Ethambutol (EMB) (PDF Version)
Antibiotic Class: N-substituted ethylenediamine
Antimicrobial Spectrum: M. tuberculosis and other mycobacteria, including M. avium
Mechanism of Action:
Ethambutol inhibits arabinotransferases involved in the biosynthetic pathway of mycobacterial cell wall
EMB generally is bacteriostatic at the doses that can be achieved in humans. As such, keeping the serum concentrations above the MIC for the entire dosing interval would be desirable from a theoretical standpoint.
Cmax: 2-6 mg/L; Tmax: about 2-3 hours; Bioavailability: at least 50%, possibly higher; not directly measured against IV dosage form. Protein binding: 20-30%
Optic neuritis is dose and concentration-dependent, being uncommon at 25 mg per kg daily, more common at higher daily doses, and more common if standard doses are given to patients with renal dysfunction. Patients should be questioned regarding visual problems, and color vision tested using Ishihara plates. Renal clearance of urates is decreased by ethambutol.
PO: 400 mg tablets
Usual dose: 25 mg per kg daily, 50 mg per kg in twice-weekly regimens
Disease State Based Dosing:
Hepatic failure: No specific recommendations, but EMB is partially metabolized so patients should be followed for possible visual changes
Renal failure: Adjustment is required for patients in renal failure or on hemodialysis. The usual daily dose should be given only 3 times weekly.
Contraindications/Warnings/Precautions: Caution in renal failure
Drug Interactions: None clearly established
Pregnancy: Generally considered safe.
Toxic: baseline visual acuity and red-green color discrimination
Brand Names/Manufacturer: Myambutol (Wyeth), generics
Eflornithine, (DL-alpha-difluoromethylornithine) is a fluorinated analogue of the uncommon amino acid ornithine.
Eflornithine is highly effective against Trypanosoma brucei gambiense and, when available, is the drug of choice in late-stage Gambian human African trypanosomiasis. Eflornithine is not effective against Trypanosoma brucei rhodesiense.
Mechanisms of Action:
Eflornithine is an irreversible suicide inhibitor of ornithine decarboxylase, the first enzyme in the biosynthesis of the polyamines putrescine and spermidine.
Mechanisms of Resistance:
The mechanisms of eflornithine resistance for T.b. gambiense have not yet been elucidated.
Eflornithine is about 50% orally bioavailable. Its elimination half-life is 3.3 h and 81% is excreted unchanged.
The recommended dosage for new cases of late-stage Gambian trypanosomiasis is 100 mg/kg every 6h IV for 14 days.
Reduce dosage in renal failure.
Hematological: anemia (up to 40%), leukopenia (20-30%) or thrombocytopenia (50%).
Seizures associated with high CSF concentrations
Diarrhea (12% IV, 50% po)
Abortion in pregnant women
Studies with eflornithine have not been done in pregnant women.