MAGNESIUM SULFATE IN DEXTROSE

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 The most common adverse reactions are flushing, sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia, circulatory collapse, cardiac and central nervous system (CNS) depression proceeding to respiratory paralysis and hypocalcemia. Bradycardia, pulmonary edema, decreased respiratory rate, lethargy, sedation, somnolence, visual disturbances, and hypermagnesemia are also reported (6) To report SUSPECTED ADVERSE REACTIONS, contact Baxter Healthcare Corporation at 1-866-888-2472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

4 CONTRAINDICATIONS Magnesium Sulfate in 5% Dextrose Injection is contraindicated in patients: • with heart block or myocardial damage • in diabetic coma • with myasthenia gravis [see Warnings and Precautions (5.6)] • Heart block or myocardial damage (4) • Diabetic coma (4) • Myasthenia gravis (4, 5.6)

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 MgSO 4 • 7H 2 O, 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 C 6 H 12 O 6 • H 2 O and the molecular weight is 198.17. It has the following structural formula: Water for Injection, USP is chemically designated H 2 O. Water can permeate from inside the Baxter VIAFLO flexible plastic container [composed of Polypropylene (PP), Polyamide (PA) and Polyethylene (PE)] 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. Dextrose Structural Formula

2 DOSAGE AND ADMINISTRATION • Administer via intravenous infusion pump (2.1) • Recommended loading dosage is 4 to 6 grams over 15 minutes followed by a recommended maintenance dosage of 1 to 2 grams every hour; maximum recommended dosage is 30 to 40 grams over 24 hours (2.2) • Obtain serum magnesium concentrations and assess clinical status to adjust the dose (2.2) • Administration beyond 5 to 7 days is not recommended (2.2 , 5.1) • In patients with severe renal impairment and/or urine output less than 0.5 mL/kg/hour, administer a 4 gram loading dose followed by a maintenance dosage of 1 gram every hour; do not exceed the maximum recommended dosage of 20 grams over 48 hours (2.3) • Do not administer Magnesium Sulfate in 5% Dextrose Injection with incompatible drugs through the same intravenous line, specifically with salicylates and alkali carbonates (2.4) 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.

1 INDICATIONS AND USAGE Magnesium Sulfate in 5% Dextrose Injection is indicated for: • Prevention of eclampsia in patients with preeclampsia • Treatment of seizures and prevention of recurrent seizures in patients with eclampsia Magnesium Sulfate in 5% Dextrose Injection is indicated for (1) : • Prevention of eclampsia in patients with preeclampsia (1) • Treatment of seizures and prevention of recurrent seizures in patients with eclampsia (1)

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.

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* 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 *For drug incompatibility information [see Dosage and Administration (2.4)] . • Neuromuscular blocking agents : Potentiation and prolongation of neuromuscular blockade is possible with the concomitant use of Magnesium Sulfate in 5% Dextrose Injection (7) • Narcotics and/or propofol : Potentiation and prolongation of analgesia and CNS depression is possible with the concomitant use of Magnesium Sulfate in 5% Dextrose Injection (7) • Dihydropyridine calcium channel blockers : An exaggerated hypotensive response is possible with the concomitant use of Magnesium Sulfate in 5% Dextrose Injection (7) • Drugs that may induce magnesium loss with concomitant use of Magnesium Sulfate in 5% Dextrose Injection : Alcohol, aminoglycosides, amphotericin B, cisplatin, cyclosporine, digitalis, loop diuretics, and thiazide diuretics (7)

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 (EC 50 ) 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) ] .

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 (EC 50 ) 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) ] .

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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 bags: • 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. Supplied in premixed single-dose bags: (3) • 0.01 grams/mL (1%) in 100 mL bag containing 1 gram of magnesium sulfate in 5% dextrose injection

MAGNESIUM SULFATE IN DEXTROSE magnesium sulfate in dextrose MAGNESIUM SULFATE HEPTAHYDRATE MAGNESIUM CATION SULFURIC ACID SODIUM HYDROXIDE DEXTROSE MONOHYDRATE WATER

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.

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.

ANDA211965

MAGNESIUM SULFATE IN DEXTROSE

magnesium sulfate in dextrose

0338-1709

HUMAN PRESCRIPTION DRUG

INTRAVENOUS

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL Container Label 100 mL NDC 0338-1709-40 Magnesium Sulfate in 5% Dextrose Injection, USP 1 g/ 100 mL (10 mg/mL) 1 g TOTAL Each 100 mL of sterile, nonpyrogenic solution contains: Magnesium Sulfate Heptahydrate 1 g (equivalent to 8.1 mEq magnesium) and dextrose, hydrous 5 g in water for injection. May contain sulfuric acid and/or sodium hydroxide for pH adjustment. pH 4.5 ( 3.5 to 6.5 ) 333 mOsmol/Liter (calc.) Single-Dose Container – Discard unused portion. For Intravenous Use. Recommended dosage: See prescribing information. Use only if solution is clear and container is undamaged. Must not be used in series connections. Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.] Protect from freezing. VIAFLO container is not made with natural rubber latex, DEHP, or PVC. Rx Only Number 07 plastics symbol 0 Bar code (01) 00303381709402 Baxter Healthcare Corporation Deerfield, IL 60015 USA Made in Ireland EZPE8501 CB-35-04-890 DO NOT USE THIS PORT symbol Lot Exp Overpouch Label 100 mL TO OPEN – TEAR AT NOTCH NDC 0338-1709-40 Magnesium Sulfate in 5% Dextrose Injection, USP 1 g/100 mL (10 mg/mL) 1g Total Each 100 mL of sterile, nonpyrogenic solution contains: Magnesium Sulfate Heptahydrate 1 g (equivalent to 8.1 mEq magnesium) and dextrose, hydrous 5 g in water for injection. May contain sulfuric acid and/or sodium hydroxide for pH adjustment. 333 mOsmol/Liter (calc.) pH 4.5 (3.5 to 6.5) DO NOT ADD SUPPLEMENTARY MEDICATION. WHENEVER POSSIBLE USE CENTRAL ROUTE. Single-Dose Container – Discard unused portion. For Intravenous Use. Recommended dosage: See prescribing information. Use only if solution is clear and container is undamaged. After removing the overwrap, check for minute leaks by squeezing container firmly. If leaks are found, discard unit as sterility may be impaired. Must not be used in series connections. The overwrap is a moisture barrier. Do not remove unit from overwrap until ready for use. Use unit promptly when pouch is opened. Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.] Protect from freezing. VIAFLO container is not made with natural rubber latex, DEHP, or PVC. 2D Barcode (91)CB1001219 Rx Only EZPE8501 CB-10-01-219 Baxter Logo Baxter Healthcare Corporation Deerfield, IL 60015 USA Made in Ireland (See Solution Container for Lot and Exp) Barcode (01) 00303381709402 Magnesium Sulfate in Dextrose Representative Container Label 0338-1709-40 Magnesium Sulfate in Dextrose Representative Overpouch Label 0338-1709-40

17 PATIENT COUNSELING INFORMATION Magnesium Sulfate in 5% Dextrose Injection is typically administered to pregnant 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)] . Baxter Logo Baxter Healthcare Corporation Deerfield, IL 60015 USA Made in Ireland Baxter and Viaflo are trademarks of Baxter International Inc. CB-30-02-634

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)] .

8.1 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 USE IN SPECIFIC POPULATIONS Patients with severe renal impairment and/or a urine output less than 100 mL every 4 hours are at greater risk for increased magnesium concentrations that may lead to toxicity (8.6) 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) ].

16 HOW SUPPLIED/STORAGE AND HANDLING Magnesium Sulfate in 5% Dextrose Injection, USP is a clear solution supplied in VIAFLO single-dose flexible plastic containers (see Table 2 ). Table 2 : How Supplied Information Magnesium Sulfate* Concentration NDC Number Product Code Container Size Total Magnesium Sulfate* Total Magnesium Ion Magnesium Ion Concentration Osmolarity** 0.01 grams/mL (1%) 0338-1709-40 EZPE8501 100 mL 1 gram 8.1 mEq 8.1 mEq/100 mL 333 mOsmol/liter *As the heptahydrate; **Osmolarity was calculated. VIAFLO container is not made with natural rubber latex, DEHP, or PVC. Storage Store at 20°C to 25°C (68°F to 77°F). [See USP Controlled Room Temperature.] Protect from freezing.