Magnesium Sulfate (magnesium sulfate in sterile water)

Dosage of magnesium sulfate must be carefully adjusted according to individual requirements and response, and administration of the drug should be discontinued as soon as the desired effect is obtained.

Clinicians should use caution when switching between different formulations of magnesium sulfate injection to ensure that patients receive the correct dose.

Geriatric patients often require a reduced dosage of magnesium sulfate because of renal impairment. In geriatric patients with severe renal impairment, dosage of the drug should not exceed 20 g in a 48-hour period; serum magnesium concentrations should be monitored in such patients.

Magnesium sulfate is usually administered IV or IM.

Magnesium sulfate also has been administered by intraosseous (IO) infusion+ in the setting of advanced cardiovascular life support (ACLS), generally when IV access is not readily available; onset of action and systemic concentrations of the drug 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 the prevention of preterm labor+, magnesium sulfate injection should be administered only by trained obstetric personnel in a hospital setting with appropriate obstetrical care facilities.

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There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Magnesium Salts, Injectable/Nondepolarizing Muscle Relaxants

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Magnesium may reduce postjunctional membrane neuromuscular blocking action of nondepolarizing muscle relaxants. Parenterally administered magnesium may potentiate the effects of the nondepolarizing muscle relaxants.

CLINICAL EFFECTS: Increased neuromuscular blockade with profound sedation, respiratory depression, coma, and/or death.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Monitor respiratory function when parenteral magnesium and nondepolarizing muscle relaxants are administered concurrently. Adjust the dose of the neuromuscular blocking agent accordingly. If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

DISCUSSION: The effects of nondepolarizing muscle relaxants have been reported to be increased in laboratory animals and in humans by concomitant administration of magnesium sulfate. Respiratory depression has been reported.

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• Hypermagnesemia

• Eaton-lambert syndrome
• Hypocalcemia
• Myasthenia gravis
• Pregnancy
• Severe renal impairment

• Kidney disease with reduction in glomerular filtration rate (GFr)

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More Frequent

• CNS depression
• Hypocalcemia
• Hypotension
• Hypothermia

Less Frequent

• Bradycardia
• Vasodilation of blood vessels

Rare or Very Rare

• Acute respiratory failure
• Bradypnea
• Cardiac arrest
• Cardiac arrhythmia
• Flaccid paralysis
• Hypermagnesemia
• Hypotonia
• Hypoventilation
• Pulmonary edema
• Respiratory depression
• Shock

More Frequent

• Flushing
• Hyperhidrosis
• Hyporeflexia

Less Frequent

• Drowsy
• Lethargy
• Sedation
• Visual changes

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The neonate is usually not compromised by excess magnesium when IM magnesium sulfate is administered to the toxemic mother; however, when magnesium sulfate therapy is administered by continuous IV infusion (especially if for more than 24 hours preceding delivery), the possibility that the neonate may show signs of magnesium toxicity, including neuromuscular or respiratory depression, is increased. In addition, prolonged use of parenteral magnesium sulfate during pregnancy has been associated with fetal hypocalcemia and skeletal abnormalities. IV magnesium should not be given during the 2 hours preceding delivery. Management of the neonate with hypermagnesemia may require resuscitation and assisted ventilation via endotracheal intubation and/or intermittent positive-pressure ventilation, as well as IV calcium. For additional information on the risks of tocolysis with magnesium sulfate, see Cautions: Adverse Effects.

Epidemiologic studies and case reports indicate that prolonged use (i.e., longer than 5-7 days) of magnesium sulfate injection during pregnancy may cause hypocalcemia and related skeletal abnormalities (e.g., osteopenia, bone demineralization, fractures) in the developing fetus. Such bone abnormalities have been described in case reports of neonates exposed in utero to magnesium sulfate; as of May 30, 2013, 18 cases were identified in the FDA's Adverse Event Reporting System (AERS). All of these cases were previously described in the medical literature. In these case reports, magnesium sulfate was parenterally administered for prolonged periods for the prevention of preterm labor (tocolysis)+, which is not an FDA-labeled indication for the drug. According to an FDA analysis of data obtained from AERS, the average duration of in utero exposure to magnesium sulfate was 9.6 weeks (range: 8-12 weeks). Complete or near complete resolution of the bone abnormalities occurred in cases where outcomes were reported. Results of several epidemiologic studies, most of which were retrospective chart reviews, also have indicated an increased incidence of skeletal abnormalities in infants born to mothers who had received IV magnesium sulfate for prolonged tocolysis (more than 5-7 days). Some of these studies also reported changes in serum biochemistry related to bone metabolism (e.g., hypermagnesemia, hyperphosphatemia, hypocalcemia, increased alkaline phosphatase concentrations) and radiographic changes consistent with the bone abnormalities observed; however, the long-term consequences of such findings are not known. Although a causal relationship has not been conclusively established, FDA states that the available evidence to date supports an association between prolonged (i.e., longer than 5-7 days) maternal administration of IV magnesium sulfate therapy and neonatal hypocalcemia and skeletal abnormalities.

Magnesium sulfate injection should be used during pregnancy only if clearly needed. If magnesium sulfate is administered to a pregnant woman for the prevention of preterm labor, the patient should be informed that efficacy and safety of such use have not been established and that use of the drug for more than 5-7 days in this setting may cause fetal harm; the shortest duration of use that can result in fetal harm is not known.

Since magnesium is distributed into milk during parenteral magnesium sulfate administration, the drug should be used with caution in nursing women. However, magnesium sulfate generally is considered to be compatible with breastfeeding. Milk concentrations of magnesium are increased for only about 24 hours after discontinuance of parenteral magnesium sulfate therapy; the amount of magnesium ingested by a nursing infant during this period is probably too small to be of clinical importance.

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