Myambutol (Ethambutol)

Ethambutol hydrochloride is an antimycobacterial medicine used as part of combination therapy. It should not be used alone for active tuberculosis because resistance can develop quickly.

Uses

Tuberculosis

Active Tuberculosis

Ethambutol is used in conjunction with other antituberculosis agents in the treatment of clinical tuberculosis.

Mycobacterium avium Complex (MAC) Infections

Off-label notice (US): Ethambutol is FDA-approved for pulmonary tuberculosis. Use in MAC (including secondary prophylaxis) is used off-label and should be guided by an experienced clinician.

Treatment of MAC Infections

Ethambutol is used in conjunction with other antimycobacterial agents in the treatment of MAC infections. For disseminated MAC disease in people with HIV, guidelines commonly include a macrolide plus ethambutol (15 mg/kg PO daily), with or without rifabutin, depending on the clinical scenario and drug interactions.

Prevention of Recurrence

To prevent recurrence of disseminated MAC infection (secondary prophylaxis), some guidelines recommend maintenance therapy after completion of initial treatment, with discontinuation considered in selected patients who achieve sustained immune recovery (e.g., CD4+ T-cell counts >100 cells/mm^3 for at least 6 months on effective antiretroviral therapy) and remain asymptomatic, per specialist guidance.

Administration

Ethambutol hydrochloride is administered orally.

Dosage

Active Tuberculosis

In the treatment of clinical tuberculosis, ethambutol should not be given alone. The manufacturer states that the usual adult dosage for use in conjunction with other antituberculosis agents in previously untreated patients is 15 mg/kg once daily. In adults who have received previous antituberculosis therapy, the usual dosage recommended by the manufacturer is 25 mg/kg daily for 60 days, followed by 15 mg/kg daily.

The ATS/CDC/IDSA weight-based tables cited in some summaries recommend (adults and children 15 years of age or older) 800 mg (40-55 kg), 1.2 g (56-75 kg), and 1.6 g (76-90 kg) for daily therapy. If a 3-times weekly regimen is used, 1.2 g (40-55 kg), 2 g (56-75 kg), and 2.4 g (76-90 kg) are listed (maximum 2.4 g). If a twice-weekly regimen is used, 2 g (40-55 kg), 2.8 g (56-75 kg), and 4 g (76-90 kg) are listed (maximum 4 g). Intermittent regimens should be used only under expert guidance.

Pediatric Dosage

The manufacturer states that ethambutol hydrochloride is not recommended for use in children younger than 13 years of age. Some TB guidance uses ethambutol in children when needed; typical dosing cited in guidelines includes 15-20 mg/kg daily (maximum 2.5 g) or 50 mg/kg twice weekly (maximum 2.5 g), with caution when it is difficult to monitor visual acuity.

Dosage in Renal Impairment

In patients with impaired renal function, doses and/or frequency of administration of ethambutol hydrochloride should be modified in response to the degree of renal impairment. Ethambutol may accumulate in renal insufficiency; reduced dosage is recommended, and monitoring for ocular toxicity is especially important.

Precautions and Contraindications

Ethambutol is generally contraindicated in patients with optic neuritis unless clinical judgment determines that it may be used. It should be used with great care in patients with visual defects, the elderly, and in patients in whom evaluation of changes in visual acuity may be difficult.

Patients should be advised to report visual disturbances immediately and to stop ethambutol pending visual evaluation. Ethambutol should be given in reduced dosage to patients with renal impairment. Ethambutol may precipitate attacks of gout.

Ocular monitoring

Testing of visual acuity should be performed before beginning ethambutol therapy and periodically during drug administration, and monthly when a patient is on a dosage of more than 15 mg/kg/day.

Pregnancy

Ethambutol has caused teratogenic effects in animals when used at high doses. US labeling advises use during pregnancy only when the potential benefit justifies the potential risk to the fetus.

Breast feeding

Ethambutol distributes into breast milk. US labeling states that use should be considered only if the expected benefit to the mother outweighs the potential risk to the infant.

Children

US labeling: ethambutol is not recommended for use in pediatric patients under 13 years of age since safe conditions for use have not been established, and it is contraindicated in patients who are unable to appreciate and report visual side effects or changes in vision. Some tuberculosis guidelines use ethambutol in younger children when needed, but monitoring for visual toxicity can be difficult; dosing and monitoring should be guided by an experienced clinician.

Possible Side Effects

Ocular effects

The most important adverse effect of ethambutol is retrobulbar neuritis (optic neuropathy) with a reduction in visual acuity, constriction of visual field, central or peripheral scotoma, and loss of red-green color discrimination. One or both eyes may be affected. The degree of visual impairment appears to depend on the dose and duration of therapy; toxicity is observed most frequently at daily doses of 25 mg/kg or more and after at least 2 months of therapy.

Ethambutol-associated optic neuropathy risk increases with higher doses and longer duration of therapy, and may occur rarely after only a few doses (possible idiosyncratic reaction). When ocular toxicity is detected early and ethambutol is discontinued promptly, the visual effects are generally reversible over a period of weeks or months; rarely, recovery may be delayed for up to 1 year or more, or the effect may be irreversible.

Other adverse effects

Other adverse effects which have been reported include confusion, disorientation, hallucinations, headache, dizziness, malaise, jaundice or transient liver dysfunction, peripheral neuropathy, thrombocytopenia, pulmonary infiltrates, eosinophilia, and gastrointestinal disturbances such as nausea, vomiting, anorexia, and abdominal pain. Hypersensitivity reactions including skin rashes, pruritus, leucopenia, fever, and joint pains have occurred but appear to be rare with ethambutol. Increased serum uric acid concentrations and precipitation of acute gout have occurred occasionally.

Drug Interactions

Coadministration with aluminum hydroxide-containing antacids may reduce absorption; it is recommended to avoid concurrent administration for at least 4 hours following ethambutol administration.

Pharmacokinetics

After a single oral dose of 25 mg/kg, peak serum ethambutol concentrations of about 2 to 5 mcg/mL appear within 2 to 4 hours; serum levels generally fall to undetectable levels by 24 hours after the last dose, except in some patients with abnormal renal function. Approximately 50% of a dose is excreted unchanged in the urine within 24 hours, and an additional 8 to 15% appears as metabolites; about 20 to 22% of the initial dose is excreted in the feces as unchanged drug. Ethambutol may accumulate in patients with renal insufficiency.

Mechanism of Action

Ethambutol is bacteriostatic in action. The drug appears to inhibit the synthesis of one or more metabolites in susceptible mycobacteria, thus causing impairment of cell metabolism, arrest of multiplication, and cell death.

Storage

Ethambutol hydrochloride tablets should be protected from light and moisture and stored in well-closed containers at 68–77°F (20–25°C); excursions permitted to 59–86°F (15–30°C).