rifabutin.txt

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 &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :847

%Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :70

%Excreted unchanged in urine &nbsp &nbsp : 5

Volume of distribution (L/kg) &nbsp &nbsp &nbsp :8–9

half-life – normal/ESRD (hrs)&nbsp &nbsp &nbsp :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 &nbsp &nbsp &nbsp &nbsp &nbsp : Maximum 300 mg daily

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp:Unlikely to be dialysed. Dose as in GFR <10 mL/min

HD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :Not dialysed. Dose as in GFR <10 mL/min

HDF/high flux &nbsp :Not dialysed. Dose as in GFR <10 mL/min

CAV/VVHD &nbsp &nbsp &nbsp:Unknown dialysability. Dose as in GFR=10–30 mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Anti-arrhythmics: metabolism of disopyramide accelerated

Antibacterials: clarithromycin and other macrolides increase concentration of rifabutin, resulting in increased risk of uveitis – reduce rifabutin dose; reduced concentration of dapsone and clarithromycin

Anticoagulants: reduced anticoagulant effect of coumarinsAntidiabetics: reduced antidiabetic effect of chlorpropamide and tolbutamide; possibly reduced antidiabetic effect with sulphonylureas

Anti-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 itraconazole

Antipsychotics: possibly reduced aripiprazole concentration – increase dose of aripiprazole

Antivirals: 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

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Route

Oral

Rate of Administration

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Comments

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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.

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