirine/lamivudine/tenofovir, an additional tablet of doravirine (100 mg) should be given 12 hours after the combination product. Consider therapy modification

Efavirenz: May decrease the serum concentration of Rifabutin. Rifabutin may decrease the serum concentration of Efavirenz. Management: If efavirenz is to be used with daily rifabutin, increase the planned rifabutin adult dose by 50%. If used with regimens where rifabutin is administered 2-3 times per week, consider doubling the rifabutin dose. Consider therapy modification

Elbasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elbasvir. Avoid combination

Elvitegravir: May increase serum concentrations of the active metabolite(s) of Rifabutin. Rifabutin may decrease the serum concentration of Elvitegravir. Management: For single-agent elvitegravir, a rifabutin dose reduction of at least 75% is required (ie, reduction to adult dose of 150 mg every other day or three times/week). Use of elvitegravir combination products with rifabutin is not recommended. Avoid combination

Encorafenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Encorafenib. Avoid combination

Entrectinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Entrectinib. Avoid combination

Enzalutamide: Rifabutin may decrease the serum concentration of Enzalutamide. Monitor therapy

Erdafitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Erdafitinib. Management: Dose modifications of erdafitinib may be required. See full monograph for details. Consider therapy modification

Erlotinib: Rifabutin may decrease the serum concentration of Erlotinib. Management: Avoid combination if possible. If combination must be used, increase erlotinib dose by 50 mg increments every 2 weeks as tolerated, to a maximum of 450 mg/day. Consider therapy modification

Estriol (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estriol (Systemic). Monitor therapy

Estriol (Topical): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estriol (Topical). Monitor therapy

Estrogen Derivatives (Contraceptive): Rifamycin Derivatives may decrease the serum concentration of Estrogen Derivatives (Contraceptive). Contraceptive failure is possible. Management: Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification

Etravirine: Rifabutin may decrease the serum concentration of Etravirine. Management: Avoid use of rifabutin with etravirine in patients also taking a protease inhibitor/ritonavir. Rifabutin (300 mg daily) may be used with etravirine if etravirine is administered without a protease inhibitor/ritonavir. Avoid combination

Everolimus: Rifabutin may decrease the serum concentration of Everolimus. Monitor therapy

Fedratinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Fedratinib. Avoid combination

FentaNYL: CYP3A4 Inducers (Moderate) may decrease the serum concentration of FentaNYL. Monitor therapy

Flibanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Flibanserin. Avoid combination

Fosamprenavir: May increase serum concentrations of the active metabolite(s) of Rifabutin. Rifabutin may increase the serum concentration of Fosamprenavir. Fosamprenavir may increase the serum concentration of Rifabutin. Management: Reduce rifabutin doses. See full monograph for specific recommendations. Consider therapy modification

Glecaprevir and Pibrentasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Glecaprevir and Pibrentasvir. Monitor therapy

Grazoprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Grazoprevir. Avoid combination

GuanFACINE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of GuanFACINE. Management: Increase the guanfacine dose by up to double when initiating guanfacine in a patient taking a moderate CYP3A4 inducer. Increase guanfacine dose gradually over 1 to 2 weeks if initiating a moderate CYP3A4 inducer in a patient already taking guanfacine. Consider therapy modification

HMG-CoA Reductase Inhibitors (Statins): Rifamycin Derivatives may decrease the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Consider use of noninteracting antilipemic agents (note: pitavastatin concentrations may increase with rifamycin treatment). Monitor for altered HMG-CoA reductase inhibitor effects. Rifabutin and fluvastatin, or possibly pravastatin, may pose lower risk. Exceptions: Pitavastatin; Rosuvastatin. Consider therapy modification

HYDROcodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of HYDROcodone. Monitor therapy

Ibrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ibrutinib. Monitor therapy

Ifosfamide: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Ifosfamide. Monitor therapy

Imatinib: Rifamycin Derivatives may decrease the serum concentration of Imatinib. Management: Avoid concurrent use of imatinib with the rifamycin derivatives when possible. If such a combination must be used, increase imatinib dose by at least 50% and monitor the patient's clinical response closely. Consider therapy modification

Indinavir: May increase serum concentrations of the active metabolite(s) of Rifabutin. Rifabutin may decrease the serum concentration of Indinavir. Indinavir may increase the serum concentration of Rifabutin. Management: Reduce rifabutin dose by 50% and increase adult indinavir dose to 1 g every 8 hours, per US labeling. Consistent with this, clinical guidelines recommend a rifabutin dose of 150 mg/day or 300 mg 3 times per week when used with indinavir/ritonavir. Consider therapy modification

Irinotecan Products: Rifabutin may decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. Rifabutin may decrease the serum concentration of Irinotecan Products. Monitor therapy

Isoniazid: Rifamycin Derivatives may enhance the hepatotoxic effect of Isoniazid. Even so, this is a frequently employed combination regimen. Monitor therapy

Istradefylline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Istradefylline. Monitor therapy

Ivacaftor: Rifabutin may decrease the serum concentration of Ivacaftor. Monitor therapy

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Ledipasvir: Rifabutin may decrease the serum concentration of Ledipasvir. Avoid combination

Lefamulin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with moderate CYP3A4 inducers unless the benefits outweigh the risks. Consider therapy modification

Lefamulin (Intravenous): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin (intravenous) with moderate CYP3A4 inducers unless the benefits outweigh the risks. Consider therapy modification

Lopinavir: May increase serum concentrations of the active metabolite(s) of Rifabutin. Rifabutin may increase the serum concentration of Lopinavir. Lopinavir may increase the serum concentration of Rifabutin. Management: Reduce rifabutin doses. Lopinavir/ritonavir US labeling recommends a decrease of at least 75%, to 150 mg every other day or 3 times per week for adults, while clinical guidelines recommend 150 mg/day or 300 mg 3 times per week. Consider therapy modification

Lorlatinib: CYP3A4 Inducers (Moderate) may enhance the hepatotoxic effect of Lorlatinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with moderate CYP3A4 inducers. If such a combination must be used, monitor AST, ALT, and bilirubin within 48 hours of starting the combination and at least three times within the first week of combined use. Consider therapy modification

Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification

Lurasidone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lurasidone. Management: Monitor for decreased lurasidone effects if combined with moderate CYP3A4 inducers and consider increasing the lurasidone dose if coadministered with a moderate CYP3A4 inducer for 7 or more days. Consider therapy modification

Macrolide Antibiotics: May decrease the metabolism of Rifamycin Derivatives. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. Consider therapy modification

Meperidine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Meperidine. Management: Consider increasing meperidine dose if concomitant use with moderate CYP3A4 inducers is required. Monitor for signs and symptoms of opioid withdrawal. Consider therapy modification

Mirodenafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mirodenafil. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Mycophenolate: Rifamycin Derivatives may decrease the serum concentration of Mycophenolate. Specifically, rifamycin derivatives may decrease the concentration of the active metabolite mycophenolic acid. Avoid combination

Naldemedine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Naldemedine. Monitor therapy

Nelfinavir: May increase serum concentrations of the active metabolite(s) of Rifabutin. Rifabutin may decrease the serum concentration of Nelfinavir. Nelfinavir may increase the serum concentration of Rifabutin. Management: Nelfinavir US prescribing information recommends decreasing the usual rifabutin dose by at least 50% when used with nelfinavir. Additionally, the preferred dose of nelfinavir when used in combination with rifabutin is 1250 mg twice daily. Consider therapy modification

Neratinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Neratinib. Avoid combination

Nevirapine: Rifabutin may decrease the serum concentration of Nevirapine. Nevirapine may decrease the serum concentration of Rifabutin. Nevirapine may increase the serum concentration of Rifabutin. Monitor therapy

Nilotinib: Rifabutin may decrease the serum concentration of Nilotinib. Monitor therapy

Nisoldipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nisoldipine. Avoid combination

Olaparib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Olaparib. Avoid combination

Palbociclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Palbociclib. Management: The US label does not provide specific recommendations concerning use with moderate CYP3A4 inducers, but the Canadian label recommends avoiding use of moderate CYP3A4 inducers. Consider therapy modification

Perampanel: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used concurrently with moderate and strong CYP3A4 inducers. Consider therapy modification

Pexidartinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pexidartinib. Monitor therapy

Pimavanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pimavanserin. Avoid combination

Pitavastatin: Rifamycin Derivatives may increase the serum concentration of Pitavastatin. Management: Limit pitavastatin dose to a maximum of 2 mg/day with concurrent rifampin. Consider therapy modification

Pitolisant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pitolisant. Monitor therapy

Pretomanid: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pretomanid. Avoid combination

Progestins (Contraceptive): Rifamycin Derivatives may decrease the serum concentration of Progestins (Contraceptive). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification

QuiNIDine: Rifamycin Derivatives may decrease the serum concentration of QuiNIDine. Management: Consider alternatives to combination treatment with quinidine and rifampin due to large potential decreases in quinidine concentrations. Monitor for decreased quinidine concentrations/effects with initiation/dose increase of any rifamycin derivative. Consider therapy modification

Raltegravir: Rifabutin may decrease the serum concentration of Raltegravir. Specifically, minimum serum concentrations (Cmin) may be reduced. Total raltegravir exposure (i.e., AUC) may be increased. Monitor therapy

Ranolazine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ranolazine. Avoid combination

Rilpivirine: Rifabutin may decrease the serum concentration of Rilpivirine. Management: Increase the rilpivirine adult dose to 50 mg/day during rifabutin treatment. Decrease back to 25 mg/day following rifabutin discontinuation. Use of rifabutin with the emtricitabine/rilpivirine/tenofovir alafenamide combination product is not recommended. Consider therapy modification

Ritonavir: May increase serum concentrations of the active metabolite(s) of Rifabutin. Ritonavir may increase the serum concentration of Rifabutin. Management: Ritonavir US prescribing information recommends reducing rifabutin doses by at least 75%. Refer to drug interaction monographs addressing concomitantly administered protease inhibitors for dosing recommendations specific to ritonavir-boosted regimens. Consider therapy modification

Rolapitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rolapitant. Monitor therapy

RomiDEPsin: Rifabutin may decrease the serum concentration of RomiDEPsin. Monitor therapy

Saquinavir: May increase serum concentrations of the active metabolite(s) of Rifabutin. Saquinavir may increase the serum concentration of Rifabutin. Rifabutin may decrease the serum concentration of Saquinavir. Management: Reduce rifabutin doses. Saquinavir US labeling recommends a decrease of at least 75%, to 150 mg every other day or 3 times per week for adults. Clinical guidelines recommend 150 mg daily or 300 mg 3 times per week when used with saquinavir/ritonavir. Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Simeprevir. Avoid combination

Sirolimus: Rifabutin may decrease the serum concentration of Sirolimus. Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Sofosbuvir: Rifabutin may decrease the serum concentration of Sofosbuvir. Avoid combination

Sonidegib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sonidegib. Avoid combination

Tacrolimus (Systemic): Rifamycin Derivatives may decrease the serum concentration of Tacrolimus (Systemic). Management: Consider alternatives when possible. If these combination are used, monitor for reduced tacrolimus concentrations/effects following rifamycin initiation/dose increase, or increased concentrations/effects following rifamycin discontinuation/dose decrease. Consider therapy modification

Tamoxifen: Rifamycin Derivatives may increase the metabolism of Tamoxifen. Consider therapy modification

Temsirolimus: Rifamycin Derivatives may decrease the serum concentration of Temsirolimus. Rifamycins will likely cause an even greater decrease in the concentration of the active metabolite sirolimus. Management: Temsirolimus prescribing information recommends against coadministration with strong CYP3A4 inducers such as rifampin; however, if concurrent therapy is necessary, an increase in temsirolimus adult dose to 50 mg/week should be considered. Consider therapy modification

Tenofovir Alafenamide: Rifabutin may decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Tipranavir: May increase serum concentrations of the active metabolite(s) of Rifabutin. Tipranavir may increase the serum concentration of Rifabutin. Management: Reduce rifabutin doses. Tipranavir US labeling recommends a decrease of at least 75%, to 150 mg every other day or 3 times per week for adults. Clinical guidelines recommend 150 mg daily or 300 mg 3 times per week when used with tipranavir/ritonavir. Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Upadacitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Upadacitinib. Monitor therapy

Velpatasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Velpatasvir. Avoid combination

Venetoclax: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Venetoclax. Avoid combination

VinCRIStine (Liposomal): Rifabutin may decrease the serum concentration of VinCRIStine (Liposomal). Monitor therapy

Vitamin K Antagonists (eg, warfarin): Rifamycin Derivatives may increase the metabolism of Vitamin K Antagonists. Monitor therapy

Voriconazole: May increase the serum concentration of Rifamycin Derivatives. Rifamycin Derivatives may decrease the serum concentration of Voriconazole. Avoid combination

Zolpidem: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zolpidem. Monitor therapy

Adverse Reactions

>10%:

Dermatologic: Skin rash (11%)

Genitourinary: Discoloration of urine (30%)

Hematologic & oncologic: Neutropenia (25%), leukopenia (10% to 17%)

1% to 10%:

Gastrointestinal: Nausea (≤6%), abdominal pain (4%), dysgeusia (3%), dyspepsia (3%), eructation (3%), vomiting (≤3%), flatulence (2%)

Hematologic & oncologic: Thrombocytopenia (5%)

Neuromuscular & skeletal: Myalgia (2%)

Miscellaneous: Fever (2%)

<1%, postmarketing, and/or case reports: Abnormal T waves on ECG, agranulocytosis, aphasia, arthralgia, bronchospasm, chest pain, Clostridioides (formerly Clostridium) difficile-associated diarrhea, confusion, corneal deposits, dyspnea, flu-like symptoms, granulocytopenia, hemolysis, hepatitis, hypersensitivity, jaundice, lymphocytopenia, myositis, pancytopenia, paresthesia, pseudomembranous colitis, seizure, skin discoloration, thrombotic thrombocytopenic purpura, uveitis

Warnings/Precautions

Concerns related to adverse effects:

• Hematologic toxicity: May be associated with neutropenia and/or thrombocytopenia (rarely); consider periodic monitoring of hematologic parameters and discontinue permanently if signs of thrombocytopenia (eg, petechial rash) (CDC [Nahid 2016]; HHS [OI adult] 2019).

• Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis, hypotension, urticaria, angioedema, acute bronchospasm, conjunctivitis, thrombocytopenia, neutropenia, and flu-like syndrome, may occur with rifamycins. Discontinue use and administer supportive care if hypersensitivity occurs.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

• Uveitis: May occur; carefully monitor patients when used in combination with macrolides or azole antifungals. If uveitis is suspected, refer patient to an ophthalmologist and consider temporarily discontinuing treatment.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment; discontinue in patients with ALT ≥3 x ULN (symptomatic) or ≥5 x ULN (regardless of symptoms) (HHS [OI adult] 2019).

• Renal impairment: Use with caution in patients with renal impairment; dosage reduction recommended in severe impairment (CrCl <30 mL/minute).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: Must not be administered for MAC prophylaxis to patients with active tuberculosis since its use may lead to the development of TB resistant to both rifabutin and rifampin. Caution that active TB in the HIV-positive patient may present atypically (ie, negative PPD or extrapulmonary manifestations).

• Contact lenses: Remove soft contact lenses during therapy since permanent staining may occur.

• Brown/orange discoloration: Urine, feces, saliva, sweat, tears, sputum, and skin may be discolored to brown/orange.

Monitoring Parameters

Periodic liver function tests, CBC with differential, platelet count, signs/symptoms of hypersensitivity or uveitis

Pregnancy Considerations

Based on human placenta perfusion studies, rifabutin crosses the placenta (Magee 1996).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience diarrhea or change in color of body fluids to brown/orange. Have patient report immediately to prescriber chest pain, flu-like symptoms, bruising, bleeding, severe loss of strength and energy, shortness of breath, vision changes, eye pain, severe eye irritation, dizziness, passing out, severe nausea, severe vomiting, cough, abnormal heartbeat, signs of infection, or signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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