SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Magnesium Sulfate 50% w/v

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

2+

Magnesium sulfate (heptahydrate) 50% w/v (approximately 2mmol Mg /ml).

3. PHARMACEUTICAL FORM

Solution for injection or infusion.

4. CLINICAL PARTICULARS

4.1. Therapeutic indications

(a)    Treatment of magnesium deficiency in hypomagnesaemia.

(b)    Prevention and control of generalised seizures in patients with severe preeclampsia or eclampsia

4.2. Posology and method of administration

Dosages should be adjusted according to the patient’s needs and responses. Plasma levels should also be monitored during treatment.

(a) Treatment of magnesium deficiency in hypomagnesaemia:

Up to 160mmol Mg by slow intravenous infusion (in glucose 5%) over up to 5 days, may be required to replace the deficit (allowing for urinary losses). Concentrations of no higher than 20%w/v should be given intravenously.

Treatment may require repetition, for example during prolonged intravenous nutrition magnesium deficit can occur, then parenteral doses of magnesium are of the order of 10 to 20mmol Mg²+ daily (often about 12mmol Mg²+ daily).

Dosage for the elderly is similar to that for younger adults. Magnesium Sulfate 50% w/v should not be given to children. Appropriate reductions in dosage should be made for patients with renal impairment.

(b) Prevention and control of seizures associated with severe pre-eclampsia and eclampsia:

An initial intravenous (IV) loading dose of typically 4g (approximately 16mmol Mg²⁺) given slowly over a period of 20 minutes or so, at a strength no higher than 20% w/v, is followed by ideally an IV infusion, or if this is not possible by regular intramuscular (IM) injections as follows:

Intravenous Maintenance Regimen: The loading dose is followed by an intravenous infusion of 1g (approximately 4mm Mg²+) per hour, continued for 24 hours after the last fit.

Intramuscular Maintenance Regimen: The loading dose is followed by 5g (approximately 20mmol Mg ), usually in 50% solution, as deep IM injection into the upper outer quadrant of each buttock. The intramuscular injection is painful.

Maintenance therapy is a further 5g every 4 hours continued for 24 hours after the last fit (provided the respiratory rate is >16 per minute, urine output >25ml per hour and knee jerks are present).

Recurrent convulsions: In both the IV an IM regimens, if convulsions recur, a further 2-4g (approximately 8-16mmol Mg ), depending on the woman’s weight, 2g if less than 70kg, is given IV over 5 minutes.

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 (approximately 80mmol Mg ) over 48 hours.

4.3.    Contraindications

Use of Magnesium Sulfate 50% w/v is contraindicated in patients with known hypersensitivity to magnesium and its salts, hepatic encephalopathy, hepatic failure, renal failure, myasthenia gravis or cardiac disease.

4.4.    Special warnings and precautions of use

Magnesium salts should be administered with caution to patients with impaired renal function; appropriate reductions in dosage should be made. Magnesium salts should be administered with caution to those receiving digitalis glycosides. Parenteral administration of magnesium salts may enhance the effect of neuromuscular blocking agents or of central nervous system depressants.

Magnesium Sulfate 50% w/v should not be used in hepatic coma if there is a risk of renal failure.

4.5. Interactions 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 (Martindale, 30^th Ed).

4.6. Pregnancy and lactation

Magnesium Sulfate 50% w/v can be administered to a patient with eclampsia if the condition is life threatening to mother and baby.

4.7. Effects on ability to drive and use machines

Not applicable.

4.8. Undesirable effects

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

Acute ingestion of magnesium sulfate 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 5 mmol of calcium.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic properties

Serum magnesium levels in the range of 1.5-2.5mmol/l cause vasodilation in the peripheral and coronary circulation and corresponding increases of 20-25% 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 QT 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 the 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 the breast milk. The major excretory pathway 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 vasodilation. At about 4-5mmol/l, concentration dependent toxicity is heralded by loss of drop-tendon reflexes, then successively by hypotension, brachycardia, and ultimately neuromuscular blockade leading to respiratory arrest.

When given intravenously magnesium sulfate has an immediate onset of action; its duration of activity is about 30 minutes. The onset of action of intramuscular magnesium sulfate is about one hour and its duration of action is three to four hours.

5.3.    Pre-clinical safety data

Magnesium sulfate has been used for many years and its adverse reaction and clinical profile are well understood, therefore no further data are provided.

6. PHARMACEUTICAL PARTICULARS 6.1. List of excipients

Bulk Water for Injections

6.2. Incompatibilities

Not applicable.

6.3. Shelf life

3 years.

Special precautions for storage

Do not freeze.

6.5 Nature and contents of container

Magnesium Sulfate 50% w/v is presented in 2ml, 5ml and 10ml type I glass ampoules and in 20ml and 50ml 20mm type I glass vials closed with a bromobutyl rubber stopper with an aluminium tamper-proof flip-top cap.

6.6. Instructions for use/handling

A 25% or 50% solution should be used for intramuscular administration. Magnesium Sulfate 50% w/v must be diluted before intravenous administration. Concentrations of up to 20% are usually used.

Chemical and physical in-use stability has been demonstrated for both 50% and diluted (20% w/v) solutions when stored protected from light in 10ml polypropylene syringes in the refrigerator and at 25°C for 28 days.. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

The solution should not be used if particles are present.

For single use only. Unused solution should be discarded in an appropriate manner.

7 MARKETING AUTHORISATION HOLDER

South Devon Healthcare Torbay PMU Long Road Paignton Devon TQ4 7TW United Kingdom

8. MARKETING AUTHORIZATION NUMBER

PL 13079/0004

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 20/05/2005

DATE OF REVISION OF THE TEXT

18/09/2012