ISONIAZID Solution for injection Ref.[7980] Active ingredients: Isoniazid

Care is required in chronic alcoholism and when prescribing isoniazid for patients with pre-existing hepatitis. Convulsions and psychotic reactions have occurred (see section 4.8), 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 These manifestations usually subside rapidly when the drug is withdrawn.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. The ‘slow acetylators’ may be more susceptible to drug-induced peripheral neuropathy (see section 4.8). 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.

Isoniazid is known to inhibit certain cytochrome P-450 enzymes and therefore can inhibit the hepatic metabolism of some drugs, in some cases leading to increased toxicity. These include the antiepileptics carbamazepine, ethosuximide, primidone, and phenytoin, the benzodiazepines diazepam and triazolam, chlorzoxazone, theophylline, and disulfiram. Plasma levels of these drugs should be monitored if concurrent therapy with Isoniazid is necessary.

Isoniazid may induce abnormalities in liver function; this may be more likely when it is administered together with rifampicin (see section 4.4).

The adverse CNS effects of cycloserine are increased by isoniazid.

Isoniazid is an inhibitor of monoamine oxidase (MAO) and diamine oxidase (DAO), therefore can reduce tyramine and histamine metabolism, causing symptoms such as headache, sweating, palpitations, flushing and hypotension. Patients should be advised against ingesting foods rich in tyramine and/or histamine during treatment with isoniazid, such as cured meat, some cheeses (e.g. matured cheeses), wine, beer and some fish (e.g. tuna, mackerel, salmon).

Prednisolone can lower plasma levels of isoniazid. Where a reduced response during concurrent use is noted, dosage adjustment of isoniazid may be necessary.

Isoniazid may reduce the therapeutic effects of levodopa.

Pregnancy

While Isoniazid is generally regarded to be safe in pregnancy, there is a possibility of an increased risk of foetal malformations occurring when Isoniazid is given in early pregnancy. If pregnancy cannot be excluded possible risks should be balanced against therapeutic benefits.

Breast-feeding

Isoniazid is excreted in breast milk at concentrations equivalent to those found in maternal plasma, ie. 6-12 mcg/ml. This could result in an infant ingesting up to 2 mg/kg/day.

Supplementation with pyridoxine is recommended for breast-feeding women and for breastfed infants, to minimise adverse reactions.

Patients should be warned of the possibility of convulsions, psychosis and optic neuritis (see section 4.8).

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.

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, Not known: cannot be estimated from the available data.

Blood and lymphatic system disorders

Not known: Agranulocytosis, Anaemia including haemolytic, sideroblastic and aplastic, Eosinophilia, Thrombocytopenia

Immune system disorders

Not known: Lupoid syndrome

Metabolism and nutrition disorders

Not known: Pellagra, Hyperglycaemia

Psychiatric disorders

Not known: Psychosis (see section 4.4)

Nervous system disorders

Not known: Peripheral neuropathy, Optic neuritis, Convulsions (see section 4.4)

Eye disorders

Not known: Optic atrophy

Vascular disorders

Not known: Vasculitis

Gastrointestinal disorders

Not known: Pancreatitis (see section 4.4)

Hepatobiliary disorders

Uncommon: Hepatitis

Not known: Function liver abnormal, Jaundice

Skin and subcutaneous tissue disorders

Rare: Toxic epidermal necrolysis, Eosinophilia systemic symptoms

Not known: Alopecia, Allergic skin reaction (including erythema multiforme), Purpura, Rash, Exfoliative dermatitis

Reproductive system and breast disorders

Not known: Gynaeco-mastia

General disorders and administration site conditions

Not known: Fever

Description of selected adverse reactions

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 (see section 4.4).

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. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard.

None known.