Magnesium sulfate Kalceks 50%

/ A.L. Medi-Market LTD,

Administered by the intravenous (preferred method) or intramuscular (painful, avoid if possible) routes.
Dosage should be tailored according to the individual’s needs and responses and should be reduced in renal impairment. Plasma magnesium concentrations should be measured to determine the rate and duration of infusion and should be monitored throughout therapy.
1 g magnesium sulfate heptahydrate = 98.6 mg or 8.1 mEq or 4 mmol Mg2+.
Treatment of magnesium deficiency in hypomagnesaemia
Adults: Intravenous Route: Up to 80 ml Magnesium sulfate (corresponding to 160 mmol ≈ 4 g Mg2+) diluted should be administered by slow intravenous infusion over a period of up to five days and titrated to clinical need. The usual regimen is 16-24 ml Magnesium sulfate (corresponding to 32-48 mmol ≈ 0.8-1.2 g Mg2+) diluted in the first 24 hours followed by 8-12 ml Magnesium sulfate (corresponding to 16-24 mmol ≈ 0.4- 0.6 g Mg2+) diluted per day for 3 or 4 days.
Intramuscular Route:
2-4 ml Magnesium sulfate (corresponding to 4-8 mmol ≈ 0.1- 0.2 g Mg2+) undiluted or 4-8 ml of Magnesium sulfate diluted to 25% solution can be given intramuscularly every 6 hours for 24 hours (a total of 4 doses).
Children and adolescents:
Neonate: 0.2 ml/kg Magnesium sulfate (corresponding to 0.4 mmol/kg ≈ 0.01 g/kg Mg2+) diluted to 20% solution (i.e. 0.5 ml/kg of a 20% solution) every 6-12 hours as required, to be given by intravenous injection over at least
10 minutes.
Child 1 month – 11 years: 0.1 ml/kg Magnesium sulfate (corresponding to 0.2 mmol/kg ≈ 0.005 g/kg Mg2+) diluted to 20% solution (i.e. 0.25 ml/kg of a 20% solution) every 12 hours as required, to be given by intravenous injection over at least 10 minutes.
Adolescent 12-17 years: 2 ml Magnesium sulfate (corresponding to 4 mmol ≈ 0.1 g Mg2+) diluted to 20% solution (i.e. 5 ml of a 20% solution) every 12 hours as required, to be given by intravenous injection over at least 10 minutes.
Prevention of hypomagnesaemia in patients receiving total parenteral nutrition
Adults: 5-10 ml Magnesium sulfate (corresponding to 10-20 mmol ≈ 0.25-0.5 g Mg2+) diluted daily, usual dose 6 ml Magnesium sulfate (corresponding to 12 mmol ≈ 0.3 g Mg2+) diluted daily, by intravenous infusion or intramuscular injection.
Neonates and infants (up to 12 months): 0.1 ml/kg Magnesium sulfate (corresponding to 0.2 mmol/kg ≈ 0.005 g/kg Mg2+) diluted daily by intravenous infusion.
Children (1-13 years) and adolescents (14-18 years): 0.05 ml/kg Magnesium sulfate (corresponding to 0.1 mmol/kg ≈ 0.0025 g/kg Mg2+) diluted daily by intravenous infusion.
Control and prevention of recurrent seizures in severe pre-eclampsia and eclampsia
Adult women: Loading dose: An initial IV loading dose of approximately 8-10 ml Magnesium sulfate (corresponding to 16-20 mmol ≈ 0.4-0.5 g Mg2+) diluted to an appropriate volume is administered over 5-15 minutes, followed either by maintenance intravenous infusion or regular IM injections for 24 hours, as follows:
IV Maintenance Regimen
The IV loading dose (above) is followed by an infusion of approximately 2 ml Magnesium sulfate (corresponding to 4 mmol ≈ 0.1 g Mg2+) diluted per hour for at least 24 hours after the last fit.
IM Maintenance Regimen
The IV loading dose (above) is immediately followed by deep IM injection of 10 ml Magnesium sulfate (corresponding to 20 mmol ≈ 0.5 g Mg2+) undiluted.
Maintenance therapy is a further 10 ml Magnesium sulfate (corresponding to 20 mmol ≈ 0.5 g Mg2+) undiluted IM every four hours, continued for 24 hours after the last fit (provided respiratory rate is > 16/min, urine output > 25ml/min and knee jerks are present).
Recurrent convulsions: In both IV and IM regimens, a further 4-8 ml Magnesium sulfate (corresponding to 8-16 mmol ≈ 0.2-0.4 g Mg2+) diluted depending on body weight [if less than 70 kg 4 ml Magnesium sulfate (corresponding to 8 mmol ≈ 0.2 g Mg2+) diluted] are given IV over a period of 5 minutes.
Method of administration
Intravenous infusion: For the intravenous route, the 50% solution requires dilution to a concentration of not more than 20% (≤ 200 mg/ml magnesium sulfate heptahydrate) – with a suitable diluent, such as 5% glucose or 0.9% sodium chloride solution. Infuse via a volumetric infusion device at a rate appropriate to the indication (see posology above).
Intravenous injection: Give by slow IV injection at a rate appropriate to the indication.
Intravenous use in children: Rate of administration should not exceed 0.02 ml/kg/min of appropriately diluted Magnesium sulfate (corresponding to 0.04 mmol/kg/min ≈ 0.001 g/kg/min Mg2+).
Deep Intramuscular injection (adults only): For the intramuscular route, the 50% solution should be used undiluted or diluted to 25%. If the total dose to be administered exceeds 5 ml, the injection volume should be divided between more than one deep muscular injection site.

* The treatment of magnesium deficiency in hypomagnesaemia.
* The prevention and treatment of hypomagnesaemia in patients receiving total parenteral nutrition.
* The control and prevention of seizures in severe pre-eclampsia.
* The control and prevention of recurrent seizures in eclampsia.

* Hypersensitivity to magnesium and its salts or to any of the excipients
* Hepatic encephalopathy, hepatic failure.
* Severe renal impairment (glomerular filtration rate under 25 ml/h), renal failure, anuria.
* Parenteral administration of the medicinal product is contraindicated in patients with heart block (class I-III) or myocardial damage and myasthenia gravis.

* Magnesium salts should be administered with caution to patients with impaired renal function and appropriate dosage reduction should be made.
* Magnesium sulfate should not be used in hepatic coma if there is a risk of renal failure.
* Magnesium salts should be administered with caution to patients with impaired renal function and appropriate dosage reduction should be made.
* Magnesium sulfate should not be used in hepatic coma if there is a risk of renal failure.
* Serum calcium levels should be routinely monitored in patients receiving magnesium sulfate.
* The serum magnesium level should be monitored during the treatment.
Monitoring of the absence of respiratory depression: the breath rate should not be under 16 breaths/min.
* The excretion of urine should not be under 25 ml/h, as it could lead to hypermagnesaemia.
* The presence of the patellar reflex should be checked.
* The medicine should be administered with caution if flushing and sweating occurs.
* An antidote of injectable calcium gluconate solution should be immediately available.
* For the intravenous use in children the rate of administration should not exceed 0.02 ml/kg/min of appropriately diluted Magnesium sulfate (corresponding to 0.04 mmol/kg/min = 0.001 g/kg/min Mg2+).
The 50% w/v solution MUST be diluted before use for IV administration; concentrations up to 20% are usually employed.
* For the intramuscular route, use good clinical practice for intramuscular injections. The 50% solution should be used undiluted or diluted to 25%. The medicine should not be administered into muscles which are emaciated or atrophied.
* For intramuscular administration, dorsogluteal muscle and sciatic nerve should be avoided.
* If the total dose to be administered exceeds 5 ml, the injection volume should be divided between more than one deep muscular injection site.
* Use caution in older or thin patients who may only tolerate up to 2 ml in a single injection. Do not use an injection site that has evidence of infection or injury. If repeating an intramuscular dose, rotate injection sites to avoid injury or discomfort to the muscles.

The frequency of undesirable effects is not known (cannot be estimated from the available data).
See prescribing information for full details.

Muscle relaxants
The action of non-depolarizing muscle relaxants is potentiated and prolonged by parenteral magnesium salts and magnesium sulfate enhances non-depolarizing muscle relaxant vecuronium action at adult muscle type nicotinic acetylcholine receptor in vitro.
Nifedipine
Profound hypotension has been reported.
Calcium channel blockers or diuretics
There is a risk of cardiopulmonary events when intravenous magnesium sulfate is used concomitantly with calcium channel blockers or diuretics (such as thiazides and furosemide).
Calcium salts
Calcium salts may reduce the efficacy of magnesium. Several magnesium activated enzymes are inhibited by calcium.
Digitalis glycosides
Magnesium salts should also be administered with caution to those patients receiving digitalis glycosides. Magnesium has been shown to block the transient inward current carried by calcium, which digitalis glucosides generate.
Neuromuscular blocking agents
Parenteral administration of magnesium salts may enhance the effects of neuromuscular blocking agents. The neuromuscular blocking effects of parenteral magnesium and aminoglycoside antibacterial agents may be additive.
CNS depressants
When barbiturates, narcotics or other hypnotics (or systemic anesthetics) are to be given in conjunction with magnesium, their dosage should be adjusted with caution because of additive depressant effects of magnesium and the risk of respiratory depression.
Drug transporters
Pretreatment with magnesium has been reported in the rat to attenuate cisplatin (CDDP)-induced nephrotoxicity (CIN). Magnesium co-administration reduced platina accumulation by regulating the expression of the renal transporters, rOct2 and rMate1 and, thereby, attenuated CIN.

Pregnancy: As eclampsia may be life-threatening to mother and baby, magnesium sulfate may be administered in this condition. Sufficient amount of magnesium may cross the placenta in mothers treated with high doses e.g. in pre-eclampsia, causing hypotonia and respiratory depression in newborns. When used in pregnant women, fetal heart rate should be monitored and use within 2 hours of delivery should be avoided.
Magnesium sulfate can cause skeletal adverse effects when administered continuously for more than 5 to 7 days to pregnant women. There are retrospective epidemiological studies and case reports documenting fetal adverse effects including hypocalcemia, skeletal demineralization, osteopenia and other skeletal adverse effects with maternal administration of magnesium sulfate for more than 5 to 7 days. The clinical significance of the observed effects is unknown.
If prolonged or repeated exposure to magnesium sulfate occurs during pregnancy monitoring of neonates for abnormal calcium or magnesium levels and skeletal adverse effects should be considered. Serum magnesium levels in preterm infants are higher than adult levels.
Lactation: Magnesium concentration of mature human milk is 31 mg/l. Based on a mean milk transfer of 0.8 l/day and a concentration of magnesium in mature breast milk of 31 mg/l, a secretion of 25 mg/day of magnesium in breast milk is estimated during the first six months of lactation.
Safety during breast-feeding has not been established.
Therefore, it is not advisable to administer magnesium sulfate during breast-feeding unless considered essential.

Symptoms
Intravenous magnesium infusions can result in hypermagnesaemia even in the presence of normal kidney function. Clinical signs of overdose will be those of hypermagnesaemia.
Patients with renal failure and metabolic derangements develop toxicity at lower doses.
Disappearance of the deep tendon reflex is a useful clinical sign to detect the onset of magnesium intoxication. Magnesium intoxication is manifested by a sharp drop in blood pressure and respiratory paralysis.
Treatment
In symptomatic hypermagnesaemia, administration of calcium, usually at a dose of 100 to 200 mg intravenously over 5 to 10 min, antagonizes the toxic effects of magnesium.
In patients with severe renal dysfunction, peritoneal dialysis or haemodialysis will rapidly and effectively lower serum magnesium levels.