rifabutin
CLINICAL USE
Antibacterial agent:Tuberculosis Mycobacterial infection
DOSE IN NORMAL RENAL FUNCTION
Prophylaxis of Mycobacterium avium in patients with low CD4 count: 300 mg dailyTreatment of non-tuberculous mycobacterial disease, in combination with other drugs: 450–600 mg dailyTreatment of pulmonary tuberculosis, in combination with other drugs: 150–450 mg daily
PHARMACOKINETICS
Molecular weight :847 %Protein binding :70 %Excreted unchanged in urine : 5 Volume of distribution (L/kg) :8–9half-life – normal/ESRD (hrs) :35–40/Unchanged DOSE IN RENAL IMPAIRMENT
GFR (mL/MIN)
30–50 Dose as in normal renal function 10–30 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/minHDF/high flux :Not dialysed. Dose as in GFR <10 mL/minCAV/VVHD :Unknown dialysability. Dose as in GFR=10–30 mL/min IMPORTANT DRUG INTERACTIONS
Potentially hazardous interactions with other drugsAnti-arrhythmics: metabolism of disopyramide acceleratedAntibacterials: clarithromycin and other macrolides increase concentration of rifabutin, resulting in increased risk of uveitis – reduce rifabutin dose; reduced concentration of dapsone and clarithromycinAnticoagulants: reduced anticoagulant effect of coumarinsAntidiabetics: reduced antidiabetic effect of chlorpropamide and tolbutamide; possibly reduced antidiabetic effect with sulphonylureasAnti-epileptics: reduced concentration of phenytoin and carbamazepine Antifungals: fluconazole, triazoles, posaconazole and voriconazole increase the concentration of rifabutin resulting in increased risk of uveitis – reduce rifabutin dose; rifabutin reduces concentration of posaconazole, voriconazole and itraconazole – increase voriconazole dose, avoid with itraconazoleAntipsychotics: possibly reduced aripiprazole concentration – increase dose of aripiprazoleAntivirals: amprenavir, atazanavir darunavir, nelfinavir and tipranavir and possibly nevirapine increase concentration of rifabutin – halve or reduce dose of rifabutin; efavirenz reduces the concentration of rifabutin – increase dose of rifabutin; indinavir increases rifabutin concentration– reduce dose of rifabutin; concentration of indinavir reduced when given together – increase indinavir dose; ritonavir increases the concentration of rifabutin resulting in increased risk of uveitis – avoid concomitant use; concentration of saquinavir reduced – avoid concomitant use unless another protease inhibitor is also givenAtovaquone: concentration of atovaquone reduced (possible therapeutic failure of atovaquone)Ciclosporin: possibly reduced ciclosporin levelsCorticosteroids: reduced level of corticosteroids – double steroid dose. Give as twice daily dosageOestrogens and progestogens: reduced contraceptive effect due to increased metabolismSirolimus: reduced sirolimus concentration – avoid Tacrolimus: possibly reduced tacrolimus trough concentration ADMINISTRATION
Reconstition
– Route
Oral Rate of Administration
–Comments
– OTHER INFORMATION
Can cause an orange-tan skin pigmentation as well as discoloured urineCan cause abnormal LFTs and hepatitis Can cause uveitis especially in combination with clarithromycin and fluconazoleRifabutin is a less potent CYP4503A enzyme inducer than rifampicin but similar interactions may occur.
See how to identify renal failure stages according to GFR calculation
See how to diagnose irreversible renal disease
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