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Drug-Susceptible Tuberculosis

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19 Antiretroviral agents (cont'd) CCR5 inhibitors Maraviroc RIF should not be used with maraviroc. RFB can be used with maraviroc. Anti-infectives Macrolide antibiotics (azithromycin, clarithromycin, erythromycin) Azithromycin has no significant interaction with rifamycins. Coadministration of clarithromycin and RFB results in significant bidirectional interactions that can increase RFB to toxic levels, increasing the risk of uveitis. Erythromycin is a CYP3A4 substrate; clearance may increase in setting of rifamycin use. Doxycycline May require use of a drug other than doxycycline. Azole antifungal agents (ketoconazole, itraconazole, voriconazole, fluconazole, posaconazole, isavuconazole) Itraconazole, ketoconazole, and voriconazole concentrations may be subtherapeutic with any of the rifamycins. Fluconazole can be used with rifamycins, but the dose of fluconazole may have to be increased. Atovaquone Consider alternate form of Pneumocystis jirovecii treatment or prophylaxis. Chloramphenicol Consider an alternative antibiotic. Mefloquine Consider alternate form of malaria prophylaxis. Hormone therapy Ethinylestradiol, norethindrone Women of reproductive potential on oral contraceptives should be advised to add a barrier method of contraception when on a rifamycin. Tamoxifen May require alternate therapy or use of a non-rifamycin-containing regimen. Levothyroxine Monitoring of serum TSH recommended; may require increased dose of levothyroxine. Narcotics Methadone RIF and RPT use may require methadone dose increase. RFB infrequently causes methadone withdrawal. Anticoagulants Warfarin Monitor prothrombin time; may require 2- to 3-fold warfarin dose increase. Table 8. Clinically Significant Drug–Drug Interactions Involving the Rifamycins a (cont'd)

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