ISONIAZID

Official guidance should always be consulted when selecting the dose regimens to be used for adults and children (according to age and body weight), the duration of therapy and the total content of the combination treatment regimen.

Posology Adults The dose of isoniazid for the treatment of tuberculosis is commonly 4 to 5 mg per kilogram body-weight daily given by mouth in single or divided doses up to a maximum of 300 mg daily. Up to 10 mg per kilogram body-weight daily may be given particularly during the first 1 to 2 weeks of treatment of tuberculous meningitis.

A dose of 15 mg per kilogram has been given two or three times weekly in intermittent treatment regimens. Elderly No dosage reduction is necessary in the elderly, but caution should be exercised due to the possible decrease in renal and hepatic function.

Paediatric population The usual daily dose for children aged three months and above is from 10 up to 15 mg per kilogram body-weight daily in single or divided doses. Isoniazid should not be used in children aged 0 to 3 months because of the lack of specific data.

e. at least 30 minutes before a meal or 2 hours after a meal. Tablets must be swallowed whole and not chewed.

Undesirable effects are listed by MedDRA System Organ Classes.

Assessment of undesirable effects is based on the following frequency groupings:

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 Frequency not known: cannot be estimated from the available data System organ class Frequency Adverse reactions Blood & lymphatic system disorders Not known Haemolytic anaemia Aplastic anaemia Agranulocytosis Metabolism & nutrition disorders Not known Hyperglycaemia Acidosis Nicotinic acid deficiency Nicotinic acid deficiency may be related to an isoniazid-induced pyridoxine deficiency which affects the conversion of tryptophan to nicotinic acid.

Psychiatric disorders Not known Psychotic disorder Elevated mood Although isoniazid usually has a mood elevating effect, mental disturbances, ranging from minor personality changes to major mental derangement have been reported; these are usually reversed on withdrawal of the drug.

Nervous system disorders Not known Peripheral neuropathy Seizure Optic neuritis Hyperreflexia may be troublesome with doses of 10 mg per kg bodyweight, Musculoskeletal and connective tissue disorders Not known Systemic lupus erythematosus Lupus-like syndrome General disorders and administration site conditions Not known Pyrexia Ear & labyrinth disorders Not known Deafness Tinnitus Vertigo These have been reported in patients with end stage renal impairment.

Vertigo may be troublesome with doses of 10 mg per kg bodyweight. Respiratory, thoracic & mediastinal disorders Not known Interstitial lung disease Gastrointestinal disorders Not known Nausea Vomiting Constipation Dry mouth Pancreatitis acute Other gastrointestinal effects Not known Acute hepatic failure Liver injury Jaundice The risk of these undesirable effects increases with age, especially over the age of 35; it may be serious and sometimes fatal with the development of necrosis.

All patients should have baseline liver function tests performed and repeated at regular intervals during treatment. If serum AST rises to more than three times normal, or there is any increase in bilirubin, treatment should be withdrawn.

Special precautions are required in patients with impaired liver function. Any deterioration in liver function in these patients is an indication for stopping treatment. Isoniazid should not be given to patients who have experienced severe adverse reactions including drug-induced liver disease.

Care should be taken in giving isoniazid to patients suffering from convulsive disorders, diabetes mellitus, chronic alcoholism, or impaired liver or kidney function or to patients taking other potentially hepatoxic agents. If symptoms of hepatitis such as malaise, fatigue, anorexia and nausea develop isoniazid should be discontinued immediately.

Isoniazid should be used with caution in patients with a history of psychosis. Advanced age, female gender, slow acetylators, malnutrition, HIV infection, pre- existing liver disease and extra-pulmonary tuberculosis were identified as risk factors for isoniazid-induced hepatotoxicity.

Patients who are at risk of neuropathy or pyridoxine deficiency, including those who are diabetic, alcoholic, malnourished, uraemic, pregnant or infected with HIV, should be given pyridoxine. Hydrogenated castor oil This product contains hydrogenated castor oil which may cause stomach upset and diarrhoea.

Severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP), which can be life-threatening or fatal, have been reported in association with isoniazid 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, isoniazid should be withdrawn immediately and an alternative treatment considered.

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