Rifabutin
Mechanism :
Rifabutin acts via the inhibition of DNA-dependent RNA polymerase in gram-positive and some gram-negative bacteria, leading to a suppression of RNA synthesis and cell death.
Indication :
- Mycobacterium Avium Complex (MAC) infection in HIV infected.
- Treatment of tuberculosis (TB) due to mycobacterium tuberculosis (MTB) as an alternative to rifampin in combination with other antitubercular agents.
Contraindications :
Hypersensitivity, Active TB; Caution if neutropenia, thrombocytopenia.
Dosing :
MAC prophylaxis:
5 mg/kg PO OD. Max: 300 mg/day.
Treatment of MAC disseminated:
10-20 mg/kg/day PO OD. Max: 300 mg/day.
Treatment of TB due to MTB as an alternative to rifampicin:
10 to 20 mg/kg/dose PO once daily. Max: 300 mg/day.
With concomitant protease inhibitors or concomitant
cobicistat,
elvitegravir,
emtricitabine or tenofovir give half the dose (Max: 150 mg/day or 300 mg 3 times a week). With concomitant
efavirenz, increase the dose by 1½-2 times. Max: 450 to 600 mg PO once daily
Adverse Effect :
Neutropenia, leukopenia, thrombocytopenia, uveitis, Clostridium difficile associated diarrhea, orange colour urine, rash, nausea, abdominal pain, headache, dyspepsia, diarrhea, eructation, vomiting, taste changes, fever, anorexia, flatulence, myalgia, asthenia, chest pain, insomnia, yellow skin.
Interaction :
Abiraterone, Acenocoumarol: Rifabutin may decrease the anticoagulant effect
Amitriptyline, Amoxapine: The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant.
Amprenavir: Amprenavir may increase the effect and toxicity of rifabutin.
Atovaquone: Rifabutin decreases the effect of atovaquone.
Indinavir: Rifabutin decreases the effect of indinavir.
Itraconazole: Rifabutin decreases the effect of itraconazole.
Ivacaftor: Strong CYP3A4 inducers may decrease levels of ivacaftor.
Josamycin: The rifamycin, rifabutin, may decrease the effect of the macrolide, josamycin.
Lovastatin: Rifabutin may decrease the effect of lovastatin by increasing its metabolism.
Mestranol: This product may cause a slight decrease of the contraceptive effect.
Methadone: The rifamycin decreases the effect of methadone.
Norethindrone: Rifabutin may decrease the contraceptive effect of norethindrone.
Nortriptyline: The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, nortriptyline, by increasing its metabolism.
Pazopanib: Affects CYP3A4 metabolism therefore will decrease levels or effect of pazopanib.
Posaconazole: Modification of drug levels for both agents.
Propafenone: Rifampin decreases the effect of propafenone.
Protriptyline: The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, protriptyline, by increasing its metabolism.
Rilpivirine: Strong inducers of CYP3A4 decrease the exposure of rilpivirine thus decreasing efficacy.
Ritonavir: Rifabutin decreases the effect of ritonavir.
Roflumilast: Affects CYP3A4 metabolism, decreases level or effect of roflumilast.
Saquinavir: Rifabutin decreases the effect of saquinavir.
Simvastatin: Rifabutin may decrease the effect of simvastatin by increasing its metabolism.
Sirolimus: The rifamycin decreases the effect of sirolimus.
Sunitinib: Possible decrease in sunitinib levels.
Tacrolimus: Carbamazepine may decrease the blood concentration of Tacrolimus.
Tamoxifen: The rifamycin decreases the effect of anti-estrogen.
Telithromycin: Rifabutin may decrease the plasma concentration of Telithromycin.
Temsirolimus: Rifabutin may increase the metabolism of Temsirolimus decreasing its efficacy.
Terbinafine: Rifabutin may increase the metabolism and clearance of Terbinafine.
Tipranavir: Tipranavir increases the concentration of Rifabutin.
Tolvaptan: Rifabutin is a CYP3A4 inducer and will decrease serum concentrations of tolvaptan and ultimately, its clinical effects.
Toremifene: The rifamycin decreases the effect of anti-estrogen.
Tramadol: Rifabutin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Trazodone: The CYP3A4 inducer, Rifabutin, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance.
Trimipramine: The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, trimipramine, by increasing its metabolism.
Vemurafenib: Strong CYP3A4 inducers may decrease levels of vemurafenib.
Verapamil, Voriconazole: Rifabutin may decrease the serum concentration of voriconazole. Voriconazole: may increase the serum concentration of rifabutin.
Warfarin: Rifabutin may decrease the anticoagulant effect of warfarin.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 30-50 | Dose as in normal renal function |
| 10-20 | Maximum 300 mg daily |
| <10 | Maximum 300 mg daily |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unlikely to be dialysed. Dose as in GFR<10 mL/min |
| HD | Not dialysed. Dose as in GFR<10 mL/min |
| HDF/High flux | Not dialysed. Dose as in GFR<10 mL/min |
| CAV/VVHD | Unknown dialysability. Dose as in GFR=10–30 mL/min |
Hepatic Dose :
Rifabutin is primarily eliminated by the liver and is an inducer of its own metabolism (via CYP3A4 induction). However, rifabutin has a long half-life (about 45 hours) due to significant distribution in the body. No dose adjustment recommended.