Ethambutol

Approved Indications:

• Tuberculosis (TB) Treatment:
• Part of combination therapy for active pulmonary and extrapulmonary tuberculosis caused by Mycobacterium tuberculosis.
• Used in initial intensive phase and continuation phase in combination with other antitubercular drugs.
• Mycobacterium avium Complex (MAC) Infection:
• Part of multidrug therapy for disseminated MAC infection, especially in immunocompromised patients (e.g., HIV/AIDS).

Off-Label / Clinically Accepted Uses:

• Treatment of infections caused by other mycobacteria species sensitive to ethambutol.
• Occasionally used in multi-drug resistant TB (MDR-TB) regimens.

Route: Oral

Adults:

• Pulmonary TB:
• 15 mg/kg once daily (range 15–25 mg/kg/day), maximum 1,600 mg/day.
• Usually given in combination with isoniazid, rifampicin, and pyrazinamide for 2 months (intensive phase), then adjusted per treatment regimen.
• Continuation Phase:
• Dose may be reduced or discontinued depending on susceptibility and clinical response.

Pediatrics:

• 15–25 mg/kg once daily, maximum 1,200 mg/day.

Elderly:

• Use standard dosing; monitor for visual toxicity.

Renal Impairment:

• Dose reduction recommended in moderate to severe renal impairment (creatinine clearance <30 mL/min).
• Dose interval may be extended to every 48 hours or adjusted according to creatinine clearance.

Hepatic Impairment:

• No specific dose adjustment required; monitor liver function due to concomitant hepatotoxic drugs.

Administration Instructions:

• Administer with food or milk to reduce gastrointestinal irritation.
• Swallow tablets whole with water.

Ethambutol inhibits the synthesis of the mycobacterial cell wall by blocking the enzyme arabinosyl transferase. This enzyme is responsible for polymerization of arabinogalactan, an essential component of the mycobacterial cell wall. Inhibition of arabinosyl transferase disrupts cell wall assembly, leading to increased cell permeability and ultimately bacteriostasis. Ethambutol’s activity is primarily bacteriostatic against Mycobacterium tuberculosis and other susceptible mycobacteria.

• Absorption:
• Well absorbed orally, with bioavailability approximately 80%.
• Distribution:
• Widely distributed in body tissues and fluids including lungs, pleural fluid, and aqueous humor.
• Metabolism:
• Partially metabolized in the liver to inactive metabolites.
• Half-life:
• Approximately 3–4 hours in patients with normal renal function; prolonged in renal impairment.
• Elimination:
• Primarily excreted unchanged via kidneys (~50%), remainder as metabolites.

• Pregnancy:
• FDA Pregnancy Category C. Animal studies have shown adverse effects at high doses; human data are limited. Use only if potential benefit justifies potential risk.
• Lactation:
• Ethambutol is excreted in breast milk in small amounts. Caution advised; breastfeeding may be continued with monitoring for adverse effects in infants.

• Primary Class: Antimycobacterial Agent
• Subclass: First-line antitubercular drug

• Known hypersensitivity to ethambutol or any excipients
• Optic neuritis or unexplained visual disturbances prior to therapy
• Severe renal impairment without dose adjustment

• Optic Neuritis:
• Dose-related risk of retrobulbar optic neuritis presenting as decreased visual acuity, red-green color blindness. Monitor vision regularly.
• Renal Impairment:
• Increased risk of toxicity; adjust dose accordingly.
• Pediatric Use:
• Monitor vision closely; young children may be unable to report visual symptoms.
• Allergic Reactions:
• Rare hypersensitivity reactions; discontinue if severe.
• Concomitant Therapy:
• Monitor for additive toxicities when combined with other antitubercular drugs.

Common:

• Visual disturbances (blurred vision, color vision changes)
• Peripheral neuropathy (rare)
• Gastrointestinal upset (nausea, vomiting)
• Rash

Serious/Rare:

• Optic neuritis (dose-dependent, potentially reversible if detected early)
• Hepatotoxicity (usually due to combination therapy)
• Allergic reactions including anaphylaxis

• Antacids: May reduce absorption of ethambutol; separate dosing by at least 2 hours.
• Other Antitubercular Drugs: Generally compatible; monitor for additive hepatotoxicity.
• Nephrotoxic Drugs: Caution with drugs that impair renal function; increased ethambutol toxicity risk.

• WHO guidelines continue to recommend ethambutol as part of first-line TB treatment regimens, especially in drug-resistant TB protocols.
• Emphasis on regular ophthalmologic monitoring to detect early visual toxicity.
• Updated dosing adjustments recommended for renal impairment in recent clinical practice guidelines.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep container tightly closed.
• Do not freeze.
• Keep out of reach of children.