Ethambutol

Ethambutol is a bacteriostatic first-line antimycobacterial added to the intensive phase to prevent selection of rifampicin resistance while susceptibility results are awaited. It adds little sterilising effect. Its dose-related optic neuropathy is the main toxicity and can cause permanent visual loss if recognised late.

Class. First-line antimycobacterial; arabinosyl transferase inhibitor.

Mechanism. Inhibits arabinosyl transferases (EmbA, EmbB, EmbC), blocking arabinogalactan synthesis in the cell wall. embB mutations cause resistance.

Pharmacokinetics. About 80% absorbed, peak at 2 to 4 hours. Half life 3 to 4 hours, prolonged in kidney failure. About 80% excreted unchanged in urine. Poor cerebrospinal fluid penetration unless the meninges are inflamed. Crosses the placenta and enters breast milk.

Drug-susceptible tuberculosis (first line). - Adults: 15 mg/kg (range 15 to 20) orally once daily; maximum 1.6 g daily. - Children: 20 mg/kg (range 15 to 25) once daily. - Duration: 2 months in the intensive phase; stop earlier when isoniazid and rifampicin susceptibility is confirmed. - Loading dose: none. Maintenance dose: none. Titration: none.

Intermittent dosing. 30 mg/kg three times weekly (maximum 2.4 g) under direct observation only.

Drug-resistant tuberculosis (specialist). 15 mg/kg daily when the isolate is susceptible, within an individualised regimen; avoid prolonged courses because optic toxicity rises with duration.

Dosing weight. Use ideal body weight in obesity.

Contraindications. Pre-existing optic neuritis, hypersensitivity and inability to report or be tested for visual change. Caution in cataract, diabetic retinopathy and alcohol use.

Serious adverse effects. Optic neuritis (reduced acuity, loss of red-green colour discrimination, central scotoma; usually bilateral), peripheral neuropathy, thrombocytopenia, hepatitis (rare), severe hypersensitivity.

Risk factors for optic toxicity. Dose over 25 mg/kg, duration over 2 months, kidney impairment, older age, diabetes, alcohol and co-prescription of other neurotoxic drugs such as linezolid.

Common adverse effects. Nausea, headache, hyperuricaemia and arthralgia.

Interactions. Aluminium antacids reduce absorption; separate by 2 hours. Additive optic and peripheral neuropathy with linezolid. Few other interactions.

Common prescribing errors. Full adult dose in kidney failure, continuing after the isolate is known susceptible, no baseline visual testing, and failing to tell the patient to report visual blurring at once.

Special groups. - Pregnancy: safe at usual dose. - Breastfeeding: compatible. - Children: correctly dosed ethambutol is safe; baseline vision testing is difficult in young children. - Older adults: reduced renal clearance raises toxicity; check creatinine. - Kidney impairment: with CrCl under 30 mL/min or on haemodialysis, 15 to 25 mg/kg three times weekly, after dialysis. - Liver impairment: no adjustment.

Formulations. Tablets 100 mg, 400 mg and fixed-dose combinations.

Administration. Once daily, with or without food.

Baseline. Visual acuity (Snellen), colour vision (Ishihara plates), creatinine and weight.

Monitoring. Ask about vision at every visit. Repeat visual acuity and colour testing monthly when treatment exceeds 2 months, the dose is high or kidney function is reduced.

Stopping thresholds. Stop at once for any new loss of acuity or colour discrimination attributed to the drug; early withdrawal usually allows recovery over weeks to months.

Referral and escalation. Urgent ophthalmology review for visual symptoms; refer if prolonged use is needed.