Magnesium sulfate acts as an osmotically active salt and is used orally as a laxative. It also acts on the smooth muscles of the bronchi & blood vessels and the myocardium, hence, it is used in the treatment of severe asthma, eclampsia, and preeclampsia in pregnant women, and in the treatment of torsade de pointes.

Magnesium sulfate Uses:

• Oral:

  • It is indicated as a laxative for the relief of occasional constipation (OTC labeling)

• Parenteral:

  • To treat and prevent hypomagnesemia
  • To treat and prevent seizures in severe preeclampsia or eclampsia, pediatric acute nephritis
  • For the treatment of cardiac arrhythmias (VT/VF) due to hypomagnesemia

• Topical:

  • It can be used as a soaking aid for minor cuts and bruises (OTC labeling)

• Off Label Use of Magnesium Sulfate in Adults:

  • Asthma especially in acute exacerbations or acute severe asthma
  • Arrhythmias: Torsades de pointes:
    • Polymorphic VT (with a pulse) associated with QT prolongation (torsades de pointes)
    • VF/pulseless VT associated with torsades de pointes

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Magnesium sulfate Dose in Adults:

• Dose represented as magnesium sulfate unless stated otherwise.

Note:

• Most of the magnesium is intracellular, serum magnesium levels are a poor reflection of repletion status.
• There may be transiently normal serum levels of magnesium, usually for a few hours after a dose is given, therefore, the aim should be for consistently high normal serum concentrations in patients with normal renal function for most efficient repletion.

Note:

• 1 g of magnesium sulfate has 98.6 mg elemental magnesium which is equal to 8.12 mEq elemental magnesium and that is equal to magnesium 4.06 mmol

Magnesium sulfate Dose in patients with an acute severe exacerbation of asthma (off-label):

• IV:
  • 2 g: stat dose: over 20 minutes
  • Recommended as adjunctive therapy in life-threatening acute severe asthma and for exacerbations that remain severe after 1 hour of intensive conventional therapy.

Magnesium sulfate Dose for Constipation (occasional):

• Oral:
  • 2 - 4 teaspoons of granules dissolved in 8 ounces of water
  • can be repeated in 6 hours.
  • Not to exceed 2 doses/day.

Magnesium sulfate Dose in Eclampsia and severe preeclampsia:

Note:

• An optimal regimen has not been identified.
• Dose adjustment required to avoid maternal toxicity. Closely monitor the renal function, respiration, and tendon patellar reflexes.
• According to Product labeling: The maximum dose of 40 g/24 hours; This may be variable by regimen.
• According to the recommendation of some sources, monitoring of both plasma magnesium for therapeutic concentrations and clinical assessment of magnesium toxicity.

 

• IV: Initial:
  • Loading dose: 4 - 6 gm over 20 - 30 minutes
  • Followed by 1 -2 gm/hour continuous infusion for at least 24 hours post-delivery.
• IM: Initial:
  • Loading dose: 10 gm, 5 g IM in each buttock
  • Then 5 g every 4 hours.

Note:

•  If unable to get venous access, IM route should be used

 

• Manufacturer's labeling:

  • IV, IM: An initial total dose of 10 to 14 g as follows:
    • Loading Dose: 4 gm intravenous infusion with simultaneous intramuscular injections of 4 - 5 gm in each buttock.
    • Maintenance dose: After the initial dose, we can administer 1 - 2 gm/hour continuous infusion or intramuscular doses of 4 - 5 gm into alternate buttocks every 4 hours.

Magnesium sulfate Dose for Hypomagnesemia:

Note:

• Treat according to severity & clinical status.
• In asymptomatic patients and one who can take orally, oral replacement therapy is better than intravenous administration.

 

• Mild deficiency:

  • IM:
    • 1 gm QID: 4 doses, or according to serum magnesium concentrations

• Mild to moderate (serum concentration 1 to 1.5 mg/dL):

  • IV:
    • 1 - 4 gm: up to 0.125 g/kg
    • If asymptomatic, administer at ≤1 gm/hour
    • Not to exceed 12 gm over 12 hours.
  • Note:
    •  Replenishment may occur over seven days, additional supplementation can be required after the initial dose

• Severe deficiency:

  • IM:
    • Up to 250 mg/kg within a 4-hours.
  • IV: Severe (<1 mg/dL):
    • 4 - 8 g: up to 0.1875 g/kg
    • if asymptomatic administer at ≤1 gm/hour
    • If symptomatic, it can be administered ≤4 gm over 4-5 minutes

• Obesity:

  • Weight >130% of ideal body weight (IBW) or body mass index (BMI) ≥30 kg/m²:

    • For maximum per kg dose for replacement, some clinicians have suggested using
      • AdjBW (men) = ([wt (kg) -IBW (kg)] x 0.3) + IBW (ideal body weight)
      • AdjBW (women) = ([wt (kg) -IBW (kg)] x 0.25) + IBW

Magnesium sulfate dose for the prevention of hypomagnesemia (parenteral nutrition supplementation):

• IV: 8- 20 mEq elemental magnesium daily

Soaking aid:

• Topical:
  • 2 cup fulls of granules magnesium dissolved per gallon of warm water
  • Can be applied as wet dressing, with a towel soaked with the solution.

Magnesium sulfate Dose in patients with Torsades de pointes (off-label use):

• Polymorphic VT (with a pulse) associated with QT prolongation (torsades de pointes):

  • IV:
    • 1- 2 gm: diluted in 50 - 100 mL D5W, administered over 15 minutes (range: 5 to 60 minutes)
    • Can be followed with continuous IV infusion of 0.5 to 1 gm/hour.

• VF/pulseless VT associated with torsades de pointes:

  • IV/IO:
    • 1 - 2 m:  diluted in 10 mL D5W, administered as a bolus dose

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Magnesium sulfate Dose in Children:

Note:

• 1,000 mg of magnesium sulfate  is equal to:
  • 98.7 mg elemental magnesium
  • 8.12 mEq elemental magnesium
  • 4.06 mmol elemental magnesium.
• Most of the magnesium is intracellular, serum magnesium is a poor reflection of repletion status
• After magnesium sulfate dose is given, serum magnesium levels can be transiently normal, therefore, aim for consistently high normal serum concentrations in patients with normal renal function for better and most efficient response.

Magnesium sulfate dose in Hypomagnesemia:

• Infants, Children, and Adolescents:

• Note: Dose according to the clinical condition and serum magnesium concentration.

  • Dose expressed as magnesium sulfate:

    • IV, IO:
      • 25- 50 mg /kg/dose QID for 2-3 doses, then recheck serum concentration
      • Maximum dose: 2,000 mg per dose

  • Dose expressed as elemental magnesium:

    • IV:
      • 2.5 - 5 mg/kg/dose QID for 2- 3 doses

Magnesium sulfate dose in occasional Constipation:

• Oral:

Note:

• OTC use: Recommended treatment duration is 7 days, should not exceed unless directed by a health care provider.

 

• Children 6 to <12 years:

  • 1 -2 level teaspoons of granules mixed with 8 ounces of water
  • can be repeated in 4 - 6 hours.
  • Not to exceed 2 doses/day.

• Children ≥12 years and Adolescents:

  • 2 - 4 teaspoons of granules mixed with 8 ounces of water
  • can be repeated in 4 - 6 hours.
  • Not to exceed 2 doses/day.

Maintenance dose of Magnesium sulfate in parenteral nutrition:

• Dose expressed as elemental magnesium:

  • IV:

    • Infants and Children <50 kg:

      • 3 - 0.5 mEq/kg/day.

    • Children >50 kg and Adolescents:

      • 10 -30 mEq/day.

Magnesium sulfate Dose in children with Torsade de pointes or VF/pulseless VT associated with torsade de pointes:

• Dose expressed as magnesium sulfate:

  • IV:

    • Infants, Children, and Adolescents:

      • IV, IO: 25 - 50 mg/kg/dose
      • Maximum dose: 2,000 mg /dose

Magnesium sulfate dose in Acute refractory status asthmaticus: Limited data available:

• Dose expressed as magnesium sulfate.

  • IV:

    • Infants, Children, and Adolescents:

      • 25 - 75 mg/kg/dose as a single dose
      • Maximum dose: 2,000 mg/dose
      • Recommended as adjunctive therapy in life-threatening acute severe asthma and in those whose exacerbations remain in the severe after 1 hour of intensive conventional therapy.

  • Oral inhalation: Nebulization (prepared from injectable formulation); given with a nebulised beta2-agonist (eg, albuterol):

    • Mild to moderate asthma: Single dose:

      • Children ≥5 years and Adolescents:
        • 5mL isotonic magnesium sulfate solution mixed with albuterol 2.5 mg (0.5 mL).
        • Magnesium was supplied as a 6.3% solution of magnesium heptahydrate, which is equivalent to anhydrous magnesium sulfate 3.18%.
        • Nebulise with 8 - 10 L/min of oxygen.
        • it has an additive effect on albuterol response.

    • Moderate to severe asthma: Three-dose series:

      • Children ≥2 years and Adolescents ≤16 years:
        • 151 mg isotonic magnesium sulfate mixed with albuterol and ipratropium to be administered every 20 minutes for 3 doses. It should be given in patients with acute severe asthma with no response to standard inhalation treatment.

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Magnesium sulfate Pregnancy Category: D

• Magnesium crosses over the placenta; the serum concentrations of magnesium in the mother and fetus are similar.
• If the maternal doses are not met, there may be fetal hypercalcemia. Hypocalcemia in fetus can cause bone abnormalities and fractures in neonates.
• It is used to prevent and treat seizures caused by severe preeclampsia, eclampsia, or eclampsia.
• Preterm delivery of magnesium sulfate can be done to protect the fetus and decrease the risk of cerebral paralysis.
• Treatment may also be beneficial if the baby is due before 32 weeks.
• Magnesium Sulfate can still be used for women at high risk of giving birth within 48 hours. However, it is not recommended. 
• Tocolytics can be used to prolong pregnancy for 48 hours to allow for the antenatal administration corticosteroids.
• Magnesium Sulfate can also be used with other tocolytics to protect the brain. However, it is more likely that there will be maternal complications.
• Pregnant women who have received magnesium with cardiac or respiratory arrest should be aware of the possibility of magnesium toxicity.
• The same medications are used to treat cardiac arrest in pregnancy as for non-pregnant women.
• ACLS guidelines should be followed when giving indications and doses.
• Because of concerns about fetal teratogenicity, it is important to not withhold appropriate medications.

Magnesium sulfate use during breastfeeding:

• Breast milk contains magnesium.
• Only 24 hours after treatment ends, breast milk magnesium concentrations increase.
•  Useful for intrapartum management in eclampsia.
• Magnesium is usually found in breast milk.
• During the first year of breastfeeding, concentrations are constant and unaffected by diet under normal conditions.
• Magnesium requirements for lactating and non-lactating women are identical
• Manufacturers recommend caution when using magnesium sulfate in breastfeeding females.

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Magnesium sulfate dose in Kidney Disease:

• Eclampsia and preeclampsia:

  • Severe renal impairment:

    • Initial:
    • Loading dose: 4 - 6 gm over 20 - 30 minutes,
    • Maintenance dose: 1 gm/hour continuous infusion for at least 24 hours after delivery.
    • As per the manufacturer, do not exceed 20 gm during a 48-hour period.
    • Note:
      • Magnesium levels should be frequently monitored to avoid adverse effects in patients with renal impairment.

• Hypomagnesemia:

  • Renal dysfunction:

    • Reduce dose by 50%
    • Use cautiously
    • Close Monitoring for hypermagnesemia.

Dose in Liver disease:

• No dose adjustment required.

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• Adverse effects on neuromuscular function may occur at lower concentrations in patients with neuromuscular disease (eg, myasthenia gravis).

Side effects of Magnesium sulfate:

• Cardiovascular:

  • Flushing (IV; dose related)
  • Hypotension (IV; rate related)
  • Vasodilation (IV; rate related)

• Endocrine & metabolic:

  • Hypermagnesemia

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Contraindications to Magnesium sulfate:

• Hypersensitivity to any ingredient of the formulation
• Heart block
• Myocardial damage
• Intravenous use for preeclampsia/eclampsia during the 2 hours prior to delivery (seeNotification(

Notice:

• According to manufacturers' labeling for some intravenous formulations, use in preeclampsia/eclampsia during the 2 hours before delivery by cesarean section is contraindicated because of interaction with neuromuscular-blocking agents intraoperatively
• Because of the increased risk of seizures, it is not recommended that magnesium sulfate be stopped before cesarean delivery. It should be continued during and before the delivery
• Some IV formulations are not recommended for use in the treatment of heart block according to manufacturer labeling
• Magnesium therapy is recommended for serious conditions that require magnesium therapy.

Warnings and precautions

• Neuromuscular disease

  • Patients with myasthenia gravis or other neuromuscular disorders should be treated with caution.

• Renal impairment

  • Patients with impaired renal function should be cautious
  • Magnesium intoxication can occur when there is too much magnesium.

Magnesium sulfate: Drug Interaction

Risk Factor C (Monitor therapy)
Calcium Channel Blockers	May enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers.
CNS Depressants	Magnesium Sulfate may enhance the CNS depressant effect of CNS Depressants.
Neuromuscular-Blocking Agents	Magnesium Salts may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents.
Ritodrine	May enhance the adverse/toxic effect of Magnesium Sulfate.
Risk Factor D (Consider therapy modification)
Alfacalcidol	May increase the serum concentration of Magnesium Salts.
Alpha-Lipoic Acid	Magnesium Salts may decrease the absorption of Alpha-Lipoic Acid. AlphaLipoic Acid may decrease the absorption of Magnesium Salts.
Bictegravir	Polyvalent Cation Containing Products may decrease the serum concentration of Bictegravir. Management: Administer bictegravir under fasting conditions at least 2 hours before or 6 hours after polyvalent cation containing products. Coadministration of bictegravir with or 2 hours after most polyvalent cation products is not recommended.
Bisphosphonate Derivatives	Polyvalent Cation Containing Products may decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of oral medications containing polyvalent cations within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Exceptions: Pamidronate; Zoledronic Acid.
Calcitriol (Systemic)	May increase the serum concentration of Magnesium Salts. Management: Consider using a non-magnesium-containing antacid or phosphate-binding product in patients also receiving calcitriol. If magnesium-containing products must be used with calcitriol, serum magnesium concentrations should be monitored closely.
Deferiprone	Polyvalent Cation Containing Products may decrease the serum concentration of Deferiprone. Management: Separate administration of deferiprone and oral medications or supplements that contain polyvalent cations by at least 4 hours.
Dolutegravir	Magnesium Salts may decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral magnesium salts. Administer the dolutegravir/rilpivirine combination product at least 4 hours before or 6 hours after oral magnesium salts.
Doxercalciferol	May enhance the hypermagnesemic effect of Magnesium Salts. Management: Consider using a non-magnesium-containing antacid or phosphate-binding product in patients also receiving doxercalciferol. If magnesium-containing products must be used with doxercalciferol, serum magnesium concentrations should be monitored closely.
Eltrombopag	Polyvalent Cation Containing Products may decrease the serum concentration of Eltrombopag. Management: Administer eltrombopag at least 2 hours before or 4 hours after oral administration of any polyvalent cation containing product.
Gabapentin	Magnesium Salts may enhance the CNS depressant effect of Gabapentin. Specifically, high dose intravenous/epidural magnesium sulfate may enhance the CNS depressant effects of gabapentin. Magnesium Salts may decrease the serum concentration of Gabapentin. Management: Administer gabapentin at least 2 hours after use of a magnesiumcontaining antacid. Monitor patients closely for evidence of reduced response to gabapentin therapy. Monitor for CNS depression if high dose IV/epidural magnesium sulfate is used.
Levothyroxine	Magnesium Salts may decrease the serum concentration of Levothyroxine. Management: Separate administration of oral levothyroxine and oral magnesium salts by at least 4 hours.
Multivitamins/Fluoride (with ADE)	Magnesium Salts may decrease the serum concentration of Multivitamins/Fluoride (with ADE). Specifically, magnesium salts may decrease fluoride absorption. Management: To avoid this potential interaction separate the administration of magnesium salts from administration of a fluoride-containing product by at least 1 hour.
Mycophenolate	Magnesium Salts may decrease the serum concentration of Mycophenolate. Management: Separate doses of mycophenolate and oral magnesium salts. Monitor for reduced effects of mycophenolate if taken concomitant with oral magnesium salts.
PenicillAMINE	Polyvalent Cation Containing Products may decrease the serum concentration of PenicillAMINE. Management: Separate the administration of penicillamine and oral polyvalent cation containing products by at least 1 hour.
Phosphate Supplements	Magnesium Salts may decrease the serum concentration of Phosphate Supplements. Management: Administer oral phosphate supplements as far apart from the administration of an oral magnesium salt as possible to minimize the significance of this interaction. Exceptions: Sodium Glycerophosphate Pentahydrate.
Quinolones	Magnesium Salts may decrease the serum concentration of Quinolones. Management: Administer oral quinolones several hours before (4 h for moxi/pe/spar-, 2 h for others) or after (8 h for moxi-, 6 h for cipro/dela-, 4 h for lome/pe-, 3 h for gemi-, and 2 h for levo-, nor-, or ofloxacin or nalidixic acid) oral magnesium salts. Exceptions: LevoFLOXacin (Oral Inhalation).
Tetracyclines	Magnesium Salts may decrease the absorption of Tetracyclines. Only applicable to oral preparations of each agent. Exceptions: Eravacycline.
Trientine	Polyvalent Cation Containing Products may decrease the serum concentration of Trientine. Management: Avoid concomitant administration of trientine and oral products that contain polyvalent cations. If oral iron supplements are required, separate the administration by 2 hours. If other oral polyvalent cations are needed, separate administration by 1 hour.
Risk Factor X (Avoid combination)
Baloxavir Marboxil	Polyvalent Cation Containing Products may decrease the serum concentration of Baloxavir Marboxil.
Calcium Polystyrene Sulfonate	Laxatives (Magnesium Containing) may enhance the adverse/toxic effect of Calcium Polystyrene Sulfonate. More specifically, concomitant use of calcium polystyrene sulfonate with magnesium-containing laxatives may result in metabolic alkalosis or with sorbitol may result in intestinal necrosis. Management: Avoid concomitant use of calcium polystyrene sulfonate (rectal or oral) and magnesium-containing laxatives.
Raltegravir	Magnesium Salts may decrease the serum concentration of Raltegravir. Management: Avoid the use of oral / enteral magnesium salts with raltegravir. No dose separation schedule has been established that adequately reduces the magnitude of interaction.
Sodium Polystyrene Sulfonate	Laxatives (Magnesium Containing) may enhance the adverse/toxic effect of Sodium Polystyrene Sulfonate. More specifically, concomitant use of sodium polystyrene sulfonate with magnesium-containing laxatives may result in metabolic alkalosis or with sorbitol may result in intestinal necrosis. Management: Avoid concomitant use of sodium polystyrene sulfonate (rectal or oral) and magnesium-containing laxatives.

 

Monitoring parameters:

• IV: Rapid administration:

  • ECG monitoring
  • Vital signs
  • Deep tendon reflexes
  • Calcium and potassium concentration, with prolonged use and in patients with renal dysfunction.
  • Renal function

• Obstetrics:

  • Patient status including vital signs
  • Oxygen saturation
  • Respiration
  • Deep tendon reflexes
  • Level of consciousness
  • Fetal heart rate
  • Maternal uterine activity
  • Renal function.
  • In patients with renal dysfunction, monitor magnesium concentrations every 4 hours (every 2 hours if serum magnesium is >8 mEq/L ).

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How to administer Magnesium sulfate?

• Injection: May be administered Intramuscular, intraosseous (IO), or intravenous
  • IM:
    • Must be diluted prior to administration for children (Adults: 25% or 50% concentration; Children: ≤20% diluted solution)

  • Eclampsia and preeclampsia:

    • can be mix with  2% lidocaine to decrease injection pain.
  • IV, IO:
    • Must be diluted to a ≤20% solution for intravenous infusion
    • It can be given as an IV push, or as a continuous intravenous infusion, or intraosseous (IO).
    • For IV push, diluted magnesium should not be given faster than 150 mg/minute
    • It can be administered as an IV or IO bolus in patients with persistent pulseless VT or VF with known hypomagnesemia or with QT prolongation (torsades de pointes).
    • Administer intravenous (IV) over 15 minutes (range: 5-60 mins) for polymorphic VT (with a pulse) associated with QT prolongation (torsades de pointes).
    • Avoid rapid administration in patients who are not in a cardiac arrest. Rapid administration may cause hypotension and asystole.
    • In acute severe asthma, may administer a single dose over 20 minutes to 60 minutes.

  • Maximal rate of infusion (routine administration for hypomagnesemia prevention or treatment):

    • Up to 50% of an intravenous dose may be excreted in the urine, therefore, slower administration improves retention: Maximum rate: 1 gm/hour in asymptomatic hypomagnesemia.
    • For doses <6 g, infuse over 8 - 12 hours  in an asymptomatic patient
    • For larger doses infuse over 24 hours in an asymptomatic patient.
    • More aggressive therapy required in severely symptomatic patients or with conditions such as preeclampsia or eclampsia (≤4 g over 4 to 5 minutes) may be given. close monitoring recommended.
• Oral:
  • For laxative purposes, dissolve the dose in 8 ounces of water.
  • To improve the taste, lemon juice may be added to the solution.
• Topical:
  • Dissolve granules to prepare a solution for use as a soaking aid or as a compress.
  • Use a towel to make a compress to apply as a wet dressing.

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Mechanism of action of Magnesium sulfate:

• Oral use causes osmotic fluid retention, which dilates the colon and increases peristaltic activity.
• It can be administered orally and acts on the motor nerve endings and myocardium.
  • Magnesium reduces acetylcholine at motor nerve terminals
  • Myocardium: Slowing down the rate of S-A node impulse creation and prolonging conduction times
• It is essential for transporting calcium, sodium, or potassium between cells.
• Magnesium can be intravenously administered to improve pulmonary function in asthma patients.
• It also relaxes the smooth muscle of the bronchi, independent from serum magnesium levels.

The beginning of action:

• Anticonvulsant:
  • IM: 1 hour
  • IV: Immediate
• Laxative:
  • Oral: 0.5 - 6 hours

Duration of anticonvulsant activity:

• IM: 3 - 4 hour
• IV: 30 minutes

Absorption:

• Oral: Slow and poo, approximately one-third absorbed

Distribution:

• Bone (50% - 60%)
• Extracellular fluid (1% - 2%)

Protein binding:

• 30%, to albumin

Excretion:

• Urine as magnesium
• feces as unabsorbed drug

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International Brand Names of Magnesium sulfate:

• Epsom Salt
• GoodSense Epsom Salt
• Cholal modificado
• Magnesii Sulfurici
• Kiddi Pharmaton
• Magnesii Sulfas
• Magnesii Sulfas Siccatus
• Magnesium Sulfuricum
• Magunesin
• Vivioptal Junior

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Magnesium sulfate Brand Names in Pakistan:

Magnesium Sulphate Injection 1 g/ml in Pakistan
Mag-S	Mass Pharma (Private) Limited

 

Magnesium Sulphate Injection 500 mg/ml in Pakistan
Magnesium Sulphate	Zafa Pharmaceutical Laboratories (Pvt) Ltd.