Calcium gluconate stabilized

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CALCIUM GLUCONATE STABILISATE (CALCIUM GLUCONATE STABILISATE)

Composition:

Active substance: calcium gluconate;

1 ml of solution contains calcium gluconate 95.5 mg;

Excipients: calcium saccharate, water for injections.

Dosage form. Solution for injection.

Main physicochemical properties: clear, colorless liquid.

Pharmacotherapeutic group. Blood substitutes and perfusion solutions. Solution for intravenous administration. Solutions used for correction of electrolyte balance disorders. Electrolytes. ATC code B05B B01.

Pharmacological properties.

Pharmacodynamics.

"Calcium gluconate (stabilized)" is a drug that regulates metabolic processes and eliminates calcium deficiency in the body; it exerts hemostatic and antiallergic effects and reduces capillary permeability.

Calcium ions are involved in nerve impulse transmission, contraction of smooth and skeletal muscles, myocardial function, and blood coagulation; they are necessary for bone tissue formation and functioning of other systems and organs. The concentration of calcium ions in blood decreases in many pathological conditions, and pronounced hypocalcemia may lead to tetany. Calcium gluconate eliminates hypocalcemia, reduces vascular permeability, and exerts antiallergic, anti-inflammatory, and hemostatic effects.

Pharmacokinetics.

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

Clinical characteristics.

Indications.

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

Contraindications.

Aluminum oxide may leach from glass vials of calcium gluconate; therefore, to limit aluminum exposure in patients—particularly those with impaired renal function and children—calcium gluconate should not be used in the preparation of total parenteral nutrition.

Do not use for repeated or long-term treatment in children (under 18 years) and patients with impaired renal function (due to the risk of aluminum toxicity).

Hypersensitivity to components of the drug; predisposition to thrombosis; hypercalcemia (e.g., in hyperparathyroidism, hypervitaminosis D, tumors with bone decalcification, renal failure, sarcoidosis, immobilization osteoporosis, milk-alkali syndrome); hypercalciuria; severe atherosclerosis; increased blood coagulability; concomitant use with cardiac glycosides; severe renal failure.

Calcium gluconate must not be administered together with ceftriaxone in the following cases:

• Premature newborns until corrected age of 41 weeks (gestational weeks + postnatal weeks);
• Full-term newborns (under 28 days of age)—due to the risk of forming an insoluble ceftriaxone-calcium complex.

Interaction with other medicinal products and other types of interactions.

When ethanol interacts with calcium gluconate, the latter precipitates as a sediment.

It is not recommended to administer together with other calcium-containing drugs.

Concomitant use with quinidine may slow intraventricular conduction and increase quinidine toxicity.

Calcium gluconate reverses neuromuscular blockade caused by aminoglycoside antibiotics.

When used concomitantly with phenytoin, calcium preparations reduce its effectiveness.

Calcium reduces the effects of calcium channel blockers. Intravenous administration of calcium gluconate before and after verapamil intake diminishes its hypotensive effect, but does not affect its antiarrhythmic action.

Combination with thiazide diuretics may lead to hypercalcemia. These drugs reduce urinary calcium excretion.

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

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

Magnesium and calcium have mutually antagonistic effects.

Special precautions for use.

Calcium levels in blood and calcium excretion should be monitored, especially in children, patients with chronic renal insufficiency or nephrolithiasis. If plasma calcium levels exceed 2.75 mmol/L or daily urinary calcium excretion exceeds 5 mg/kg, treatment must be discontinued immediately due to the risk of developing cardiac arrhythmias.

To reduce the risk of nephrolithiasis, it is recommended to consume an adequate amount of fluids.

Before filling the syringe with calcium gluconate solution, ensure that no ethyl alcohol residues remain in it, as calcium gluconate may precipitate due to interaction with alcohol.

Calcium salts should be used cautiously and only after careful assessment of indications in patients with nephrocalcinosis, heart diseases, sarcoidosis, patients receiving adrenaline, and elderly individuals.

Calcium salts are irritants; therefore, the injection site should be continuously monitored to prevent extravasation injury.

Calcium gluconate is physically incompatible with many compounds (see section "Incompatibilities"); therefore, caution is required when administering medicinal products to avoid combined use of incompatible components or their interaction after separate administration.

Serious complications, including fatal outcomes, have been observed due to microcrystallization of insoluble calcium salts in the body after separate administration of physically incompatible solutions or parenteral nutrition mixtures containing calcium and phosphates.

Fatal cases have been reported in full-term and preterm neonates up to 1 month of age associated with formation of insoluble ceftriaxone–calcium complexes in the lungs and kidneys. At least one of these patients received ceftriaxone and calcium at different times.

Available scientific data do not confirm formation of intravascular ceftriaxone–calcium complexes in patients of other age groups. In vitro studies have shown that neonates have an increased risk of forming insoluble ceftriaxone–calcium complexes compared to other age groups.

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

However, in patients aged 28 days and older, ceftriaxone and calcium-containing solutions may be administered sequentially if infusions are given at different sites or if the infusion system is replaced or thoroughly flushed with saline solution to prevent precipitate formation. Sequential infusions of ceftriaxone and calcium-containing preparations should be avoided in cases of hypovolemia.

Solutions containing calcium should be administered slowly to minimize peripheral vasodilation and cardiac depression.

Intravenous injections must be accompanied by monitoring of heart rate (HR) or ECG due to the risk of bradycardia, vasodilation, or arrhythmias in case of rapid administration.

When administering large doses parenterally, monitoring of plasma and urinary calcium levels should be performed.

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

Patients should avoid taking high doses of vitamin D.

Use during pregnancy or breastfeeding.

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

The use of this 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 passes into breast milk. A decision on whether to discontinue breastfeeding or to stop/omit calcium gluconate therapy should be made based on the benefits of breastfeeding for the child and the benefits of treatment for the mother.

Ability to influence reaction speed when driving or operating machinery.

There are no data on negative effects of the medicinal product on reaction speed when driving or operating machinery.

Administration and Dosage

Administer intravenously or intramuscularly.

For adults and children aged 14 years and older, administer 5–10 mL of a 10% solution once daily, depending on the nature of the disease and the patient's condition—daily, every other day, or every two days.

For children, according to age, the 10% calcium gluconate solution should be administered intravenously in the following doses: under 6 months of age – 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.

Calcium gluconate injection may be diluted with 5% glucose or 0.9% sodium chloride. Avoid dilution in solutions containing bicarbonate, phosphate, or sulfate.

Geriatric Patients

Although there is no direct evidence that advanced age affects tolerance to calcium gluconate injection, factors sometimes associated with aging—such as impaired renal function and malnutrition—may indirectly influence tolerance and may necessitate dosage reduction. Renal function declines with age, and when prescribing this medicinal product to elderly patients, it should be noted that calcium gluconate injection is contraindicated (see section "Contraindications") for repeated or prolonged use in patients with impaired renal function.

Dosage and administration should be reviewed according to updated safety data.

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

Serum calcium levels should be closely monitored during therapy.

Administration Method

The preparation should be warmed to body temperature before administration. The solution should be administered slowly in adults and children. The intravenous administration rate should not exceed 2 mL (0.45 mmol of calcium) per minute. The patient should be in a supine position. Close observation of the patient is required during injection (monitoring should include heart rate or ECG control).

Children

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

Intramuscular administration of this medicinal product is not recommended in children under 14 years of age due to the risk of developing necrosis.

Overdose

Overdose may lead to hypercalcemia, manifested by anorexia, nausea, vomiting, constipation, abdominal pain, muscle weakness, polydipsia, polyuria, dehydration, bone pain, psychiatric disorders, nephrocalcinosis, nephrolithiasis, drowsiness, confusion, hypertension, and in severe cases, cardiac arrhythmias, cardiac arrest, and coma. If intravenous injection is too rapid, symptoms of hypercalcemia may occur, including chalky taste, hot flashes, and hypotension.

Treatment
The goal of treatment is to reduce hypercalcemia. Infusion of sodium chloride may be used to increase intracellular fluid volume, and subsequent administration of furosemide may enhance calcium excretion. However, thiazide diuretics should be avoided, as they may enhance renal calcium reabsorption. Calcitonin may be used as an antidote when all other methods have failed and the patient continues to exhibit acute symptoms. Hemodialysis or peritoneal dialysis may be considered if other measures are ineffective and the patient continues to have acute symptoms.

During treatment of overdose, serum electrolyte levels 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 — <1,000;

very rare: <1/10,000;

unknown frequency: frequency cannot be estimated from available data.

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

Cardiac disorders

Unknown frequency: bradycardia, arrhythmias.

Vascular disorders

Unknown frequency: hypotension, vasodilation, circulatory collapse (possibly fatal), flushes, mostly after rapid injection.

Gastrointestinal disorders

Unknown frequency: nausea, vomiting, diarrhea.

General disorders and administration site conditions

Unknown frequency: feeling of warmth, sweating.

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

Ceftriaxone-calcium precipitation

Rare, severe, and in some cases fatal adverse reactions have been reported in preterm and term neonates (age <28 days) treated with intravenous ceftriaxone and calcium. Post-mortem findings revealed ceftriaxone-calcium precipitates in the lungs and kidneys. The high risk of precipitation in neonates is due to their small blood volume and the long elimination half-life of ceftriaxone compared to adults (see sections "Contraindications", "Special precautions").

Adverse reactions due to incorrect administration technique

Unknown frequency: skin calcinosis with subsequent possible detachment and necrosis due to extravasation have been reported. Skin redness, burning sensation or pain during intravenous injection may indicate accidental extravascular injection, which can lead to tissue necrosis.

Shelf life. 5 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions. Store in the original packaging, protected from light, at a temperature not exceeding 25 °C. Do not refrigerate. Keep out of the reach of children.

Incompatibility.

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

Physical incompatibility with amphotericin, cephalothin solution, cefamandole, ceftriaxone, sodium novobiocin, dobutamine hydrochloride, prochlorperazine, tetracycline.

Packaging. 5 ml or 10 ml in a vial; 5 or 10 vials per pack.

5 ml or 10 ml in a vial; 5 vials per blister; 1 or 2 blisters per pack.

Prescription category. Prescription only.

Manufacturer. JSC "Farmak".

Manufacturer's address and place of business.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.