MAGNESIUM SULFATE injection

Magnesium Sulfate by

Drug Labeling and Warnings

Magnesium Sulfate by is a Prescription medication manufactured, distributed, or labeled by WG Critical Care, LLC, HQ Specialty Pharma Corporation, InfoRLife SA. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

  • 1 INDICATIONS AND USAGE

    Magnesium Sulfate in 5% Dextrose Injection, USP is indicated for:

    • Prevention of eclampsia in patients with preeclampsia
    • Treatment of seizures and prevention of recurrent seizures in patients with eclampsia
  • 2 DOSAGE AND ADMINISTRATION

    2.1 Important Administration Instructions

    Magnesium Sulfate in 5% Dextrose Injection is:

    • A clear solution. Visually inspect Magnesium Sulfate in 5% Dextrose Injection for particulate matter and discoloration prior to administration. Do not administer unless solution is clear and colorless to slightly yellow.
    • For intravenous use only
    • Administered via intravenous infusion pump

    Magnesium Sulfate in 5% Dextrose Injection does not require dilution prior to intravenous administration.

    After removing the overwrap, check for minute leaks by squeezing the container fully. Do not administer Magnesium Sulfate in 5% Dextrose Injection if there is a leak or there is greater than 2 mL of water in the overwrap [see Description (11)].

    Do not administer Magnesium Sulfate in 5% Dextrose Injection with incompatible drugs through the same intravenous line [see Dosage and Administration (2.4)]. Do not use Magnesium Sulfate in 5% Dextrose Injection in series connections.

    2.2 Recommended Dosage

    • The recommended loading dosage of Magnesium Sulfate in 5% Dextrose Injection in patients with eclampsia or preeclampsia is 4 to 6 grams over 15 minutes followed by a recommended maintenance dosage of 1 to 2 grams every hour.
    • Obtain serum magnesium concentrations and assess clinical status to adjust the dosage.
    • In patients with eclampsia, consider targeting the maintenance dosage to achieve serum magnesium concentrations of 3 to 6 mg per 100 mL (2.5 to 5 mEq per liter). For patients with recurrent eclampsia, consider giving an additional 2 gram intravenous bolus.
    • For patients with eclampsia, therapy should continue until seizures cease.
    • The maximum recommended dosage is 30 to 40 grams of magnesium sulfate over 24 hours.
    • Administration of Magnesium Sulfate in 5% Dextrose Injection beyond 5 to 7 days is not recommended [see Warnings and Precautions (5.1)].

    2.3 Dosage in Patients with Severe Renal Impairment and/or Oliguria

    • In patients with severe renal impairment and/or a urine output less than 0.5 mL/kg/hour, initiate Magnesium Sulfate in 5% Dextrose Injection with a 4 gram loading dose followed by a maintenance dosage of 1 gram every hour.
    • Titrate the magnesium sulfate maintenance dosage to maintain concentrations in the target range through frequent monitoring of magnesium concentrations and observation for clinical signs of magnesium toxicity (e.g., facial edema, diminished strength of deep tendon reflexes, respiratory depression). A lower maintenance dosage requirement is likely in these patients.
    • Do not exceed the maximum recommended dosage of 20 grams of Magnesium Sulfate in 5% Dextrose Injection over 48 hours.

    2.4 Drug Incompatibilities

    Magnesium Sulfate in 5% Dextrose Injection is not compatible with administration of a variety of solutions and forms precipitates of magnesium salts. Before using Magnesium Sulfate in 5% Dextrose Injection with another parenteral product, investigate potential incompatibilities. Incompatible products that should not be coadministered include salicylates and alkali carbonates.

  • 3 DOSAGE FORMS AND STRENGTHS

    Magnesium Sulfate in 5% Dextrose Injection, USP is a clear and colorless to slightly yellow solution supplied in single-dose, single port bag:

    • 0.01 grams per mL (1%):
    • ▪ 100 mL bag containing 1 gram of magnesium sulfate in 5% dextrose injection

    Each 100 mL contains 5 grams of hydrous dextrose in Water for Injection.

  • 4 CONTRAINDICATIONS

    Magnesium Sulfate in 5% Dextrose Injection is contraindicated in patients:

  • 5 WARNINGS AND PRECAUTIONS

    5.1 Fetal-Neonatal Toxicity with Prolonged Use

    Continuous administration of magnesium sulfate beyond 5 to 7 days in pregnant women can lead to hypocalcemia and bone abnormalities in the developing fetus, including skeletal demineralization and osteopenia. In addition, cases of neonatal fracture have been reported.

    Neonates of women receiving Magnesium Sulfate in 5% Dextrose Injection (especially with prolonged maternal use) are at risk for magnesium toxicity including hyporeflexia, hypotonia, and respiratory depression. There is one reported case of neonatal death as the result of magnesium toxicity after transplacental exposure.

    The shortest duration of magnesium sulfate treatment that can lead to fetal harm is not known. Administration of Magnesium Sulfate in 5% Dextrose Injection beyond 5 to 7 days is not recommended.

    5.2 Risk of Magnesium Toxicity

    Patients receiving Magnesium Sulfate in 5% Dextrose Injection are at risk for magnesium toxicity including respiratory depression, acute renal failure and rarely, pulmonary edema.

    Monitor clinical signs of magnesium toxicity (for example, facial edema, diminished strength of deep tendon reflexes, respiratory depression) and magnesium concentrations during infusions of Magnesium Sulfate in 5% Dextrose Injection. Clinical indications of a safe dosage regimen include the presence of the patellar reflex (knee jerk) and absence of respiratory depression (approximately 16 breaths or more per minute). Serum magnesium concentrations usually sufficient to control convulsions range from 3 to 6 mg per 100 mL (2.5 to 5 mEq per liter). The strength of the deep tendon reflexes begins to diminish when serum magnesium concentrations exceed 4 mEq per liter. Reflexes may be absent at concentration of 10 mEq per liter, at which point respiratory paralysis is a potential hazard. An injectable calcium salt should be immediately available to counteract the potential hazards of magnesium toxicity in patients with preeclampsia and eclampsia. If there is significant magnesium toxicity, stop the Magnesium Sulfate in 5% Dextrose Injection infusion and recheck serum magnesium concentration.

    Patients with renal impairment are at greater risk of magnesium toxicity because magnesium is excreted by the body solely by the kidneys [see Use in Specific Populations (8.6)]. Urine output should be maintained at a level of 100 mL per 4 hours. Monitoring serum magnesium levels and the patient's clinical status is essential to avoid the consequences of overdosage in patients with preeclampsia. Discontinuation of the magnesium infusion is recommended when urine output is less than 100 mL every 4 hours to avoid magnesium toxicity, especially if serum creatinine is increasing progressively.

    5.3 Risk of Elevated Blood Glucose

    Solutions containing dextrose should be used with caution in patients with known prediabetes or diabetes mellitus given the risk of elevated blood glucose.

    5.4 Co-administration with Unapproved Tocolytics

    Do not use Magnesium Sulfate in 5% Dextrose Injection with unapproved tocolytics (e.g., beta adrenergic agents such as terbutaline, or with calcium channel blockers such as nifedipine). Serious adverse events including pulmonary edema and hypotension have occurred [see Drug Interactions (7)].

    5.5 Aluminum Toxicity

    Magnesium Sulfate in 5% Dextrose Injection contains aluminum that may be toxic (Magnesium Sulfate in 5% Dextrose Injection contains less than 25 mcg/L of aluminum). Aluminum may reach toxic concentrations with prolonged parenteral administration in patients with renal impairment.

    Patients with renal impairment who receive parenteral concentrations of aluminum at greater than 4 to 5 mcg/kg/day, accumulate aluminum at concentrations associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

    5.6 Exacerbation of Myasthenia Gravis

    Magnesium Sulfate in 5% Dextrose Injection is contraindicated in patients with known myasthenia gravis.

    Use of magnesium sulfate in patients with underlying myasthenia gravis can precipitate a myasthenic crisis. Myasthenic crisis is a life-threatening condition characterized by neuromuscular respiratory failure. Symptoms of myasthenic crisis may include difficulty swallowing, ptosis, facial droop, weakness and/or difficulty breathing that may require intubation.

    If myasthenic crisis is suspected, discontinue use of Magnesium Sulfate in 5% Dextrose Injection immediately. Secure the patient's airway. Consider intensive care unit admission and elective intubation, if respiratory failure is anticipated. Once the airway is secure, confirm the diagnosis. Therapies include plasmapheresis and plasma exchange or intravenous immunoglobulin (IVIG) and immunomodulating therapy in addition to high-dose glucocorticoids.

  • 6 ADVERSE REACTIONS

    The following adverse reactions have been identified in clinical studies or postmarketing reports. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

    Cardiovascular:

    hypotension, circulatory collapse, cardiac depression including bradycardia

    Central Nervous System:

    central nervous system depression leading to respiratory paralysis, visual disturbances, flushing, sweating, hypothermia

    Metabolic:

    hypocalcemia with signs of tetany, hypermagnesemia

    Neurologic:

    lethargy, sedation, somnolence, myasthenic crisis

    Neuromuscular:

    depressed deep tendon reflexes, flaccid paralysis

    Pulmonary:

    decreased respiratory rate, pulmonary edema
  • 7 DRUG INTERACTIONS

    Table 1 presents the potential clinical impact of medications that may be commonly administered concomitantly with Magnesium Sulfate in 5% Dextrose Injection in the clinical setting.

    Table 1: Potential Clinically Significant Drug Interactions with Magnesium Sulfate in 5% Dextrose Injection*
  • * For drug incompatibility information [see Dosage and Administration (2.4)].
    		•

    Neuromuscular Blocking Agents

    Clinical Impact:

    • Potentiation and prolongation of neuromuscular blockade is possible with the concomitant use of magnesium sulfate and neuromuscular blocking agents [see Clinical Pharmacology (12.2)].
    • The underlying mechanism of this interaction may involve suppression of peripheral neuromuscular function by decreasing acetylcholine release, reduction of endplate sensitivity, and decreased muscle fiber excitability with magnesium sulfate therapy.

    Intervention:

    • Monitor respiration and the depth of neuromuscular blockade frequently (e.g., train-of-four monitoring) when a neuromuscular blocking agent is used concomitantly with Magnesium Sulfate in 5% Dextrose Injection.
    • Adjust the dosage of the neuromuscular blocking agent accordingly to maintain the desired level of musculoskeletal activity. The amount of reversal agent(s) required to achieve adequate reversal of the neuromuscular blocking agent(s) may also be increased.

    Examples:

    • Depolarizing neuromuscular blockers: succinylcholine
    • Non-depolarizing neuromuscular blockers: atracurium, cisatracurium, pancuronium, rocuronium, vecuronium

    Narcotics and/or Propofol

    Clinical Impact:

    • Potentiation and prolongation of analgesia and CNS depression is possible with the concomitant use of Magnesium Sulfate in 5% Dextrose Injection with narcotics and/or propofol. The potential for magnesium sulfate to affect other CNS depressants is unknown [see Clinical Pharmacology (12.2)].
    • The underlying mechanism of this interaction may involve antagonism of N-methyl-D-aspartate (NMDA) by magnesium sulfate therapy.

    Intervention:

    • Monitor the depth of CNS depression frequently using a reliable instrument.
    • Adjust the narcotic and/or propofol dosage accordingly to maintain the desired level of analgesia and sedation.

    Examples:

    • Narcotics and propofol

    Dihydropyridine Calcium Channel Blockers

    Clinical Impact:

    • An exaggerated hypotensive response is possible with the concomitant use of Magnesium Sulfate in 5% Dextrose Injection with dihydropyridine calcium channel blockers. The potential for magnesium sulfate to affect other calcium channel blockers (e.g., diltiazem and verapamil) is unknown [see Clinical Pharmacology (12.2)].

    Intervention:

    • Monitor vital signs (heart rate, blood pressure, respiration) frequently.
    • Supportive care and/or discontinuation of the calcium channel blocker may be required.

    Examples:

    • Amlodipine, clevidipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine, and nisoldipine

    Drugs that May Induce Magnesium Loss

    Clinical Impact:

    • Reduced magnesium concentrations may impact efficacy

    Intervention:

    • Monitor magnesium concentrations frequently and adjust the Magnesium Sulfate in 5% Dextrose Injection dosage to maintain concentrations in the target range [see Dosage and Administration (2)].

    Examples:

    • Alcohol, aminoglycosides, amphotericin B, cisplatin, cyclosporine, digitalis, loop diuretics, thiazide diuretics
  • 8 USE IN SPECIFIC POPULATIONS

    8.1 Pregnancy

    Risk Summary

    Magnesium Sulfate in 5% Dextrose Injection is indicated in pregnant women for the prevention of eclampsia in women with preeclampsia and the treatment of seizures and prevention of recurrent seizures in women with eclampsia. Fetal, neonatal, and maternal risks are discussed throughout the labeling.

    Clinical Considerations

    Labor or Delivery:

    Magnesium Sulfate in 5% Dextrose Injection is not approved for the treatment of pre-term labor.

    Administration of Magnesium Sulfate in 5% Dextrose Injection to pregnant women longer than 5 to 7 days may lead to hypocalcemia and bone abnormalities in the developing fetus, including skeletal demineralization and osteopenia [see Warnings and Precautions (5.1)].

    8.2 Lactation

    The use of intravenous magnesium in pregnant women increases human milk magnesium concentrations only slightly and oral absorption of magnesium by the infant is poor. The effect of intravenous magnesium on milk production is unknown. The developmental and health benefits to the neonate of breastfeeding should be considered along with the mother's clinical need for Magnesium Sulfate in 5% Dextrose Injection and any potential adverse effects on the breastfed infant from Magnesium Sulfate in 5% Dextrose Injection or from the underlying maternal condition.

    8.4 Pediatric Use

    The safety and effectiveness of Magnesium Sulfate in 5% Dextrose Injection have been established for the prevention of eclampsia in adolescents with preeclampsia and the treatment of seizures and prevention of recurrent seizures in adolescents with eclampsia. Dosing recommendation in pregnant adolescent patients are the same as for pregnant adult patients [see Dosage and Administration (2.2)].

    8.6 Renal Impairment

    Magnesium is excreted solely by the kidneys. Patients with severe renal impairment (urine output less than 100 mL per 4 hours) are at greater risk for increased magnesium concentrations that may lead to magnesium toxicity [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)]. In patients with severe renal impairment, dosage reduction is recommended and the maximum recommended dosage is lower than patients with normal renal function [see Dosage and Administration (2.3)].

  • 10 OVERDOSAGE

    Manifestations of magnesium toxicity include a drop in blood pressure, difficulty breathing, and disappearance of the patellar reflex. As serum magnesium rises above 4 mEq per liter, the deep tendon reflexes decrease. As the serum magnesium level approaches 10 mEq per liter, the tendon reflexes disappear and respiratory paralysis may occur [see Warnings and Precautions (5.2)]. Other signs and symptoms of magnesium overdosage include flushing, sweating, hypotension, weakness, hypothermia, circulatory collapse, cardiac and central nervous system depression proceeding to respiratory paralysis, cardiac arrest, and prolongation of PR and QRS intervals. Patients with renal impairment and underlying neuromuscular diseases such as myasthenia gravis may experience magnesium intoxication at lower magnesium concentrations (Magnesium Sulfate in 5% Dextrose Injection is contraindicated in patients with myasthenia gravis).

    If patient is experiencing magnesium toxicity, immediately discontinue Magnesium Sulfate in 5% Dextrose Injection. Artificial respiration may be required. Administer an injectable calcium salt to counteract the potential hazards of magnesium toxicity [see Warnings and Precautions (5.2)].

    Hypermagnesemia in the newborn (after administration of Magnesium Sulfate in 5% Dextrose Injection to the mother) may require resuscitation and assisted ventilation via endotracheal intubation or intermittent positive pressure ventilation as well as intravenous calcium.

  • 11 DESCRIPTION

    Magnesium Sulfate in 5% Dextrose Injection, USP is a sterile, nonpyrogenic solution of magnesium sulfate heptahydrate and dextrose in water for injection for intravenous use. Each 100 mL contains 1 gram of magnesium sulfate heptahydrate and dextrose, hydrous 5 grams in water for injection [see How Supplied/Storage and Handling (16)]. Magnesium Sulfate in 5% Dextrose Injection, USP may contain sulfuric acid and/or sodium hydroxide for pH adjustment. The pH is 4.5 (3.5 to 6.5).

    Magnesium Sulfate, USP heptahydrate is chemically known as sulfuric acid magnesium salt (1:1), heptahydrate and chemically designated MgSO4 ∙ 7H2O, with a molecular weight of 246.47. It occurs as colorless crystals or white powder freely soluble in water.

    Dextrose, USP is chemically designated D-glucose, monohydrate, a hexose sugar freely soluble in water. The molecular formula is C6H12O6 ∙ H2O and the molecular weight is 198.17. It has the following structural formula:

    Chemical Structure

    Water for Injection, USP is chemically designated H2O.

    Water can permeate from inside the flexible plastic container (polyvinylchloride) into the overwrap [see Dosage and Administration (2.1)] but not in amounts sufficient to affect the solution significantly. Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the plastic container materials. Exposure to temperatures above 25°C (77°F) during transport and storage will lead to minor losses in moisture content. Higher temperatures lead to greater losses. It is unlikely that these minor losses will lead to clinically significant changes within the expiration period.

  • 12 CLINICAL PHARMACOLOGY

    12.1 Mechanism of Action

    Magnesium prevents seizures in patients with preeclampsia and controls seizures in patients with eclampsia by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse. Magnesium has a depressant effect on the central nervous system [see Drug Interactions (7)]. Magnesium acts peripherally to produce vasodilation.

    12.2 Pharmacodynamics

    With intravenous administration of magnesium sulfate the onset of anticonvulsant action is immediate and lasts about 30 minutes. The estimated magnesium concentration (above baseline) required to elicit half-maximum effect (EC50) on systolic and diastolic blood pressure in pregnant women with preeclampsia that received intravenous magnesium sulfate therapy was reported to be 1.5 and 1.8 mEq per liter (1.9 and 2.2 mg per dL), respectively, in a published study. Effective anticonvulsant serum concentrations range from 2.5 to 7.5 mEq per liter.

    Drug Interaction Studies

    The following information is based upon published case reports and clinical studies that could not be confirmed by an adequately controlled study, but still warrant consideration given the potential risks involved [see Drug Interactions (7)].

    Neuromuscular Blocking Agents:

    Potentiation and prolongation of neuromuscular blockade requiring modification of the neuromuscular blocking agent dosage and/or increased reversal agent requirements were reported in preeclamptic women who received magnesium sulfate treatment who underwent subsequent surgery (for example, caesarian section) with anesthesia that included either a depolarizing (d-tubocurarine, succinylcholine) or nondepolarizing neuromuscular blocking agent (vecuronium, rocuronium).

    Narcotics and/or Propofol:

    Potentiation and prolongation of analgesic and/or sedative effects as well as a reduced requirement for an intravenous narcotic (fentanyl, sufentanil, tramadol), intrathecal narcotic (fentanyl), and/or intravenous propofol was reported in magnesium sulfate treated patients who required surgery or intensive care that also included narcotic and/or propofol therapy.

    Dihydropyridine Calcium Channel Blockers:

    An exaggerated hypotensive response (blood pressure 80–93/49–60 mm Hg) was reported in preeclamptic women who received oral nifedipine in addition to magnesium sulfate treatment. Blood pressure returned to previous levels within approximately 30 minutes with supportive care.

    12.3 Pharmacokinetics

    Distribution

    Approximately 1 to 2% of total body magnesium is located in the extracellular fluid space. Magnesium is 30% bound to albumin.

    Elimination

    The average half-life and systemic clearance of magnesium sulfate in preeclamptic women is approximately 4 to 5 hours and 4 to 5 liters per hour, respectively.

    Excretion:

    Magnesium is excreted solely by the kidney at a rate proportional to the serum concentration and glomerular filtration.

    Specific Populations

    Patients with Renal Impairment:

    Plasma magnesium concentrations of 7 to 12.3 mEq per liter (8.6 to 15.1 mg per dL) were reported in preeclamptic women with a urine output less than 100 mL per 4 hours that received 20 grams of magnesium sulfate intravenously over 2 to 8 hours in a published study [see Dosage and Administration (2.3) and Use in Specific Populations (8.6)].

  • 13 NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    Studies with Magnesium Sulfate in 5% Dextrose Injection have not been performed to evaluate carcinogenic potential, mutagenic potential or effects on fertility.

  • 16 HOW SUPPLIED/STORAGE AND HANDLING

    Magnesium Sulfate in 5% Dextrose Injection, USP is supplied in a single-dose, single port bag with an aluminum overwrap. The infusion bags and ports are not made with natural rubber latex.

    NDC NumberPackaging ConfigurationContainer SizeTotal Magnesium Sulfate*Total Magnesium IonMagnesium Sulfate* ConcentrationMagnesium Ion ConcentrationOsmolarity†
  • * As the heptahydrate;
  • † Osmolarity was calculated.
    		•

    44567-410-24

    24 bags per carton

    100 mL

    1 gram

    8.1 mEq

    0.01 grams/mL (1%)

    8.1 mEq/100 mL

    333 mOsmol/

    liter

    Storage

    WARNING: DO NOT USE FLEXIBLE CONTAINER IN SERIES CONNECTIONS.
    Store at 20°C to 25°C (68°F to 77°F). [See USP Controlled Room Temperature.]
    PROTECT FROM FREEZING

  • 17 PATIENT COUNSELING INFORMATION

    Magnesium Sulfate in 5% Dextrose Injection is typically administered to pregnancy women in emergent situations. When feasible, advise the patient and family of the following:

    Fetal-Neonatal Toxicity Reported With Prolonged Use

    Continuous administration of Magnesium Sulfate in 5% Dextrose Injection in pregnant women beyond 5 to 7 days can lead to hypocalcemia and bone abnormalities in the developing fetus, including skeletal demineralization and osteopenia. In addition, cases of neonatal fracture have been reported [see Warnings and Precautions (5.1)].

    Risk of Magnesium Toxicity

    Pregnant women receiving Magnesium Sulfate in 5% Dextrose Injection are at risk for magnesium toxicity, including facial edema, diminished strength of deep tendon reflexes, and respiratory depression [see Warnings and Precautions (5.2)].

  • SPL UNCLASSIFIED SECTION

    Manufactured for:
    WG Critical Care, LLC
    Paramus, NJ 07652

    Made in Switzerland

  • PRINCIPAL DISPLAY PANEL - 100 mL Bag Overwrap

    NDC: 44567-410-24 100 mL

    Magnesium Sulfate
    in 5% Dextrose Injection, USP
    (0.081 mEq Mg++/mL) 10 mg/mL

    1 g Total

    Magnesium Sulfate in 5% Dextrose Injection, USP 1 g Total bag label image
  • INGREDIENTS AND APPEARANCE
    MAGNESIUM SULFATE 
    magnesium sulfate injection
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 44567-410
    Route of AdministrationINTRAVENOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    MAGNESIUM SULFATE HEPTAHYDRATE (UNII: SK47B8698T) (MAGNESIUM CATION - UNII:T6V3LHY838) MAGNESIUM SULFATE HEPTAHYDRATE1 g  in 100 mL
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 44567-410-2424 in 1 CARTON03/08/2016
    1100 mL in 1 BAG; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA20734903/08/2016
    Labeler - WG Critical Care, LLC (829274633)
    Registrant - HQ Specialty Pharma Corporation (962364332)
    Establishment
    NameAddressID/FEIBusiness Operations
    InfoRLife SA481732753MANUFACTURE(44567-410)
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