Magnesium sulfate-darnitsa

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Magnesium sulfate-Darnitsa (Magnesium sulfate-Darnitsa)

Composition:

active substance: magnesium sulfate heptahydrate;

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

excipients: water for injections, hydrochloric acid.

Pharmaceutical form. Injection solution.

Main physical and chemical properties: clear, colorless liquid.

Pharmacotherapeutic group. Electrolyte solutions. ATC code B05XA05.

Pharmacological properties.

Pharmacodynamics.

When administered parenterally, exhibits hypotensive, arteriolar dilating, antiarrhythmic, sedative, anticonvulsant, diuretic, spasmolytic, and tocolytic effects. Replenishes magnesium deficiency in the body and acts as a physiological antagonist of calcium. Regulates metabolic processes, neuron-chemical transmission, and muscle excitability, impedes calcium ion influx through the presynaptic membrane, reduces acetylcholine levels in the peripheral and central nervous systems, produces dose-dependent sedative, hypnotic, or narcotic effects, and exerts spasmolytic action. Decreases excitability of the respiratory center; when administered in high doses, may cause respiratory depression.

The hypotensive and antiarrhythmic effects of magnesium are due to reduced excitability of cardiomyocytes, restoration of ionic balance, stabilization of cellular membranes, interference with sodium influx, slow calcium influx, and unidirectional potassium flux, dilation of coronary arteries, reduction of total peripheral vascular resistance, platelet aggregation, as well as spasmolytic and sedative effects.

The sedative and anticonvulsant actions of magnesium are associated with decreased release of acetylcholine from neuromuscular synapses, inhibition of neuromuscular transmission, and direct suppressive effects on the central nervous system.

Tocolytic action develops due to inhibition of myometrial contractility (reduced uptake, binding, and distribution of calcium in smooth muscle cells), vasodilation, and increased uterine blood flow. Magnesium exerts spasmolytic effects in cases of urinary retention and acts as an antidote in poisoning with salts of heavy metals.

Systemic effects occur almost immediately after intravenous administration and within 1 hour after intramuscular injection, with durations of approximately 30 minutes and 3–4 hours, respectively.

Pharmacokinetics.

Magnesium crosses the blood-brain barrier and placenta, and is excreted into breast milk, where its concentration is twice that in plasma. It is eliminated by the kidneys, with renal excretion rate proportional to plasma concentration and glomerular filtration rate. The plasma concentration at which anticonvulsant effects occur ranges from 2 to 3.5 mmol/L.

Clinical characteristics.

Indications.

• Hypertensive crisis; ventricular cardiac arrhythmias (torsades de pointes tachycardia); convulsive syndrome; eclampsia; hypomagnesemia; increased magnesium requirements;
• in complex therapy of preterm labor; exertional angina; poisoning with heavy metal salts; tetraethyllead; soluble barium salts (antidote).

Contraindications.

Increased individual sensitivity to the components of the medicinal product; arterial hypotension, pronounced bradycardia (heart rate less than 55 beats/min), 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 action to magnesium ions, which leads to a reduction in pharmacological effects of magnesium sulfate when used concomitantly. Enhances the effect of medicinal products that suppress the central nervous system (narcotics, analgesics). When used concomitantly with muscle relaxants and nifedipine, neuromuscular blockade is enhanced. Concomitant use with calcium channel blockers, such as nifedipine, may lead to calcium balance disturbance and muscle function impairment.

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. Dose adjustment may be required.

Propafenone – the effect of both medicinal products is enhanced, and the risk of toxic effects increases.

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

Special precautions for use.

Prior to initiating therapy, serum magnesium levels should be determined. In adults, normal plasma magnesium levels range from 0.75 to 1.26 mmol/L.

When using this medicinal product, 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), use of cardiac glycosides, calcitonin, thyroxine, and during 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 medicinal product should not exceed 20 g of magnesium sulfate (81 mmol Mg²⁺) within 48 hours. Intravenous bolus administration of magnesium sulfate is contraindicated in patients with oliguria or severe renal impairment. Urinary tract infections accelerate precipitation of ammonium-magnesium phosphates; therefore, magnesium therapy is temporarily not recommended 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 disorders. During prolonged therapy, 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 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.

During pregnancy, magnesium sulfate should be used with particular caution and only after assessing serum magnesium levels, when the expected therapeutic benefit outweighs the potential risk to the fetus. When used for analgesia during labor, possible inhibition of uterine muscle contractility should be considered, which may necessitate the use of agents stimulating labor.

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

Ability to influence 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.

Route of Administration and Dosage.

Administer intramuscularly, intravenously slowly, or by intravenous infusion. Frequency of administration and dosage are individual and depend on the indication and therapeutic response. When administered by infusion, the medicinal product 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 pregnant women.

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), with intramuscular administration, increase the total 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 medicinal product (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 infusions 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 blood pressure levels, a decrease in the severity of angina may also be observed.

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

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).

Alternatively, initial administration may be given as a loading dose of 8 mL over at least 5 minutes, followed by infusion of 20 mL of the medicinal product diluted with 0.9% sodium chloride solution or 5% glucose solution over at least 6 hours; or administer 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. In adults, administer 5–10–20 mL intramuscularly. In children, administer intramuscularly at a dose of 0.08–0.16 mL/kg (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, 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 continuous infusion at 4–8 mL/hour (1–2 g/hour), with constant monitoring of tendon reflexes and respiratory function. Continue therapy until seizure activity ceases. Maximum daily dose is 40 g of magnesium sulfate; in cases of renal impairment, maximum dose is 20 g/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 of the medicinal product intramuscularly or 5–10 mL intravenously after dilution 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 a dose of 0.2 mL/kg/day, increasing the dose to 0.8 mL/kg/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);
• 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, uterine atony.

Treatment: The specific antidote is calcium preparations (calcium chloride or gluconate), which should be administered intravenously slowly. In moderate hypermagnesemia, furosemide may be administered. Respiratory depression should be treated with intravenous injection 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.

Respiratory, thoracic and mediastinal disorders: dyspnea, respiratory depression.

Gastrointestinal disorders: nausea, vomiting.

Renal and urinary disorders: polyuria.

Metabolism and nutrition disorders: hypocalcemia, hypophosphatemia, hyperosmolar dehydration.

Nervous system disorders: headache, dizziness, general weakness, somnolence, confusion, loss of consciousness, decreased tendon reflexes, diplopia, speech disturbances, tremor and limb numbness.

Psychiatric disorders: depression, anxiety.

Cardiovascular disorders: arterial hypotension, bradycardia, palpitations, conduction disorders, flushing, prolonged PQ interval and widened QRS complex on ECG, arrhythmia, coma, cardiac arrest.

Immune system disorders: hypersensitivity reactions, including anaphylactic shock, angioneurotic edema.

Skin and subcutaneous tissue disorders: hyperemia, pruritus, rash, urticaria.

Musculoskeletal and connective tissue disorders: muscle weakness.

Reproductive system and breast disorders: uterine atony.

General disorders and administration site reactions: hyperthermic syndrome, chills, increased sweating, hyperemia, swelling, pain.

Shelf life. 5 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25°C. Do not freeze. 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 above 10 mmol/mL in total parenteral nutrition mixtures, fat emulsion separation may occur.

Packaging.

5 mL in an ampoule; 5 ampoules in a blister pack; 2 blister packs in a carton. 10 mL in an ampoule; 5 ampoules in a blister pack; 2 blister packs in a carton.

Prescription status. Prescription only.

Manufacturer. JSC "Pharmaceutical Company "Darnitsya".

Manufacturer's address and place of business.

13, Borispilska Street, Kyiv, 02093, Ukraine.