Dyna Ethambutol 400 mg FC tablets.

DYNA ETHAMBUTOL 400 mg is indicated for the treatment of tuberculosis in combination with other anti-tubercular medicine, in adults and children over 12 years of age.

DYNA ETHAMBUTOL 400 mg should not be used alone in the initial treatment or in re-treatment. Therapy in general should be continued until bacteriological conversion has become permanent and maximal clinical improvement has occurred.

Adults and children over 12 years: The dosage must be adjusted according to the body mass of the patient.

Adults: For primary treatment: The usual adult dose of DYNA ETHAMBUTOL 400 mg is 15 mg/kg given once a day, with concomitant medicines being used at their recommended dosage levels.

For re-treatment: For the first 60 days of treatment, DYNA ETHAMBUTOL 400 mg should be administered in a single daily dose of 25 mg/kg. Thereafter the dosage should be reduced to 15 mg/kg with concomitant medicines being maintained at their recommended dosage levels.

Special populations

• Renal impairment: DYNA ETHAMBUTOL 400 mg accumulates in patients with impaired renal function and adjustment of dosage is necessary.
• Elderly: Dosage as for adults.
• Paediatric population: DYNA ETHAMBUTOL 400 mg is not recommended for use in children under 5 years.

Method of administration

For oral use. DYNA ETHAMBUTOL 400 mg can be taken with or without food. Missed dose: Doctors should advise patients who forget to take DYNA ETHAMBUTOL 400 mg to take a dose as soon as possible and then continue with the normal dose. Patients should not take a double dose to compensate for the missed dose.

• Hypersensitivity to ethambutol or to any of the ingredients of DYNA ETHAMBUTOL 400 mg (see section 6.1)
• in patients with known optic neuritis
• children under 5 years of age.

Ocular toxicity:

DYNA ETHAMBUTOL 400 mg may produce decreases in visual acuity which appear to be due to optic neuritis. Visual changes may be unilateral or bilateral. This effect is generally reversible when administration of DYNA ETHAMBUTOL 400 mg is discontinued promptly. However, irreversible blindness has been reported. It is recommended that patients undergo a full ophthalmic examination before starting treatment. This should include visual acuity, colour vision, perimetry and ophthalmoscopy. Each eye must be tested separately and both eyes together. It should also be given with great care in patients with reduced visual acuity, such as the elderly, and in children in whom evaluation of changes in visual acuity may be difficult. Tests of visual acuity and red-green discrimination prior to the start of therapy, and periodically thereafter, are strongly recommended and DYNA ETHAMBUTOL 400 mg should be withdrawn if vision deteriorates.

Gout: Use of DYNA ETHAMBUTOL 400 mg should be carefully considered in patients with a history of gout. DYNA ETHAMBUTOL 400 mg may precipitate attacks of gout.

Renal impairment: DYNA ETHAMBUTOL 400 mg should be given in reduced dosage to patients with renal impairment and dosage adjustments may be needed according to serum concentrations.

Hepatic impairment: Liver function tests should be performed in patients who develop symptoms suggestive of hepatitis or who become generally unwell during treatment with DYNA ETHAMBUTOL 400 mg. Serum concentrations of ethambutol should not exceed 5 u03bcg/ml.

Other: Consideration should be given to current clinical guidance on the appropriate use of anti-tuberculous medicines.

Concurrent administration of DYNA ETHAMBUTOL 400 mg with other neurotoxic medicines may increase the potential for neurotoxicity, such as optic and peripheral neuritis. Aluminium containing antacids may delay the absorption of DYNA ETHAMBUTOL 400 mg. Avoid concurrent administration of DYNA ETHAMBUTOL 400 mg with aluminium containing antacids for at least 4 hours.

Pregnancy: The safety of DYNA ETHAMBUTOL 400 mg in pregnancy and lactation has not been established.

Breastfeeding: DYNA ETHAMBUTOL 400 mg crosses the placenta and is excreted in breast milk. Teratogenic effects have been seen in animals.

Visual disturbances associated with retrobulbar optic neuritis causing a restriction in visual acuity, constriction of visual field, dark spots in the visual field, red-green colour blindness are the most important side effects of DYNA ETHAMBUTOL 400 mg when considering the patientu2019s ability to safely drive or operate machinery (see section 4.8). Dizziness, disorientation, numbness and paraesthesia are also among possible side effects that may affect a patient's ability to drive or operate machinery. These effects on sharpness of sight, clarity of vision, field of vision and impaired red-green colour vision should be borne in mind when considering the patientu2019s ability to safely drive or operate machinery.

Summary of the safety profile

Tabulated summary of adverse reactions

System Organ Class Frequency Side effects

• Blood and lymphatic system disorders Less frequent Thrombocytopenia, leucopenia, neutropenia
• Immune system disorders Less frequent Frequency unknown Hypersensitivity (such as fever; skin rash, nausea) Anaphylactic reactions
• Metabolism and nutrition disorders Less frequent Hyperuricaemia, precipitation of gout
• Psychiatric disorders Less frequent Disorientation, mental confusion, possible hallucinations
• Nervous system disorders Less frequent Frequency unknown Headache, dizziness, numbness and tingling of the extremities due to peripheral neuritis, peripheral neuropathy, burning pain, weakness (hands and feet) Tremor
• Eye disorders Frequent Retrobulbar optic neuritis causing a restriction in visual acuity, constriction of visual field, dark spots in the visual field, red-green colour blindness, loss of vision, eye pain, retinal haemorrhage
• Vascular disorders Less frequent Hypotension
• Respiratory, thoracic and mediastinal disorders Less frequent Pneumonitis, pulmonary infiltrates, with or without eosinophilia
• Gastrointestinal disorders Less frequent Frequency unknown Nausea, vomiting, anorexia, abdominal pain and gastrointestinal upset (diarrhoea) Flatulence, metallic taste, loss of appetite, upset stomach
• Hepatobiliary disorders Less frequent Frequency unknown Jaundice Liver toxicity, transient and asymptomatic elevations in liver function tests, hepatic reactions with hepatitis, hepatic failure
• Skin and subcutaneous tissue disorders Less frequent Rash, pruritus, urticaria, photosensitive lichenoid eruptions, bullous dermatitis, Stevens-Johnson syndrome, epidermal necrolysis, erythema multiforme
• Musculoskeletal, connective tissue and bone disorders Less frequent Joint pain
• Renal and urinary disorders Less frequent Interstitial nephritis
• General disorders and administrative site conditions Less frequent Malaise, fever

Description of selected adverse reactions

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. 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 medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions to SAHPRA via the online service for adverse drug reaction reporting by following the link: https://www.sahpra.org.za/Publications/Index/8. An email can be sent directly to the company, [email protected] to ensure safety of the product.

Signs and symptoms: Symptoms of overdosage may be any of those listed under section 4.8 above. Typically, symptoms include gastrointestinal disturbances, vomiting, fever, headache, anorexia, dizziness, hallucinations and/or visual disturbances.

Management of overdose: Changes in visual acuity should be carefully evaluated and if necessary the administration of DYNA ETHAMBUTOL 400 mg should be discontinued. Blood concentrations of DYNA ETHAMBUTOL 400 mg after overdosage may be reduced by haemodialysis or peritoneal dialysis. There is no specific antidote, but gastric lavage should be employed if necessary followed by supportive and symptomatic treatment.