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Rifabutin: Drug information

Rifabutin: Drug information
(For additional information see "Rifabutin: Patient drug information" and see "Rifabutin: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Mycobutin
Brand Names: Canada
  • Mycobutin
Pharmacologic Category
  • Antitubercular Agent;
  • Rifamycin
Dosing: Adult
Mycobacterium avium complex infection

Mycobacterium avium complex infection:

Note: Rule out tuberculosis (TB) disease (active TB) before initiating rifabutin (Ref).

Prophylaxis in patients with HIV:

Primary prophylaxis (patients with CD4 count <50 cells/mm3 who are not initiated on fully suppressive antiretroviral therapy) (alternative agent): Oral: 300 mg once daily; may discontinue prophylaxis when patient is initiated on effective antiretroviral therapy (ART) (Ref).

Secondary prophylaxis (adjunctive agent): Oral: 300 mg once daily in combination with clarithromycin or azithromycin (plus ethambutol); may discontinue when patient has completed ≥12 months of therapy, has no signs/symptoms of M. avium complex disease, and has sustained (>6 months) CD4 count >100 cells/mm3 in response to ART (Ref).

Treatment (off-label use):

Disseminated disease in patients with HIV: Oral: 300 mg once daily as part of an appropriate combination regimen. Some experts reserve for patients with high mycobacterial loads (>2 log CFU/mL of blood), or in the absence of ART (Ref).

Pulmonary disease, nonsevere noncavitary nodular/bronchiectatic disease in patients without cystic fibrosis: Oral: 300 mg 3 times weekly as part of an appropriate combination regimen; continue treatment until patient is culture negative on therapy for ≥1 year (Ref).

Pulmonary disease, severe nodular/bronchiectatic disease, cavitary disease, or disease in patients with cystic fibrosis: Oral: 150 to 300 mg once daily as part of an appropriate combination regimen; continue treatment until patient is culture negative on therapy for ≥1 year (Ref).

Tuberculosis

Tuberculosis (alternative agent) (off-label use): Oral:

Treatment of drug-susceptible tuberculosis (excludes meningitis) (as an alternative/substitute for rifampin): Note: Always administer in combination with other antitubercular drugs (Ref).

5 mg/kg/dose (usual dose: 300 mg) once daily as part of an appropriate multidrug regimen (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute: No dosage adjustment necessary. The manufacturer's labeling recommends considering a dose reduction of 50% if toxicity is suspected; however, AUC values reported in patients with CrCl <30 mL/minute have been similar to those found in healthy volunteers (Ref).

Dosing: Hepatic Impairment: Adult

Mild impairment: No dosage adjustment necessary.

Moderate to severe impairment: There are no dosage adjustments provided in manufacturer's labeling (has not been studied).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Rifabutin: Pediatric drug information")

Mycobacterium avium complex infection

Mycobacterium avium complex (MAC) infection:

Prophylaxis: Note: Rule out active tuberculosis before initiating rifabutin for prophylaxis (Ref).

HIV-exposed/-infected:

Primary prophylaxis (alternative agent): Children ≥6 years and Adolescents: Oral: 300 mg once daily. Primary prophylaxis may be discontinued in children after ≥6 months of antiretroviral therapy (ART) and upon meeting age-specific CD4 cell count targets for >3 months (≥6 years: >100 cells/mm3); primary prophylaxis may be discontinued in adolescents once effective ART is initiated (Ref).

Chronic maintenance therapy (secondary prophylaxis) (adjunctive agent):

Children ≥6 years: Oral: 5 mg/kg/dose once daily; maximum dose: 300 mg/dose; use as part of an appropriate combination regimen; may discontinue when patient has completed ≥12 months of MAC therapy and ≥6 months of ART, has no signs and symptoms of MAC disease, and has sustained (≥6 months) CD4 cell count above age-specific target (≥6 years: 100 cells/mm3) (Ref).

Adolescents: Oral: 300 mg once daily as part of an appropriate combination regimen; may discontinue when patient has completed ≥12 months of MAC therapy, has no signs and symptoms of MAC disease, and has sustained (>6 months) CD4 count >100 cells/mm3 in response to ART (Ref).

Non-HIV-exposed or infected: Infants, Children, and Adolescents: Oral: 5 mg/kg/dose once daily; maximum dose: 300 mg/dose (Ref).

Treatment:

Disseminated disease: Note: Addition of rifabutin to standard combination regimen is controversial; it has been suggested for use in patients with severe disease or at higher risk of mortality or emergence of drug resistance (Ref).

Infants, Children, and Adolescents: Oral: 10 to 20 mg/kg/dose once daily as part of an appropriate combination regimen for ≥12 months; maximum dose: 300 mg/dose (Ref).

Pulmonary disease: Children and Adolescents: Oral: 5 to 10 mg/kg/dose once daily as part of an appropriate combination regimen; maximum dose: 300 mg. Continue treatment until patient is culture negative on therapy for ≥12 months (Ref).

Tuberculosis, active, drug-susceptible treatment

Tuberculosis, active, drug-susceptible treatment (alternative agent): Limited data available; optimal dose not established (Ref):

Note: Always use in combination with other antitubercular drugs (Ref). Any regimens using less than once-daily dosing should be administered as directly observed therapy (DOT). Some experts recommend DOT for all pediatric patients (Ref).

Infants, Children, and Adolescents: Oral: 5 mg/kg/dose once daily or 5-times-weekly (DOT); maximum dose: 300 mg/dose (Ref). A higher dose of 10 to 20 mg/kg/dose once daily (maximum dose: 300 mg/dose) has also been recommended (Ref).

Duration of therapy: Treatment regimens consist of an initial 2-month intensive phase of a 4-drug regimen, followed by a 2-drug continuation phase of rifamycin plus isoniazid. Duration of continuation phase is ≥4 months; should be longer for cavitary disease with positive cultures at completion of intensive phase (7 months), bone and joint disease (≥4 to 7 months), and CNS disease (7 to 10 months) (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no pediatric-specific recommendations. The manufacturer's labeling recommends considering a dose reduction of 50% in adults with CrCl <30 mL/minute if toxicity is suspected; however, based on experience in adult patients, dosage adjustment likely unnecessary (Ref).

Dosing: Hepatic Impairment: Pediatric

There are no pediatric-specific recommendations; based on experience in adult patients, no dosing adjustment necessary for mild impairment; has not been studied in severe impairment.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Dermatologic: Skin rash (11%)

Genitourinary: Discoloration of urine (30%)

Hematologic & oncologic: Leukopenia (10% to 17%), neutropenia (25%)

1% to 10%:

Gastrointestinal: Abdominal pain (4%), dysgeusia (3%), dyspepsia (3%), eructation (3%), flatulence (2%), nausea (6%), nausea and vomiting (3%), vomiting (1%)

Hematologic & oncologic: Thrombocytopenia (5%)

Neuromuscular & skeletal: Myalgia (2%)

Miscellaneous: Fever (2%)

<1%:

Cardiovascular: Abnormal T waves on ECG, chest pain

Dermatologic: Skin discoloration

Hematologic & oncologic: Hemolysis, pancytopenia, thrombotic thrombocytopenic purpura

Hepatic: Hepatitis, jaundice

Nervous system: Aphasia, confusion, paresthesia, seizure

Neuromuscular & skeletal: Arthralgia, myositis

Ophthalmic: Corneal deposits, uveitis

Respiratory: Dyspnea, flu-like symptoms

Postmarketing:

Gastrointestinal: Clostridioides difficile associated diarrhea, Clostridioides difficile colitis

Hematologic & oncologic: Agranulocytosis, eosinophilia, granulocytopenia, lymphocytopenia

Hypersensitivity: Hypersensitivity reaction

Respiratory: Bronchospasm

Contraindications

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

Canadian labeling: Additional contraindications (not in US labeling): Concomitant use with rilpivirine containing prolonged release suspension for injection.

Warnings/Precautions

Concerns related to adverse effects:

• Dermatologic reactions: Cases of severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, have been reported. Discontinue treatment immediately and institute appropriate therapy if signs or symptoms of SCAR develop.

• 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 2020]).

• 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 Clostridioides difficile and pseudomembranous colitis; C. difficile 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 2020]).

Other warnings/precautions:

• Appropriate use: Must not be administered for mycobacterium avium complex prophylaxis to patients with tuberculosis (TB) disease (active TB) since its use may lead to the development of TB resistant to both rifabutin and rifampin. Caution that TB disease in the HIV-infected patient may present atypically (ie, negative purified protein derivative 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.

Dosage Forms: US

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

Capsule, Oral:

Mycobutin: 150 mg

Generic: 150 mg

Generic Equivalent Available: US

Yes

Pricing: US

Capsules (Mycobutin Oral)

150 mg (per each): $23.35

Capsules (Rifabutin Oral)

150 mg (per each): $11.61 - $17.49

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

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

Capsule, Oral:

Mycobutin: 150 mg

Administration: Adult

May be administered with meals to minimize nausea or vomiting.

Administration: Pediatric

Oral: May administer with food to minimize nausea, vomiting, or other gastrointestinal upset; if patient unable to swallow capsule, may be opened and mixed with applesauce.

Use: Labeled Indications

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

Use: Off-Label: Adult

M. avium complex infection, treatment; Tuberculosis infection (latent tuberculosis); Tuberculosis, treatment (drug susceptible) (excludes meningitis)

Medication Safety Issues
Sound-alike/look-alike issues:

Rifabutin may be confused with rifAMPin, rifapentine

Metabolism/Transport Effects

Substrate of CYP1A2 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP2C9 (weak), CYP3A4 (moderate), UGT1A4

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

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

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

Acalabrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Acalabrutinib. Risk C: Monitor therapy

ALfentanil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ALfentanil. Management: If concomitant use of alfentanil and moderate CYP3A4 inducers is necessary, consider dosage increase of alfentanil until stable drug effects are achieved. Monitor patients for signs of opioid withdrawal. Risk D: Consider therapy modification

ALPRAZolam: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ALPRAZolam. Risk C: Monitor therapy

AmLODIPine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of AmLODIPine. Risk C: Monitor therapy

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

Apremilast: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Apremilast. Risk C: Monitor therapy

Aprepitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Aprepitant. Risk C: Monitor therapy

ARIPiprazole: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ARIPiprazole. Risk C: Monitor therapy

ARIPiprazole Lauroxil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor therapy

Artemether and Lumefantrine: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Artemether and Lumefantrine. Risk C: Monitor therapy

Asunaprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Asunaprevir. Risk X: 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 rifabutin 150 mg daily (with or without 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. Risk D: Consider therapy modification

Atogepant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with CYP3A4 inducers. When used for treatment of chronic migraine, use of atogepant with CYP3A4 inducers should be avoided. Risk D: Consider therapy modification

Atorvastatin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Atorvastatin. Risk C: Monitor therapy

Atovaquone: May decrease the serum concentration of Rifabutin. Rifabutin may decrease the serum concentration of Atovaquone. Risk X: Avoid combination

Avacopan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avacopan. Risk X: Avoid combination

Avanafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avanafil. Risk X: Avoid combination

Avapritinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avapritinib. Risk X: Avoid combination

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

Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification

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

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

Bedaquiline: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Bedaquiline. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bedaquiline. Risk X: Avoid combination

Belumosudil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Belumosudil. Risk C: Monitor therapy

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

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

Bortezomib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bortezomib. Risk C: Monitor therapy

Bosutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bosutinib. Risk C: Monitor therapy

Brexpiprazole: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Brexpiprazole. Risk C: Monitor therapy

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. Risk D: Consider therapy modification

Buprenorphine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Buprenorphine. Risk C: Monitor therapy

BusPIRone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of BusPIRone. Risk C: Monitor therapy

Cabotegravir: Rifabutin may decrease the serum concentration of Cabotegravir. Additionally, rifabutin may decrease rilpivirine concentrations, a drug often coadministered with IV cabotegravir. Management: Do not use long-acting injectable cabotegravir (Cabenuva) with rifabutin. Cabotegravir dose adjustments required if extended-release suspension (Apretude) is coadministered with rifabutin. No interaction expected with cabotegravir tablets. Risk D: Consider therapy modification

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

Cannabis: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Risk C: Monitor therapy

Capivasertib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Capivasertib. Risk X: Avoid combination

Capmatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Capmatinib. Risk X: Avoid combination

CarBAMazepine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of CarBAMazepine. Risk C: Monitor therapy

Cariprazine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cariprazine. Risk X: Avoid combination

Ceritinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ceritinib. Risk C: Monitor therapy

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. Risk X: Avoid combination

Clarithromycin: Rifabutin may increase serum concentrations of the active metabolite(s) of Clarithromycin. Rifabutin may decrease the serum concentration of Clarithromycin. Clarithromycin may increase the serum concentration of Rifabutin. Management: Consider alternatives to this combination when possible. If combined, consider use of lower rifabutin doses and monitor patients for increased rifabutin toxicities. Additionally, monitor for reduced clarithromycin efficacy when these agents are combined. Risk D: Consider therapy modification

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

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

Cobicistat: May increase the serum concentration of Rifabutin. Management: Avoid if possible. Clinical practice guidelines do not recommend this combination. Cobicistat labeling recommends rifabutin 150 mg every other day. Monitor for rifabutin toxicities (eg, neutropenia, uveitis) if combined. Risk D: Consider therapy modification

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

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

Copanlisib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Copanlisib. Risk C: Monitor therapy

Crizotinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Crizotinib. Risk C: Monitor therapy

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

CYP3A4 Inducers (Strong): May decrease the serum concentration of Rifabutin. Risk C: Monitor therapy

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Rifabutin. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Rifabutin. Risk C: Monitor therapy

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. Risk D: Consider therapy modification

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

Daridorexant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Daridorexant. Risk X: Avoid combination

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 labeling recommends a decrease of at least 75%, to a maximum of 150 mg every other day for adults. Clinical guidelines recommend 150 mg/day when used with darunavir/ritonavir. Risk D: Consider therapy modification

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

Dasatinib: CYP3A4 Inducers (Moderate) may increase the serum concentration of Dasatinib. Risk C: Monitor therapy

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

Delavirdine: Rifabutin may decrease the serum concentration of Delavirdine. Delavirdine may increase the serum concentration of Rifabutin. Risk X: Avoid combination

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

DiazePAM: CYP3A4 Inducers (Moderate) may decrease the serum concentration of DiazePAM. Risk C: Monitor therapy

Dienogest: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dienogest. Risk C: Monitor therapy

DilTIAZem: CYP3A4 Inducers (Moderate) may decrease the serum concentration of DilTIAZem. Risk C: Monitor therapy

Disopyramide: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Disopyramide. Risk C: Monitor therapy

Dolutegravir: Rifabutin may decrease the serum concentration of Dolutegravir. Risk C: Monitor therapy

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. Risk D: Consider therapy modification

DOXOrubicin (Conventional): CYP3A4 Inducers (Moderate) may decrease the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination

DroNABinol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of DroNABinol. Risk C: Monitor therapy

Dronedarone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dronedarone. Risk C: Monitor therapy

Duvelisib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Duvelisib. Management: Avoid if possible. If used, on day 12 of combination increase duvelisib from 25 mg twice daily to 40 mg twice daily or from 15 mg twice daily to 25 mg twice daily. Resume prior duvelisib dose 14 days after stopping moderate CYP3A4 inducer. Risk D: Consider therapy modification

Dydrogesterone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dydrogesterone. Risk C: Monitor therapy

Edoxaban: Rifabutin may decrease the serum concentration of Edoxaban. Risk C: Monitor therapy

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 dose by 50% to a dose of 450 mg to 600 mg daily. If used with regimens where rifabutin is administered 2 to 3 times per week, consider doubling the rifabutin dose. Risk D: Consider therapy modification

Elacestrant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elacestrant. Risk X: Avoid combination

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

Elexacaftor, Tezacaftor, and Ivacaftor: Rifabutin may decrease the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Specifically, the serum concentration of ivacaftor may be decreased. Risk C: Monitor therapy

Eliglustat: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Eliglustat. Risk C: Monitor therapy

Elvitegravir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elvitegravir. Risk C: Monitor therapy

Encorafenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Encorafenib. Risk C: Monitor therapy

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

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

Erlotinib: Rifabutin may decrease the serum concentration of Erlotinib. Management: Avoid concomitant use of erlotinib with rifabutin when possible. If such a combination cannot be avoided, consider increasing the erlotinib dose by 50 mg increments at 2 week intervals as tolerated, to a maximum of 450 mg/day. Risk D: Consider therapy modification

Estrogen Derivatives: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy

Etoposide: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Etoposide. Risk C: Monitor therapy

Etoposide Phosphate: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy

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. Risk X: Avoid combination

Everolimus: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Everolimus. Risk C: Monitor therapy

Exemestane: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Exemestane. Risk C: Monitor therapy

Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination

Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination

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

Felodipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Felodipine. Risk C: Monitor therapy

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

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fexinidazole: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Fexinidazole. Risk X: Avoid combination

Finerenone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Finerenone. Risk X: Avoid combination

Flibanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Flibanserin. Risk X: 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 during fosamprenavir coadministration, by at least 50% when used with fosamprenavir alone or 75% (to a dose of 150 mg every other day or 3 times per week) when used with fosamprenavir/ritonavir. Risk D: Consider therapy modification

Fosaprepitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite aprepitant. Risk C: Monitor therapy

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

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

Fruquintinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Fruquintinib. Management: Avoid this combination when possible. If combined, continue the same fruquintinib dose, but monitor for reduced fruquintinib efficacy. Risk D: Consider therapy modification

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Ganaxolone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ganaxolone. Management: Avoid concomitant use of ganaxolone and moderate CYP3A4 inducers whenever possible. If combined, consider increasing the dose of ganaxolone, but do not exceed the maximum recommended daily dose. Risk D: Consider therapy modification

Gefitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Gefitinib. Risk C: Monitor therapy

Gemigliptin: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Gemigliptin. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Gemigliptin. Risk C: Monitor therapy

Gepirone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Gepirone. Risk C: Monitor therapy

Glasdegib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Glasdegib. Management: Avoid use of glasdegib and moderate CYP3A4 inducers whenever possible. If combined, increase glasdegib dose from 100 mg daily to 200 mg daily or from 50 mg daily to 100 mg daily. Resume previous glasdegib dose 7 days after discontinuation of the inducer. Risk D: Consider therapy modification

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

GuanFACINE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of GuanFACINE. Management: Increase extended-release guanfacine dose by up to double when initiating guanfacine in patients taking CYP3A4 inducers or if initiating a CYP3A4 inducer in a patient already taking extended-release guanfacine. Monitor for reduced guanfacine efficacy. Risk D: Consider therapy modification

Hormonal Contraceptives: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a moderate CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification

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

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

Ibrexafungerp: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ibrexafungerp. Risk X: Avoid combination

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

Idelalisib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Idelalisib. Risk C: 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. Risk C: Monitor therapy

Imatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Imatinib. Risk C: Monitor therapy

Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy

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 indinavir dose to 1,000 mg every 8 hours when these agents are combined. Risk D: Consider therapy modification

Infigratinib: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Infigratinib. Risk X: Avoid combination

Irinotecan Products: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, concentrations of SN-38 may be reduced. Risk C: Monitor therapy

Isavuconazonium Sulfate: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Moderate) may decrease isavuconazole serum concentrations. Risk C: Monitor therapy

Isradipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Isradipine. Risk C: Monitor therapy

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

Itraconazole: May increase the serum concentration of Rifabutin. Rifabutin may decrease the serum concentration of Itraconazole. Risk X: Avoid combination

Ivabradine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ivabradine. Risk X: Avoid combination

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

Ixabepilone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ixabepilone. Risk C: Monitor therapy

Ixazomib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ixazomib. Risk C: Monitor therapy

Ketamine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ketamine. Risk C: Monitor therapy

Ketoconazole (Systemic): Rifabutin may decrease the serum concentration of Ketoconazole (Systemic). Ketoconazole (Systemic) may increase the serum concentration of Rifabutin. Management: The use of ketoconazole concurrently with or within 2 weeks of rifabutin is not recommended. If combined, monitor patients closely for evidence of diminished clinical response to ketoconazole and for increased rifabutin toxicities. Risk D: Consider therapy modification

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

Lapatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lapatinib. Risk C: Monitor therapy

Larotrectinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Larotrectinib. Management: Double the larotrectinib dose if used together with a moderate CYP3A4 inducer. Following discontinuation of the moderate CYP3A4 inducer, resume the previous dose of larotrectinib after a period of 3 to 5 times the inducer's half-life. Risk D: Consider therapy modification

Ledipasvir: Rifabutin may decrease the serum concentration of Ledipasvir. Risk X: 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. Risk D: 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. Risk D: Consider therapy modification

Lemborexant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lemborexant. Risk X: Avoid combination

Lenacapavir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lenacapavir. Risk X: Avoid combination

Leniolisib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Leniolisib. Risk X: Avoid combination

Lercanidipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lercanidipine. Risk C: Monitor therapy

Levamlodipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Levamlodipine. Risk C: Monitor therapy

Levoketoconazole: Rifabutin may decrease the serum concentration of Levoketoconazole. Risk X: Avoid combination

Levomethadone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Levomethadone. Risk C: Monitor therapy

LinaGLIPtin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of LinaGLIPtin. Risk C: Monitor therapy

Lonafarnib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lonafarnib. Risk X: Avoid combination

Lopinavir: May increase serum concentrations of the active metabolite(s) of Rifabutin. Lopinavir may increase the serum concentration of Rifabutin. Management: Reduce rifabutin doses. Clinical guidelines recommend 150 mg daily. Lopinavir/ritonavir prescribing information recommends a decrease of at least 75% (ie, to 150 mg every other day or 3 times per week). Risk D: 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, increase lorlatinib to 125 mg daily. Monitor for reduced lorlatinib efficacy and consider closer monitoring of AST, ALT, and bilirubin. Risk D: Consider therapy modification

Lovastatin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lovastatin. Risk C: Monitor therapy

Lumacaftor and Ivacaftor: Rifabutin may decrease the serum concentration of Lumacaftor and Ivacaftor. Specifically, the serum concentration of ivacaftor may be decreased. Risk C: Monitor therapy

Lumateperone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lumateperone. Risk X: Avoid combination

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. Risk D: Consider therapy modification

Macitentan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Macitentan. Risk C: Monitor therapy

Maraviroc: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice/day, but only if not receiving a strong CYP3A4 inhibitor. Not recommended for pediatric patients not also receiving a strong CYP3A4 inhibitor. Contraindicated in patients with CrCl less than 30 mL/min. Risk D: Consider therapy modification

Maribavir: Rifabutin may decrease the serum concentration of Maribavir. Risk X: Avoid combination

Mavacamten: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mavacamten. Risk X: Avoid combination

Mefloquine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mefloquine. Risk C: Monitor therapy

Meperidine: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Meperidine. Specifically, concentrations of normeperidine, the CNS stimulating metabolite, may be increased. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Meperidine. Risk C: Monitor therapy

Methadone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Methadone. Risk C: Monitor therapy

MethylPREDNISolone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of MethylPREDNISolone. Risk C: Monitor therapy

Mianserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mianserin. Risk C: Monitor therapy

Midazolam: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Midazolam. Risk C: Monitor therapy

Midostaurin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Midostaurin. Risk C: Monitor therapy

MiFEPRIStone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of MiFEPRIStone. Management: Avoid combined use in patients treated for Cushing's disease. When used for pregnancy termination, mifepristone efficacy may be reduced and an alternative pregnancy termination procedure may be warranted. Ensure a follow-up assessment after combined use. Risk D: Consider therapy modification

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

Mitapivat: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mitapivat. Management: Consider alternatives to this combination when possible. If combined, monitor hemoglobin and titrate mitapivat beyond 50 mg twice daily, if needed, but do not exceed doses of 100 mg twice daily. Risk D: Consider therapy modification

Mobocertinib: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Mobocertinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mobocertinib. Risk X: Avoid combination

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

Naloxegol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Naloxegol. Risk C: 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: Decrease 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. Rifabutin doses may also need to be adjusted. Risk D: Consider therapy modification

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

Netupitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Netupitant. Risk C: Monitor therapy

Nevirapine: May increase serum concentrations of the active metabolite(s) of Rifabutin. Nevirapine may increase the serum concentration of Rifabutin. Risk C: Monitor therapy

NIFEdipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of NIFEdipine. Risk C: Monitor therapy

Nilotinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nilotinib. Risk C: Monitor therapy

Nilvadipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nilvadipine. Risk C: Monitor therapy

NiMODipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of NiMODipine. Risk C: Monitor therapy

Nirmatrelvir and Ritonavir: May increase serum concentrations of the active metabolite(s) of Rifabutin. Nirmatrelvir and Ritonavir may increase the serum concentration of Rifabutin. Management: Decrease the rifabutin dose by at least 75%, to a maximum of 150 mg every other day or 3 times weekly, during coadministration with nirmatrelvir and ritonavir. Monitor for increased rifabutin adverse effects (eg, rash, urine discoloration, neutropenia). Risk D: Consider therapy modification

Nirogacestat: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nirogacestat. Risk X: Avoid combination

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

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

Oliceridine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Oliceridine. Risk C: Monitor therapy

Olmutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Olmutinib. Risk C: Monitor therapy

Olutasidenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Olutasidenib. Risk X: Avoid combination

Omaveloxolone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Omaveloxolone. Risk X: Avoid combination

Orelabrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Orelabrutinib. Risk X: Avoid combination

Osimertinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Osimertinib. Risk C: Monitor therapy

OxyCODONE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of OxyCODONE. Risk C: Monitor therapy

PACLitaxel (Conventional): CYP3A4 Inducers (Moderate) may decrease the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy

PACLitaxel (Protein Bound): CYP3A4 Inducers (Moderate) may decrease the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy

Pacritinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pacritinib. Risk X: Avoid combination

Palbociclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Palbociclib. Risk C: Monitor therapy

Palovarotene: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Palovarotene. Risk X: Avoid combination

PAZOPanib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of PAZOPanib. Risk C: Monitor therapy

Pemigatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pemigatinib. Risk X: Avoid combination

Perampanel: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Perampanel. Management: Increase perampanel starting dose to 4 mg/day if used with moderate CYP3A4 inducers. Increase perampanel dose by 2 mg/day no more than once weekly based on response and tolerability. Dose adjustments may be needed if the inducer is discontinued. Risk D: Consider therapy modification

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

Piperaquine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Piperaquine. Risk C: Monitor therapy

Pirtobrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pirtobrutinib. Management: Avoid concomitant use if possible. If combined, if the current pirtobrutinib dose is 200 mg once daily, increase to 300 mg once daily. If current pirtobrutinib dose is 50 mg or 100 mg once daily, increase the dose by 50 mg. Risk D: Consider therapy modification

PONATinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of PONATinib. Risk C: Monitor therapy

Posaconazole: Rifabutin may decrease the serum concentration of Posaconazole. Posaconazole may increase the serum concentration of Rifabutin. Management: Avoid coadministration of posaconazole and rifabutin if possible. If coadministration cannot be avoided, monitor patients for rifabutin adverse effects (eg, neutropenia, uveitis) and lack of posaconazole efficacy. Risk D: Consider therapy modification

Pralsetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pralsetinib. Management: If this combo cannot be avoided, increase pralsetinib dose from 400 mg daily to 600 mg daily; from 300 mg daily to 500 mg daily; and from 200 mg daily to 300 mg daily. Risk D: Consider therapy modification

Praziquantel: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Praziquantel. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for reduced praziquantel efficacy. If possible, stop the moderate CYP3A4 inducer 2 to 4 weeks before praziquantel initiation. Risk D: Consider therapy modification

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

PredniSONE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of PredniSONE. Risk C: Monitor therapy

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

QUEtiapine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of QUEtiapine. Risk C: Monitor therapy

QuiNIDine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of QuiNIDine. Risk C: Monitor therapy

QuiNINE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of QuiNINE. Risk C: Monitor therapy

Quizartinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Quizartinib. Risk X: Avoid combination

Raltegravir: Rifabutin may decrease the serum concentration of Raltegravir. Risk C: Monitor therapy

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

Regorafenib: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Regorafenib. Risk C: Monitor therapy

Repaglinide: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Repaglinide. Risk C: Monitor therapy

Repotrectinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Repotrectinib. Risk X: Avoid combination

Ribociclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ribociclib. Risk C: Monitor therapy

Rilpivirine: Rifabutin may decrease the serum concentration of Rilpivirine. Management: Increase rilpivirine dose to 50 mg/day during rifabutin treatment. Use of rifabutin with emtricitabine/rilpivirine/tenofovir alafenamide product is not recommended. Use with IV cabotegravir/rilpivirine is contraindicated. Risk D: Consider therapy modification

Rimegepant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rimegepant. Risk X: Avoid combination

Ripretinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ripretinib. Management: Avoid this combination if possible. If concomitant use is required, increase ripretinib to 150 mg twice daily. Decrease ripretinib to 150 mg once daily 14 days after stopping a moderate CYP3A4 inducer. Monitor patients for ripretinib response and toxicity Risk D: Consider therapy modification

RisperiDONE: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of RisperiDONE. CYP3A4 Inducers (Moderate) may decrease the serum concentration of RisperiDONE. Risk C: Monitor therapy

Ritlecitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ritlecitinib. Risk C: Monitor therapy

Ritonavir: May increase serum concentrations of the active metabolite(s) of Rifabutin. Ritonavir may increase the serum concentration of Rifabutin. Management: Ritonavir labeling recommends reducing rifabutin doses by at least 75% (ie, 150 mg every other day or 3 times per week). Clinical practice guidelines recommend rifabutin 150 mg daily if combined with ritonavir-boosted protease inhibitors. Risk D: Consider therapy modification

Roflumilast (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Roflumilast (Systemic). CYP3A4 Inducers (Moderate) may decrease the serum concentration of Roflumilast (Systemic). Risk C: Monitor therapy

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

Samidorphan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Samidorphan. Risk C: Monitor therapy

Saquinavir: May increase serum concentrations of the active metabolite(s) of Rifabutin. Rifabutin may decrease the serum concentration of Saquinavir. Saquinavir may increase the serum concentration of Rifabutin. 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 when used with other protease inhibitors. Risk D: Consider therapy modification

Selpercatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Selpercatinib. Risk X: Avoid combination

Selumetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Selumetinib. Risk X: Avoid combination

Sertraline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sertraline. Risk C: Monitor therapy

Sildenafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sildenafil. Risk C: Monitor therapy

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

Simvastatin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Simvastatin. Risk C: Monitor therapy

Sirolimus (Conventional): Rifabutin may decrease the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy

Sirolimus (Protein Bound): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sirolimus (Protein Bound). Risk C: 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. Risk D: Consider therapy modification

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

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

SORAfenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of SORAfenib. Risk C: Monitor therapy

Sotorasib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sotorasib. Risk C: Monitor therapy

Sparsentan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sparsentan. Risk C: Monitor therapy

SUFentanil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of SUFentanil. Risk C: Monitor therapy

SUNItinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of SUNItinib. Risk C: Monitor therapy

Suvorexant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Suvorexant. Risk C: Monitor therapy

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

Tadalafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tadalafil. Risk C: Monitor therapy

Tamoxifen: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tamoxifen. Risk C: Monitor therapy

Tasimelteon: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tasimelteon. Risk C: Monitor therapy

Tazemetostat: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tazemetostat. Risk X: Avoid combination

Temsirolimus: Rifabutin may decrease serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be decreased. Rifabutin may decrease the serum concentration of Temsirolimus. Risk C: Monitor therapy

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

Tetrahydrocannabinol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tetrahydrocannabinol. Risk C: Monitor therapy

Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor therapy

Tezacaftor and Ivacaftor: Rifabutin may decrease the serum concentration of Tezacaftor and Ivacaftor. Specifically, the serum concentration of ivacaftor may be decreased. Risk C: Monitor therapy

Thiotepa: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Thiotepa. Risk C: Monitor therapy

Ticagrelor: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ticagrelor. Risk C: Monitor therapy

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 prescribing information 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 when used with tipranavir/ritonavir. Risk D: Consider therapy modification

Tivozanib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tivozanib. Risk C: Monitor therapy

Tofacitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tofacitinib. Risk C: Monitor therapy

Tolvaptan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tolvaptan. Risk C: Monitor therapy

Toremifene: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Toremifene. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Toremifene. Risk C: Monitor therapy

Trabectedin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Trabectedin. Risk C: Monitor therapy

TraMADol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of TraMADol. Risk C: Monitor therapy

TraZODone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of TraZODone. Risk C: Monitor therapy

Triazolam: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Triazolam. Risk C: Monitor therapy

Tucatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tucatinib. Risk C: Monitor therapy

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification

Ubrogepant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a moderate CYP3A4 inducer. Risk D: Consider therapy modification

Ulipristal: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ulipristal. Risk X: Avoid combination

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

Valbenazine: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Valbenazine. Risk C: Monitor therapy

Vandetanib: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Vandetanib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vandetanib. Risk C: Monitor therapy

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

Vemurafenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vemurafenib. Risk C: Monitor therapy

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

Verapamil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Verapamil. Risk C: Monitor therapy

Vilazodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vilazodone. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Rifamycin Derivatives may decrease the serum concentration of Vitamin K Antagonists. Management: Consider alternatives if possible. If combined, monitor for reduced anticoagulant effects if a rifamycin derivative is initiated in a vitamin K antagonist treated patient. Vitamin K antagonist dose adjustments will likely be required. Risk D: Consider therapy modification

Voclosporin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Voclosporin. Risk X: Avoid combination

Vonoprazan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vonoprazan. Risk X: Avoid combination

Vorapaxar: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vorapaxar. Risk X: Avoid combination

Voriconazole: Rifabutin may decrease the serum concentration of Voriconazole. Voriconazole may increase the serum concentration of Rifabutin. Risk X: Avoid combination

Vortioxetine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vortioxetine. Risk C: Monitor therapy

Voxelotor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and moderate CYP3A4 inducers. If unavoidable, increase the voxelotor dose to 2,000 mg once daily. For children ages 4 to less than 12 years, weight-based dose adjustments are required. See full monograph for details. Risk D: Consider therapy modification

Voxilaprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Voxilaprevir. Risk X: Avoid combination

Zaleplon: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zaleplon. Risk C: Monitor therapy

Zanubrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zanubrutinib. Management: Avoid this combination if possible. If coadministration of zanubrutinib and a moderate CYP3A4 inducer is required, increase the zanubrutinib dose to 320 mg twice daily. Risk D: Consider therapy modification

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

Zopiclone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zopiclone. Risk C: Monitor therapy

Zuranolone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zuranolone. Risk X: Avoid combination

Food Interactions

High-fat meal may decrease the rate but not the extent of absorption. Management: May administer with meals.

Pregnancy Considerations

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

Breastfeeding Considerations

It is not known if rifabutin is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Rifabutin may be used as an optional adjunctive agent in the treatment of disseminated M. avium complex in patients with HIV. The Health and Human Services perinatal HIV guidelines do not recommend breastfeeding for patients in the United States with HIV when safer infant feeding options are available (HHS [perinatal] 2023).

Dietary Considerations

May be taken with meals.

Monitoring Parameters

Periodic LFTs, CBC with differential, platelet count, signs/symptoms of hypersensitivity, severe cutaneous adverse reactions, or signs/symptoms of uveitis.

Mechanism of Action

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

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Readily, 53%

Distribution: Vd: Adults: 9.3 ± 1.5 L/kg

Protein binding: 85%

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

Bioavailability: Absolute: HIV: 20%

Half-life elimination: Terminal: 45 hours (range: 16 to 69 hours)

Time to peak, serum: 2 to 4 hours

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

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: AUC is increased 71% in patients with CrCl <30 mL/minute.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Mycobutin;
  • (AR) Argentina: Tambux;
  • (AT) Austria: Mycobutin;
  • (AU) Australia: Mycobutin;
  • (BD) Bangladesh: Myconil;
  • (BE) Belgium: Mycobutin;
  • (CH) Switzerland: Mycobutin;
  • (CO) Colombia: Rifbutin;
  • (CZ) Czech Republic: Mycobutin;
  • (DE) Germany: Mycobutin;
  • (ES) Spain: Ansatipin;
  • (FI) Finland: Ansatipin;
  • (FR) France: Ansatipine | Mycobutin;
  • (GB) United Kingdom: Mycobutin;
  • (GR) Greece: Ansatipine | Mycobutin;
  • (HK) Hong Kong: Mycobutin;
  • (HU) Hungary: Mycobutin;
  • (IE) Ireland: Mycobutin;
  • (IL) Israel: Mycobutin;
  • (IN) India: Macbutin;
  • (IT) Italy: Mycobutin;
  • (JP) Japan: Mycobutin;
  • (KE) Kenya: Mycobutin;
  • (KR) Korea, Republic of: Mycobutin;
  • (LT) Lithuania: Mycobutin;
  • (LU) Luxembourg: Mycobutin;
  • (LV) Latvia: Mycobutin;
  • (MA) Morocco: Mycobutin;
  • (MY) Malaysia: Mycobutin;
  • (NL) Netherlands: Mycobutin;
  • (NO) Norway: Ansatipin | Mycobutin;
  • (NZ) New Zealand: Mycobutin;
  • (PL) Poland: Mycobutin;
  • (PR) Puerto Rico: Mycobutin;
  • (PT) Portugal: Mycobutin | Rifabutina;
  • (RU) Russian Federation: Farbutin | Mycobutin | Mycobutin ross | Rifabutin ferein | Verbutin;
  • (SE) Sweden: Ansatipin;
  • (SI) Slovenia: Mycobutin;
  • (TR) Turkey: Mycobutin;
  • (TW) Taiwan: Mycobutin | Ributin;
  • (UA) Ukraine: Mycobutin;
  • (UG) Uganda: Mycobutin;
  • (ZA) South Africa: Mycobutin;
  • (ZM) Zambia: Mycobutin
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Topic 9863 Version 380.0

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