rifabutin (Mycobutin)

Introduction

Tradename: Mycobutin.

Indications

• prevention of disseminated Mycobacterium avium complex (MAC) in patients with advanced HIV infection
• treatment of tuberculosis in combination with other agents

Contraindications

• leukopenia (WBC < 1000/mm3)
• thrombocytopenia (platelets < 50,000/mm3)

pregnancy category = b

safety in lactation = ?

Dosage

• 300 mg PO QD, or 150 mg PO BID
• 150 mg PO QD if concurrent use of protease inhibitor (indinavir or nelfinavir are protease inhibitors of choice)

Capsule: 150 mg.

Pharmacokinetics

• distributes to body tissues including lungs, liver, spleen, eyes & kidneys
• protein binding 85%
• metabolized in the liver by cyt P450 3A4 to active & inactive metabolites
• terminal elimination 1/2life: 16-69 hours
• renal & biliary clearance of unchanged drug is 10%
• 30% excreted in the feces

elimination via liver

protein binding = 85 %

1/2life = 16-69 hours

Adverse effects

• common (> 10%)
  • discolored urine, neutropenia, leukopenia, rash
• less common (1-10%)
  • nausea/vomiting, abdominal pain, diarrhea, flatulence, anorexia, headache, myalgia, anemia, thrombocytopenia
• uncommon (< 1%)
  • chest pain, fever, insomnia, dyspepsia, taste disturbance
• other
  • uveitis
  • hepatitis
  • severe arthralgia
  • thrombocytopenia

Drug interactions

• clarithromycin, fluconazole & antiretroviral protease inhibitors increase serum levels of rifabutin
  • dosage adjustment may be required
• indinavir or nelfinavir are protease inhibitors of choice with rifabutin
• rifabutin increases levels of
  • saquinavir
  • clarithromycin
• rifabutin may decrease ketoconazole levels
• any drug that inhibits cyt P450 3A4 may increase levels of rifabutin
• any drug that induces cyt P450 3A4 may diminish levels of rifabutin
• rifabutin induces cyt P450 3A4, thus induces its own metabolism & metabolism of other cyt P450 3A4 substrates

• drug interaction(s) anticonvulsants with anti-bacterial agents
• drug interaction(s) of antibiotics with warfarin

Laboratory

• rifabutin in serum/plasma

More general terms

• rifamycin (rifamycin SV, Rifocin, Aemcolo)

Additional terms

• cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5281022
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=51619