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remarkable [30:<50 cells/mm 3 ): 300 mg once daily (HHS [OI adult 2017)]; alternatively, per the manufacturer, 150 mg twice daily with food may be used in patients with GI upset. May discontinue when CD4 count> 100 cells/mm 3 for 3 months in response to antiretroviral therapy (ART) (HHS [OI adult 2017]). Note: If effective ART is initiated immediately and viral suppression is achieved, some experts do not recommend routine initiation of MAC primary prophylaxis, regardless of initial CD4 count (IAS-USA [Gunthard 2016]). Treatment (off-label use): 300 mg once daily as optional adjunct therapy with clarithromycin or azithromycin (plus ethambutol) (HHS [OI adult 2017]) 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 (HHS [OI adult 2015]) 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). LTBI treatment is not associated with clinical benefit or recommended in HIV infected patients who are anergic and who have not had recent contact with anyone with infectious TB (HHS [OI adult 2015]) 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 (Nahid 2016). HIV-infected patients (and not receiving protease inhibitors, efavirenz, rilpivirine or elvitegravir/cobicistat/emtricitabine/tenofovir): 5 mg/kg/day (usual dose: 300 mg) once daily or intermittently 3 times weekly as part of a multidrug regimen (HHS [OI adult 2015]). Dosing: Geriatric Refer to adult dosing. Dosing: Pediatric Mycobacterium avium complex disease in HIV-exposed/-infected patients (off-label use): Oral: Prophylaxis for recurrence of Mycobacterium avium complex (MAC): Infants and Children: 5 mg/kg (maximum dose: 300 mg) once daily as an optional add-on to primary therapy of clarithromycin and ethambutol (CDC 2009). Prophylaxis for first episode of MAC: Children 6 years: 300 mg once daily (CDC 2009). Treatment of severe MAC: Infants and Children: 10 to 20 mg/kg (maximum dose: 300 mg) once daily, in addition to primary therapy of clarithromycin and ethambutol (CDC 2009). Adolescents (disseminated disease): Refer to adult dosing. Tuberculosis, treatment of drug-susceptible disease (as an alternative/substitute for rifampin) (excludes meningitis) (off-label use): Oral: Non-HIV-infected patients: Children and Adolescents: Appropriate dosing is unknown; estimated at 5 mg/kg/dose once daily (Nahid 2016) HIV-exposed/-infected patients: Infants and Children: 10 to 20 mg/kg (maximum dose: 300 mg) once daily or intermittently 2 to 3 times weekly (CDC 2009). Adolescents (and not receiving protease inhibitors, efavirenz, rilpivirine or elvitegravir/cobicistat/emtricitabine/tenofovir): Refer to adult dosing. Tuberculosis, LTBI treatment (to prevent TB) in HIV-infected patients (alternative to preferred therapy) (off-label use): Adolescents: Refer to adult dosing. Dosing: Renal Impairment CrCl 30 mL/minute: No dosage adjustment necessary. CrCl <30 mL/minute: Reduce dose by 50% Dosing: Hepatic Impairment Mild impairment: No dosage adjustment necessary. Moderate to severe impairment: There are no dosage adjustments provided in manufacturer's labeling (has not been studied). 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 (Strong) may decrease the serum concentration of Abemaciclib. Avoid combination Abiraterone Acetate: CYP3A4 Inducers (Strong) may decrease the serum concentration of Abiraterone Acetate. Management: Avoid whenever possible. If such a combination cannot be avoided, increase abiraterone acetate dosing frequency from once daily to twice daily during concomitant use. Avoid combination Acalabrutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Acalabrutinib. Management: Avoid co-administration of strong CYP3A inducers in patients taking acalabrutinib. If strong CYP3A inducers cannot be avoided, increase the dose of acalabrutinib to 200 mg twice daily. Consider therapy modification 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 (Strong) may decrease the serum concentration of Antihepaciviral Combination Products. Avoid combination Apixaban: CYP3A4 Inducers (Strong) may decrease the serum concentration of Apixaban. Avoid combination Apremilast: CYP3A4 Inducers (Strong) may decrease the serum concentration of Apremilast. Avoid combination Aprepitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Aprepitant. Avoid combination ARIPiprazole: CYP3A4 Inducers (Strong) may decrease the serum concentration of ARIPiprazole. Management: Double the oral aripiprazole dose and closely monitor. Reduce oral aripiprazole dose to 10-15 mg/day (for adults) if the inducer is discontinued. Avoid use of strong CYP3A4 inducers for more than 14 days with extended-release injectable aripiprazole. Consider therapy modification ARIPiprazole Lauroxil: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Patients taking the 441 mg dose of aripiprazole lauroxil increase their dose to 662 mg if used with a strong CYP3A4 inducer for more than 14 days. No dose adjustment is necessary for patients using the higher doses of aripiprazole lauroxil. Consider therapy modification Artemether: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Artemether. Specifically, dihydroartemisinin concentrations may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Artemether. Avoid combination Asunaprevir: CYP3A4 Inducers (Strong) 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. Atazanavir 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 with atazanavir/ritonavir. Consider therapy modification Atovaquone: Rifamycin Derivatives may decrease the serum concentration of Atovaquone. Avoid combination Axitinib: CYP3A4 Inducers (Strong) 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 (Strong) may decrease the serum concentration of Bedaquiline. Avoid combination Benperidol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Benperidol. Monitor therapy Boceprevir: Rifabutin may decrease the serum concentration of Boceprevir. Boceprevir may increase the serum concentration of Rifabutin. Avoid combination Bortezomib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bortezomib. Avoid combination Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy Bosutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bosutinib. Avoid combination Brentuximab Vedotin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Monitor therapy Brexpiprazole: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brexpiprazole. Management: If brexpiprazole is used together with a strong CYP3A4 inducer, the brexpiprazole dose should gradually be doubled over the course of 1 to 2 weeks. Consider therapy modification Brigatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brigatinib. Avoid combination Buprenorphine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Buprenorphine. Monitor therapy BusPIRone: Rifamycin Derivatives may decrease the serum concentration of BusPIRone. Management: The degree to which rifampin alters buspirone concentrations warrants the consideration of an alternative to buspirone that is not metabolized by CYP3A4. If these agents are used together, buspirone dose adjustments may be needed. Consider therapy modification Cabozantinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cabozantinib. Management: Avoid use of strong CYP3A4 inducers with cabozantinib if possible. If combined, cabozantinib dose adjustments are recommended and vary based on the cabozantinib product used and the indication for use. See monograph for details. Consider therapy modification Calcifediol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Calcifediol. 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 Cannabidiol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabidiol. Monitor therapy Cannabis: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Monitor therapy Cariprazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cariprazine. Avoid combination Ceritinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ceritinib. Avoid combination Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination Clarithromycin: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Clarithromycin. Clarithromycin may increase the serum concentration of CYP3A4 Inducers (Strong). CYP3A4 Inducers (Strong) 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 may impair clarithromycin efficacy. Consider therapy modification Clindamycin (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Clindamycin (Systemic). Refer to the specific clindamycin (systemic) - rifampin drug interaction monograph for information concerning that combination. Monitor therapy Clopidogrel: Rifamycin Derivatives may enhance the adverse/toxic effect of Clopidogrel. Specifically,clopidogrel antiplatelet effects may be enhanced. Monitor therapy CloZAPine: CYP3A4 Inducers (Strong) may decrease the serum concentration of CloZAPine. Avoid combination Cobimetinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cobimetinib. Avoid combination Copanlisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Copanlisib. Avoid combination Corticosteroids (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Corticosteroids (Systemic). Exceptions: Hydrocortisone (Systemic); PrednisoLONE (Systemic); PredniSONE. Monitor therapy Crizotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Crizotinib. Avoid combination 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 (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. Exceptions: Buprenorphine; Etizolam; HYDROcodone; Zolpidem. Consider therapy modification 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 (Strong) may decrease the serum concentration of Daclatasvir. 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 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 (Strong) may decrease the serum concentration of Dasabuvir. Avoid combination Dasatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dasatinib. Management: Avoid when possible. If such a combination cannot be avoided, consider increasing dasatinib dose and monitor clinical response and toxicity closely. Consider therapy modification Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy Deflazacort: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Deflazacort. Avoid combination Delamanid: CYP3A4 Inducers (Strong) may decrease the serum concentration of Delamanid. 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 Dexamethasone (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Dexamethasone (Systemic). Management: Consider dexamethasone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced steroid efficacy. Consider therapy modification Dienogest: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dienogest. Management: Avoid use of dienogest for contraception when using medications that induce CYP3A4 and for at least 28 days after discontinuation of a CYP3A4 inducer. An alternative form of contraception should be used during this time. Avoid combination Diethylstilbestrol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Diethylstilbestrol. Monitor therapy Doxercalciferol: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Doxercalciferol. Monitor therapy DOXOrubicin (Conventional): CYP3A4 Inducers (Strong) may decrease the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to strong CYP3A4 inducers in patients treated with doxorubicin. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification Dronabinol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronabinol. Monitor therapy Dronedarone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronedarone. Avoid combination 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 Eliglustat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Eliglustat. 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 Enzalutamide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Enzalutamide. Management: Consider using an alternative agent that has no or minimal CYP3A4 induction potential when possible. If this combination cannot be avoided, increase the dose of enzalutamide from 160 mg daily to 240 mg daily. Avoid combination Erlotinib: CYP3A4 Inducers (Strong) 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 (Strong) may decrease the serum concentration of Estriol (Systemic). Monitor therapy Estriol (Topical): CYP3A4 Inducers (Strong) 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 Etizolam: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etizolam. Monitor therapy Etoposide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etoposide. Management: When possible, seek alternatives to strong CYP3A4-inducing medications in patients receiving etoposide. If these combinations cannot be avoided, monitor patients closely for diminished etoposide response. Consider therapy modification Etoposide Phosphate: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etoposide Phosphate. Management: When possible, seek alternatives to strong CYP3A4-inducing medications in patients receiving etoposide phosphate. If these combinations cannot be avoided, monitor patients closely for diminished etoposide phosphate response. Consider therapy modification Etravirine: Rifabutin may decrease the serum concentration of Etravirine. Management: Avoid concomitant use with rifabutin if a protease inhibitor/ritonavir combination is also used. Monitor therapy Everolimus: CYP3A4 Inducers (Strong) may decrease the serum concentration of Everolimus. Management: Avoid concurrent use of strong CYP3A4 inducers, but if strong CYP3A4 inducers cannot be avoided, consider gradually (in 5 mg increments) increasing the everolimus dose from 10 mg/day to 20 mg/day (adult doses). Avoid combination Evogliptin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Evogliptin. Monitor therapy Exemestane: CYP3A4 Inducers (Strong) may decrease the serum concentration of Exemestane. Management: Exemestane U.S. product labeling recommends using an increased dose (50 mg/day) in patients receiving concurrent strong CYP3A4 inducers. The Canadian product labeling does not recommend a dose adjustment with concurrent use of strong CYP3A4 inducers. Consider therapy modification FentaNYL: CYP3A4 Inducers (Strong) may decrease the serum concentration of FentaNYL. Monitor therapy Flibanserin: CYP3A4 Inducers (Strong) 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 Gefitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Gefitinib. Management: In the absence of severe adverse reactions, increase gefitinib dose to 500 mg daily in patients receiving strong CYP3A4 inducers; resume 250 mg dose 7 days after discontinuation of the strong inducer. Carefully monitor clinical response. Consider therapy modification Gemigliptin: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Gemigliptin. CYP3A4 Inducers (Strong) may decrease the serum concentration of Gemigliptin. Avoid combination Glecaprevir and Pibrentasvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Glecaprevir and Pibrentasvir. Monitor therapy Grazoprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Grazoprevir. Avoid combination GuanFACINE: CYP3A4 Inducers (Strong) may decrease the serum concentration of GuanFACINE. Management: Increase the guanfacine dose by up to double when initiating concomitant therapy with strong CYP3A4 inducers. Increase guanfacine dose gradually over 1-2 weeks if strong CYP3A4 inducer therapy is just beginning. 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 (Strong) may decrease the serum concentration of HYDROcodone. Monitor therapy Hydrocortisone (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Hydrocortisone (Systemic). Monitor therapy Ibrutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ibrutinib. Avoid combination Idelalisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Idelalisib. Avoid combination Ifosfamide: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Ifosfamide. CYP3A4 Inducers (Strong) may decrease 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 Imatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Imatinib. Management: Avoid concurrent use of imatinib with strong CYP3A4 inducers 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: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Irinotecan Products. Avoid combination Isavuconazonium Sulfate: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Strong) may decrease isavuconazole serum concentrations. Avoid combination Isoniazid: Rifamycin Derivatives may enhance the hepatotoxic effect of Isoniazid. Even so, this is a frequently employed combination regimen. Monitor therapy Itraconazole: CYP3A4 Inducers (Strong) may decrease the serum concentration of Itraconazole. Avoid combination Ivabradine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivabradine. Avoid combination Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivacaftor. Avoid combination Ixabepilone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ixabepilone. Management: Avoid this combination whenever possible. If this combination must be used, a gradual increase in ixabepilone dose from 40 mg/m 2 to 60 mg/m 2 (given as a 4-hour infusion), as tolerated, should be considered. Consider therapy modification Ixazomib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ixazomib. Avoid combination Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy Lapatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lapatinib. Management: If therapy overlap cannot be avoided, consider titrating lapatinib gradually from 1,250 mg/day up to 4,500 mg/day (HER2 positive metastatic breast cancer) or 1,500 mg/day up to 5,500 mg/day (hormone receptor/HER2 positive breast cancer) as tolerated. Avoid combination Ledipasvir: Rifabutin may decrease the serum concentration of Ledipasvir. Avoid combination Linagliptin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Linagliptin. Management: Strongly consider using an alternative to any strong CYP3A4 inducer in patients who are being treated with linagliptin. If this combination is used, monitor patients closely for evidence of reduced linagliptin effectiveness. 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 Lumefantrine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lumefantrine. Avoid combination Lurasidone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lurasidone. Avoid combination Macitentan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Macitentan. Avoid combination Macrolide Antibiotics: May decrease the metabolism of Rifamycin Derivatives. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. Consider therapy modification Manidipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Manidipine. Management: Consider avoiding concomitant use of manidipine and strong CYP3A4 inducers. If combined, monitor closely for decreased manidipine effects and loss of efficacy. Increased manidipine doses may be required. Consider therapy modification Maraviroc: CYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice daily when used with strong CYP3A4 inducers. This does not apply to patients also receiving strong CYP3A4 inhibitors. Do not use maraviroc with strong CYP3A4 inducers in patients with CrCl less than 30 mL/min. Consider therapy modification MethylPREDNISolone: CYP3A4 Inducers (Strong) may decrease the serum concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced steroid efficacy. Consider therapy modification Midostaurin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Midostaurin. Avoid combination MiFEPRIStone: CYP3A4 Inducers (Strong) may decrease the serum concentration of MiFEPRIStone. Avoid combination Mirodenafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Mirodenafil. Management: Consider avoiding the concomitant use of mirodenafil and strong CYP3A4 inducers. If combined, monitor for decreased mirodenafil effects. Mirodenafil dose increases may be required to achieve desired effects. Consider therapy modification 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 (Strong) may decrease the serum concentration of Naldemedine. Avoid combination Naloxegol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Naloxegol. Avoid combination 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 (Strong) may decrease the serum concentration of Neratinib. Avoid combination Netupitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Netupitant. 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 NIFEdipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of NIFEdipine. Avoid combination Nilotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib. Avoid combination NiMODipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of NiMODipine. Avoid combination Nisoldipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nisoldipine positively


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