SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Myambutol Tablets 100mg Ethambutol Tablets 100mg

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each Ethambutol Tablet contains 100mg of Ethambutol Hydrochloride (EP).

3.    PHARMACEUTICAL FORM

Slightly mottled yellow coated tablets.

4    CLINICAL PARTICULARS

4.1.    Therapeutic Indications

The primary treatment and re-treatment of tuberculosis and for prophylaxis in cases of inactive tuberculosis or large-tuberculin-positive reaction. Ethambutol should only be used in conjunction with other anti-tuberculous drugs to which the patients organisms are susceptible.

4.2. Posology and Method of Administration

Route of administration: Oral Posology

The dosage of Ethambutol must be adjusted according to the body weight of the patient.

Adults

For primary treatment and prophylaxis: Ethambutol should be administered in a single daily oral dose of 15mg/kg, concomitant drugs being maintained at their recommended dosage levels.

For re-treatment: For the first 60 days of treatment, Ethambutol should be administered in a single daily oral dose of 25mg/kg. Thereafter the dosage should be reduced to 15mg/kg, concomitant drugs being maintained at their recommended dosage levels.

For primary treatment and re-treatment: For the first 60 days of treatment, a single daily oral dose of 25mg/kg. Thereafter the dosage should be reduced to 15mg/kg, concomitant drugs being maintained at their recommended dosage levels.

For prophylaxis: A single daily oral dose of 15mg/kg, concomitant drugs being used at their recommended dosage levels.

Elderly

As for adults: However, patients with decreased renal function may need to have the dosage adjusted as determined by blood levels of Ethambutol.

In order to obtain maximum effect due to high serum levels, drug administration should be once daily.

4.3    Contraindications

Ethambutol is contra-indicated in patients who are known to be hypersensitive to the drug. It is also contra-indicated in patients with known optic neuritis and poor vision unless clinical judgement determines that it may be used.

4.4    Special warnings and precautions for use

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, but if used the dose should be reduced and the plasma-drug concentration monitored. Toxic effects are more common if renal function is impaired.

Because this drug has a unique effect on the eye, it is recommended that patients undergo a full ophthalmic examination before starting treatment. This should include visual acuity, colour vision, perimetry and ophthalmoscopy. Many physicians consider that routine ophthalmological examination for adults is not thereafter necessary, but patients should be informed the importance of reporting any change in vision. However, routine ophthalmological examinations may be considered desirable when treating young children.

4.5    Interaction with other medicinal products and other forms of interaction

None

Pregnancy and Lactation

There are no adequate data from the use of ethambutol 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 or women of childbearing potential unless the potential benefit to the mother is considered to outweigh any possible risk to the foetus.

4.7. Effects on Ability to Drive and Use Machines

Patients who suffer from visual impairment during treatment with ethambutol should not drive or operate machinery.

4.8 Undesirable effects

Frequency: 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 & lymphatic system disorders:

Very rare: Thrombocytopenia, leucopenia, neutropenia

Immune system disorders:

Very rare: Hypersensitivity, anaphylactoid reactions, (see also Skin and subcutaneous tissue disorders)

Metabolic & nutrition disorders:

Uncommon: Hyperuricaemia Very rare: Gout

Nervous system & psychiatric disorders:

Rare: Peripheral neuropathy, numbness, paraesthesia of the extremities,

Very rare: headache, dizziness, mental confusion, disorientation, hallucinations Eye disorders

Uncommon: Optic neuritis (decreased visual acuity, loss of vision, scotoma, colour blindness, visual disturbance, visual field defect, eye pain)

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.

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.

The change may be unilateral or bilateral and hence both eyes must be tested individually. The effects are generally reversible when administration of the

drug is discontinued promptly. In rare cases recovery may be delayed for up to one year or more and the effect may possibly be irreversible in these cases.

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 dosages without toxicity.

Respiratory, thoracic & mediastinal disorders:

Very rare: Pneumonitis, pulmonary infiltrates, with or without eosinophilia Gastrointestinal disturbances:

Gastrointestinal disorders such as anorexia, nausea, vomiting, abdominal pain and diarrhoea have been noted in patients on multiple drug anti-tuberculosis therapy including ethambutol although not in test patients receiving ethambutol as sole therapy.

Hepatobiliary disorders:

Hepatic reactions with hepatitis, jaundice, abnormal liver function test values, and very rarely, hepatic failure, have been reported in patients treated with multiple drug therapy including ethambutol. Liver function tests should be performed in patients who develop symptoms suggestive of hepatitis or who become generally unwell during treatment.

Skin & subcutaneous tissue disorders:

Rare: Rash, pruritus, urticaria Very rare: photosensitive lichenoid eruptions, bullous dermatitis, Stevens Johnson syndrome, epidermal necrolysis

Renal & urinary disorders

Very rare: Interstitial nephritis

Other: Very rare: Malaise, joint pains, pyrexia.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

4.9. Overdose

No specific antidote, but gastric lavage should be employed if necessary.

5 PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic Properties

Ethambutol is bacteriostatic. It is effective against Mycobacterium tuberculosis and M. bovis with an MIC of 0.5 - 8 pg per ml. While it has activity against some atypical mycobacteria including M. Kansarii, activity against other micro-organisms has not yet been reported.

It is effective against tubercle bacilli resistant to other tuberculostatics. Crossresistance has not yet been reported. Primary resistance to ethambutol is uncommon but resistant strains of M. tuberculosis are readily produced if ethambutol is used alone.

5.2. Pharmacokinetic Properties

Ethambutol is readily absorbed after oral administration and this absorption is not significantly impaired by food. After a single dose of 25mg/kg body weight, within 4 hours peak plasma concentrations of up to 5pg/ml are obtained, by 24 hours the concentration decreases to less than 1pg/ml. Most of a dose is excreted unchanged in the urine and up to 20% in faeces, within 48 hours. From 8 - 15% of a dose appears in urine as inactive metabolites.

Ethambutol readily diffuses into red blood cells and into the cerebrospinal fluid when the meninges are inflamed. It has also been reported to cross the placenta.

5.3. Pre-clinical Safety Data

Nothing further of relevance to prescriber.

6 PHARMACEUTICAL PARTICULARS

6.1. List of Excipients

Sucrose; gelatin 125 bloom; sorbitol solution 70%; quinoline yellow (E104); magnesium stearate; stearic acid.

Coating for tablets: Shellac solution 40%; Colorcon Opaglos Regular*; talc

*Colorcon Opaglos Regular contains. Shellac; polyvinylpyrrolidone; acetylated monoglyceride; industrial methylated spirits

6.2. Incompatibilities

None.

6.3. Shelf Life

60 months.

6.4. Special Precautions for Storage

Ethambutol should be stored at room temperature (15-30°C) in either the original pack or in containers which prevent access of moisture.

6.5. Nature and Content of Container

Polypropylene bottles with plastic screw-on caps containing 100 or 500 tablets.

OR

Tamper-evident, white polypropylene bottles with plastic screw-on caps containing 28 or 56 tablets.

OR

Glass bottles with screw-on caps containing 28, 56, 100 or 500 tablets

6.6 Special instructions for disposal

None

7. MARKETING AUTHORISATION HOLDER

Genus Pharmaceuticals Holdings Limited T/A Genus Pharmaceuticals Linthwaite,

Huddersfield,

HD7 5QH, UK

PL 17225/0004

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

06/04/2009

10    DATE OF REVISION OF THE TEXT

14/01/2015