TERATOGENIC EFFECTS SECTION.

Teratogenic Effects. Magnesium Sulfate in Water for Injection can cause fetal abnormalities when administered beyond 5-7 days to pregnant women. There are retrospective epidemiological studies and case reports documenting fetal abnormalities such as hypocalcemia, skeletal demineralizations, osteopenia and other skeletal abnormalities with continuous maternal administration of magnesium sulfate for more than 5-7 days.1-12 Magnesium Sulfate in Water for Injection should be used during pregnancy only if clearly needed. If this drug is used during pregnancy the woman should be apprised of the potential harm to the fetus.

ADVERSE REACTIONS SECTION.

ADVERSE REACTIONS The adverse effects of parenterally administered magnesium usually are the result of magnesium intoxication. These include flushing, sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia, circulatory collapse, cardiac and central nervous system depression proceeding to respiratory paralysis. Hypocalcemia with signs of tetany secondary to magnesium sulfate therapy for eclampsia has been reported.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

Carcinogenesis, Mutagenesis, Impairment of Fertility Studies with Magnesium Sulfate in Water for Injection have not been performed to evaluate carcinogenic potential, mutagenic potential or effects on fertility.

OVERDOSAGE SECTION.

OVERDOSAGE Magnesium intoxication is manifested by sharp drop in blood pressure and respiratory paralysis. Disappearance of the patellar reflex is useful clinical sign to detect the onset of magnesium intoxication. In the event of overdosage, artificial ventilation must be provided until calcium salt can be injected intravenously to antagonize the effects of magnesium.. For Treatment of Overdose Artificial respiration is often required. Intravenous calcium, 10 to 20 mL of 5% solution (diluted if desirable) with isotonic sodium chloride for injection) is used to counteract effects of hypermagnesemia. Subcutaneous physostigmine, 0.5 to mg may be helpful.Hypermagnesemia in the newborn may require resuscitation and assisted ventilation via endotracheal intubation or intermittent positive pressure ventilation as well as intravenous calcium.

CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY Magnesium (Mg++) is an important cofactor for enzymatic reactions and plays an important role in neurochemical transmission and muscular excitability.Magnesium prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse. Magnesium is said to have depressant effect on the central nervous system, but it does not adversely affect the mother, fetus or neonate when used as directed in eclampsia or pre-eclampsia. Normal serum magnesium levels range from 1.3 to 2.1 mEq/liter.As serum magnesium rises above mEq/liter, the deep tendon reflexes are first decreased and then disappear as the serum level approaches 10 mEq/liter. At this level respiratory paralysis may occur. Heart block also may occur at this or lower serum levels of magnesium.Magnesium acts peripherally to produce vasodilation. With low doses only flushing and sweating occur, but larger doses cause lowering of blood pressure. The central and peripheral effects of magnesium poisoning are antagonized to some extent by intravenous administration of calcium.With intravenous administration the onset of anticonvulsant action is immediate and lasts about 30 minutes. Following intramuscular administration the onset of action occurs in about one hour and persists for three to four hours. Effective anticonvulsant serum levels range from 2.5 to 7.5 mEq/liter.. Pharmacokinetics AbsorptionIntravenously administered magnesium is immediately absorbed.DistributionApproximately 1-2% of total body magnesium is located in the extracellular fluid space. Magnesium is 30% bound to albumin.MetabolismMagnesium is not metabolized.ExcretionMagnesium is excreted solely by the kidney at rate proportional to the serum concentration and glomerular filtration.Special PopulationsRenal InsufficiencyMagnesium is excreted solely by the kidney. In patients with severe renal insufficiency, the dose should be lower and frequent serum magnesium levels must be obtained (see DOSAGE AND ADMINISTRATION).Hepatic InsufficiencyMagnesium is excreted solely by the kidney. No dosing adjustments are necessary in hepatic insufficiency.Drug-Drug InteractionsDrug induced renal losses of magnesium occur with the following drugs or drug classes:AminoglycosidesAmphotericin BCyclosporineDiureticsDigitalisCisplatinAlcohol.

CONTRAINDICATIONS SECTION.

CONTRAINDICATIONS Intravenous magnesium should not be given to mothers with toxemia of pregnancy during the two hours preceding delivery.

DESCRIPTION SECTION.

DESCRIPTION Magnesium Sulfate in Water for Injection is sterile, nonpyrogenic solution of magnesium sulfate heptahydrate in water for injection. May contain sulfuric acid and/or sodium hydroxide for pH adjustment. The pH is 4.5 (3.5 to 6.5). It is available in 4% and 8% concentrations. See HOW SUPPLIED section for the content and characteristics of available dosage forms and sizes.Magnesium Sulfate, USP heptahydrate is chemically designated MgSO4 7H2O, colorless crystals or white powder freely soluble in water.Water for Injection, USP is chemically designated H2O.VIAFLO container is flexible plastic container fabricated from multilayer sheeting composed of Polypropylene (PP), Polyamide (PA) and Polyethylene (PE). The amount of water that can permeate from the container into the overwrap is insufficient to affect the solution significantly. Solutions in contact with the flexible container can leach out certain of the containers chemical components in very small amounts within the expiration period. The suitability of the container material has been confirmed by tests in animals according to USP biological tests for plastic containers. Exposure to temperatures above 25C/77F 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.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION Magnesium Sulfate in Water for Injection is intended for intravenous use only. For the management of pre-eclampsia or eclampsia, intravenous infusions of dilute solutions of magnesium (1% to 8%) are often given in combination with intramuscular injections of 50% Magnesium Sulfate Injection, USP. Therefore, in the clinical conditions cited below, both forms of therapy are noted, as appropriate.Continuous maternal administration of magnesium sulfate in pregnancy beyond 5-7 days can cause fetal abnormalities.. In Pre-Eclampsia or Eclampsia In severe pre-eclampsia or eclampsia, the total initial dose is 10 to 14 of magnesium sulfate. To initiate therapy, g of Magnesium Sulfate in Water for Injection may be administered intravenously. The rate of intravenous infusion should generally not exceed 150 mg/minute, or 3.75 mL of 4% concentration (or its equivalent) per minute, except in severe eclampsia with seizures. Simultaneously, to g (32.5 to 40.6 mEq) of magnesium sulfate may be administered intramuscularly into each buttock using undiluted 50% Magnesium Sulfate Injection. After the initial intravenous dose, some clinicians administer to g/hour by constant intravenous infusion.Subsequent intramuscular doses of to g of magnesium sulfate may be injected into alternate buttocks every four hours, depending on the continuing presence of the patellar reflex, adequate respiratory function, and absence of signs of magnesium toxicity. Therapy should continue until paroxysms cease.A serum magnesium level of mg/100 mL is considered optimal for control of seizures. total daily (24 hr) dose of 30 to 40 magnesium sulfate should not be exceeded. In the presence of severe renal insufficiency, frequent serum magnesium concentrations must be obtained and the maximum recommended dosage of magnesium sulfate is 20 per 48 hours.Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.Do not administer unless solution is clear. Discard unused portion.

HOW SUPPLIED SECTION.

HOW SUPPLIED Magnesium Sulfate in Water for Injection is supplied in single-dose flexible plastic containers as follows:Product CodeNDC No.Size ContainerTotal Magnesium SulfateTotal Magnesium IonMagnesium Sulfate ConcentrationMagnesium Ion ConcentrationOsmolarity (calc.)EZPE80010338-1708-4050 mL2g16.25 mEq4% (40 mg/mL)16.25 mEq/50 mL325 mOsmol/LiterEZPE80030338-1715-40100 mL4 g32.5 mEq4% (40 mg/mL)32.5 mEq/100 mL325 mOsmol/LiterEZPE80020338-1719-4050 mL4g32.5 mEq8% (80 mg/mL)32.5 mEq/50 mL649 mOsmol/LiterAs the heptahydrate.WARNING: DO NOT USE FLEXIBLE CONTAINER IN SERIES CONNECTIONS.The container closure is not made with natural rubber latex. Non-PVC, Non-DEHP, Sterile.Store at 20 to 25C (68 to 77F). [See USP Controlled Room Temperature.] Protect from freezing.

INDICATIONS & USAGE SECTION.

INDICATIONS AND USAGE Magnesium Sulfate in Water for Injection is indicated for the prevention and control of seizures in preeclampsia and eclampsia, respectively. When used judiciously it effectively prevents and controls the convulsions of eclampsia without producing deleterious depression of the central nervous system of the mother or infant. However, other effective drugs are available for this purpose.

LABOR & DELIVERY SECTION.

Labor and Delivery. Continuous administration of magnesium sulfate is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of Magnesium Sulfate in Water for Injection outside of its approved indication in pregnant women should be by trained obstetrical personnel in hospital setting with appropriate obstetrical care facilities.

NONTERATOGENIC EFFECTS SECTION.

Nonteratogenic Effects. When administered by continuous intravenous infusion (especially for more than 24 hours preceding delivery) to control convulsions in toxemic woman, the newborn may show signs of magnesium toxicity, including neuromuscular or respiratory depression. (see OVERDOSAGE).

NURSING MOTHERS SECTION.

Nursing Mothers. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Magnesium Sulfate in Water for Injection is administered to nursing woman.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL Container Label50 mL NDC 0338-1708-40 Magnesium Sulfatein Water for Injection2 Total 2g/50 mL 40 mg per mLEach 50 mL of sterile, nonpyrogenic solution contains:Magnesium Sulfate Heptahydrate g (equivalent to 16.25 mEqmagnesium) in water for injection. May contain sulfuric acid and/or sodium hydroxide for pH adjustment.pH 4.5 (3.5 to 6.5) 325 mOsmol/Liter (calc.)Single-Dose Container Discard unused portion. For IntravenousInfusionRecommended dosage: See prescribing information. Use only ifsolution is clear and container is undamaged. Must not be usedin series connections. Store at 20 to 25C (68 to 77F). [See USPControlled Room Temperature.] Protect from freezing. VIAFLOcontainer is not made with natural rubber latex, DEHP, or PVC.Rx OnlyRecycle 07 logoBarcode(01) 00303381708405Baxter Logo Baxter Healthcare CorporationDeerfield, IL 60015 USAMade in IrelandEZPE8001CB-35-04-891DO NOT USETHIS PORTDo not use this port logoLOT EXPContainer Label100 mLNDC 0338-1715-40Magnesium Sulfatein Water for Injection4 g/100 mL (40 mg per mL)4gtotalEach 100 mL of sterile, nonpyrogenic solution contains:Magnesium Sulfate Heptahydrate g (equivalent to 32.5 mEqmagnesium) in water for injection. May contain sulfuric acid and/or sodium hydroxide for pH adjustment.pH 4.5 (3.5 to 6.5) 325 mOsmol/Liter (calc.)Single-Dose Container Discard unused portion. For IntravenousInfusionRecommended dosage: See prescribing information. Use only ifsolution is clear and container is undamaged. Must not be usedin series connections. Store at 20 to 25C (68 to 77F). [See USPControlled Room Temperature.] Protect from freezing. VIAFLOcontainer is not made with natural rubber latex, DEHP, or PVC.Rx OnlyRecycle 07 logoBarcode(01) 00303381715403Baxter Logo Baxter Healthcare CorporationDeerfield, IL 60015 USAMade in IrelandEZPE8003CB-35-04-893DO NOT USETHIS PORTDo not use this port logoLOT EXPContainer Label50 mLNDC 0338-1719-40Magnesium Sulfatein Water for Injection4 g/50 mL (80 mg per mL) 4g totalEach 50 mL of sterile, nonpyrogenic solution contains:Magnesium Sulfate Heptahydrate g (equivalent to 32.5 mEqmagnesium) in water for injection. May contain sulfuric acid and/or sodium hydroxide for pH adjustment.pH 4.5 (3.5 to 6.5) 649 mOsmol/Liter (calc.)Single-Dose Container Discard unused portion. For IntravenousInfusionRecommended dosage: See prescribing information. Use only ifsolution is clear and container is undamaged. Must not be usedin series connections. Store at 20 to 25C (68 to 77F). [See USPControlled Room Temperature.] Protect from freezing. VIAFLOcontainer is not made with natural rubber latex, DEHP, or PVC.Rx OnlyRecycle 07 logoBarcode(01) 0030338179401Baxter Logo Baxter Healthcare CorporationDeerfield, IL 60015 USAMade in IrelandEZPE8002CB-35-04-892DO NOT USETHIS PORTDo not use this port logoLOT EXPOverpouch Label50 mL NDC 0338-1708-40Magnesium Sulfatein Water for Injection2gTotal2 g/50 mL (40 mg/mL)Each 50 mL of sterile, nonpyrogenic solution contains:Magnesium Sulfate Heptahydrate g (equivalent to 16.25 mEq magnesium) inwater for injection. May contain sulfuric acid and/or sodium hydroxide for pHadjustment.325 mOsmol/Liter (calc.) pH 4.5 (3.5 to 6.5)DO NOT ADD SUPPLEMENTARY MEDICATION. WHENEVER POSSIBLE USECENTRAL ROUTE.Single-Dose Container Discard unused portion. For Intravenous Infusion.Recommended dosage: See prescribing information. Use only if solution isclear and container is undamaged. After removing the overwrap, check forminute leaks by squeezing container firmly. If leaks are found, discard unit assterility may be impaired. Must not be used in series connections.The overwrap is moisture barrier. Do not remove unit from overwrap untilready for use. Use promptly once overpouch is opened. Store at 20 to 25C (68to 77F). [See USP Controlled Room Temperature.] Protect from freezing.2D Barcode(91)CB1001192Rx OnlyEZPE8001CB-10-01-192Baxter LogoBaxter Healthcare CorporationDeerfield, IL 60015 USAMade in Ireland(See Solution Container for Lot and Exp)Barcode(01) 00303381708405Overpouch Label100 mL NDC 0338-1715-40Magnesium Sulfatein Water for Injection4 g/100 mL (40 mg/mL)4gTotalEach 100 mL of sterile, nonpyrogenic solution contains: Magnesium SulfateHeptahydrate g (equivalent to 32.5 mEq magnesium) in water for injection.May contain sulfuric acid and/or sodium hydroxide for pH adjustment.325 mOsmol/Liter (calc.) pH 4.5 (3.5 to 6.5)DO NOT ADD SUPPLEMENTARY MEDICATION. WHENEVER POSSIBLE USECENTRAL ROUTE.Single-Dose Container Discard unused portion. For Intravenous Infusion.Recommended dosage: See prescribing information. Use only if solution isclear and container is undamaged. After removing the overwrap, check forminute leaks by squeezing container firmly. If leaks are found, discard unit assterility may be impaired. Must not be used in series connections.The overwrap is moisture barrier. Do not remove unit from overwrap untilready for use. Use promptly once overpouch is opened. Store at 20 to 25C (68to 77F). [See USP Controlled Room Temperature.] Protect from freezing.2D Barcode(91)CB1001194Rx OnlyEZPE8003CB-10-01-194Baxter LogoBaxter Healthcare CorporationDeerfield, IL 60015 USAMade in Ireland(See Solution Container for Lot and Exp)Barcode(01) 00303381715403Overpouch Label50 mL NDC 0338-1719-40Magnesium Sulfatein Water for Injection4 g/50 mL (80 mg/mL)4gTotalEach 50 mL of sterile, nonpyrogenic solution contains: Magnesium SulfateHeptahydrate g (equivalent to 32.5 mEq magnesium) in water for injection.May contain sulfuric acid and/or sodium hydroxide for pH adjustment.649 mOsmol/Liter (calc.) pH 4.5 (3.5 to 6.5)DO NOT ADD SUPPLEMENTARY MEDICATION. WHENEVER POSSIBLE USECENTRAL ROUTE.Single-Dose Container Discard unused portion. For Intravenous Infusion.Recommended dosage: See prescribing information. Use only if solution isclear and container is undamaged. After removing the overwrap, check forminute leaks by squeezing container firmly. If leaks are found, discard unit assterility may be impaired. Must not be used in series connections.The overwrap is moisture barrier. Do not remove unit from overwrap untilready for use. Use promptly once overpouch is opened. Store at 20 to 25C (68to 77F). [See USP Controlled Room Temperature.] Protect from freezing.2D Barcode(91)CB1001193Rx OnlyEZPE8002CB-10-01-193Baxter LogoBaxter Healthcare CorporationDeerfield, IL 60015 USAMade in Ireland(See Solution Container for Lot and Exp)Barcode(01) 00303381719401. Magnesium Sulfate in Water Representative Container Label 0338-1708-40. Magnesium Sulfate in Water Representative Container Label 0338-1715-40. Magnesium Sulfate in Water Representative Container Label 0338-1719-40.jpg. Magnesium Sulfate in Water Representative Overpouch Label 0338-1708-40. Magnesium Sulfate in Water Representative Overpouch Label 0338-1715-40. Magnesium Sulfate in Water Representative Overpouch Label 0338-1719-40.

PHARMACOKINETICS SECTION.

Pharmacokinetics AbsorptionIntravenously administered magnesium is immediately absorbed.DistributionApproximately 1-2% of total body magnesium is located in the extracellular fluid space. Magnesium is 30% bound to albumin.MetabolismMagnesium is not metabolized.ExcretionMagnesium is excreted solely by the kidney at rate proportional to the serum concentration and glomerular filtration.Special PopulationsRenal InsufficiencyMagnesium is excreted solely by the kidney. In patients with severe renal insufficiency, the dose should be lower and frequent serum magnesium levels must be obtained (see DOSAGE AND ADMINISTRATION).Hepatic InsufficiencyMagnesium is excreted solely by the kidney. No dosing adjustments are necessary in hepatic insufficiency.Drug-Drug InteractionsDrug induced renal losses of magnesium occur with the following drugs or drug classes:AminoglycosidesAmphotericin BCyclosporineDiureticsDigitalisCisplatinAlcohol.

PRECAUTIONS SECTION.

PRECAUTIONS Because magnesium is removed from the body solely by the kidneys, the drug should be used with caution in patients with renal impairment. Urine output should be maintained at level of 100 mL every four hours. Monitoring serum magnesium levels and the patients clinical status is essential to avoid the consequences of overdosage in toxemia. Clinical indications of safe dosage regimen include the presence of the patellar reflex (knee jerk) and absence of respiratory depression (approximately 16 breaths or more/minute). Serum magnesium levels usually sufficient to control convulsions range from to mg/100 mL (2.5 to mEq/liter). The strength of the deep tendon reflexes begins to diminish when serum magnesium levels exceed mEq/liter. Reflexes may be absent at 10 mEq magnesium/liter, where respiratory paralysis is potential hazard. An injectable calcium salt should be immediately available to counteract the potential hazards of magnesium intoxication in eclampsia.Magnesium Sulfate in Water for Injection should be administered slowly to avoid producing hypermagnesemia.. Carcinogenesis, Mutagenesis, Impairment of Fertility Studies with Magnesium Sulfate in Water for Injection have not been performed to evaluate carcinogenic potential, mutagenic potential or effects on fertility.. Pregnancy (See WARNINGS and PRECAUTIONS). Teratogenic Effects. Magnesium Sulfate in Water for Injection can cause fetal abnormalities when administered beyond 5-7 days to pregnant women. There are retrospective epidemiological studies and case reports documenting fetal abnormalities such as hypocalcemia, skeletal demineralizations, osteopenia and other skeletal abnormalities with continuous maternal administration of magnesium sulfate for more than 5-7 days.1-12 Magnesium Sulfate in Water for Injection should be used during pregnancy only if clearly needed. If this drug is used during pregnancy the woman should be apprised of the potential harm to the fetus.. Nonteratogenic Effects. When administered by continuous intravenous infusion (especially for more than 24 hours preceding delivery) to control convulsions in toxemic woman, the newborn may show signs of magnesium toxicity, including neuromuscular or respiratory depression. (see OVERDOSAGE). Labor and Delivery. Continuous administration of magnesium sulfate is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of Magnesium Sulfate in Water for Injection outside of its approved indication in pregnant women should be by trained obstetrical personnel in hospital setting with appropriate obstetrical care facilities.. Nursing Mothers. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Magnesium Sulfate in Water for Injection is administered to nursing woman.

PREGNANCY SECTION.

Pregnancy (See WARNINGS and PRECAUTIONS). Teratogenic Effects. Magnesium Sulfate in Water for Injection can cause fetal abnormalities when administered beyond 5-7 days to pregnant women. There are retrospective epidemiological studies and case reports documenting fetal abnormalities such as hypocalcemia, skeletal demineralizations, osteopenia and other skeletal abnormalities with continuous maternal administration of magnesium sulfate for more than 5-7 days.1-12 Magnesium Sulfate in Water for Injection should be used during pregnancy only if clearly needed. If this drug is used during pregnancy the woman should be apprised of the potential harm to the fetus.. Nonteratogenic Effects. When administered by continuous intravenous infusion (especially for more than 24 hours preceding delivery) to control convulsions in toxemic woman, the newborn may show signs of magnesium toxicity, including neuromuscular or respiratory depression. (see OVERDOSAGE).

REFERENCES SECTION.

REFERENCES 1.Yokoyama K, Takahashi N, Yada Y. Prolonged maternal magnesium administration and bone metabolism in neonates. Early Human Dev. 2010; 86(3):187-91. Epub 2010 Mar 12.2.Wedig KE, Kogan J, Schorry EK et al. Skeletal demineralization and fractures caused by fetal magnesium toxicity. Perinatol. 2006; 26(6):371-4.3.Nassar AH, Sakhel K, Maarouf H, et al. Adverse maternal and neonatal outcome of prolonged course of magnesium sulfate tocolysis. Acta Obstet Gynecol Scan. 2006; 85(9):1099-103.4.Malaeb SN, Rassi A, Haddad MC. Bone mineralization in newborns whose mothers received magnesium sulphate for tocolysis of premature labor. Pediatr Radiol. 2004; 34(5):384-6. Epub 2004 Feb 18.5.Matsuda Y, Maeda Y, Ito M, et al. Effect of magnesium sulfate treatment on neonatal bone abnormalities. Gynecol Obstet Invest. 1997; 44(2):82-8.6.Schanler RJ, Smith LG, Burns PA. Effects of long-term maternal intravenous magnesium sulfate therapy on neonatal calcium metabolism and bone mineral content. Gynecol Obstet Invest. 1997; 43(4):236-41.7.Santi MD, Henry GW, Douglas GL. Magnesium sulfate treatment of preterm labor as cause of abnormal neonatal bone mineralization. Pediatr Orthop. 1994; 14(2):249-53.8.Holocomb WL, Shackelford GD, Petrie RH. Magnesium tocolysis and neonatal bone abnormalities: controlled study. Obstet Gynecol. 1991; 78(4):611-4.9.Cumming WA, Thomas VJ. Hypermagnesemia: cause of abnormal metaphyses in the neonate. Am Roentgenol. 1989; 152(5):1071-2.10.Lamm CL, Norton KL, Murphy RJ. Congenital rickets associated with magnesium sulfate infusion for tocolysis. Pediatr. 1988; 113(6):1078-82.11.McGuinness GA, Weinstein MM, Cruikshank DP, et al. Effects of magnesium sulfate treatment on perinatal calcium metabolism. II. Neonatal responses. Obstet Gynecol. 1980; 56(5):595-600. 12.Riaz M, Porat R, Brodsky NL, et al. The effect of maternal magnesium sulfate treatment on newborns: prospective controlled study. Perinatol. 1998; 18(6 pt 1):449-54.. 1.Yokoyama K, Takahashi N, Yada Y. Prolonged maternal magnesium administration and bone metabolism in neonates. Early Human Dev. 2010; 86(3):187-91. Epub 2010 Mar 12.. 2.Wedig KE, Kogan J, Schorry EK et al. Skeletal demineralization and fractures caused by fetal magnesium toxicity. Perinatol. 2006; 26(6):371-4.. 3.Nassar AH, Sakhel K, Maarouf H, et al. Adverse maternal and neonatal outcome of prolonged course of magnesium sulfate tocolysis. Acta Obstet Gynecol Scan. 2006; 85(9):1099-103.. 4.Malaeb SN, Rassi A, Haddad MC. Bone mineralization in newborns whose mothers received magnesium sulphate for tocolysis of premature labor. Pediatr Radiol. 2004; 34(5):384-6. Epub 2004 Feb 18.. 5.Matsuda Y, Maeda Y, Ito M, et al. Effect of magnesium sulfate treatment on neonatal bone abnormalities. Gynecol Obstet Invest. 1997; 44(2):82-8.. 6.Schanler RJ, Smith LG, Burns PA. Effects of long-term maternal intravenous magnesium sulfate therapy on neonatal calcium metabolism and bone mineral content. Gynecol Obstet Invest. 1997; 43(4):236-41.. 7.Santi MD, Henry GW, Douglas GL. Magnesium sulfate treatment of preterm labor as cause of abnormal neonatal bone mineralization. Pediatr Orthop. 1994; 14(2):249-53.. 8.Holocomb WL, Shackelford GD, Petrie RH. Magnesium tocolysis and neonatal bone abnormalities: controlled study. Obstet Gynecol. 1991; 78(4):611-4.. 9.Cumming WA, Thomas VJ. Hypermagnesemia: cause of abnormal metaphyses in the neonate. Am Roentgenol. 1989; 152(5):1071-2.. 10.Lamm CL, Norton KL, Murphy RJ. Congenital rickets associated with magnesium sulfate infusion for tocolysis. Pediatr. 1988; 113(6):1078-82.. 11.McGuinness GA, Weinstein MM, Cruikshank DP, et al. Effects of magnesium sulfate treatment on perinatal calcium metabolism. II. Neonatal responses. Obstet Gynecol. 1980; 56(5):595-600. 12.Riaz M, Porat R, Brodsky NL, et al. The effect of maternal magnesium sulfate treatment on newborns: prospective controlled study. Perinatol. 1998; 18(6 pt 1):449-54.

SPL UNCLASSIFIED SECTION.

For Treatment of Overdose Artificial respiration is often required. Intravenous calcium, 10 to 20 mL of 5% solution (diluted if desirable) with isotonic sodium chloride for injection) is used to counteract effects of hypermagnesemia. Subcutaneous physostigmine, 0.5 to mg may be helpful.Hypermagnesemia in the newborn may require resuscitation and assisted ventilation via endotracheal intubation or intermittent positive pressure ventilation as well as intravenous calcium.

WARNINGS SECTION.

WARNINGS FETAL HARM: Continuous administration of magnesium sulfate beyond 5-7 days to pregnant women can lead to hypocalcemia and bone abnormalities in the developing fetus. These bone abnormalities include skeletal demineralization and osteopenia. In addition, cases of neonatal fracture have been reported. The shortest duration of treatment that can lead to fetal harm is not known. Magnesium sulfate should be used during pregnancy only if clearly needed. If magnesium sulfate is given for treatment of preterm labor, the woman should be informed that the efficacy and safety of such use have not been established and that use of magnesium sulfate beyond 5-7 days may cause fetal abnormalities.Parenteral use in the presence of renal insufficiency may lead to magnesium intoxication.