Magnesium sulfate

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

Composition:

Active substance: magnesium sulfate heptahydrate;

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

Excipient: water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear, colorless liquid.

Pharmacotherapeutic group. Plasma substitutes and infusion solutions. Electrolyte solutions. ATC code B05X A05.

Pharmacological properties.

Pharmacodynamics.

Magnesium is a physiological antagonist of calcium, a metabolic cofactor for most metabolic reactions, including those related to energy synthesis and release. It reduces catecholamine secretion, regulates the function of Na⁺-K⁺-ATPase, neurotransmission, and muscle excitability. It decreases acetylcholine levels in the central and peripheral nervous systems, thereby exerting sedative, analgesic, anticonvulsant, spasmolytic, cholagogue, 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 reduces 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. With increased dosage, magnesium may produce negative inotropic and muscle-relaxing effects.

Pharmacokinetics.

After parenteral administration, magnesium rapidly distributes into organs and tissues, crosses the blood-brain barrier and placenta, and penetrates into breast milk at high concentrations. The drug is primarily excreted 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. In complex therapy of preterm labor, exertional angina, poisoning with heavy metal salts, tetraethyllead, and soluble barium salts (antidote).

Contraindications.

Hypersensitivity to the components of the drug; arterial hypotension; pronounced bradycardia (heart rate less than 55 beats per minute); atrioventricular block; conditions caused by calcium deficiency and respiratory center depression; cachexia; renal function disorders; severe hepatic or renal insufficiency; myasthenia; malignant neoplasms.

Interaction with other medicinal products and other types of interactions.

Calcium ions have antagonistic effects on magnesium ions, leading to reduced pharmacological effects of magnesium sulfate when used concomitantly. 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. Concurrent 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, and nonselective inhibitors of neuronal monoamine reuptake is reduced.

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

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

Impairs absorption of tetracycline group antibiotics; intestinal obstruction is possible; reduces the effect of streptomycin and tobramycin.

Special precautions for use.

Before initiating therapy, serum magnesium levels should be determined. In adults, the normal plasma magnesium concentration ranges from 0.75 to 1.26 mmol/L.

When using the drug, it should be noted that increased urinary excretion of magnesium occurs with expansion of extracellular fluid, renal vasodilation, hypercalcemia, increased urinary sodium excretion, administration of osmotic diuretics (urea, mannitol, glucose), "loop" diuretics (furosemide, ethacrynic acid, thiazides), and during treatment with cardiac glycosides, calcitonin, thyreoidin, or prolonged administration of desoxycorticosterone acetate (more than 3–4 days). Excretion of magnesium is slowed by parathyroid hormone administration. In renal insufficiency, magnesium excretion is reduced and repeated doses may lead to its accumulation. Therefore, in elderly patients and in patients with severe renal dysfunction, 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 impairment. Urinary tract infections accelerate precipitation of ammonium-magnesium phosphates; therefore, magnesium therapy is temporarily contraindicated in such cases. Impaired elimination of magnesium after parenteral administration of magnesium sulfate may result in hypermagnesemia.

Use with caution in patients with myasthenia gravis and respiratory tract diseases. During prolonged treatment, monitoring of the cardiovascular system, tendon reflexes, renal function, and respiratory rate is recommended.

Intravenous administration of magnesium sulfate must be performed slowly; too rapid infusion may lead to hypermagnesemia (symptoms include nausea, paresthesia, sedative effect, hypoventilation up to apnea, and diminished deep tendon reflexes). Concurrent parenteral administration of vitamin B6 and insulin enhances the efficacy of magnesium therapy.

If simultaneous intravenous administration of magnesium sulfate and calcium preparations is required, they should be administered into separate veins. It should be kept in mind 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 serum magnesium concentrations, and only when the expected therapeutic benefit outweighs the potential risk to the fetus. During labor analgesia, one should consider the possible inhibition of uterine muscle contractility, which may necessitate the use of agents that stimulate labor.

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

Ability to influence the reaction rate when operating a vehicle or other machinery.

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

Administration and Dosage.

Administer intramuscularly, by slow intravenous injection, or as an intravenous infusion. The frequency of administration and dosage are individual and depend on the indications and therapeutic response. When administered by infusion, the drug should be diluted 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 pregnancy.

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 intramuscular dose to 1 mL/kg (250 mg/kg), administered 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 administer 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 by intramuscular injection. The treatment course consists of 15–20 injections; along with a reduction in blood pressure levels, a decrease in the severity of angina may also be observed.

Hypertensive crisis. Administer 10–20 mL intramuscularly or by slow intravenous bolus injection.

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

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

Seizure syndrome. For adults, administer 5–10–20 mL intramuscularly. 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 by intramuscular injection (may be combined with concomitant administration of neuroleptics).

In cases of pre-eclampsia or eclampsia, administer intramuscularly or intravenously. Initially, administer 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/hour), with continuous monitoring of tendon reflexes and respiratory function. Continue therapy until seizure activity ceases. The maximum daily dose is 40 g of magnesium sulfate; in cases of renal impairment, the maximum dose is 20 g per 48 hours.

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

Urinary retention. In cases of urinary retention and lead colic, administer 5–10 mL of the drug intramuscularly or 5–10 mL intravenously after dilution fivefold 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 a 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 a 1% magnesium sulfate solution.

Neonates. In neonates with intracranial hypertension and severe asphyxia, initiate intramuscular administration at a dose of 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, administered over 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 drug may be used in pediatric practice.

Overdose.

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

reduction in deep tendon reflexes (2–3.5 mmol/L);

prolongation of the PQ interval and widening of the 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).

Additionally, hyperhidrosis, anxiety, lethargy, polyuria, and uterine atony may occur.

Treatment: the specific antidote is calcium preparations (calcium chloride or gluconate), which should be administered slowly intravenously. In moderate hypermagnesemia, furosemide may be prescribed. Respiratory depression should be treated with intravenous administration of 5–10 mL of 10% calcium chloride solution, oxygen inhalation, and artificial ventilation of the lungs. In severe cases, peritoneal dialysis or hemodialysis is indicated. Prescribe symptomatic agents to correct cardiovascular and central nervous system functions.

Side effects.

Cardiovascular system: arterial hypotension, bradycardia, palpitations, conduction disturbances, flushing/sensation of warmth, prolongation of the 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, decreased tendon reflexes, diplopia, anxiety, speech disturbances, tremor and numbness of limbs.

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. 5 years.

Storage conditions. Store at a temperature not exceeding 25 °C.

Keep out of reach of children.

Incompatibility.

Pharmaceutically incompatible (precipitate forms) 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. At Mg²⁺ concentrations exceeding 10 mmol/mL in total parenteral nutrition mixtures, separation of lipid emulsions may occur.

Packaging. 5 mL or 10 mL in an ampoule; 5 ampoules in a blister pack; 2 blister packs in a carton; 5 mL or 10 mL in an ampoule; 10 ampoules in a box; 5 mL in an ampoule; 5 ampoules in a blister pack sealed with paper.

Prescription status. Prescription only.

Manufacturer: JSC "Halychfarm".

Manufacturer's address and place of business activity.

6/8 Opryshkovska St., Lviv, 79024, Ukraine.