Ethambutol Dispersible tablets

Indications

• Pulmonary tuberculosis
• Tuberculosis in combination therapy

Dosage

Children: For children, refer to the BNF for Children for appropriate dosing guidance.

Adults: The usual adult dose is 15 mg/kg daily, up to a maximum of 1.6 g per day, in combination with other anti-tuberculosis agents.

Mechanism of action

Ethambutol diffuses into Mycobacterium cells and inhibits the arabinosyltransferases (embA, embB, and embC). This inhibition prevents the formation of arabinogalactan and lipoarabinomannan, which are essential for the integrity of the bacterial cell wall. The resultant decrease in arabinogalactan reduces binding sites for mycolic acid, leading to its accumulation and consequently impairing cell division. Additionally, reduced levels of lipoarabinomannan interfere with the interaction of mycobacteria with host cells. Ethambutol's bacteriostatic action is effective only when the bacteria are actively dividing.

Pharmacodynamics

Ethambutol is indicated for use in combination with other anti-tuberculosis drugs for the treatment of pulmonary tuberculosis. Its long duration of action allows for daily administration, which is beneficial for patient adherence. However, it is important for patients to be informed about potential side effects, including the risk of optic neuritis and hepatic toxicity, which are associated with its use.

Pharmacokinetics

Ethambutol is well absorbed from the gastrointestinal tract, with a peak plasma concentration occurring approximately 2 to 4 hours after administration. It has a volume of distribution that suggests good tissue penetration. The drug is primarily excreted unchanged in the urine, with a half-life of about 3 to 4 hours in individuals with normal renal function. Dosage adjustments may be necessary in patients with renal impairment.

Contra-indications

• Optic neuritis
• Severe renal impairment

Adverse effects

• Optic neuritis
• Visual disturbances
• Nausea
• Vomiting
• Loss of appetite
• Rash
• Hepatic toxicity

Interactions

• Antacids may reduce absorption
• Aluminium-containing antacids may decrease ethambutol serum concentration

Precautions

• Regular monitoring of visual acuity is recommended
• Use with caution in patients with renal impairment
• Periodic liver function tests may be necessary

Pregnancy

Ethambutol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Ethambutol is excreted in breast milk; caution should be exercised when administered to a nursing mother.

Storage

Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.

Formulations

• Tablets
• Oral suspension

Indications

• Tuberculosis, in combination with other drugs (standard treatment)
• Multiple-drug resistant pulmonary tuberculosis, in combination with other drugs

Dosage

Children: Child: 20 mg/kg once daily for 2 months (initial phase) or 30 mg/kg 3 times a week for 2 months (initial phase).

Adults: Adult: 15 mg/kg once daily for 2 months (initial phase) or 100 mg twice daily for 24 weeks, continue appropriate combination therapy after delamanid.

Mechanism of action

Ethambutol inhibits the enzyme arabinosyl transferase, which is involved in the biosynthesis of the mycobacterial cell wall component, arabinogalactan. This inhibition disrupts the integrity of the bacterial cell wall, leading to bacterial cell death.

Pharmacodynamics

Ethambutol exhibits bacteriostatic activity against M. tuberculosis. Its action is concentration-dependent, and effectiveness can be enhanced when used in combination with other antitubercular agents. Resistance can develop through mutations in the gene encoding arabinosyl transferase, leading to decreased drug efficacy.

Pharmacokinetics

Ethambutol is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 2 to 4 hours post-administration. The drug has a half-life of approximately 3 to 5 hours and is primarily excreted unchanged in urine. Dose adjustments may be necessary in patients with renal impairment, as the drug's clearance is significantly affected by renal function.

Contra-indications

• Optic neuritis
• Poor vision

Adverse effects

• Anxiety
• Appetite decreased
• Asthenia
• Chest pain
• Cough
• Depression
• Dyslipidaemia
• Dyspnoea
• Ear pain
• Electrolyte imbalance
• Gastrointestinal discomfort
• Haemoptysis
• Headache
• Hyperhidrosis
• Hypertension
• Hypotension
• Malaise
• Muscle weakness
• Nausea
• Oropharyngeal pain

Interactions

• Cycloserine
• Deltyba (Delamanid)

Precautions

• Monitor serum albumin and electrolytes before and during treatment
• Monitor blood-cycloserine concentration if creatinine clearance is less than 50 mL/min
• Use with caution in elderly and young children
• Patients should be able to report symptomatic visual changes accurately

Pregnancy

Manufacturer advises use only if potential benefit outweighs risk, as it crosses the placenta.

Breast-feeding

Present in milk, but amount is too small to be harmful.

Storage

Dispense in original container (contains desiccant).

Formulations

• Capsule
• Tablet

Mechanism of action

Ethambutol diffuses into _Mycobacterium_ cells. Once inside the cell, ethambutol inhibits the arabinosyltransferases (embA, embB, and embC), preventing formation of the cell wall components arabinogalactan and lipoarabinomannan, and preventing cell division. Decreased concentrations of arabinogalactan in the cell wall reduces the number of binding sites for mycolic acid, leading to the accumulation of mycolic acid, trehalose monomycolate, and trehalose dimycolate. Lipoarabinomannan is a component of a cell surface molecule involved in the interaction with host cells. Reduced levels of lipoarabinomannan may interfere with mycobacterial interaction with host cells. Ethambutol is bacteriostatic in action. Although the exact mechanism of action has not been fully elucidated, the drug appears to inhibit the synthesis of one or more metabolites in susceptible bacteria resulting in impairment of cellular metabolism, arrest of multiplication, and cell death. Ethambutol is active against susceptible bacteria only when they are undergoing cell division.

Pharmacodynamics

Ethambutol is indicated in combination with other anti-tuberculosis drugs in the treatment of pulmonary tuberculosis. It has a long duration of action as it is administered daily, and a moderate therapeutic window. Patients should be counselled regarding the risk of optic neuritis and hepatic toxicity.