Introduction
Ethambutol is a bacteriostatic antimycobacterial agent primarily used as first-line therapy in combination regimens for the treatment of tuberculosis. Discovered in 1961, it remains a cornerstone of tuberculosis management worldwide due to its efficacy and generally favorable safety profile when used appropriately.
Mechanism of Action
Ethambutol inhibits arabinosyl transferase (EmbB), an enzyme essential for the biosynthesis of arabinogalactan, a critical component of the mycobacterial cell wall. By disrupting cell wall synthesis, ethambutol compromises bacterial structural integrity and leads to bacteriostatic activity against Mycobacterium tuberculosis. The drug is most active against actively dividing bacilli.
Indications
- First-line treatment of pulmonary tuberculosis (always in combination with other antituberculosis drugs)
- Treatment of extrapulmonary tuberculosis (as part of combination therapy)
- Atypical mycobacterial infections (as part of combination regimens)
Dosage and Administration
Adults:- Intensive phase: 15-20 mg/kg/day (maximum 1.6 g/day)
- Continuation phase: 15 mg/kg/day
- 15-20 mg/kg/day (maximum 1 g/day)
- CrCl 10-50 mL/min: 15-25 mg/kg every 24-36 hours
- CrCl <10 mL/min: 15-25 mg/kg every 48 hours
- Oral administration only
- Single daily dose, preferably on an empty stomach
- Tablets may be crushed if swallowing difficulty exists
Pharmacokinetics
Absorption: Rapidly but incompletely absorbed (75-80% bioavailability) Distribution: Widely distributed throughout body tissues and fluids, including cerebrospinal fluid (CSF concentrations approximately 10-50% of serum levels) Metabolism: Partial hepatic metabolism (approximately 20%) Elimination: Primarily renal excretion (50% as unchanged drug, 8-15% as metabolites) Half-life: 3-4 hours (prolonged in renal impairment)Contraindications
- Hypersensitivity to ethambutol or any component of the formulation
- Optic neuritis (unless benefits outweigh risks)
- Inability to comply with visual monitoring
- Children under 5 years (due to difficulty monitoring vision)
Warnings and Precautions
Boxed Warning: Risk of optic neuritis which may result in decreased visual acuity, scotomas, color blindness, and visual field defects- Perform baseline ophthalmological examination before initiation
- Monitor visual acuity and color discrimination monthly during therapy
- Discontinue immediately if ocular toxicity develops
- Use with caution in patients with renal impairment, diabetes, cataracts, or ocular inflammatory conditions
- May cause hyperuricemia; monitor patients with gout
Drug Interactions
- Aluminum-containing antacids: Decreased ethambutol absorption (separate administration by at least 4 hours)
- Neurotoxic drugs (isoniazid, chloramphenicol): Increased risk of neurotoxicity
- Zidovudine: Potential increased risk of peripheral neuropathy
Adverse Effects
Common (>10%):- Hyperuricemia
- Elevated liver enzymes
- Nausea, abdominal discomfort
- Rash, pruritus
- Arthralgia
- Headache
- Dizziness
- Gastrointestinal upset
- Optic neuritis (dose- and duration-dependent)
- Peripheral neuropathy
- Thrombocytopenia
- Anaphylaxis
- Hepatitis
Monitoring Parameters
Baseline:- Complete ophthalmologic examination (visual acuity, color vision, visual fields)
- Liver function tests
- Renal function tests
- Serum uric acid
- Complete blood count
- Monthly visual acuity and color discrimination testing
- Monthly questioning about visual symptoms
- Liver function tests periodically
- Renal function monitoring in patients with pre-existing impairment
- Uric acid levels in symptomatic patients
Patient Education
- Take medication exactly as prescribed; complete full course of therapy
- Report any visual changes immediately (blurred vision, changes in color perception, visual field defects)
- Regular eye examinations are essential during treatment
- Do not miss doses to prevent development of drug resistance
- May take with food if gastrointestinal upset occurs
- Inform all healthcare providers about ethambutol use
- Store at room temperature away from moisture
References
1. American Thoracic Society, CDC, and Infectious Diseases Society of America. Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline. Am J Respir Crit Care Med. 2019;200(10):e93-e142.
2. Nahid P, Mase SR, Migliori GB, et al. Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline. Am J Respir Crit Care Med. 2019;200(10):e93-e142.
3. Ziganshina LE, Squire SB. Fluoroquinolones for treating tuberculosis. Cochrane Database Syst Rev. 2008;(1):CD004795.
4. van der Heijden YF, Karim F, Mufamadi G, et al. Ethambutol-related optic neuropathy in South Africa: a case series and systematic review of the literature. J Trop Med. 2017;2017:9587289.
5. Package Insert: Myambutol® (ethambutol hydrochloride) tablets. FDA-approved labeling.
6. World Health Organization. Guidelines for treatment of drug-susceptible tuberculosis and patient care. 2017 update.
Note: This information is intended for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for medication decisions.