Ethambutol Hydrochloride

Registered South African indications:

• Tuberculosis

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Patients with known optic neuritis
• Children under 5 years of age

Contraindications registered in other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients
• Contraindicated in patients with known optic neuritis and poor vision unless clinical judgement determines that it may be used

• Pregnancy
• Breastfeeding
• Renal impairment 
• Hepatic impairment 
• Pre-existing visual defects
• Children
• Patients with language or communication difficulties 
• Gout

Forms avail. in SA and covered in this monograph: fct, tab

Dosages below include: 

• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages

South African Standard Treatment Guidelines indications and dosages

Mycobacterium tuberculosis - intensive phase
- 2 months intensive phase given in combination as standard dose 4-drug therapy (RHZE)

• 30-37kg: Oral (fct, tab): 550mg, dly; Treatment duration: 2months
• 38-54kg: Oral (fct, tab): 825mg, dly; Treatment duration: 2months
• 55-70kg: Oral (fct, tab): 1100mg, dly; Treatment duration: 2months
• >71kg: Oral (fct, tab): 1375mg, dly; Treatment duration: 2months
  (STG, PHC 2020; STG, Adult 2019)

Management of selected antiretroviral adverse drug reactions (drug-induced liver injury) (Additional agents required)

• Oral (fct, tab): 800-1200mg, dly
  (STG, Adult 2023)

Disseminated mycobacteriosis (non-tuberculous) (Additional agent required)

• Oral (fct, tab): 15-20mg/kg, dly; Treatment duration: Can be stopped when treatment has been continued for at least 12 months AND the CD4 count has increased to >100 cells/mm³ on ART
  (STG, Adult 2023)

Isoniazid monoresistant tuberculosis (Additional agents required)

• Oral (fct, tab): 15mg/kg, dly; Treatment duration: At least 6 months
  (STG, Adult 2019)

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South African registered indications and dosages

Tuberculosis
- In combination with other anti-tubercular medicine

Primary treatment

• Oral (fct, tab): 15mg/kg, once daily

Re-treatment

• Oral (fct, tab): Initial: 25mg/kg, once daily for the first 60 days; Thereafter: 15mg/kg, once daily

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Ethambutol should not be used alone in the initial treatment or in re-treatment of tuberculosis. The dosage must be adjusted according to the body mass of the patient and concomitant medicines should be used at their recommended dosage levels

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Therapy should generally be continued until bacteriological conversion has become permanent and maximal clinical improvement has occurred

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Ethambutol 400mg tablets can be taken with or without food

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Missed dose: Advise patients who forget to take ethambutol 400mg to take a dose as soon as possible and then continue with the normal dose. Patients should not take
a double dose to compensate for the missed dose

Paed. forms avail. in SA and covered in this monograph: fct, tab

Dosages below include: 

• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages

South African Standard Treatment Guidelines indications and dosages

Mycobacterium avium complex
- In combination with a macrolide and rifampicin

• Oral (fct, tab): 20-25mg/kg, once dly
  (STG, Paed. 2023)

Pulmonary tuberculosis
- In combination with other anti-tubercular medicine

• Oral (fct, tab): 15-25mg/kg/day; Max: 1200mg/24hrs
  (STG, Paed. 2023; STG, PHC 2020)

Tuberculosis disease - severe/ Complicated pulmonary TB
- 2 months intensive phase given in combination as standard dose 4-drug therapy (RHZE)

Up to 8 years

• See below dosing table
  (STG, Paed. 2023; STG, PHC 2020)

Pre-treatment body weight	Daily dose
2-2.9kg	50mg
3-3.9kg	75mg
4-7.9kg	125mg
8-11.9kg	200mg
12-15.9kg	300mg
16-24.9kg	400mg
25-29.9kg	600mg

Older than 8 years and adolescents

• See below dosing table
  (STG, Paed. 2023; STG, PHC 2020)

Pre-treatment body weight	Daily dose
25–37.9kg	550mg
38–54.9kg	825mg
55–70.9kg	1100mg
>71kg	1375mg

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South African registered indications and dosages

Tuberculosis
- In combination with other anti-tubercular medicine

Younger than 5 years

• Contraindicated

Between 5-12 years

• No specific dosing recommendations provided

Older than 12 years

• See adult dosage

Decisions related to dose adjustment/discontinuing TB regimen must be discussed in advance with Pulmonologists/Infectious Disease specialists, and cases must be dealt with individually

Pregnancy 

• Caution
• There are no adequate and well-controlled studies in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown
• Ethambutol should not be used in pregnant women unless the potential benefit to the mother is considered to outweigh any possible risks

Breastfeeding

• Caution; not recommended
• There are no adequate and well-controlled studies breastfeeding women. The potential risk for humans is unknown
• Ethambutol should not be used in breastfeeding women unless the potential benefit to the mother is considered to outweigh any possible risks

South African recommendations

• Caution; dose adjustment recommended
  Ethambutol hydrochloride accumulates in patients with impaired renal function and dosage adjustments may be needed according to serum concentrations

Recommendations in other jurisdictions

• Mild to moderate: Caution; no dose adjustment recommended 
  Renal function should be checked before treatment with antituberculous drugs and appropriate dosage adjustments made. Ethambutol should preferably be avoided in patients with renal impairment
• Severe (CrCl<30ml/min): Caution; dose adjustment recommended
  If used, where creatinine clearance is less than 30ml/min, recommended dose: 15–25mg/kg (max. 2.5g) 3 times a week and plasma ethambutol concentration should be monitored
  (See additional prescribing points)

• Caution; no dose adjustment recommended 

•  No dose adjustment recommended

Central Nervous System Disorders

• Peripheral neuritis
• Parasthesia
• Numbness
• Burning pain
• Weakness 
• Dizziness
• Headache
• Tremor
• Confusion
• Disorientation
• Hallucination

Respiratory Disorders

• Pulmonary infiltrates with or without eosinophilia 

Gastrointestinal Disorders

• Metallic taste
• Nausea and vomiting
• Anorexia
• Flatulence
• Abdominal pain
• Loss of appetite
• Gastrointestinal upset

Hepatobiliary Disorders

• Jaundice
• Transient increase in liver enzymes

Genitourinary Disorders

• Nephrotoxicity

Endocrine and Metabolic Disorders

• Hyperuricaemia

Musculoskeletal Disorders

• Joint pain
• Gout

Skin and Subcutaneous Tissue Disorders

• Rash
• Pruritus
• Urticaria
• Photosensitive lichenoid eruptions
• Bullous dermatitis
• Stevens Johnson syndrome
• Epidermal necrolysis

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity
• Allergic reactions
• Anaphylaxis
• Allergic pneumonitis
• Thrombocytopenia
• Leukopenia
• Neutropenia
• Eosinophilia

Sensory Disorders

• Visual disturbances
• Optic neuritis 
• Blurred vision
• Eye pain
• Impairment of colour vision
• Constriction of visual field
• Loss in vision 
• Retinal haemorrhage

Other 

• Fever

• Aluminium hydroxide

• Visual testing 
• Renal function
• Hepatic function
• Full blood count

Therapeutic drug monitoring (TDM)

• It is crucial that any dose changes (initiation, maintenance, adjustments) must be guided by plasma trough levels (TDM-guided dosing)
• The next dose should be calculated based on current eGFR/CrCl reading and the plasma ethambutol trough levels
• Both therapeutic range-based, peak-based, or fixed percentage adjustment must be avoided

Ethambutol is a synthetic bacteriostatic agent. The exact mechanisim of action is unknown. It diffuses into the mycobacteria and appears to suppress multiplication by interfering with RNA synthesis. It is only effective against mycobacteria which is dividing. Nearly all strains of M. tuberculosis , M.bovis and M. kansasii are sensitive, it has no effect on other micro-organisms. It is effective against tubercle bacilli resistant to other tuberculostatics. Primary resistance to ethambutol is uncommon but resistant strains of M. tuberculosis are readily produced if ethambutol is used alone.

Tablet 400mg

• Dyna Ethambutol (Pharma Dynamics)
• Ethambutol Medivision (Medivision)
• Sandoz Ethambutol (Sandoz)

COMBINATION PREPARATIONS

Isoniazid/ Rifampicin/ Pyrazinamide/ Ethambutol hcl

Tablet 75mg/150mg/400mg/275mg

• Antib-4 (Medicine Dev)
• Rifafour E-275 (Sanofi)
• Rimstar 4-Fdc (Sandoz)