ethambutol (Myambutol)

Introduction

Tradename: Myambutol. (ethambutol HCl)

Indications

• treatment of tuberculosis in combination with other anti-tuberculous agents
• used in combination with clarithromycin for disseminated Mycobacterium avium intracellulare

Dosage

Tuberculosis:

• 15-25 mg/kg PO QD
• 50 mg/kg (max 2.5 g) twice a week

MAI: 15 mg/kg/day as a single oral dose (max 1 g)

Tabs: 100 & 400 mg.

Dosage adjustment in renal failure

Table

creatinine clearance	dosage
> 50-90 mL/min*	every 24 hours
10-50 mL/min	every 24-36 hours
< 10 mL/min#	every 48 hours

* same dose for continuous arteriovenous hemofiltration

# dose after hemodialysis

Pharmacokinetics

• 80% is absorbed when taken orally
• peak plasma levels 2-4 hours after oral ingestion
• serum concentrations about 4 ug/mL
• 1-5 ug/mL inhibitory for most strains of M. tuberculosis
• distributes to most tissues & fluids
• highest concentrations found in the lung, kidney, RBC & saliva
• CSF levels low even in the presence of meningeal inflammation
• elimination
  • 80% in urine
  • 1/2life if 4-6 hours (7-15 hours ESRD)

elimination via liver

elimination via kidney

1/2life = 4 hours

elimination by hemodialysis = -

Monitor

• BUN, serum creatinine every 6 months
• complete blood count (CBC) every 6 months
• liver function tests every 6 months
• eye exams at baseline & periodically thereafter
  • patients on > 15 mg/kg/day should have monthly eye exams
  • monitor visual acuity & color vision

Adverse effects

• hyperuricemia & gout
• abdominal pain
• nausea/vomiting
• rash
• headache
• confusion, disorientation
• fever
• peripheral neuritis
• retrobulbar (optic) neuritis (most serious & frequent)
  • blurred vision
  • central scotoma
  • red-green color blindness
  • dose-related, < 1% for doses of 15 mg/kg
  • frequency increased in patients with renal failure
• fever
• pruritus
• abnormal liver function tests

Drug interactions

• aluminum salts may decrease ethambutol absorption

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

Mechanism of action

• inhibits bacterial RNA synthesis
• impairs bacterial metabolism
• bacteriostatic for M. tuberculosis & other replicating bacteria
• only active when bacteria are actively dividing

More general terms

• anti-tuberculous agent

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3279
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=14052
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=14051