MAGNESIUM SULFATE IN WATER

INDICATIONS AND USAGE Magnesium Sulfate in Water for Injection is indicated for the prevention and control of seizures in pre-eclampsia 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.

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 Eclampsia In severe pre-eclampsia or eclampsia, the total initial dose is 10 to 14 g of magnesium sulfate. To initiate therapy, 4 g of Magnesium Sulfate in Water for Injection may be administered intravenously. The rate of I.V. infusion should generally not exceed 150 mg/minute, or 3.75 mL of a 4% concentration (or its equivalent) per minute, except in severe eclampsia with seizures. Simultaneously, 4 to 5 g (32.5 to 40.6 mEq) of magnesium sulfate may be administered intramuscularly into each buttock using undiluted 50% Magnesium Sulfate Injection, USP. After the initial I.V. dose, some clinicians administer 1 to 2 g/hour by constant I.V. infusion. Subsequent intramuscular doses of 4 to 5 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 6 mg/100 mL is considered optimal for control of seizures. A total daily (24 hr) dose of 30 to 40 g magnesium sulfate should not be exceeded. In the presence of severe renal insufficiency, frequent serum magnesium concentrations must be obtained and the maximum dosage of magnesium sulfate is 20 g 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.

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 Athenex Pharmaceutical Division, LLC. at 1-855-273-0154 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Drug-Drug Interactions: Drug induced renal losses of magnesium occur with the following drugs or drug classes: Aminoglycosides Cyclosporine Digitalis Alcohol Amphotericin B Diuretics Cisplatin

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 4% and 8% concentrations. See HOW SUPPLIED section for the content and characteristics of available dosage forms and fill volumes. 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. Not made with natural rubber latex, DEHP or PVC. The plastic container is a copolymer of ethylene and propylene formulated and developed for parenteral drugs. The copolymer contains no plasticizers. The safety of the plastic container has been confirmed by biological evaluation procedures. The material passes Class Vl testing as specified in the U.S. Pharmacopeia for Biological Tests — Plastic Containers. The container/solution unit is a closed system and is not dependent upon entry of external air during administration. The container has two ports, one is for the intravenous administration set covered by a tamperproof barrier and the other is a blocked port. Refer to the DIRECTIONS FOR USE of the container to properly identify the ports. No vapor barrier is necessary.

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 I.V. 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 I.V. calcium.

HOW SUPPLIED Magnesium Sulfate in Water for Injection is supplied in single-dose flexible plastic containers as follows: 2 grams per 50 mL NDC Size Container Total Magnesium Sulfate ** Total Magnesium Ion Magnesium Sulfate ** Concentration Magnesium Ion Concentration Osmolarity (calc.) Bags per Carton 83634-500-81 50 mL* 2 grams 16.25 mEq 4% (40 mg per mL) 16.25 mEq/50 mL 325 mOsmol/Liter 24 bags per carton 83634-500-83 50 mL* 2 grams 16.25 mEq 4% (40 mg per mL) 16.25 mEq/50 mL 325 mOsmol/Liter 30 bags per carton 4 grams per 100 mL NDC Size Container Total Magnesium Sulfate ** Total Magnesium Ion Magnesium Sulfate ** Concentration Magnesium Ion Concentration Osmolarity (calc.) Bags per Carton 83634-500-82 100 mL 4 grams 32.5 mEq 4% (40 mg per mL) 32.5 mEq/100 mL 325 mOsmol/Liter 24 bags per carton 4 grams per 50 mL * Partial fill container 50 mL volume in 100 mL container. ** As the heptahydrate. NDC Size Container Total Magnesium Sulfate ** Total Magnesium Ion Magnesium Sulfate ** Concentration Magnesium Ion Concentration Osmolarity (calc.) Bags per Carton 83634-501-81 50 mL* 4 grams 32.5 mEq 8% (80 mg per mL) 32.5 mEq/50 mL 649 mOsmol/Liter 24 bags per carton 83634-501-82 50 mL* 4 grams 32.5 mEq 8% (80 mg per mL) 32.5 mEq/50 mL 649 mOsmol/Liter 30 bags per carton WARNING: DO NOT USE FLEXIBLE CONTAINER IN SERIES CONNECTIONS. Storage Conditions Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from freezing. Sterile, Nonpyrogenic, Preservative-free. The container closure is not made with natural rubber latex.