ISONIAZID

Isoniazid 50 mg/2 ml Solution for Injection is for intramuscular, intravenous, intrapleural, or intrathecal injection. Adults and children The usual intramuscular or intravenous dose for adults is 200 to 300 mg as a single daily dose, for children 100 to 300 mg daily (10 - 20 mg/kg), but doses much larger than these are sometimes given, especially in conditions such as tuberculous meningitis.

It is recommended to give an intravenous dose slowly as an undiluted bolus injection, although other methods may be employed. Neonates The recommended intravenous or intramuscular dose for neonates is 3-5 mg/kg with a maximum of 10 mg/kg daily.

6). The elderly No dosage reduction is necessary in the elderly. Intrapleural use 50 to 250 mg may be instilled intrapleurally after aspiration of pus, the dosage of oral isoniazid on that day being correspondingly reduced. The ampoule solution is also used for the local treatment of tuberculous ulcers, for irrigation of fistulae, etc.

Intrathecal use:

It should be noted that CSF concentrations of isoniazid are approximately 90% of plasma concentrations. Where intrathecal use is required, 25 - 50 mg daily has been given to adults and 10 - 20 mg daily for children, according to age.

It is usual to give Isoniazid together with other antituberculous therapy, as determined by current practice and/or sensitivity testing. It is recommended that pyridoxine be given during Isoniazid therapy to minimise adverse reactions, especially in malnourished patients and those predisposed to neuropathy (eg.

8). Patients with renal impairment No dosage reduction of Isoniazid is necessary when given to patients with mild renal failure. Patients with severe renal failure (glomerular filtration rate of less than 10 ml/minute) and slow acetylator status might require a dose reduction of about 100mg to maintain trough plasma levels at less than 1 mcg/ml.

Isonaizid is removed by both haemodialysis and peritoneal dialysis therefore isoniazid should be administered immediately after dialysis. Patients with hepatic impairment The possible risks of administration of Isoniazid to patients with pre-existing non- tuberculous hepatic disease should be balanced against the benefits expected from treating tuberculosis.

Side-effects have been reported mainly in association with high doses or in slow acetylators who develop higher blood levels of the drug. Tabulated list of adverse reactions Undesirable effects are listed by MedDRA System Organ Classes.

4). Peripheral neuropathy may be preventable with pyridoxine. Severe and sometimes fatal hepatitis may occur with isoniazid therapy. 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. uk/yellowcard.

Care is required in chronic alcoholism and when prescribing isoniazid for patients with pre-existing hepatitis. 8), especially in patients with a previous history of these conditions. These manifestations usually subside rapidly when the drug is withdrawn.

Isoniazid should therefore be given with caution to patients with convulsive disorders and should be avoided in those with manic or hypomanic psychoses. Isoniazid is metabolised by acetylation, which is subject to genetic variation.

8). However, dose adjustment is not normally required. In patients with porphyria, isoniazid should only be used where no safer alternative is available. Precautions should be considered in these patients. It is recommended if isoniazid-induced pancreatitis is proven that the drug should be permanently avoided.

Isoniazid, especially if given with rifampicin, may induce abnormalities in liver function, particularly in patients with pre-existing liver disorders, in the elderly, the very young and the malnourished. Monthly review is suggested to detect and limit the severity of this side-effect by stopping treatment if plasma transaminases exceed three times the upper limit of normal.

Severe cutaneous adverse reactions (SCARs) such as 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.

If the patient has developed a serious reaction such as SJS, TEN, DRESS or AGEP with the use of Isoniazid, treatment with Isoniazid must not be restarted in this patient at any time.

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