Drug class: Anticonvulsants, Miscellaneous

Medically reviewed by Drugs.com on Sep 10, 2024. Written by ASHP.

Introduction

Anticonvulsant parenterally; electrolyte; required cofactor for numerous human enzyme systems.

Uses for Magnesium Sulfate

Prevention and Control of Seizures

Used parenterally for prevention and control of seizures in toxemias (preeclampsia or eclampsia) of pregnancy and in various other conditions. (See Preeclampsia and Eclampsia and also see Other Seizure Etiologies under Uses.)

Preeclampsia and Eclampsia

Generally considered anticonvulsant drug of choice for prevention and control of seizures in severe preeclampsia or in eclampsia; appears to be more effective than phenytoin in preeclampsia, and more effective than phenytoin and diazepam in eclampsia.

The American College of Obstetricians and Gynecologists (ACOG) strongly recommends intrapartum/postpartum use of magnesium sulfate in women with severe preeclampsia to prevent eclampsia.

Routine use not recommended in women with preeclampsia without severe features (e.g., systolic BP ≥160 mm Hg or diastolic BP ≥110 mm Hg, thrombocytopenia, impaired liver or renal function, pulmonary edema, new-onset cerebral or visual disturbances). Individualize decision to initiate therapy in these patients based on the presence of certain warning signs of seizures (e.g., headache, altered mental state, blurred vision, scotomata, clonus, right upper quadrant pain).

Clinical course of preeclampsia may change rapidly and unexpectedly; monitor patients closely and initiate therapy if progression to severe preeclampsia occurs.

ACOG strongly recommends administration of parenteral magnesium sulfate in patients with eclampsia; continue therapy for ≥24 hours after last seizure.

Other Seizure Etiologies

May be used parenterally to control seizures associated with epilepsy, glomerulonephritis, or hypothyroidism, since low plasma concentrations of magnesium may be a contributing cause of seizures in these conditions.

Has been used for immediate control of life-threatening seizures in children with acute nephritis.

Prevention and Treatment of Hypomagnesemia

Used to correct or prevent hypomagnesemia in patients receiving total parenteral nutrition.

Also used in the treatment of acute hypomagnesemia accompanied by signs of tetany similar to those of hypocalcemia; usually, serum magnesium concentrations are below the lower limits of normal (1.5–2.5 or 3 mEq/L), and serum calcium concentrations are either normal (4.3–5.3 mEq/L) or elevated in such cases.

Preterm Labor and Fetal Neuroprotection

Has been used to inhibit uterine contractions in preterm labor (tocolysis)^{† [off-label]} and prolong gestation when considered beneficial. However, efficacy and safety not established and not labeled by FDA for this use.

ACOG and other experts support the short-term (≤48 hours) obstetric use of magnesium sulfate for appropriate conditions and durations of therapy. This includes short-term (i.e., ≤48 hours) prolongation of pregnancy to allow time for administration of antenatal corticosteroids; corticosteroid administration prior to anticipated preterm birth is strongly associated with decreased neonatal morbidity and mortality.

Also may be used for fetal neuroprotection prior to preterm delivery to reduce the risk of cerebral palsy^{† [off-label]}.

May be contraindicated by maternal or fetal conditions. (See Contraindications under Cautions.)

Do not use for >5–7 days for tocolysis; such prolonged use in pregnant women has been associated with adverse fetal effects (e.g., hypocalcemia, osteopenia, bone demineralization, fractures). (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

ACOG states that maintenance treatment with tocolytic drugs is not recommended because it is not effective in preventing preterm birth and improving neonatal outcomes.

Limited data indicate that combination therapy with another tocolytic agent may be more effective than single-agent therapy, but may increase risk of maternal morbidity; use with caution.

Concurrent use of magnesium sulfate and nifedipine may be particularly risky and potentially harmful. (See Specific Drugs under Interactions.)

Arrhythmias

Used IV successfully for the treatment of life-threatening arrhythmias such as atypical VT^{† [off-label]} (torsades de pointes).

Considered one of several preferred drugs in the treatment of polymorphic VT suspected of being torsades de pointes^{† [off-label]} in patients in whom initial attempts at correcting or managing potential precipitating factors (e.g., ischemic cardiac events, electrolyte imbalance, drugs known to prolong the QT interval) have not been successful.

Should not be used routinely during cardiac arrest, but may be considered when arrest rhythm is associated with torsades de pointes.

Has been used IV in the management of paroxysmal atrial tachycardia when other measures have failed and there is no evidence of myocardial damage.

Acute MI

Has been administered IV adjunctively to reduce cardiovascular morbidity and mortality (e.g., through reduction in ventricular arrhythmias and/or limitation of infarct size and reperfusion injury) associated with acute MI^{† [off-label]}; however, evidence of benefit is contradictory.

Should not be used routinely in patients with acute MI, but may be reasonable in patients with documented magnesium deficiency or torsades de pointes.

Acute Asthma

Has been used in the treatment of acute asthma^†.

There is some evidence that the drug may improve pulmonary function (i.e., peak expiratory flow rate and forced expiratory volume in 1 second) and reduce hospitalizations, particularly in patients with severe exacerbations.

Although current evidence does not support routine use in all patients with acute asthma, may be beneficial, and thus may be considered, in patients with severe acute asthma.

Barium Poisoning

Has been administered IV to counteract the intense muscle stimulating effects of barium poisoning.

Magnesium Sulfate Dosage and Administration

Administration

Administer IV or IM.

Also has been administered by intraosseous (IO) infusion^† in the ACLS setting, generally when IV access is not readily available; onset of action and systemic concentrations are comparable to those achieved with venous administration.

When used in pregnant women for conditions other than those labeled by the FDA such as for prevention of preterm labor^†, administer only by trained obstetric personnel in a hospital setting with appropriate obstetrical care facilities. Hospitals that use magnesium sulfate for fetal neuroprotection^† should develop uniform and specific guidelines for such use.

IV Administration

Concentration should not exceed 200 mg/mL (20%) for IV administration.

Must dilute magnesium sulfate 50% injection prior to IV administration; alternatively, may use a commercially available prediluted solution of magnesium sulfate in 5% dextrose or sterile water for injection.

Rate of Administration

Usually, do not exceed 150 mg/minute (e.g., 1.5 mL/minute of a 10% concentration or equivalent) except in patients with seizures associated with severe eclampsia.

Standardize 4 Safety

Standardized concentrations for magnesium sulfate have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. For additional information on S4S (including updates that may be available), see [Web].

See ISMP for best practices.[Web];[Web]

dosing units differ from concentration units

IM Administration

Adults: Generally, use concentration of 250 mg/mL (25%) or 500 mg/mL (50%).

Infants and children: Usually, use concentration ≤200 mg/mL (20%). However, higher concentrations (e.g., 50%) have been used.

Dosage

Adjust dosage carefully according to individual requirements and response; discontinue as soon as the desired effect is obtained.

Each gram of magnesium sulfate heptahydrate contains 8.1 mEq of magnesium.

Use caution when switching between different parenteral formulations to ensure that patients receive the correct dose.

Pediatric Patients

Pediatric Advanced Life Support (PALS)

Torsades de Pointes† or Suspected Hypomagnesemia

IV/IO^†

Some experts recommend 25–50 mg/kg (up to 2 g) over 10–20 minutes (or faster in torsades de pointes).

Hypomagnesemia

Prevention

Additive in Total Parenteral Infusion

Infants: Usually, 2–10 mEq of magnesium daily.

Maintenance requirements not precisely known.

Treatment

IV or IM

Some experts recommend 25–50 mg/kg (up to 2 g) every 4–6 hours for 3–4 doses; repeat as needed.

For deficiency that is not severe in older children, some manufacturers have recommended 1 g (2 mL of 50% solution) once or twice daily by IM injection.

Use serum magnesium values to guide continued dosage.

Acute Asthma

IV

Single dose of 25–75 mg/kg (maximum 2 g) over 20 minutes recommended for moderate to severe exacerbation of reactive airway disease.

Adults

Prevention and Control of Seizures

Preeclampsia and Eclampsia

Various dosing regimens have been recommended.

For management of preeclampsia or eclampsia, dilute (1–8%) solutions are often given by IV infusion in combination with IM injections using 50% magnesium sulfate.

IV with IM

Severe preeclampsia or eclampsia: Manufacturer states that an IV dose of 4–5 g diluted in 250 mL of 5% dextrose injection or 0.9% sodium chloride injection may be given simultaneously with IM injections of up to 10 g (5 g or 10 mL of undiluted 50% solution administered into each buttock). Total initial dose: 10–14 g.

Alternatively, initial dose of 4 g may be given IV by diluting the 50% solution to a concentration of 10 or 20%; may then inject 40 mL of a 10% solution or 20 mL of a 20% solution IV over 3–4 minutes. Administer subsequent 4- to 5-g doses (8–10 mL of the undiluted 50% injection) IM into alternate buttocks every 4 hours as needed, depending on the continuing presence of the patellar reflex and adequate respiratory function.

After the initial IV dose, some clinicians administer a maintenance IV infusion of 1–2 g/hour.

Continue therapy until paroxysms cease.

Serum magnesium concentration of 6 mg/dL is considered optimal for seizure control.

IV

For prevention or treatment of eclamptic seizures, ACOG recommends IV loading dose of 4–6 g, followed by a maintenance IV infusion of 1–2 g/hour for ≥24 hours.

Other Seizure Etiologies

IM or IV

For seizures associated with epilepsy, glomerulonephritis, or hypothyroidism: Usually, 1 g.

Hypomagnesemia

Prevention

IV Infusion

Additive in total parenteral nutrition: Usually, 8–24 mEq daily.

Maintenance requirements are not precisely known.

Treatment

IM

Mild deficiency: Usually, 1 g (8.12 mEq or 2 mL of the 50% solution) every 6 hours for 4 doses.

Alternatively, for deficiency that is not severe: 1 g (2 mL of the 50% solution) once or twice daily has been given; use serum magnesium concentrations to guide continued dosing.

Severe deficiency: If necessary, may administer up to 250 mg (about 2 mEq or 0.5 mL of the 50% solution) per kg of body weight within a 4-hour period.

Alternatively, for severe deficiency: 1–5 g (2–10 mL of the 50% solution) daily in divided doses has been given and repeated daily until serum levels are normal.

Use caution to prevent exceeding the renal excretory capacity.

IV infusion

For severe deficiency: 5 g (approximately 40 mEq) added to 1 L of 5% dextrose injection or 0.9% sodium chloride injection infused slowly over 3 hours.

Preterm Labor†

Carefully adjust rate and duration of infusion according to the patient’s response as indicated (by uterine response, maternal and fetal tolerance).

Administration for prolonged periods (i.e., >5–7 days) may cause adverse fetal effects. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Monitoring of serum magnesium concentrations may be useful to minimize the risk of toxicity (e.g., respiratory depression, cardiotoxicity, maternal tetany, muscular paralysis, hypotension) and to determine the maximum safe infusion rate.

Monitor amount and rate of IV fluid administration to avoid circulatory overload.

Observe for signs and symptoms of pulmonary edema.

IV Infusion

Acute tocolytic therapy: Loading dose of 4–6 g over 20 minutes; after contractions cease, follow with maintenance infusions of 2–4 g/hour for 12–24 hours as tolerated.

Arrhythmias

Atypical VT (Torsades de Pointes)†

IV

Some experts recommend 1–2 g over 15 minutes.

Dose of 1–6 g over several minutes also used, followed in some cases by 3–20 mg/minute by IV infusion for 5–48 hours, depending on response and serum magnesium concentrations.

Torsades de pointes associated with cardiac arrest^†: Some experts recommend 1–2 g bolus dose in 10 mL 5% dextrose injection.

IO^†

Torsades de pointes associated with cardiac arrest^†: Some experts recommend 1–2 g bolus dose in 10 mL 5% dextrose injection.

Acute Asthma†

IV

Usually, 2 g over 20 minutes.

Barium Poisoning

IV

Usually, 1–2 g to counteract the intense muscle stimulating effects of barium.

Prescribing Limits

Pediatric Patients

Pediatric Advanced Life Support (PALS)

Torsades de Pointes† or Suspected Hypomagnesemia

IV/IO^†

Maximum single dose of 2 g.

Hypomagnesemia

IV or IM

Maximum single dose of 2 g.

Acute Asthma

IV

Maximum single dose of 2 g.

Adults

Prevention and Control of Seizures

Preeclampsia and Eclampsia

IV with IM

Do not exceed total dosage of 30–40 g daily.

Special Populations

Renal Impairment

Prevention and Control of Seizures

Preeclampsia and Eclampsia

IV with IM

Maximum 20 g/48 hours in severe renal impairment.

Geriatric Patients

Often require reduced dosage because of impaired renal function. In severe renal impairment, do not exceed 20 g in a 48-hour period; monitor serum magnesium concentrations.

Cautions for Magnesium Sulfate

Contraindications

• Parenteral administration in heart block or myocardial damage.

• Tocolytic therapy in general may be contraindicated by some maternal or fetal conditions (e.g., nonreassuring fetal status, chorioamnionitis, fetal demise, lethal congenital or chromosomal abnormalities, maternal bleeding with hemodynamic instability, severe preeclampsia or eclampsia, preterm premature rupture of membranes [may consider use in the absence of maternal infection for maternal transport and/or corticosteroid administration]).

• Tocolytic therapy with magnesium sulfate may be contraindicated in myasthenia gravis.

• In toxemia of pregnancy during 2 hours prior to delivery.

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; hypocalcemia and related skeletal abnormalities (e.g., bone demineralization, osteopenia, fractures) observed in neonates with prolonged (>5–7 days) in utero exposure to parenterally administered magnesium sulfate. Evidence of such fetal toxicity based principally on case reports and epidemiologic studies. In these reports, magnesium sulfate was administered IV for periods >5–7 days for prevention of preterm labor (tocolysis)^†, which is not an FDA-labeled use.

Increased possibility of neonatal toxicity (including neuromuscular or respiratory depression) with prolonged continuous IV infusion before delivery (especially for >24 hours); IM use does not usually compromise neonate.

Neonatal hypermagnesemia management may require resuscitation and assisted ventilation via endotracheal intubation and/or intermittent positive-pressure ventilation, as well as IV calcium.

If administered for preterm labor, inform patient that efficacy and safety of magnesium sulfate for this use have not been established and that use of the drug for >5–7 days in this setting may cause fetal harm. The shortest duration of use that can result in fetal harm is not known.

Toxicity

Principal hazard is hypermagnesemia, most immediate life-threatening effect is respiratory depression; have IV calcium (e.g., calcium gluconate) readily available for use as antidote.

Adverse effects of parenteral therapy are caused by magnesium intoxication.

Toxic manifestations (may begin at serum magnesium concentrations of 4 mEq/L) include neurologic symptoms (e.g., muscular weakness, flaccid paralysis, ataxia, drowsiness, confusion, depression of reflexes), flushing, sweating, vasodilation, hypotension, hypothermia, depression of cardiac function, bradycardia, cardiac arrhythmias, circulatory collapse, hypoventilation, and CNS depression; can proceed to fatal respiratory paralysis.

Observe carefully, and monitor serum magnesium concentrations to avoid overdosage and toxicity.

During tocolytic therapy, observe carefully and monitor serum magnesium concentrations to minimize the risk of toxicity (e.g., respiratory depression, cardiotoxicity, maternal tetany, muscular paralysis, hypotension).

Hypocalcemia with signs of tetany can occur during tocolytic use.

Patellar reflex disappearance is useful to detect intoxication onset. Test knee jerk reflexes before each dose; if absent, give no additional magnesium until they return.

Make sure respiration rate is ≥16/minute prior to each dose.

Do not continue dosage unless urine output is 100 mL or more during the 4 hours preceding each dose.

If overdosage occurs, provide artificial ventilation until a calcium salt can be given IV.

In adults, IV administration of 5–10 mEq of calcium (e.g., 10–20 mL of 10% calcium gluconate) usually will reverse respiratory depression or heart block caused by magnesium intoxication.

Peritoneal dialysis or hemodialysis may be required in extreme cases of hypermagnesemia.

Some preparations contain aluminum; risk of aluminum accumulation and associated toxicity (e.g., CNS and bone toxicities) with prolonged parenteral administration in patients with impaired renal function. Premature neonates are at particularly high risk.

Maternal Pulmonary Edema

Risk of maternal pulmonary edema with tocolytic therapy; development during the initial 24 hours is uncommon.

Etiology is unclear; risk factors include excessive hydration, multiple gestation, occult sepsis, and underlying cardiac disease.

Adjunctive corticosteroid therapy apparently is not an important risk factor .

Reduce risk by limiting fluid intake to 2.5–3 L daily, limiting sodium intake, and maintaining maternal pulse <130 bpm.

Monitor amount and rate of IV fluid administration to avoid circulatory overload; observe carefully for signs/symptoms of pulmonary edema.

Hypocalcemia

Clinically important hypocalcemia with signs of tetany has occurred after use for eclampsia. Changes in calcium and phosphorus balance should be anticipated in each case of parenteral magnesium administration.

Major Toxicities

Respiratory Depression

See Warnings under Cautions.

General Precautions

Use with caution if flushing and sweating occur.

CNS Depressants

Adjust dosage carefully with concomitant use; have IV calcium (e.g., calcium gluconate) readily available for use as antidote for magnesium toxicity. (See Specific Drugs under Interactions.)

Laboratory Tests

Confirm hypomagnesemia, monitor serum magnesium concentrations. (See Warnings under Cautions.)

Specific Populations

Pregnancy

Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Use during pregnancy only if clearly needed; apprise patient of potential hazard to fetus.

Do not give IV during the 2 hours preceding delivery.

Lactation

Distributed into milk. Caution if used in nursing women, but generally considered compatible with breast-feeding.

Milk magnesium concentrations increased for only about 24 hours after discontinuance of parenteral magnesium; amount ingested by a nursing infant during this period is probably too small to be of clinical importance.

Pediatric Use

Although one manufacturer states safety and efficacy not established in children, other manufacturers make no pediatric restrictions.

Geriatric Use

Often requires reduced dosage because of impaired renal function. (See Geriatric Patients under Dosage and Administration.)

Renal Impairment

Administer with caution in renal impairment; danger of magnesium intoxication.

Reduce dosage and obtain frequent serum magnesium concentrations in severe renal impairment. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Flushing, sweating, hypotension, depression of reflexes, flaccid paralysis, hypothermia, circulatory collapse, depression of cardiac function, CNS depression, respiratory paralysis, hypocalcemia, tetany.

Drug Interactions

Specific Drugs

Magnesium Sulfate Pharmacokinetics

Absorption

Onset

IV administration: Immediate onset.

IM administration: About 1 hour.

Duration

IV administration: About 30 minutes.

IM administration: 3–4 hours.

Plasma Concentrations

Effective anticonvulsant serum magnesium concentrations: 2.5–7.5 mEq/L.

Monitor for hypermagnesemia (serum concentrations >2.5 mEq/L); toxic effects (e.g., depression of deep-tendon reflexes) may begin at 4 mEq/L.

At 10 mEq/L, deep-tendon reflexes disappear and respiratory paralysis may occur; complete heart block can occur at about 10 mEq/L.

Serum magnesium >12 mEq/L may be fatal.

Distribution

Extent

Crosses the placenta.

Distributes into milk.

Elimination

Elimination Route

Excreted by the kidneys; interindividual variability in rate but directly proportional to serum concentration and glomerular filtration.

Stability

Storage

Parenteral

Injection

20–25°C; avoid freezing.

Magnesium Sulfate in 5% Dextrose Injection

20–25°C; avoid freezing.

Actions

• Hypermagnesemia (serum magnesium concentrations >2.5 mEq/L) may depress the CNS and block peripheral neuromuscular transmission, producing anticonvulsant effects.

• Exact mechanism is not fully known; excess magnesium appears to decrease the amount of acetylcholine liberated by the motor nerve impulse.

• Magnesium ions slow the rate of the SA node impulse formation and prolong conduction time in animals.

• IV infusion prolongs PR interval, H (atria-His bundle) interval, antegrade AV nodal effective refractory period, and SA conduction time in humans.

• Required cofactor for >300 enzyme systems.

• Required for both anaerobic and aerobic energy generation and for glycolysis.

• Described as nature’s physiologic calcium-channel blocking agent.

• During magnesium depletion, intracellular calcium increases, which can cause muscle cramps, hypertension, and coronary and cerebral vasospasms.

• Plays an important role in BP regulation; hypertension may be associated with magnesium deficiency and magnesium may decrease BP in hypertension.

• Important role in bone and mineral homeostasis and can directly affect bone cell formation and influence hydroxyapatite crystal formation and growth; deficiency may be risk factor for osteoporosis.

• Insulin resistance and impaired insulin secretion with deficiency.

Advice to Patients

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. If administered for preterm labor, inform patient that efficacy and safety for this use have not been established and that use of the drug for >5–7 days may cause fetal harm.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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Frequently asked questions

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