Drugs List

Therapeutic Indications

Uses

Tuberculosis - prophylaxis
Tuberculosis: continuation phase treatment
Tuberculosis: initial phase treatment in combination with other drugs
Tuberculosis: Re-treatment after previous tuberculosis therapy

Unlicensed Uses

Tuberculosis: Fully supervised intermittent therapy (DOT)

Contraindications

Optic neuritis
Poor vision

Precautions and Warnings

Children under 5 years
Renal impairment

Reduce dose in patients with renal impairment
Advise visual disturbances may affect ability to drive or operate machinery
Must be used in combination with other anti-tuberculous drugs
Treatment to be initiated and supervised by a specialist
Monitor renal function prior to initiating treatment
Perform eye tests before treatment
Monitor ophthalmic function
Avoid antacids within 4 hours of dose
Advise patient to discontinue therapy if any disturbances of vision occur

As ethambutol can affect the eyes, an ophthalmic examination should be conducted before treatment begins. The examination should include visual acuity, colour vision, perimetry, and ophthalmoscopy. If any deterioration in vision occurs, patients should be advised to discontinue ethambutol immediately and seek medical advice. Routine ophthalmic examinations are advised during the treatment of young children. Use with caution in children under 5 years of age as they are less capable of accurately reporting visual changes.

Effects on the eye are generally reversible when ethambutol is discontinued promptly. Recovery of visual acuity usually occurred over a period of weeks to months after discontinuation of ethambutol. Ethambutol has then been reintroduced at reduced doses without causing toxicity. In rare cases, effects on the eye can persist for up to one year and effects may be irreversible in some cases.

Pregnancy and Lactation

Pregnancy

The manufacturer suggests that ethambutol should not be used during pregnancy or in women of child-bearing potential unless the potential benefits to the mother outweigh the possible risks to the foetus.

There is no adequate data from the use of ethambutol during human pregnancy.

Animal studies have shown reproductive toxicity. The potential risks for humans is not known.

Schaefer suggests ethambutol, along with isoniazid and rifampicin, are considered to be the first line anti-tuberculous drugs, and that untreated tuberculosis represents a greater hazard to the mother and her foetus than treatment of the disease.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

The amount of ethambutol excreted in human breast milk is considered to be too low to be harmful.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal liver function tests
Anaphylactoid reaction
Anorexia
Bullous dermatoses
Colour blindness (red/green)
Confusion
Diarrhoea
Disorientation
Dizziness
Eosinophilia
Epidermal necrolysis
Eye pain
Gastro-intestinal disturbances
Gout
Hallucinations
Headache
Hepatic failure
Hepatic impairment
Hepatitis
Hypersensitivity reactions
Hyperuricaemia
Impaired vision
Interstitial nephritis
Jaundice
Joint pain
Leucopenia
Lichenoid rash
Malaise
Nausea
Neutropenia
Numbness of extremities
Optic neuritis
Paraesthesia in extremities
Peripheral neuropathy
Pneumonitis
Pruritus
Pulmonary infiltrates
Pyrexia
Rash
Reduced visual acuity
Stevens-Johnson syndrome
Thrombocytopenia
Urticaria
Visual disturbances
Visual field defects
Vomiting

Presentation

Tablets containing ethambutol hydrochloride

Drugs List

Therapeutic Indications

Uses

Tuberculosis - prophylaxis
Tuberculosis: continuation phase treatment
Tuberculosis: initial phase treatment in combination with other drugs
Tuberculosis: Re-treatment after previous tuberculosis therapy

Unlicensed Uses

Tuberculosis: Fully supervised intermittent therapy (DOT)

Dosage

Ethambutol should only be used in combination with other anti-tuberculosis drugs.

Peak concentration (2 to 2.5 hours after dose) should be 2 to 6 mg/litre (7 to 22 micromol/litre). Trough (pre-dose) concentration should be less than 1 mg/litre (4 micromol/litre).

The tablets should be administered once daily in order to obtain maximum effect due to high serum levels.

Adults

Children

Neonates

Patients with Renal Impairment

Contraindications

Optic neuritis
Poor vision

Precautions and Warnings

Children under 5 years
Renal impairment

Reduce dose in patients with renal impairment
Advise visual disturbances may affect ability to drive or operate machinery
Must be used in combination with other anti-tuberculous drugs
Treatment to be initiated and supervised by a specialist
Monitor renal function prior to initiating treatment
Perform eye tests before treatment
Monitor ophthalmic function
Avoid antacids within 4 hours of dose
Advise patient to discontinue therapy if any disturbances of vision occur

As ethambutol can affect the eyes, an ophthalmic examination should be conducted before treatment begins. The examination should include visual acuity, colour vision, perimetry, and ophthalmoscopy. If any deterioration in vision occurs, patients should be advised to discontinue ethambutol immediately and seek medical advice. Routine ophthalmic examinations are advised during the treatment of young children. Use with caution in children under 5 years of age as they are less capable of accurately reporting visual changes.

Effects on the eye are generally reversible when ethambutol is discontinued promptly. Recovery of visual acuity usually occurred over a period of weeks to months after discontinuation of ethambutol. Ethambutol has then been reintroduced at reduced doses without causing toxicity. In rare cases, effects on the eye can persist for up to one year and effects may be irreversible in some cases.

Pregnancy and Lactation

Pregnancy

The manufacturer suggests that ethambutol should not be used during pregnancy or in women of child-bearing potential unless the potential benefits to the mother outweigh the possible risks to the foetus.

There is no adequate data from the use of ethambutol during human pregnancy.

Animal studies have shown reproductive toxicity. The potential risks for humans is not known.

Schaefer suggests ethambutol, along with isoniazid and rifampicin, are considered to be the first line anti-tuberculous drugs, and that untreated tuberculosis represents a greater hazard to the mother and her foetus than treatment of the disease.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

The amount of ethambutol excreted in human breast milk is considered to be too low to be harmful.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal liver function tests
Anaphylactoid reaction
Anorexia
Bullous dermatoses
Colour blindness (red/green)
Confusion
Diarrhoea
Disorientation
Dizziness
Eosinophilia
Epidermal necrolysis
Eye pain
Gastro-intestinal disturbances
Gout
Hallucinations
Headache
Hepatic failure
Hepatic impairment
Hepatitis
Hypersensitivity reactions
Hyperuricaemia
Impaired vision
Interstitial nephritis
Jaundice
Joint pain
Leucopenia
Lichenoid rash
Malaise
Nausea
Neutropenia
Numbness of extremities
Optic neuritis
Paraesthesia in extremities
Peripheral neuropathy
Pneumonitis
Pruritus
Pulmonary infiltrates
Pyrexia
Rash
Reduced visual acuity
Stevens-Johnson syndrome
Thrombocytopenia
Urticaria
Visual disturbances
Visual field defects
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: February 2013

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Ethambutol Tablets 100 mg. Genus Pharmaceuticals Holdings Limited. Revised March 2010.

Summary of Product Characteristics: Ethambutol Tablets 400 mg. Genus Pharmaceuticals Holdings Limited. Revised March 2010.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 29 August 2017