ETHAMBUTOL Film-coated tablet Ref.[8342] Active ingredients: Ethambutol

Ocular toxicity

Ethambutol may produce a unique type of visual impairment which is generally reversible and which appears to be due to optic neuritis and to be related to dose and duration of treatment.

Ethambutol causes ocular toxicity and patients should be advised to report any changes of visual acuity. Less than 1% of patients undergoing treatment with the higher dose regimen of 25mg/kg/day for two months, and 15mg/kg/day thereafter, have exhibited decrease in visual acuity. It is recommended that patients undergo a full ophthalmic examination before starting treatment. This should include visual acuity, colour vision, perimetry and ophthalmoscopy and should be monitored every four weeks during treatment. For patients with pre-existing visual defects or renal insufficiency the frequency of tests should be increased to every second or third week or more, depending on clinical assessment. Each eye should be tested separately as ocular toxicity can be unilateral or bilateral. Opthalmologic examination should include tests for black-white/chromatic visual acuity (e.g. Snellen eye chart and 65-test) and opthalmoscopy.

Patients who are unable to report their visual acuity should be more closely monitored for any signs of deterioration during treatment with ethambutol. Ethambutol should be used in young children and those with language or communication difficulties, where appropriate, with advice concerning the need to report visual side-effects being given to parents or other family members. However, routine ophtalmological examinations may be considered desirable when treating young children

Ethambutol therapy should be stopped immediately if visual disturbances are observed (see section 4.8).

Any negative effects on vision are generally reversible when administration of the drug is discontinued promptly and recovery of visual acuity has usually occurred over a period of weeks to months after the drug was discontinued. Patients have then received Ethambutol at lower doses without toxicity.

In rare cases, recovery may be delayed for up to one year or more or the effects may be irreversible.

Renal impairment

Renal function should be checked before treatment with antituberculosis drugs and appropriate dosage adjustments made. Ethambutol should preferably be avoided in patients with renal impairment, but if used the dose should be reduced and the plasma-drug concentration monitored. Toxic effects are more common if renal function is impaired.

Hepatic impairment

Liver function tests should be performed in patients who develop symptoms suggestive of hepatitis or who become generally unwell during treatment.

Other Warnings

Consideration should be given to current clinical guidance on the appropriate use of antituberculous drugs.

Aluminium hydroxide impairs the absorption of ethambutol. Acid suppressing drugs or antacids that do not contain aluminium hydroxide should be used during ethambutol therapy.

Pregnancy

The potential for risk in humans is unknown as there are no adequate and well controlled studies in pregnant or lactating women. Studies in animals have shown reproductive toxicity. Ethambutol should not therefore be used during pregnancy, in women of childbearing potential or in lactating women unless the potential benefit to the mother is considered to outweigh any possible risks.

Breast-feeding

Ethambutol/metabolites have been identified in breastfed newborns/infants of treated women. There is insufficient information on the effects of ethambutol in newborns/infants.

Breast-feeding is not recommended during Ethambutol treatment unless the benefit of breast-feeding to the child is considered to outweigh any possible risks

Ethambutol may produce a unique type of visual impairment (see section 4.8). Dizziness, disorientation, numbness and paraesthesia of the extremities has been reported. Therefore, patients should be advised not to drive or operate machinery if they experience any of these effects.

The most important adverse effect resulting from Ethambutol use is retrobulbar neuritis with a reduction in visual acuity.

The adverse event data below contains all reactions that are considered at least possibly related to Ethambutol and is based on data collected, mainly from published literature post authorisation.

The undesirable effects have been arranged by body system, organ class and absolute frequency, and are defined using the following convention:

Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000)

Blood and lymphatic system disorders

rare: thrombocytopenia

very rare: leukopenia, neutropenia, eosinophilia

Immune system disorders

very rare: hypersensitivity, anaphylactoid reactions, allergic reactions, anaphylaxis, allergic pneumonitis.

Metabolism and nutrition disorders

uncommon: hyperuricaemia

very rare: gout

Psychiatric disorders

very rare: mental confusion, hallucination

Nervous system disorders

rare: peripheral neuritis, peripheral neuropathy, paraesthesia especially in the extremities, numbness

very rare: burning pain, weakness (hands and feet), dizziness, headache, disorientation

unknown: tremor

Eye disorders

common: visual disturbances caused by optic neuritis/retrobulbar neuritis*(decreased visual acuity, loss of vision, scotoma, colour blindness, visual disturbance, visual field defect, eye pain)

Respiratory, thoracic and mediastinal disorders

very rare: pneumonitis, pulmonary infiltrates, with or without eosinophilia

Gastrointestinal disorders

not known: nausea, vomiting, anorexia, abdominal pain & diarrhoea have been noted in patients on multiple drug anti- tuberculosis therapy including ethambutol although not in test patients receiving ethambutol as sole therapy, flatulence, metallic taste, loss of appetite, upset stomach

Hepatobiliary disorders¹

not known: hepatitis, jaundice, transient increase in liver enzymes, abnormal liver function test values have been reported in patients treated with multiple drug therapy including ethambutol.

very rare: hepatic failure,

Musculoskeletal and connective tissue disorders

very rare: joint pains

Skin & subcutaneous Tissue disorders

rare: rash, pruritus, urticaria

very rare: photosensitive lichenoid eruptions, bullous dermatitis, Stevens Johnson syndrome, epidermal necrolysis

Renal and urinary disorders

very rare: nephrotoxicity including interstitial nephritis

General disorders and administration site conditions

very rare: malaise, pyrexia

^* This effect is thought to be dose related, and frequency is dependent on both dose and duration of treatment. It occurs most frequently with doses of 25 mg/kg body weight and after two months of therapy, however optic neuritis has also occurred after only a few days of therapy. The effect is often reversible upon discontinuation of therapy. To avoid permanent damage visual acuity should be checked regularly during treatment and therapy discontinued immediately when visual disturbances occur.

Visual disturbances may be unilateral or bilateral; therefore each eye should be tested separately (see section 4.4). Typical signs include: blurred vision, eye pain, impairment of colour vision (red-green colour blindness), constriction of visual field (central or peripheral scotoma), and any loss in vision. Recovery of visual acuity has usually occurred over a period of weeks to months after the drug was discontinued, and patients have then received Ethambutol at lower dosage without toxicity

¹ Liver function tests should be performed in patients who develop symptoms suggestive of hepatitis or who become generally unwell during treatment.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. t allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme at: www.mhra.go.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

None.