Magnesium Sulphuricum Biotika 20%

SUMMARY OF PRODUCT CHARACTERISTICS 

1.  NAME OF THE MEDICINAL PRODUCT 

                 MAGNESIUM SULFURICUM Biotika 10% 
                 MAGNESIUM SULFURICUM Biotika 20%

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
Active substance: 
                                Magnesium sulphate heptahydrate 1000 mg in 10 ml (10%). 
                                Magnesium sulphate heptahydrate 2000 mg in 10 ml (20%)
For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM 
Solution for injection 
Clear, colorless liquid. 

4. CLINICAL PARTICULARS
4. 1  Therapeutic indications 
Auxiliary treatment of seizure conditions and in tendency to them (tetanus, preeclampsia, eclampsia, tetany, spasmophilic neuropathy), hypomagnesaemia: children with primary congenital hypomagnesemia, adults with malabsorption after persistent diarrhea, chronic alcoholism, long-term parenteral nutrition. Tocolytic treatment.

4.2  Posology and method of administration 
a) Dosage for children: 
Children 10 mg / kg of body weight is administered intramuscularly, in 10% solution for injection, the dose is repeated as necessary.  When hypomagnesemia is present it may be given intravenously even in children. 
b) Dosage for adults: 
Dosage is strictly individual, usually 10-20 ml of 10% or 20% solution for injection in a slow intravenous injection (rate of 1.5 ml / min), intramuscularly or exceptionally subcutaneously  (painful), if necessary, repeatedly.  The doctor is oriented according to patellar reflex. 
 The maximum single dose is 1-4 grams, the daily dose is 1-8 g. 

4.3  Contraindications 
Absolute: hypermagnesemia, overdose symptoms, muscle hypotonia, vigility decrease.

4.4  Special warnings and precautions for use 
 In renal function impairment and in hyperkalaemia, caution is necessary. 

4.5  Interactions with other medicinal products and other forms of interaction
Magnesium ions antagonize the effect of calcium on the myocardium and muscle tone. When muscle relaxants, antibiotics from the group of aminoglycosides, of vancomycin and bacitracin are co-administered the risk of neuromuscular blockade might develop. The preparation reduces the absorption of tetracycline by formation of complexes with Mg 2 +. It potentiates  effects of some antibiotics (streptomycin, neomycin, kanamycin, vancomycin, bacitracin) and central suppressive effects of narcotics and hypnotics.

4.6  Pregnancy and lactation 
 When administered in advanced pregnancy it might cause fetal depression and debility. During intravenous continuous infusion, which lasts longer than 24 hours, the increase of  possibility of neuromuscular and respiratory depression in fetus is present..  Small amount of Mg 2 + is excreted in breast milk. 

4.7  Effects on ability to drive and use machines 
At the therapeutic doses, there is no risk of attention reduction.

4.8  Undesirable effects 
 They occur commonly in overdose or in intoxication with magnesium. There are present in about 5% of the treated patients, older patients are more vulnerable. There are manifested as a muscle weakness to the complete weakening, nausea, peripheral vasodilatation with hyperaemia and hot flushes, drop in blood pressure, impaired heart function to AV -blockade, increased sweating, somnolence, weakening and disappearance of the reflexes, the possibility of depression and paralysis of respiration.  There is the increased risk of hypermagnesemia with effects on respiration, heart rate and muscle activity in renal impairment. 

4.9.  Overdose 
Correlation between levels of magnesium in plasma and toxic symptoms: 
 0.8 to 1.5 mmol / l, normal level 
 2.0 to 3.5 mmol / l pre-eclampsia, eclampsia, convulsions 
 3.5 to 5.0 mmol / l of deep tendon reflexes weakening, hypotension, CNS depression 
 6.0 to 7.5 mmol / l, respiratory paralysis 
 more than 7.5 mmol / l the effect on cardiac impulse 
 more than 12.5 mmol / l cardiac arrest 
 Manifestations of overdose migh be caused by hypermagnesemia above 2.5 mmol / l already.  Symptoms are: nausea, respiratory depression, muscle weakness, mental dullness and confusion, peripheral vasodilation, hypotension, cardiac arrhythmias and cardiac arrest. 
 ECG signs are: extension of the AV conduction, QRS enlargement and an increase in the T wave.  Manifestations are evident at concentrations above 6 mmol / l  and at levels above 8 mmol / l constitute a serious threat to life. 
 Treatment: 
 Some cardiovascular and neurological effects of magnesium may be antagonized by calcium ions.  When kidney function preserved the adequate diuresis by isoosmolar solutions is suitable.  In massive overdose or in renal failure there is necessary to perform hemodialysis or peritoneal dialysis. 

5. PHARMACOLOGICAL PROPERTIES 
5.1  Pharmacodynamic properties 
Pharmacotherapeutic group: Ionic product, muscle relaxants
ATC code: A12CC02
Mechanism of effect 
Magnesium is a cofactor of enzyme systems that operate in neurochemical transmission and muscular excitability.  Magnesium ions inhibit the release of acetylcholine from presynaptic nerve endings of cholinergic nerve fibers and in the neuromuscular plate of skeletal muscle. Magnesium ions have a significant modulating effect on the contraction of smooth muscle and the myocardium by reducing the gradient of calcium. 

5.2  Pharmacokinetic properties 
After intramuscular administration of magnesium sulphate therapeutic levels are reached in about 60 minutes and lasts for 3-4 hours.  After intravenous administration the onset of effect is immediate after application and lasts 30 minutes.  Normal plasma concentrations range from 0.8 to 1.5 mmol / l.  Anticonvulsant levels after intravenous injection are in the range of 1.2 to 3.6 mmol / l.  About 33% of magnesium in plasma is bound to plasma proteins. 
In hypermagnesemia  97% of magnesium is excreted by kidneys.  Maximum clearance of magnesium is directly proportional to creatinine clearance, and accumulation of toxic levels of magnesium in patients with renal insufficiency might easily occur. Renal excretion is increased with diuretics.  About 1% of magnesium is excreted in faeces.  Small quantities are excreted in breast milk and in saliva. 

5.3  Preclinical safety data
Preclinical data that are based on conventional pharmacology studies of safety, repeated dose toxicity, genotoxicity, carcinogenicity and reproductive toxicity studies reveal no special hazard for humans.

6. PHARMACEUTICAL PARTICULARS 
6.1  List of excipients 
Water for injection 

6.2  Incompatibilities 
In the infusion preparation must not be co-administered with protein hydrolysates.

6.3  Shelf life 
5 years

6.4  Special precautions for storage 
Store at temperatures between +10 ° C to +25 ° C. 

6.5  Nature and contents of container 
Clear glass with a label, insert a PVC, box. 
 Package Size: 5 ampoules of 10 ml 

6.6 Special precautions for disposal
No special requirements.

7. MARKETING AUTHORISATION HOLDER 
BB Pharma Pod Višňovkou 1662/21, 140 00 Prague 4, Czech Republic
8. MARKETING AUTHORISATION NUMBER(S) 
39 / 805 / 92-S / C (10%) 
39/ 806/ 92-S/C (20%) 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 December 18th, 1992
10. DATE OF REVISION OF THE TEXT
November 16th, 2005