Magnesium Sulfate - Magnesium Sulfate Heptahydrate injection, Solution prescribing information
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.
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 to 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 per 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 Sagent Pharmaceuticals, Inc. at 1-866-625-1618 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
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% concentration. See HOW SUPPLIED section for the content and characteristics of available dosage forms and sizes.
Magnesium Sulfate heptahydrate, USP 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.
The flexible plastic container is fabricated from a specially formulated polypropylene. Water can permeate from inside the container into the overwrap 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.
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 a 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 4 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
Absorption: Intravenously administered magnesium is immediately absorbed.
Distribution: Approximately 1 to 2% of total body magnesium is located in the extracellular fluid space. Magnesium is 30% bound to albumin.
Metabolism: Magnesium is not metabolized.
Excretion: Magnesium is excreted solely by the kidney at a rate proportional to the serum concentration and glomerular filtration.
Special Populations
Renal Insufficiency: Magnesium 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 Insufficiency: Magnesium is excreted solely by the kidney. No dosing adjustments are necessary in hepatic insufficiency.
Drug-Drug Interactions: Drug induced renal losses of magnesium occur with the following drugs or drug classes:
| Aminoglycosides | Amphotericin B |
| Cyclosporine | Diuretics |
| Digitalis | Cisplatin |
| Alcohol |
HOW SUPPLIED
Magnesium Sulfate in Water for Injection is supplied as follows:
| NDC | Magnesium Sulfate in Water for Injection (40 mg per mL) | Package Factor |
| 25021-612-81 | 2 grams per 50 mL Single-Dose flexible container bag | 10 bags per carton |
| 25021-612-82 | 4 grams per 100 mL Single-Dose flexible container bag | 10 bags per carton |
Magnesium Sulfate in Water for Injection is a clear, colorless solution.
• Partial fill container 50 mL volume in 100 mL container. | |||||
•• As the heptahydrate. | |||||
| Size Container | Total Magnesium Sulfate•• | Total Magnesium Ion | Magnesium Sulfate•• Concentration | Magnesium Ion Concentration | Osmolarity (Calc.) |
| 50 mL• | 2 g | 16.25 mEq | 4% (40 mg per mL) | 16.25 mEq/50 mL | 325 mOsmol/Liter |
| 100 mL | 4 g | 32.5 mEq | 4% (40 mg per mL) | 32.5 mEq/100 mL | 325 mOsmol/Liter |
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.]
Avoid excessive heat. Do not freeze.
Discard unused portion.
Sterile, Nonpyrogenic, Preservative-free, PVC-free, DEHP-free. The container and container closure are not made with natural rubber latex.
