Magnesium sulfate

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

Composition:

Active substance: magnesium sulfate;

1 ml of solution contains magnesium sulfate heptahydrate 250 mg;

Excipient: 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, thereby exerting 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 cause 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 following intravenous administration and 3–4 hours following intramuscular administration.

Clinical characteristics.

Indications.

Hypertensive crisis, ventricular cardiac arrhythmias (tachycardia of "torsade de pointes" type); convulsive syndrome; eclampsia, hypomagnesemia, increased magnesium requirements. In complex therapy of 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 medicinal product; arterial hypotension; pronounced bradycardia (heart rate (HR) 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 to magnesium ions, leading to reduced pharmacological effects of magnesium sulfate when used concomitantly. The drug potentiates the action of medicinal products that depress the central nervous system (narcotics, analgesics). When used simultaneously 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 developing conduction disturbances and atrioventricular block.

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

Excretion of mexiletine 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, possible intestinal obstruction, reduces the effect of streptomycin and tobramycin.

Special precautions for use.

Before starting therapy, the magnesium level in blood should be determined. In adults, normal plasma magnesium concentration ranges from 0.75 to 1.26 mmol/L.

When using the drug, it should be taken into account that increased urinary excretion of magnesium occurs in conditions associated 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), use of cardiac glycosides, calcitonin, thyreoidin, and during prolonged administration of desoxycorticosterone acetate (more than 3–4 days). Excretion of magnesium is slowed by administration of parathyroid hormone. In renal insufficiency, magnesium excretion is reduced and its accumulation may occur after repeated doses. Therefore, in elderly patients and patients with severe renal impairment, the dose of the drug should not exceed 20 g of magnesium sulfate (81 mmol Mg²⁺) over 48 hours. Magnesium sulfate should not be administered intravenously rapidly in patients with oliguria or severe renal dysfunction. 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 lead to hypermagnesemia.

Use with caution in myasthenia gravis and respiratory disorders. 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. Rapid infusion may result in hypermagnesemia (symptoms include nausea, paresthesia, sedative effect, hypoventilation up to apnea, and diminished deep tendon reflexes). Concomitant 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 noted that magnesium levels depend on calcium levels in the body.

Use during pregnancy or breastfeeding.

Magnesium sulfate should be used during pregnancy with particular caution and only if the expected therapeutic benefit outweighs the potential risk to the fetus, taking into account serum magnesium concentration. When used for analgesia during labor, possible inhibition of uterine muscle contractility should be considered, which may require administration of agents stimulating labor.

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

Ability to affect reaction rate while driving or operating machinery.

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

Administration and Dosage

Administer intramuscularly, intravenously slowly, or as an intravenous infusion. The frequency and dosage are individual and depend on the indication and therapeutic response. For infusion, dilute the drug 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) and administer 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 intramuscularly daily. 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 intravenously as a slow 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 dose up to 4 g of magnesium sulfate). It is also possible to administer an initial 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 administer 8 mL initially over at least 30 minutes, followed by an infusion over at least 12 hours.

Ischemic stroke. Administer 10–20 mL intravenously 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 preeclampsia or eclampsia, administer intramuscularly or intravenously. Initially, administer 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 slow infusion at 4–8 mL/hour (1–2 g/hour), with continuous monitoring of tendon reflexes and respiratory function. Continue therapy until seizure cessation. The maximum daily dose is 40 g of magnesium sulfate; in case 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 urinary retention and lead colic, administer 5–10 mL intramuscularly or 5–10 mL intravenously diluted fivefold with 25% magnesium sulfate solution (also administer as an enema).

As an antidote. In mercury, arsenic, or tetraethyl lead 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 a 1% magnesium sulfate solution.

Neonates. In neonates with intracranial hypertension and severe asphyxia, administer intramuscularly starting 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, 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 can be used in pediatric practice.

Overdose.

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

reduction of 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 intravenously slowly. In moderate hypermagnesemia, furosemide may be prescribed. Respiratory depression should be managed by 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. 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 heat, 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 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 site of administration: hyperemia, swelling, pain.

Shelf life.

2 years.

Storage conditions.

Store in original packaging 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. In total parenteral nutrition mixtures, separation of lipid emulsions may occur when Mg2+ concentration exceeds 10 mmol/mL.

Packaging. 5 mL or 10 mL in ampoules; 10 or 100 ampoules per pack, or 5 ampoules in a blister, 2 blisters per pack.

Prescription status.

By prescription only.

Manufacturer.

Private Joint-Stock Company "Lekhim-Kharkiv".

Manufacturer's address and location of business activity.

36 Severina Pototskoho Street, Kharkiv, Kharkiv Oblast, 61115, Ukraine.