Calcium gluconate-zdorovya (stabilized)

INSTRUCTION FOR MEDICAL USE of the medicinal product CALCIUM GLUCONATE-ZDOROVYE (stabilised) (CALCIUM GLUCONATE-ZDOROVYE (stabilisate))

Composition:

Active substance: calcium gluconate;

1 ml of solution contains 95 mg calcium gluconate for injection;

Excipients: calcium saccharate, concentrated hydrochloric acid or sodium hydroxide, water for injections;

1 ml of solution contains 8.93 mg of calcium (Ca2+) in total, equivalent to 100 mg of calcium gluconate.

Medicinal form. Solution for injection.

Main physicochemical properties: clear, colourless or slightly coloured solution.

Pharmatherapeutic group. Calcium preparations. ATC code A12AA03.

Pharmacological properties.

Pharmacodynamics.

A drug that regulates metabolic processes and replenishes calcium deficiency in the body; exerts hemostatic and antiallergic effects and reduces capillary permeability.

Calcium ions are involved in the transmission of nerve impulses, contraction of smooth and striated muscles, myocardial function, and blood coagulation; they are essential for bone tissue formation and proper functioning of other systems and organs. The concentration of calcium ions in the blood decreases in many pathological conditions; pronounced hypocalcemia may lead to tetany. In addition to correcting hypocalcemia, calcium compounds reduce vascular permeability and exert antiallergic, anti-inflammatory, and hemostatic effects.

Pharmacokinetics.

After parenteral administration, the drug is evenly distributed throughout all tissues and organs. In blood plasma, calcium is present in ionized form. It crosses the placental barrier and is excreted into breast milk. It is mainly eliminated from the body by the kidneys.

Clinical characteristics.

Indications.

Hypofunction of the parathyroid glands, increased excretion of calcium from the body (particularly during prolonged dehydration); as an adjunct in allergic diseases (serum sickness, urticaria, angioedema) and allergic complications of drug therapy; to reduce vascular permeability in pathological processes of any origin (exudative phase of inflammation, hemorrhagic vasculitis, radiation sickness); in parenchymal hepatitis, toxic liver damage, nephritis, eclampsia, hyperkalemia, hyperkalemic form of periodic paralysis, skin diseases (skin pruritus, eczema, psoriasis), as a hemostatic agent, and also as an antidote in poisoning with magnesium salts, oxalic acid or its soluble salts, and soluble salts of hydrofluoric acid.

Contraindications.

Hypersensitivity to the components of the drug. Predisposition to thrombosis, severe renal failure, severe hypercalciuria, pronounced atherosclerosis, sarcoidosis, increased blood coagulation, concomitant use with cardiac glycosides.

Aluminum oxide may leach from calcium gluconate glass ampoules; therefore, to limit aluminum exposure in patients, especially those with impaired kidney function and children (under 18 years), calcium gluconate should not be used for the preparation of total parenteral nutrition.

Repeated and long-term treatment in children (under 18 years) and patients with impaired kidney function (due to the risk of aluminum effects on the body).

Hypercalcemia (e.g., hyperparathyroidism, vitamin D intoxication, malignancies with bone decalcification, renal failure, immobilization osteoporosis, milk-alkali syndrome).

Calcium gluconate must not be administered concomitantly with ceftriaxone due to the risk of forming an insoluble ceftriaxone-calcium complex in the following cases:

• Preterm newborns aged ≤ 41 weeks postmenstrual age (gestational age + postnatal age);
• Term newborns (aged ≤ 28 days).

Interaction with other medicinal products and other types of interactions.

The drug counteracts neuromuscular blockade induced by aminoglycoside antibiotics. Concomitant use with thiazide diuretics may lead to hypercalcemia. When used simultaneously with phenytoin, calcium preparations reduce its effect. These preparations decrease urinary calcium excretion.

Concomitant administration with other calcium-containing drugs is not recommended.

Calcium reduces the effects of calcium channel blockers. Intravenous administration of calcium gluconate before and after verapamil intake reduces the latter's antihypertensive effect but does not affect its antiarrhythmic action. Concomitant use with quinidine may result in slowed intraventricular conduction and increased quinidine toxicity.

Parenteral administration of calcium gluconate is not recommended during treatment with cardiac glycosides due to enhanced cardiotoxic effects. The effects of digoxin and other cardiac glycosides are potentiated in the presence of calcium.

When ethanol interacts with calcium gluconate, the latter precipitates.

Administration of calcium with adrenaline reduces its beta-adrenergic effect in patients after cardiac surgery.

Magnesium and calcium have mutually antagonistic effects.

Special precautions for use.

It is necessary to monitor blood calcium levels and calcium excretion, especially in children, patients with chronic renal insufficiency or nephrolithiasis. If plasma calcium levels exceed 2.75 mmol/L or 24-hour urinary calcium excretion exceeds 5 mg/kg, treatment should be discontinued immediately due to the risk of developing cardiac arrhythmias.

Calcium salts should be administered with caution and only after careful determination of indications in patients with nephrocalcinosis, heart diseases, sarcoidosis, patients receiving adrenaline, and elderly individuals.

Calcium salts are irritants. The injection site should be monitored continuously to prevent tissue damage due to extravasation.

To reduce the risk of nephrolithiasis, adequate fluid intake is recommended.

Calcium gluconate is physically incompatible with many compounds (see section "Incompatibilities"). Caution is required to avoid mixing calcium gluconate with incompatible drugs in the same container or in the bloodstream after separate administration. Serious complications, including fatal outcomes, have occurred following microcrystallization of insoluble calcium salts in the body after separate administration of physically incompatible solutions or total parenteral nutrition solutions containing calcium and phosphates.

Fatal reactions due to precipitation of ceftriaxone-calcium complexes in the lungs and kidneys have been reported in premature and full-term newborns up to 1 month of age. At least one of these patients received ceftriaxone and calcium at different times via different infusion systems. Currently, there are no data confirming the formation of intravascular precipitates in patients other than neonates treated with ceftriaxone and calcium-containing solutions or any other calcium-containing products. In vitro studies have shown that neonates have an increased risk of ceftriaxone-calcium precipitation compared to other age groups.

For patients of any age, ceftriaxone must not be mixed or administered simultaneously with any intravenous solutions containing calcium, even via different infusion systems or at different injection sites.

However, for patients aged 28 days and older, ceftriaxone and calcium-containing solutions may be administered sequentially, one after the other, provided they are administered through different infusion systems at different sites or the infusion line is replaced or thoroughly flushed with saline solution between administrations to prevent precipitation. Sequential infusions of ceftriaxone and calcium-containing drugs should be avoided in cases of hypovolemia.

Before filling a syringe with calcium gluconate solution, ensure that no ethanol residues remain, as their interaction causes calcium gluconate to precipitate.

Solutions containing calcium must be administered slowly to minimize peripheral vasodilation and cardiac suppression.

Intravenous injections should be accompanied by monitoring of heart rate (HR) or ECG due to the risk of bradycardia, vasodilation, or arrhythmias if administered too rapidly.

When large doses are administered parenterally, monitoring of plasma and urinary calcium levels is required.

In patients receiving calcium salts, careful assessment of calcium balance should be performed to prevent tissue accumulation of calcium.

The use of high doses of vitamin D should be avoided.

Use during pregnancy or breastfeeding.

Calcium crosses the placenta, and its concentration in fetal tissues is higher than in maternal blood.

The use of the medicinal product during pregnancy or breastfeeding is possible, taking into account the benefit-risk ratio for the mother and potential risk to the fetus (child).

The prescribed dose should be carefully calculated. Serum calcium levels should be regularly monitored to avoid hypercalcemia, which may be harmful to the fetus. Calcium is excreted in breast milk. A decision regarding discontinuation of breastfeeding or discontinuation/avoidance of calcium gluconate administration should be made based on the benefits of breastfeeding for the child and the benefits of treatment for the mother.

Ability to affect reaction speed when driving or operating machinery.

There is no information indicating that the medicinal product affects psychomotor reaction speed.

Method of administration and dosage.

Administer intravenously or intramuscularly.

Warm the ampoule containing the solution to body temperature before administration. Inject the solution slowly. The rate of intravenous administration should not exceed 2 mL (0.45 mmol of calcium) per minute. The patient must be in a supine position. Close monitoring of the patient is required during injection (monitoring should include pulse rate or ECG control).

For adults and children aged 14 years and older: administer 5–10 mL of the drug daily or every 1–2 days, depending on the course of the disease and the patient's condition.

For children, the intravenous dose depends on age: infants under 6 months – 0.1–1 mL; 7–12 months – 1–1.5 mL; 1–3 years – 1.5–2 mL; 4–6 years – 2–2.5 mL; 7–14 years – 3–5 mL.

When administering less than 1 mL of solution, dilute the single dose to the appropriate volume (syringe volume) with 0.9% sodium chloride solution or 5% glucose solution. Avoid dilution in solutions containing bicarbonate, phosphate, or sulfate.

Elderly patients.

Although there is no direct evidence that advanced age affects tolerance to calcium gluconate injections, factors sometimes associated with aging—such as impaired renal function and malnutrition—may indirectly influence tolerance and may require dosage reduction.

Dosages and administration methods should be reviewed according to updated safety data.

Normal plasma calcium concentration ranges from 2.25 to 2.75 mmol/L, or 4.5–5.5 mEq/L. Treatment should aim to restore or maintain this level.

Serum calcium levels should be carefully monitored during therapy.

Children.

This drug should not be used routinely in the treatment of children (under 18 years of age).

Intramuscular administration is not recommended for children under 14 years of age due to the risk of necrosis.

Overdose.

Symptoms: hypercalcemia may develop. Symptoms of hypercalcemia may include anorexia, nausea, vomiting, constipation, abdominal pain, muscle weakness, polydipsia, polyuria, dehydration, bone pain, psychiatric disturbances, nephrocalcinosis, nephrolithiasis, drowsiness, confusion, hypertension; in severe cases—cardiac arrhythmias, cardiac arrest, and coma. If intravenous injection is too rapid, symptoms of hypercalcemia may occur, along with a chalky taste, hot flashes, and hypotension.

Treatment. The goal of treatment is to reduce hypercalcemia. Infusion of sodium chloride to expand extracellular fluid volume, followed by administration of furosemide, may enhance calcium excretion. However, thiazide diuretics should be avoided, as they may increase renal calcium reabsorption. Calcitonin may be used to reduce serum calcium concentration. Hemodialysis or peritoneal dialysis may be considered if other measures fail and the patient continues to exhibit acute symptoms.

During treatment of overdose, serum electrolytes should be closely monitored.

Adverse Reactions

The frequency of adverse effects listed below is defined as follows:

very common: ≥1/10;

common: ≥1/100 — <1/10;

uncommon: ≥1/1,000 — <1/100;

rare: ≥1/10,000 — <1/1,000;

very rare: <1/10,000;

frequency not known: cannot be estimated from the available data.

Systemic adverse effects and cardiovascular system effects are likely to occur as symptoms of acute hypercalcemia due to intravenous overdose or excessively rapid administration. Their occurrence and frequency are directly dependent on the rate and dose of administration.

Gastrointestinal disorders: frequency not known: nausea, vomiting; diarrhea.

Cardiac disorders: frequency not known: bradycardia, arrhythmias.

Vascular disorders: frequency not known: hypotension, vasodilation, circulatory collapse, sometimes fatal, flushing, mostly after rapid infusion.

General disorders and administration site reactions: frequency not known: sensation of warmth, sweating.

Allergic and anaphylactic reactions, up to and including anaphylactic shock, may occur very rarely.

Ceftriaxone-calcium precipitation

Rare, severe, and in some cases fatal adverse reactions have been reported in premature and full-term neonates (age <28 days) treated with intravenous ceftriaxone and calcium.

Ceftriaxone-calcium precipitate has been found post-mortem in the lungs and kidneys. The high risk of precipitation in neonates is due to their small blood volume and the prolonged elimination half-life of ceftriaxone compared to adults (see sections "Contraindications", "Special precautions").

Adverse reactions due to incorrect administration technique

Frequency not known: cases of skin calcinosis have been reported, which may lead to subsequent skin sloughing and necrosis following extravasation. Skin redness, burning sensation, or pain during intravenous injection may indicate accidental extravascular injection, which can lead to tissue necrosis.

Shelf life. 3 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Incompatibilities.

Calcium salts are incompatible with oxidizing agents, citrates, carbonate and bicarbonate solutions, phosphates, tartrates (salts of tartaric acid), and sulfates.

Physical incompatibility with amphotericin, sodium cephalothin, cefamandole, cefazolin, ceftriaxone, sodium novobiocin, dobutamine hydrochloride, prochlorperazine, tetracyclines.

Packaging.

5 ml in ampoules, 5×2 in blisters in a box, 10 in a box; 10 ml in ampoules, 10 in a box.

Classification.

Prescription only.

Manufacturer.

LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA".

Manufacturer's address and place of business.

22, Shevchenka Street, Kharkiv, Kharkiv region, 61013, Ukraine.