Summary of Product Characteristics (SmPC) - Ethambutol 400 mg film-coated tablets
1 NAME OF THE MEDICINAL PRODUCT
Ethambutol 400 mg Film-coated Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains 400 mg of ethambutol hydrochloride For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Film-coated tablet.
Grey, round biconvex, film coated tablet
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-tuberculosis medicinal products to which the patient’s organisms are susceptible. Before prescribing Ethambutol tablets, consideration should be given to official guidance on the appropriate use of antimicrobial agents
4.2 Posology and method of administration
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 15 mg/kg, concomitant drugs being maintained at their recommended dosage levels. For re-treatment
For the first 60 days of treatment, a single daily oral dose of 25 mg/kg. Thereafter the dosage should be reduced to 15 mg/kg, concomitant drugs being maintained at their recommended dosage levels.
Children
For primary treatment and re-treatment
For the first 60 days of treatment, a single daily oral dose of 25 mg/kg. Thereafter the dosage should be reduced to 15 mg/kg, concomitant drugs being used at their recommended dosage levels.
For prophylaxis
A single daily oral dose of 15 mg/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.
Renal Impairment
Renal function should be checked before treatment with antituberculosis medicinal products and appropriate dosage adjustments made. Ethambutol tablets should preferably be avoided in patients with renal impairment If used, where creatinine clearance is less than 30 mL/minute, use 15–25 mg/kg (max. 2.5 g) 3 times a week and plasma ethambutol concentration should be monitored.
Method of administration
Oral use only.
4.3 Contraindications
Ethambutol is contraindicated in patients with:
- a known hypersensitivity to ethambutol or to any of the excipients listed in section 6.1.
- a known optic neuritis and poor vision unless clinical judgement determines that it may be used.
4.4 Special warnings and precautions for use
Ocular toxicity
Because this drug has a unique effect on the eye, 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 25 mg/kg/day for two months, and 15 mg/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. Any change may be unilateral or bilateral and hence both eyes should be tested individually.
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.
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 dosages 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.
Skin and subcutaneous tissue disorders
Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported post-marketing in association with ethambutol treatment.
At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions.
If signs and symptoms suggestive of these reactions appear, ethambutol should be withdrawn immediately and an alternative treatment considered (as appropriate).
If the patient has developed a serious reaction such as SJS, TEN or DRESS with the use of ethambutol, treatment with ethambutol must not be restarted in this patient at any time.
Children
In children, the presentation of a rash can be mistaken for the underlying infection or an alternative infectious process, and physicians should consider the possibility of a reaction to ethambutol in children that develop symptoms of rash and fever during therapy with ethambutol.
Excipient
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.
4.5 Interaction with other medicinal products and other forms of interaction
Aluminium hydroxide may impair the absorption of ethambutol. Therefore, antacids containing this ingredient should be avoided during treatment with ethambutol.
4.6 Fertility, pregnancy and lactation
Pregnancy
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 tablet is not recommended during pregnancy and in women of childbearing potential 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.
Breastfeeding is not recommended during ethambutol treatment unless the benefit of breastfeeding to the child is considered to outweigh any possible risks.
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.
Numbness, paraesthesia, dizziness, disorientation are also among possible side effects that may affect a patient's ability to drive or operate machinery, if affected, patients should not drive or operate machinery.
4.8 Undesirable effects
Frequencies are defined using the following convention:
Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).
Blood and lymphatic system disorders
Rare: thrombocytopenia.
Very rare: leukopenia, neutropenia.
Immune system disorders
Very rare: hypersensitivity, anaphylactoid reactions (see also Skin and subcutaneous tissue disorders).
Metabolism and nutrition disorders
Uncommon: hyperuricaemia.
Very rare: gout.
Nervous system disorders
Rare: peripheral neuropathy, numbness, paraesthesia of the extremities.
Very rare: headache, dizziness, disorientation.
Psychiatric disorders
Very rare: mental confusion, hallucinations.
Eye disorders
Uncommon: optic 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
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 (SJS), toxic epidermal necrolysis (TEN).
Not known: drug reaction with eosinophilia and systemic symptoms (DRESS) (see section 4.4).
Renal and urinary disorders
Very rare: interstitial nephritis.
General disorders and administration site conditions
Very rare: malaise, pyrexia.
Musculoskeletal and connective tissue disorders
Very rare: joint pain.
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 or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
Symptoms
The overdosage symptoms includes gastrointestinal disturbances, vomiting, fever, headache, anorexia, dizziness, hallucinations and/or visual disturbances Management
There is no specific antidote, but gastric lavage should be employed if necessary.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Other drugs for treatment of tuberculosis
ATC Code : J04AK02
Mechanism of action
Ethambutol is bacteriostatic.
Mechanism of resistance
Cross-resistance 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.
Spectrum of antibacterial activity
Ethambutol is effective against Mycobacterium tuberculosi and M.bovis with an MIC of 0.5 – 8µg per ml. The exact mechanism of action is unknown. While it has activity against some atypical mycobacteria including M.Kansasii, activity against other micro-organisms has not yet been reported.
It is effective against tubercle bacilli resistant to other tuberculostatics.
5.2 Pharmacokinetic properties
Absorption
Ethambutol is readily absorbed after oral administration and this absorption is not significantly impaired by food.
Distribution
After a single oral dose of 25 mg/kg body weight, within 4 hours peak plasma concentrations of up to 5 µg/ml are obtained, by 24 hours the concentration decreases to less than 1µg/ml. 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.
Metabolism and Excretion
Most of a dose is excreted unchanged in the urine and up to 20% in the faeces, within 48 hours. From 8 – 15% of a dose appears in the urine as inactive metabolites.
5.3 Preclinical safety data
Ethambutol has been shown to be teratogenic in pregnant mice and rabbits when given in high doses. When pregnant mice or rabbits were treated with high doses of ethambutol hydrochloride, fetal mortality was slightly but not significantly (P>0.05) increased. Female rats treated with ethambutol hydrochloride displayed slight but insignificant (>0.05) decreases in fertility and litter size. In foetuses born of mice treated with high doses of ethambutol hydrochloride during pregnancy, a low incidence of cleft palate, exencephaly and abnormality of the vertebral column were observed. Minor abnormalities of the cervical vertebra were seen in the newborn of rats treated with high doses of ethambutol hydrochloride during pregnancy. Rabbits receiving high doses of ethambutol hydrochloride during pregnancy gave birth to two foetuses with monophthalmia, one with a shortened right forearm accompanied by bilateral wrist-joint contracture and one with hare lip and cleft palate.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium starch glycolate
Maize starch
Povidone
Colloidal anhydrous silica
Microcrystalline cellulose
Magnesium stearate
Coating material (polydextrose, hypromellose, titanium Dioxide (E171), macrogol, iron oxide black (E172), iron oxide yellow (E172).
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
Do not store above 25°C.
6.5 Nature and contents of container
Al/PVC/PE/PVDC blisters. Pack size of 56 tablets.
PP tablet containers. Pack size of 56 tablets.
6.6 Special precautions for disposal
No special requirements for disposal.
7 MARKETING AUTHORISATION HOLDER
Dawa Ltd
5 Sandridge Close, Harrow,
Middlesex, HA1 1XD
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 30684/0132
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
20/01/2025
10 DATE OF REVISION OF THE TEXT
11/12/2025