SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Magnesium Sulphate Injection BP 20%w/v

2.    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Magnesium Sulphate Ph Eur 4g (quantified    as the heptahydrate)

Water for Injections Ph Eur to 20ml.

3.    PHARMACEUTICAL FORM

Sterile Solution for Injection

4.    CLINICAL PARTICULARS

4.1    Therapeutic indications

Treatment of magnesium deficiency in hypomagnesaemia.

To prevent further seizures associated with eclampsia.

4.2    Posology and method of administration

Dosage should be individualised according to patient’s needs and responses. Plasma levels should also be monitored throughout therapy.

a) Treatment of magnesium deficiency in hypomagnesaemia:

Adults and the Elderly:

Up to 160 mmols of magnesium ions (200ml of a 20% solution) by slow intravenous infusion (in glucose 5%) over up to 5 days, may be required to replace the deficit (allowing for urinary losses). There are no data for the use by the IM route of the 20% solution.

Children:

Magnesium supplement in deficiency: 100mg/kg (0.5ml/kg of 20% solution or 0.4mmols/kg of magnesium ions) as a single dose, repeated every 12 hours as necessary.

Convulsions associated with low magnesium levels: 20-40mg/kg (0.1-0.2ml/kg of a 20% solution or 0.08-0.16 mmols/kg of magnesium ions) repeated every 4-6 hours as necessary.

There is very limited published data to suggest that an IM dosage should not exceed a concentration of 20%.

Renal Failure:

Doses must be reduced in renal failure. Caution must be observed to prevent exceeding the renal excretory capacity. The dosage should not exceed 20g in 48 hours (100ml of a 20% solution or 80mmols of magnesium ions).

b) To prevent further seizures associated with eclampsia:

Intravenous Maintenance Regimen

A loading dose of 4g/20ml or 16 mmols/20ml of magnesium ions IV (20ml of a 20% solution) or in some cases 5g/25ml or 20 mmols/25ml IV, as described above, is followed by an infusion of 1g/h continued for 24h after the last fit.

Recurrent Convulsions: In the IV regimen, if convulsions recur, a further 2-4g/10-20ml or 8-16 mmols/10-20ml of magnesium ions (depending on the woman’s weight, 2g if less than 70Kg) is given IV over 5 min.

Appropriate reductions in dosage should be made for patients with renal impairment; a suggested dose reduction in severe renal impairment is a maximum of 20g (80 mmols of magnesium ions) over 48 hours.

4.3 Contraindications

Hypersensitivity to magnesium and its salts.

Hepatic encephalopathy, hepatic failure or renal failure.

Parenteral magnesium salts should generally be avoided in patients with heart block.

4.4 Special warnings and precautions for use

Magnesium salts should be administered with caution to patients with impaired renal function; appropriate reductions in dosage should be made (Refer to ‘Posology and Method of Administration’ above).

Parenteral magnesium should be used with caution in individuals with myasthenia gravis, to prevent an exacerbation of the condition or the precipitation of a myasthenic crisis. A risk-benefit assessment should be performed in individual cases prior to initiation of treatment.

Magnesium sulphate should not be used in hepatic coma if there is risk of renal failure.

4.5 Interaction with other medicinal products and other forms of interaction

Muscle Relaxants: non-depolarising muscle relaxants such as tubocurarine are enhanced by parenteral magnesium salts.

Nifedipine: profound hypotension was produced in two women who were given oral Nifedipine.

Magnesium salts should also be administered with caution to those receiving digitalis glycosides. Parenteral administration of magnesium salts may enhance the effects of neuromuscular blocking agents or of central nervous system depressants.

CNS Depressants: When barbiturates, opiates, general anaesthetics, or other CNS depressants are administered concomitantly with magnesium sulphate, dosage of these agents must be carefully adjusted because of the additive central depressant effects.

4.6 Pregnancy and lactation

In the medical situation of a patient having Eclampsia, Magnesium Sulphate can be administered to relieve this condition, which may be life threatening to mother and baby.

4.7 Effects on ability to drive and use machines

Not applicable.

4.8 Undesirable effects

Magnesium salts are relatively poorly absorbed following oral administration, but in patients with impaired renal function there may be sufficient accumulation to produce toxic effects.

Excessive administration of magnesium leads to the development of hypermagnesaemia. Symptoms of hypermagnesaemia may include nausea, vomiting, flushing of the skin, thirst, hypotension due to peripheral vasodilatation, drowsiness, confusion, loss of tendon reflexes due to neuromuscular blockade, muscle weakness, respiratory depression, cardiac arrhythmias, coma, and cardiac arrest.

Acute ingestion of Magnesium Sulphate and similar magnesium-containing compounds may also cause gastrointestinal irritation and watery diarrhoea.

4.9 Overdose

Appropriate action should be taken to reduce the blood level of magnesium to avoid hypermagnesaemia. Neuromuscular blockade associated with hypermagnesaemia may be reversed with calcium salts, such as Calcium Gluconate, which should be administered intravenously in a dose equivalent to

2.5 to 5mmol of calcium.

5.    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Serum magnesium levels in the range of 1.5 - 2.5mmol/l cause vasodilatation in the peripheral and coronary circulation, and corresponding increases of 2025% in cardiac output and coronary blood flow. There is little change in heart rate or blood pressure. The Atrium-His interval is slightly prolonged as a result of the electrophysiological actions of magnesium. Any direct inhibition is offset by the reflex response to a drop in peripheral vascular resistance, and the Q-T interval is unchanged, thus the function of the SAN is little altered. Within this concentration range there are no detectable effects on CNS function or neuromuscular transmission.

At a serum magnesium level of 1-3mmol/l platelet disaggregation has been reported; possibly mediated by stimulation of prostacyclin release from vascular endothelium.

5.2 Pharmacokinetic properties

The concentration of magnesium in plasma is normally tightly regulated in the range of 0.75-0.95mmol/l.

Small and clinically irrelevant amounts are excreted in breast milk. The major excretory pathway of magnesium is renal, and both oral and intravenous loads are rapidly eliminated in this way. In renal impairment there may be accumulation of magnesium.

The potential for magnesium toxicity is greater in parenteral administration than with oral dosing.

At plasma concentrations of up to 4mmol/l, the only adverse effect likely to be seen is flushing due to peripheral vasodilatation. At about 4-5mmol/l, concentration-dependant toxicity is heralded by loss of deep-tendon reflexes, then successively by hypotension, bradycardia and ultimately neuromuscular blockade leading to respiratory arrest.

When given intravenously, Magnesium Sulphate has an immediate onset of action, and its duration of activity is about 30mins. The onset of action of intramuscular magnesium sulphate is about one hour, and its duration of action is three to four hours.

5.3 Preclinical safety data

This product has been available for many years and its side effects and clinical profile are well-understood, therefore no further data is provided.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Water for Injections Ph Eur.

Hydrochloric Acid, Dilute Ph Eur Sodium Hydroxide Ph Eur

6.2 Incompatibilities

Not applicable

6.3 Shelf life

2 years

6.4 Special precautions for storage

Protect from light.

Keep in outer carton.

6.5 Nature and contents of container

Neutral Type 1 glass ampoules 20ml, containing a 20% w/v sterile solution for injection of Magnesium Sulphate Ph Eur.

6.6 Instructions for use/handling

Discard any unused solution at the end of the session in the appropriate manner. Do not use the product if the packaging is damaged.

7. MARKETING AUTHORISATION HOLDER

Aurum Pharmaceuticals Ltd

Bampton Road

Harold Hill

Romford

Essex

RM3 8UG

8. MARKETING AUTHORISATION NUMBER

PL 12064 / 0048

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

15 ^th January 1999

10. DATE OF (PARTIAL) REVISION OF TEXT

November 2003