Magnesium sulfate

INSTRUCTIONS FOR MEDICAL USE OF MEDICINAL PRODUCT MAGNESIUM SULFATE (MAGNESIUM SULFATE)

Composition:

Active substance: magnesium sulfate heptahydrate;

1 ml of solution contains 250 mg of magnesium sulfate heptahydrate;

Excipients: sodium hydroxide, hydrochloric acid diluted, water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear, colorless liquid.

Pharmacotherapeutic group. Plasma substitutes and infusion solutions. Electrolyte solution. ATC code B05XA05.

Pharmacological Properties

Pharmacodynamics

Magnesium is a physiological antagonist of calcium and a metabolic cofactor for most metabolic reactions, including those associated with energy synthesis and release. It reduces catecholamine secretion, regulates the function of Na⁺-K⁺-ATPase, neurotransmission, and muscle excitability, and decreases acetylcholine levels in the central and peripheral nervous systems. As a result, it exerts sedative, analgesic, anticonvulsant, spasmolytic, choleretic, and tocolytic effects. The drug dilates coronary and peripheral arteries, reduces arterial blood pressure and cardiac afterload, and inhibits the development of myocardial reperfusion injury. It decreases the frequency of ventricular and supraventricular arrhythmias and slows conduction in the area of the sinoatrial and atrioventricular nodes.

The antiplatelet properties of magnesium are associated with reduced synthesis of thromboxane A₂ and lipoxygenase derivatives (12-HETE), as well as stimulation of prostacyclin and high-density lipoprotein synthesis. At higher doses, magnesium may produce negative inotropic and muscle-relaxant effects.

Pharmacokinetics

After parenteral administration, magnesium rapidly distributes into organs and tissues, crosses the blood-brain barrier and placenta, and passes into breast milk in high concentrations. The drug is excreted predominantly in the urine.

Systemic effects develop within 1 minute after intravenous administration and within 1 hour after intramuscular administration. The duration of action of magnesium is 30 minutes after intravenous administration and 3–4 hours after intramuscular administration.

Clinical characteristics.

Indications.

Hypertensive crisis, ventricular cardiac arrhythmias (torsades de pointes); convulsive syndrome; eclampsia; hypomagnesemia; increased magnesium requirements. Use as part of combination therapy for preterm labor, exertional angina, poisoning with salts of heavy metals, tetraethyllead, and soluble barium salts (antidote).

Contraindications.

Increased individual sensitivity to the components of the drug; arterial hypotension; marked bradycardia (heart rate less than 55 beats per minute); atrioventricular block; conditions associated with calcium deficiency and respiratory center depression; cachexia; renal function disorders; severe hepatic or renal insufficiency; myasthenia gravis; malignant neoplasms.

Interaction with other medicinal products and other types of interactions.

Calcium ions exert an antagonistic effect on magnesium ions, resulting in reduced pharmacological effects of magnesium sulfate when both are administered simultaneously. The drug enhances the effects of medicinal products that depress the central nervous system (narcotics, analgesics). When used concomitantly with muscle relaxants and nifedipine, neuromuscular blockade is enhanced. Simultaneous use with calcium channel blockers such as nifedipine may lead to calcium imbalance and impaired muscle function.

Barbiturates, narcotic analgesics, and antihypertensive agents increase the risk of respiratory center depression. Cardiac glycosides increase the risk of conduction disturbances and atrioventricular block.

The effect of antithrombotic agents, vitamin K antagonists, isoniazid, non-selective inhibitors of neuronal reuptake of monoamines is reduced.

Mexiletine elimination may be slowed, thus requiring dose adjustment of mexiletine.

Propafenone: the effect of both drugs is enhanced, increasing the risk of toxic effects.

The medicinal product interferes with the absorption of tetracycline-group antibiotics, may cause intestinal obstruction, and reduces the effect of streptomycin and tobramycin.

Special precautions for use.

Before starting therapy, the magnesium level in the blood should be determined. In adults, the normal magnesium level in blood plasma is 0.75–1.26 mmol/L.

When using the drug, it should be taken into account that increased magnesium excretion in urine occurs with an increase in extracellular fluid, renal vasodilation, hypercalcemia, increased urinary sodium excretion, administration of osmotic diuretics (urea, mannitol, glucose), "loop" diuretics (furosemide, ethacrynic acid, thiazides), use of cardiac glycosides, calcitonin, thyroiodine, and prolonged administration of desoxycorticosterone acetate (more than 3–4 days). Magnesium excretion is slowed by parathyroid hormone administration. In renal insufficiency, magnesium excretion is reduced, and repeated administration may lead to its accumulation. Therefore, for elderly patients and patients with severe renal function impairment, the dose of the drug should not exceed 20 g of magnesium sulfate (81 mmol Mg²⁺) over 48 hours. Intravenous administration of magnesium sulfate should not be performed rapidly in patients with oliguria or severe renal function impairment. Urinary tract infections accelerate precipitation of ammonium-magnesium phosphates; therefore, magnesium therapy is temporarily not recommended. After parenteral administration of magnesium sulfate, impaired magnesium excretion may lead to hypermagnesemia.

Use with caution in myasthenia and respiratory disorders. During prolonged use of the drug, monitoring of the cardiovascular system, tendon reflexes, renal function, and respiratory rate is recommended.

Intravenous administration of magnesium sulfate must be performed slowly. Rapid infusion may lead to hypermagnesemia (symptoms: nausea, paresthesia, sedative effect, hypoventilation up to apnea, decreased deep tendon reflexes). Concurrent parenteral administration of vitamin B₆ and insulin enhances the effectiveness of magnesium therapy.

If simultaneous intravenous administration of magnesium sulfate and calcium preparations is required, they should be administered into different veins. It should be noted that magnesium levels depend on calcium levels in the body.

Use during pregnancy or breastfeeding.

During pregnancy, magnesium sulfate should be used with particular caution, taking into account magnesium blood concentrations, only when the expected therapeutic benefit outweighs the potential risk to the fetus. When using analgesia during labor, possible suppression of uterine muscle contractility should be considered, which may require the use of agents that stimulate labor.

If use of the drug is necessary, breastfeeding should be discontinued.

Ability to affect reaction speed when driving vehicles or operating machinery.

Patients should be warned about the need for caution when operating potentially hazardous machinery or driving vehicles, as the drug has a sedative effect.

Administration and Dosage.

Administer intramuscularly, slowly intravenously, or as an intravenous infusion. Frequency of administration and dosage are individual and depend on the indication and therapeutic response. For infusion, dilute the medicinal product with 0.9% sodium chloride solution or 5% glucose solution. During intravenous injection, the rate of administration should generally not exceed 150 mg/min (0.6 mL/min), except in the treatment of arrhythmias and eclampsia in pregnant women.

Prepared infusion solutions must be used immediately after preparation (they are not suitable for storage).

Hypomagnesemia. In moderate hypomagnesemia (0.5–0.7 mmol/L), administer 4 mL (1 g of magnesium sulfate) intramuscularly every 6 hours to adults.

In severe hypomagnesemia (< 0.5 mmol/L), increase the total dose to 1 mL/kg (250 mg/kg) when administered intramuscularly, given in divided doses over 4 hours. For intravenous infusion in severe hypomagnesemia, add 20 mL of the drug (5 g of magnesium sulfate) to 1 L of 0.9% sodium chloride solution or 5% glucose solution and infuse over at least 3 hours.

The maximum daily dose for intravenous administration is 72 mL (18 g). If necessary, repeat the infusion over several days.

Arterial hypertension. In stage I–II arterial hypertension, administer 5–10–20 mL daily intramuscularly. The treatment course consists of 15–20 injections; along with reduction in arterial pressure, a decrease in severity of angina may occur.

Hypertensive crisis. Administer 10–20 mL intramuscularly or slowly intravenous bolus.

Cardiac arrhythmias. To control arrhythmias, administer 4–8 mL (1–2 g of magnesium sulfate) intravenously over 5–10 minutes; repeat the injection if necessary (total administration up to 4 g of magnesium sulfate). Initial loading dose of 8 mL may be administered over at least 5 minutes, followed by infusion of 20 mL of the drug diluted with 0.9% sodium chloride solution or 5% glucose solution over at least 6 hours, or initial dose of 8 mL over at least 30 minutes followed by infusion over at least 12 hours.

Ischemic stroke. 10–20 mL intravenously daily for 5–7 days.

Seizure syndrome. Administer 5–10–20 mL intramuscularly to adults. For children, administer intramuscularly at a dose of 0.08–0.16 mL/kg body weight (20–40 mg/kg).

Pregnancy toxemia. Administer 10–20 mL 1–2 times daily intramuscularly (can be combined with concomitant administration of neuroleptics).

In cases of pre-eclampsia or eclampsia, administer intramuscularly or intravenously. Initially, give a single dose of 10 mL intramuscularly into each buttock, or 16 mL (4 g of magnesium sulfate) intravenously over 3–4 minutes. Subsequently, continue administration intramuscularly at 16–20 mL (4–5 g) every 4 hours, or intravenously by drip at 4–8 mL/hour (1–2 g/h), with continuous monitoring of tendon reflexes and respiratory function. Continue therapy until seizure activity ceases. Maximum daily dose is 40 g of magnesium sulfate; in case of renal impairment, limit to 20 g/48 hours.

Pain relief during labor. Administer 5–10–20 mL intramuscularly; if needed, combine magnesium sulfate with analgesics.

Urinary retention. In cases of urinary retention and lead colic, administer 5–10 mL intramuscularly or 5–10 mL intravenously diluted 5-fold with 25% magnesium sulfate solution (also may be administered as an enema).

As an antidote. In mercury, arsenic, or tetraethyllead poisoning, administer 5–10 mL intravenously of 25% magnesium sulfate solution diluted 2.5–5 times. In poisoning with soluble barium salts, administer 4–8 mL intravenously or perform gastric lavage with 1% magnesium sulfate solution.

Neonates. In neonates with intracranial hypertension and severe asphyxia, administer intramuscularly starting at 0.2 mL/kg body weight per day, increasing the dose to 0.8 mL/kg body weight per day by the 3rd–4th day, for 3–8 days as part of combination therapy. To correct magnesium deficiency in neonates, administer 0.5–0.8 mL/kg once daily for 5–8 days.

Children.

The medicinal product may be used in pediatric practice.

Overdose.

Symptoms: signs of hypermagnesemia in order of increasing serum magnesium concentration:

• decreased deep tendon reflexes (2–3.5 mmol/L);
• prolonged PQ interval and widened QRS complex on ECG (2.5–5 mmol/L);
• loss of deep tendon reflexes (4–5 mmol/L);
• respiratory center depression (5–6.5 mmol/L);
• cardiac conduction disturbances (7.5 mmol/L);
• cardiac arrest (12.5 mmol/L).

In addition, hyperhidrosis, anxiety, lethargy, polyuria, and uterine atony may occur.

Treatment: specific antidotes are calcium preparations (calcium chloride or gluconate), which should be administered slowly intravenously. In moderate hypermagnesemia, furosemide may be administered. To reverse respiratory depression, administer 5–10 mL of 10% calcium chloride solution intravenously, oxygen inhalation, and artificial ventilation of the lungs. In severe cases, peritoneal dialysis or hemodialysis is indicated. Symptomatic agents correcting cardiovascular and central nervous system functions should also be administered.

Adverse Reactions.

Cardiovascular system: arterial hypotension, bradycardia, palpitations, conduction disturbances, flushing/sensation of warmth, prolonged PQ interval and widening of the QRS complex on ECG, arrhythmia, coma, cardiac arrest.

Respiratory system: dyspnea, respiratory depression.

Nervous system: headache, dizziness, general weakness, somnolence, confusion, loss of consciousness, depression, diminished tendon reflexes, diplopia, anxiety, speech disturbances, tremor and numbness of extremities.

Musculoskeletal system: muscle weakness.

Gastrointestinal tract: nausea, vomiting.

Allergic reactions: anaphylactic shock, angioneurotic edema, hyperthermic syndrome, chills.

Skin: hyperemia, pruritus, rash, urticaria, increased sweating.

Urinary system: polyuria.

Reproductive system and mammary glands: uterine atony.

Metabolic and nutritional disorders: hypocalcemia, hypophosphatemia, hyperosmolar dehydration.

Local reactions at injection site: hyperemia, swelling, pain.

Shelf life. 2 years.

Storage conditions.

Store at a temperature not exceeding 25 °C in the original packaging. Do not freeze. Keep out of reach of children.

Incompatibility.

Pharmaceutically incompatible (forms a precipitate) with calcium preparations, ethanol (at high concentrations), carbonates, bicarbonates and phosphates of alkali metals, arsenic acid salts, barium, strontium, clindamycin phosphate, sodium hydrocortisone succinate, polymyxin B sulfate, procaine hydrochloride, salicylates and tartrates. In total parenteral nutrition mixtures, when Mg²⁺ concentration exceeds 10 mmol/mL, separation of lipid emulsions may occur.

Packaging.

5 mL in a vial; 5 vials in a blister pack; 2 blister packs in a cardboard box.

Prescription category. Prescription only.

Manufacturer.

LLC "Yuria-Pharm".

Manufacturer's address and location of business activity.

108, Kozbirska St., Cherkasy, Cherkasy region, 18030, Ukraine. Tel.: (044) 281-01-01.