ethambutol
antitubercular agent· Brands: Myambutol, Etibi, ServambutolPO
Mechanism of action
Ethambutol inhibits arabinosyl transferase, an enzyme essential for the synthesis of arabinogalactan in the mycobacterial cell wall. This disrupts the cell wall structure, increasing permeability and enhancing the activity of other antitubercular agents. Ethambutol is bacteriostatic against actively dividing Mycobacterium tuberculosis.
Pharmacokinetics
Ethambutol is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring about 2 to 4 hours after an oral dose. It distributes widely into body tissues, including red blood cells, kidneys, lungs, and, when the meninges are inflamed, cerebrospinal fluid. Approximately 50% of the administered dose is excreted unchanged in the urine, and the rest is metabolised in the liver. The elimination half-life is about 3 to 4 hours and is prolonged in renal impairment.
Indications & dosing
Pulmonary and extrapulmonary tuberculosis (initial phase, in combination with other antitubercular drugs)
Take at the same time each day. Monitor visual acuity and red-green colour vision. Usually limited to initial 2 months of therapy.
- adult · PO: 15 mg/kg once daily · Take at the same time each day. Monitor visual acuity and red-green colour vision. Usually limited to initial 2 months of therapy.
Pulmonary and extrapulmonary tuberculosis (initial phase, in combination with other antitubercular drugs)
Not recommended for children under 2 years due to difficulty in monitoring visual acuity. Monitor visual symptoms if possible.
- pediatric · PO: 15 mg/kg once daily · Not recommended for children under 2 years due to difficulty in monitoring visual acuity. Monitor visual symptoms if possible.
Non-tuberculous mycobacterial infection (e.g., Mycobacterium avium complex)
Used in combination with other agents; licensed for this indication in some regions; consult local guidance for duration and dosing.
- adult · PO: 15 mg/kg once daily · Used in combination with other agents; licensed for this indication in some regions; consult local guidance for duration and dosing.
Contraindications & precautions
- Hypersensitivity to ethambutol
- Optic neuritis · Ethambutol can exacerbate optic nerve damage.
- Pre-existing visual impairment (e.g., cataracts, diabetic retinopathy) · Monitoring of visual acuity is difficult.
- Severe renal impairment · Ethambutol is renally excreted; accumulation may cause toxicity.
- Perform baseline visual acuity and colour vision tests before starting ethambutol, and monitor regularly during treatment.
- Advise patients to report any visual changes, including blurred vision or changes in colour perception, immediately.
- Adjust the dose in patients with renal impairment according to renal function.
- Use with caution in patients with pre-existing ocular disease or visual impairment.
- Ethambutol is not recommended for children too young to cooperate with visual acuity testing (usually under 5 years of age).
- Monitor liver function periodically in patients with hepatic disease.
Adverse effects
- Optic neuritisserious
- Visual disturbances (decreased visual acuity, colour vision)
- Peripheral neuropathyserious
- Nausea
- Headache
- Rash
- Hepatotoxicityserious
- Anaphylaxisserious
Renal & hepatic adjustment
- eGFR 30–60: Reduce dose or increase interval; e.g. 15 mg/kg daily or 25 mg/kg three times a week.
- eGFR 10–29: Use with caution; reduce dose and extend interval, e.g. 15 mg/kg three times a week.
- eGFR 0–9: Avoid or use only if benefits outweigh risks; consider alternative therapy. (avoid)
Monitoring, pregnancy & toxicity
- Visual acuity · Baseline, then monthly
- Colour vision (Ishihara) · Baseline, then monthly
- Visual fields · Baseline, then if symptoms or abnormal visual acuity
- Renal function · Baseline, then periodically, especially in those with renal impairment
- Serum uric acid · Baseline, then if symptoms of gout or hyperuricaemia
- Pregnancy: Ethambutol is considered safe in pregnancy and is a standard component of anti-TB therapy. No evidence of teratogenicity. Use when required, monitoring visual function.
- Toxicity: Optic neuropathy (retrobulbar neuritis) causing reduced visual acuity, colour vision defects, and visual field loss · Discontinue ethambutol immediately and refer to an ophthalmologist. Symptoms are often reversible if detected early, but can be permanent if treatment continues.
- Toxicity: Hyperuricaemia and gout · Monitor serum uric acid; manage with general measures for hyperuricaemia; consider an alternative anti-TB drug if severe.
- Toxicity: Hypersensitivity reactions (e.g. rash, pruritus) · Stop the drug and manage symptoms; consider an alternative anti-TB drug.
Clinical notes
Ethambutol is used in combination with other antitubercular drugs for the treatment of all forms of tuberculosis. It is usually given during the intensive phase, commonly at a dosage of 15 to 25 mg/kg once daily. The most important adverse effect is optic neuritis, presenting as decreased visual acuity, loss of red-green colour discrimination, and visual field defects. Visual testing should be performed before and during treatment, particularly in patients receiving high doses or those with renal impairment. Caution is needed in children who cannot cooperate with visual testing. The drug is contraindicated in patients with pre-existing optic neuritis.
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BNF; local tuberculosis guidelines