Magnesium Sulfate

INDICATIONS AND USAGE Magnesium Sulfate Injection, USP is suitable for replacement therapy in magnesium deficiency, especially in acute hypomagnesemia accompanied by signs of tetany similar to those observed in hypocalcemia. In such cases, the serum magnesium (Mg ++ ) level is usually below the lower limit of normal (1.5 to 2.5 mEq/liter) and the serum calcium (Ca ++ ) level is normal (4.3 to 5.3 mEq/liter) or elevated. In total parenteral nutrition (TPN), magnesium sulfate may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy. Magnesium Sulfate Injection, USP is also indicated for the prevention and control of seizures (convulsions) in pre-eclampsia and eclampsia, respectively.

DOSAGE AND ADMINISTRATION: 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. Both IV and IM administration are appropriate. IM administration of the undiluted 50% solution results in therapeutic plasma levels in 60 minutes, whereas IV doses will provide a therapeutic level almost immediately. The rate of IV injection should generally not exceed 150 mg/minute (1.5 mL of a 10% concentration or its equivalent), except in severe eclampsia with seizures (see below). Continuous maternal administration of magnesium sulfate injection in pregnancy beyond 5 to 7 days can cause fetal abnormalities. Solutions for IV infusion must be diluted to a concentration of 20% or less prior to administration. The diluents commonly used are 5% Dextrose Injection, USP and 0.9% Sodium Chloride Injection, USP. Deep IM injection of the undiluted (50%) solution is appropriate for adults, but the solution should be diluted to a 20% or less concentration prior to such injection in children. In Magnesium Deficiency In the treatment of mild magnesium deficiency, the usual adult dose is 1 g, equivalent to 8.12 mEq of magnesium (2 mL of the 50% solution) injected IM every six hours for four doses (equivalent to a total of 32.5 mEq of magnesium per 24 hours). For severe hypomagnesemia, as much as 250 mg (approximately 2 mEq) per kg of body weight (0.5 mL of the 50% solution) may be given IM within a period of four hours if necessary. Alternatively, 5 g (approximately 40 mEq) can be added to one liter of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP for slow IV infusion over a three-hour period. In the treatment of deficiency states, caution must be observed to prevent exceeding the renal excretory capacity. In Hyperalimentation In TPN, maintenance requirements for magnesium are not precisely known. The maintenance dose used in adults ranges from 8 to 24 mEq (1 to 3 g) daily; for infants, the range is 2 to 10 mEq (0.25 to 1.25 g) daily. In Pre-eclampsia or Eclampsia In severe pre-eclampsia or eclampsia, the total initial dose is 10 to 14 g of magnesium sulfate. Intravenously, a dose of 4 to 5 g in 250 mL of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP may be infused. Simultaneously, IM doses of up to 10 g (5 g or 10 mL of the undiluted 50% solution in each buttock) are given. Alternatively, the initial IV dose of 4 g may be given by diluting the 50% solution to a 10 or 20% concentration; the diluted fluid (40 mL of a 10% solution or 20 mL of a 20% solution) may then be injected IV over a period of three to four minutes. Subsequently, 4 to 5 g (8 to 10 mL of the 50% solution) are injected IM into alternate buttocks every four hours as needed, depending on the continuing presence of the patellar reflex and adequate respiratory function. Alternatively, after the initial IV dose, some clinicians administer 1 to 2 g/hour by constant IV infusion. Therapy should continue until paroxysms cease. A serum magnesium level of 6 mg/100 mL is considered optimal for control of seizures. A total daily (24 hr) dose of 30 to 40 g should not be exceeded. In the presence of severe renal insufficiency, the maximum dosage of magnesium sulfate is 20 grams/48 hours and frequent serum magnesium concentrations must be obtained. Continuous use of magnesium sulfate in pregnancy beyond 5 to 7 days can cause fetal abnormalities. Other uses In counteracting the muscle-stimulating effects of barium poisoning, the usual dose of magnesium sulfate is 1 to 2 g given IV. For controlling seizures associated with epilepsy, glomerulonephritis or hypothyroidism, the usual adult dose is 1 g administered IM or IV. In paroxysmal atrial tachycardia, magnesium should be used only if simpler measures have failed and there is no evidence of myocardial damage. The usual dose is 3 to 4 g (30 to 40 mL of a 10% solution) adm …

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

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. To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions CNS Depressants — When barbiturates, narcotics or other hypnotics (or systemic anesthetics), or other CNS depressants are to be given in conjunction with magnesium, their dosage should be adjusted with caution because of additive CNS depressant effects of magnesium. CNS depression and peripheral transmission defects produced by magnesium may be antagonized by calcium. Neuromuscular Blocking Agents — Excessive neuromuscular block has occurred in patients receiving parenteral magnesium sulfate and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution. Cardiac Glycosides — Magnesium sulfate should be administered with extreme caution in digitalized patients, because serious changes in cardiac conduction which can result in heart block may occur if administration of calcium is required to treat magnesium toxicity.

DESCRIPTION Magnesium Sulfate in Water for Injection is a 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 a 3%, 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 MgSO 4 • 7H 2 O, colorless crystals or white powder freely soluble in water. Water for Injection, USP is chemically designated H 2 O. VIAFLO container is a flexible plastic container fabricated from a 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 container’s 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 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.

OVERDOSAGE: Magnesium intoxication is manifested by a sharp drop in blood pressure and respiratory paralysis. Disappearance of the patellar reflex is a useful clinical sign to detect the onset of magnesium intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected IV to antagonize the effects of magnesium. For Treatment of Overdose Artificial respiration is often required. Intravenous calcium, 10 to 20 mL of a 5% solution (diluted if desirable) with isotonic sodium chloride for injection) is used to counteract effects of hypermagnesemia. Subcutaneous physostigmine, 0.5 to 1 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 IV calcium.

For Treatment of Overdose Artificial respiration is often required. Intravenous calcium, 10 to 20 mL of a 5% solution (diluted if desirable) with isotonic sodium chloride for injection) is used to counteract effects of hypermagnesemia. Subcutaneous physostigmine, 0.5 to 1 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 IV calcium.

HOW SUPPLIED Magnesium Sulfate in Water for Injection is supplied in single-dose flexible containers as follows: Product Code Unit of Sale Total Magnesium Sulfate* Total Magnesium Ion Magnesium Sulfate* Concentration Magnesium Ion Concentration Osmolarity (calc.) Unit of Use 610605 NDC 63323-106-05 Unit of 24 2 g 16.25 mEq 4% (40 mg/mL) 16.25 mEq/50 mL 325 m0smol/Liter NDC 63323-106-02 50 mL fill in a 100 mL free flex Bag 610601 NDC 63323-106-01 Unit of 24 4g 32.5 mEq 4% (40 mg/mL) 32.5 mEq/100 mL 325 m0smol/Liter NDC 63323-106-00 100 mL fill in a 100 mL free flex Bag 610615 NDC 63323-106-15 Unit of 24 20 g 162.3 mEq 4% (40 mg/mL) 32.5 mEq/100 mL 325 m0smol/Liter NDC for unit of use not present on Labeling 500 mL fill in a 500 mL free flex Bag 610610 NDC 63323-106-10 Unit of 24 40 g 325 mEq 4% (40 mg/mL) 32.5 mEq/100 mL 325 m0smol/Liter NDC for unit of use not present on Labeling 1,000 mL fill in a 1,000 mL free flex Bag 610705 NDC 63323-107-05 Unit of 24 4 g 32.5 mEq 8% (80 mg/mL) 32.5 mEq/50 mL 649 m0smol/Liter NDC 63323-107-01 50 mL fill in a 100 mL free flex Bag *As the heptahydrate. WARNING: DO NOT USE FLEXIBLE CONTAINER IN SERIES CONNECTIONS. This container is not made with natural rubber latex or polyvinyl chloride (PVC), Non-DEHP. Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from freezing.