Isoniazid Ampoules 50 mg / 2 ml.

1. Name Of The Medicinal Product

Isoniazid Ampoules 50 mg/2 ml.

2. Qualitative And Quantitative Composition

Each ampoule contains 50 mg Isoniazid BP in 2 ml of solution.

3. Pharmaceutical Form

Ampoules

4. Clinical Particulars

4.1 Therapeutic Indications

For all forms of pulmonary and extra-pulmonary tuberculosis.

4.2 Posology And Method Of Administration

Isoniazid ampoules are 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. Isoniazid may be present in the milk of lactating mothers.

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 10 - 50mg daily be given during Isoniazid therapy to minimise adverse reactions, especially in malnourished patients and those predisposed to neuropathy (eg. diabetics and alcoholics).

4.3 Contraindications

Isoniazid should not be given to patients with a history of sensitivity to isoniazid.

4.4 Special Warnings And Precautions For Use

Use in renal and hepatic 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. 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.

Care is also required in chronic alcoholism and when prescribing isoniazid for patients with pre-existing hepatitis. Convulsions and psychotic reactions have occurred, 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. However, dose adjustment is not normally required.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Isoniazid may inhibit the metabolism of phenytoin, primidone and carbamazepine. Plasma levels of these drugs should be monitored if concurrent therapy with Isoniazid is necessary. See also statement under 4.8 regarding Rifampicin.

4.6 Pregnancy And Lactation

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. 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.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Isoniazid is generally well tolerated. Side-effects have been reported mainly in association with high doses or in slow acetylators who develop higher blood levels of the drug. Fever, peripheral neuropathy (preventable with pyridoxine), optic neuritis and atrophy, allergic skin conditions (including erythema multiforme), and rarely lupoid syndrome, pellagra, purpura and haematological reactions have occurred during isoniazid therapy. Hyperglycaemia and gynaeco-mastia have been reported with isoniazid treatment. 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. There is conflicting opinion as to the relationship of this side-effect to acetylator status.

4.9 Overdose

In severe poisoning the main risk is of epileptiform convulsions. In addition any of the side-effects listed above may occur together with metabolic acidosis and hyperglycaemia. Treatment should be directed to the control of convulsions and large doses of pyridoxine may limit the occurrence of other adverse effects. Metabolic acidosis may require sodium bicarbonate infusion. The drug is removed by dialysis.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Isoniazid is a highly active tuberculostatic drug, and at high concentrations it is bactericidal to mycobacterium tuberculosis, possibly acting by interference with the synthesis of mycolic acid (a constituent of the bacterial cell wall).

5.2 Pharmacokinetic Properties

Isoniazid is not appreciably protein-bound and diffuses readily throughout the body. It affects intracellular as well as extracellular bacilli. The primary metabolic route involves acetylation the rate of which is determined genetically.

5.3 Preclinical Safety Data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Hydrochloric Acid

Water for Injections BP

6.2 Incompatibilities

None known.

6.3 Shelf Life

Three years.

6.4 Special Precautions For Storage

The recommended maximum storage temperature is 25ºC.

Protect from light.

6.5 Nature And Contents Of Container

Colourless glass ampoules coded with dark red and orange colour ring each containing 2 ml of solution, in packs of 10 ampoules.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

Alliance Pharmaceuticals Limited

Avonbridge House

Bath Road

Chippenham

Wiltshire

SN15 2BB

UK

8. Marketing Authorisation Number(S)

PL 16853/0109

9. Date Of First Authorisation/Renewal Of The Authorisation

21 April 1992

10. Date Of Revision Of The Text

27^th July 2010