Myambutol (Ethambutol)

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

Uses

Tuberculosis

Active tuberculosis

Ethambutol is used together with other anti-tuberculosis medicines to treat clinical tuberculosis.

Mycobacterium avium complex (MAC) infections

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

Treatment of MAC infections

Ethambutol is used with other antimycobacterial medicines in the treatment of Mycobacterium avium complex (MAC) infection. For disseminated MAC disease in people with HIV, UK guidance usually recommends a macrolide plus ethambutol 15 mg/kg daily, and rifabutin 300 mg daily may also be included depending on the clinical situation and the risk of drug interactions.

Prevention of recurrence

To help prevent recurrence of disseminated MAC infection (secondary prophylaxis), some guidelines recommend maintenance treatment after initial treatment has finished. Stopping treatment may be considered in selected patients who have sustained immune recovery (for example, CD4+ T-cell counts >100 cells/mm^3 for at least 6 months on effective antiretroviral therapy) and remain symptom-free, in line with specialist guidance.

Administration

Ethambutol hydrochloride is taken by mouth.

Dosage

Active tuberculosis

In the treatment of clinical tuberculosis, ethambutol should not be given alone. The manufacturer states that the usual adult dosage, used together with other anti-tuberculosis medicines in previously untreated patients, is 15 mg/kg once daily. In adults who have had previous anti-tuberculosis treatment, the usual dosage recommended by the manufacturer is 25 mg/kg daily for 60 days, followed by 15 mg/kg daily.

UK tuberculosis guidance summaries may present weight-based dosing bands for adults and children aged 15 years and over rather than citing ATS/CDC/IDSA tables directly. Where intermittent regimens are considered, dosing should follow specialist tuberculosis guidance, and these regimens should be used only under expert supervision.

Paediatric dosage

The manufacturer states that ethambutol hydrochloride is not recommended for children younger than 13 years of age. Some TB guidance uses ethambutol in children when needed; typical dosing cited in guidelines includes 15 to 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 ethambutol hydrochloride should be adjusted according to the degree of renal impairment. Ethambutol may build up in renal insufficiency, so a reduced dosage is recommended and monitoring for eye toxicity is especially important.

Precautions and Contraindications

Ethambutol is generally contraindicated in patients with optic neuritis unless clinical judgement determines that it may be used. It should be used with great care in patients with visual defects, older people, and in patients in whom it may be difficult to assess changes in visual acuity.

Patients should be advised to report visual disturbances immediately and to stop taking ethambutol until their vision has been assessed. Ethambutol should be given in a reduced dosage to patients with renal impairment. Ethambutol may trigger attacks of gout.

Ocular monitoring

Visual acuity should be tested before starting ethambutol treatment and periodically during treatment, and monthly when a patient is taking more than 15 mg/kg/day.

Pregnancy

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

Breastfeeding

Ethambutol passes into breast milk. UK prescribing information states that use should be considered only if the expected benefit to the mother outweighs any potential risk to the infant.

Children

UK prescribing information: ethambutol is not recommended for children under 13 years of age because safe conditions for use have not been established, and it is contraindicated in patients who are unable to recognise 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 side effect of ethambutol is retrobulbar neuritis (optic neuropathy), with reduced visual acuity, constriction of the visual field, central or peripheral scotoma, and loss of red-green colour discrimination. One or both eyes may be affected. The degree of visual impairment appears to depend on the dose and length of treatment; toxicity is seen most often at daily doses of 25 mg/kg or more and after at least 2 months of treatment.

The risk of ethambutol-associated optic neuropathy increases with higher doses and longer treatment, and may rarely occur after only a few doses (a possible idiosyncratic reaction). When eye toxicity is detected early and ethambutol is stopped 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 reported side effects include confusion, disorientation, hallucinations, headache, dizziness, malaise, jaundice or temporary liver dysfunction, peripheral neuropathy, thrombocytopenia, pulmonary infiltrates, eosinophilia, and gastrointestinal disturbances such as nausea, vomiting, loss of appetite, and abdominal pain. Hypersensitivity reactions including skin rashes, pruritus, leucopenia, fever, and joint pain have occurred but appear to be rare with ethambutol. Increased serum uric acid concentrations and attacks of acute gout have occasionally occurred.

Drug interactions

Coadministration with aluminium hydroxide-containing antacids may reduce absorption. It is recommended to avoid taking them at the same time for at least 4 hours after ethambutol.

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 faeces as unchanged drug. Ethambutol may accumulate in patients with renal insufficiency.

Mechanism of action

Ethambutol is bacteriostatic. The medicine appears to inhibit the synthesis of one or more metabolites in susceptible mycobacteria, 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 tightly closed containers at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F).