Magnesium Sulphate Injection Bp 50%W/V
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Magnesium Sulphate Injection BP 50%w/v
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Magnesium Sulphate Heptahydrate BP 5g/ 2.5g/ 1g/
10ml 5ml 2ml
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:
Up to 40g MgSO4 (equivalent 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).
b) To prevent further seizures associated with eclampsia:
An initial intravenous (IV) loading dose is followed for 24h by either an IV infusion, or regular intramuscular (IM) injections.
Intramuscular Maintenance Regimen
A loading dose of 4g MgSO4 (approx. 16mmol Mg2+) IV (usually in 20% solution) over 5min (minimum, preferably 10-15 min) is followed immediately by 5g MgSO4 (approx. 20mmol Mg2+) (usually in 50% solution) as a deep IM injection into the upper outer quadrant of each buttock.
Maintenance therapy is a further 5g MgSO4 (approx. 20mmol Mg ) IM every 4h, continued for 24h after the last fit (provided the respiratory rate is >16/min, urine output >25ml/h, and knee jerks are present).
Intravenous Maintenance Regimen
2+
A loading dose of 4g MgSO4 (approx. 16mmol Mg ) IV (or in some cases 5g MgSO4 (approx. 20mmol Mg ) IV), as described above, is followed by an infusion of 1g/h continued for 24h after the last fit.
Recurrent Convulsions: In both the IM and IV regimens, if convulsions recur, a further 2-4g MgSO4 (approx. 16mmol Mg ) (depending on the woman’s weight, 2g MgSO4 (approx. 8mmol Mg2+) if less than 70Kg) is given IV over 5 min.
* The Eclampsia Trial Collaborative Group (Duley L et al) (1995) Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial., The Lancet, Vol. 345, pp. 1455-1463.
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 MgSO4 (approx. 80mmol Mg ) over 48 hours.
4.3. Contra-indications
Hypersensitivity to magnesium and its salts.
Hepatic encephalopathy, hepatic failure or renal failure.
Parenteral magnesium salts should generally be avoided in patients suffering from 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). 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.
For intramuscular use a 25% or 50% solution is used. For intravenous use this solution must be diluted before use. Concentrations of up to 20% are usually employed.
Magnesium sulphate should not be used in hepatic coma if there is risk of renal failure.
Magnesium salts should be used with caution in patients suffering from myasthenia gravis.
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 is associated with the concomitant use of parenteral magnesium salts and nifedipine in pre-eclampsia.
Suxamethonium: parenteral magnesium salts enhance the effects of suxamethonium. 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 and respiratory depression due to neuromuscular blockade, slurred speech, double vision, muscle weakness, bradycardia, 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
Magnesium is an essential constituent of many enzyme systems, particularly those involved in energy generation; the largest stores are in the skeleton.
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 BP Hydrochloric Acid BP Sodium Hydroxide BP
6.2. Incompatibilities
Not applicable
6.3. Shelf Life
3 years
6.4. Special Precautions for Storage
Do not store above 25 oC.
6.5. Nature and Contents of Container
Neutral Type 1 glass ampoules 2, 5 and 10ml, containing a 50% w/v sterile solution for injection of Magnesium Sulphate BP.
6.6 Special precautions for disposal
For intramuscular use a 25% or 50% solution is used. For intravenous use this solution must be diluted before use. Concentrations of up to 20% are usually employed.
Discard any unused solution at the end of the session in the appropriate manner.
7
MARKETING AUTHORISATION HOLDER
Aurum Pharmaceuticals Limited
Bampton Road
Harold Hill
Romford
Essex
RM3 8UG
8 MARKETING AUTHORISATION NUMBER(S)
PL 12064/0013
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
25/06/2009
10 DATE OF REVISION OF THE TEXT
15/05/2008