ETHAMBUTOL HYDROCHLORIDE

Clinical safety rating: safe

Human studies have proved safety

How it works

Inhibits arabinosyl transferase (emb) involved in cell wall synthesis of mycobacteria, specifically inhibiting polymerization of arabinose into arabinan, a component of arabinogalactan.

What the body does with it

Metabolism	Hepatic metabolism via oxidation to metabolite (aldehyde intermediate) and then to dicarboxylic acid; approximately 20% metabolized.
Excretion	Renal: ~80% as unchanged drug and metabolites via glomerular filtration and tubular secretion; fecal: ~15%; biliary: <2%.
Half-life	3–4 hours in normal renal function; prolonged to 7–15 hours in moderate renal impairment and up to 30 hours in severe renal impairment; clinical context: requires dosing adjustment when creatinine clearance <30 mL/min.
Protein binding	20–30% bound to serum albumin.
Volume of Distribution	1.6 L/kg (range 1.0–2.5 L/kg); indicates extensive tissue distribution, with high concentrations in erythrocytes, lungs, and cerebrospinal fluid in inflamed meninges.
Bioavailability	Oral: ~80% (range 75–85%); absorption is reduced by food (decreased rate but not extent).
Onset of Action	Oral: 2–4 weeks for clinical improvement in tuberculosis; peak serum concentrations achieved 2–4 hours after oral administration.
Duration of Action	24 hours with daily dosing; clinical note: bactericidal activity is concentration-dependent, and once-daily dosing achieves high peak concentrations enhancing efficacy.

Classification & Brands

Dosing & administration

15 mg/kg orally once daily (range 15-25 mg/kg); typically 800-1600 mg daily.

Dosage form	TABLET
Renal impairment	CrCl 10-50 mL/min: 50% of normal dose every 24 hours; CrCl < 10 mL/min: 50% of normal dose every 48 hours.
Liver impairment	No specific dose adjustment recommended; caution in severe hepatic impairment.
Pediatric use	15-20 mg/kg orally once daily (maximum 1 g/day) as part of combination therapy; for intermittent therapy, 30 mg/kg three times weekly.
Geriatric use	Use lower end of dosing range (15 mg/kg) due to age-related renal decline; monitor for optic neuritis.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Aluminum hydroxide may decrease absorption Can cause optic neuritis leading to decreased visual acuity and color blindness.

Breastfeeding

Excreted into breast milk; milk-to-plasma ratio approximately 0.2. Amount is considered safe for term infants with normal renal function; no adverse effects reported. Monitor infant for possible gastrointestinal disturbances or rash. Use with caution in infants <1 month or with G6PD deficiency.

Teratogenic Risk

FDA Pregnancy Category B. Animal studies have not demonstrated fetal harm. In humans, ethambutol crosses the placenta. Optic neuritis has been reported in neonates exposed in utero. Use only if clearly needed; risk of untreated tuberculosis outweighs potential risks. First trimester: no evidence of increased malformations but limited data. Second and third trimesters: no specific risks reported, but monitor for ocular effects.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Common Effects	Optic neuritis
Serious Effects

Absolute Contraindications

["Known hypersensitivity to ethambutol or any component","Pre-existing optic neuritis","Severe renal impairment (e.g., creatinine clearance < 30 mL/min) unless dose adjusted with monitoring"]

Clinical Precautions

Precautions

["Optic neuritis (may lead to decreased visual acuity, color blindness, or visual field defects); monitor visual acuity and color discrimination at baseline and monthly.","Hepatotoxicity (elevated liver enzymes, hepatitis); monitor hepatic function.","Hyperuricemia and acute gouty arthritis (decreases renal urate excretion); monitor serum uric acid.","Renal impairment (dose adjustment required).","Peripheral neuropathy (especially in patients with renal impairment)."]

Clinical Tips & Counseling

Drug interactions

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