EMB-Fatol 400

For the primary treatment and re-treatment of tuberculosis and for prophylaxis in cases of inactive tuberculosis or large-tuberculin-positive reaction.

EMB-Fatol 400 should only be used in conjunction with other anti-tuberculosis drugs to which the patient's organisms are susceptible.

Consideration should be given to official guidance on the appropriate use of antimicrobial agents.

Posology

For oral use.

Dosage should be determined according to the body weight of the patient. The usual daily dosage is 15-25mg/kg body weight given as a single dose.

EMB-Fatol 400 should not be used as a sole anti-tuberculosis agent, but should be given with at least one other anti-tuberculosis drug to avoid development of resistant strains.

Adults

For primary treatment and prophylaxis: EMB-Fatol 400 should be administered in a single daily dose of 15 mg/kg body weight; concomitant drugs should be maintained at their usual recommended dosage.

For re-treatment: For the first 60 days of treatment, EMB-Fatol 400 should be administered in a single daily dose of 25 mg/kg body weight. Thereafter the dosage should be reduced to 15 mg/kg body weight; concomitant drugs should be maintained at their usual recommended dosage levels.

Children

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

For prophylaxis: A single daily dose of 15 mg/kg body weight; concomitant drugs being maintained at their usual recommended dosage levels.

As children may be less likely or unable to report ocular toxicity, particular caution may be warranted.

Older people Dosage as for adults. However, patients with decreased renal function may need to have the dosage adjusted as determined by blood levels of EMB-Fatol 400.

Known hypersensitivity to EMB-Fatol 400 or to any of the other ingredients.

Known optic neuritis or retrobulbar neuritis, unless clinical judgement determines that the benefit outweighs the potential risk.

Ocular toxicity:

EMB-Fatol 400 causes ocular toxicity and patients should be advised to report any changes of 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 EMB-Fatol 400. EMB-Fatol 400 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

EMB-Fatol 400 therapy should be stopped immediately if visual disturbances are observed.

Renal impairment:

Renal function should be checked before treatment with antituberculosis drugs and appropriate dosage adjustments made. EMB-Fatol 400 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.

EMB-Fatol 400 may produce a unique type of visual impairment. 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 EMB-Fatol 400 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 EMB-Fatol 400 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:

* 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. 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 EMB-Fatol 400 at lower dosage without toxicity

¹Liver 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. 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

Symptoms: Gastrointestinal disturbances, vomiting, fever, headache, anorexia, dizziness, hallucinations and/or visual disturbances.

Treatment: There is no specific antidote, but gastric lavage should be employed if necessary.

ATC Code : J04AK02 - Other drugs for treatment of tuberculosis

EMB-Fatol 400 is bacteriostatic. It 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.

Cross-resistance has not yet been reported. Primary resistance to EMB-Fatol 400 is uncommon but resistant strains of M.tuberculosis are readily produced if EMB-Fatol 400 is used alone.

Absorption: EMB-Fatol 400 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 bodyweight, within 4 hours peak plasma concentrations of up to 5µg/ml are obtained, by 24 hours the concentration decreases to less than 1µg/ml. EMB-Fatol 400 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.

• R52.1 – Chronic intractable pain
• R52.2 – Other chronic pain
• R52.9 – Unspecified pain

None.

None.

• R52.1 – Chronic intractable pain
• R52.2 – Other chronic pain
• R52.9 – Unspecified pain