Calcium gluconate-Darnitsa

APPROVED

by the Order of the Ministry of Health of Ukraine

09.11.2021 No. 2465

Marketing Authorization

No. UA/19046/01/01

PACKAGE LEAFLET

for medical use of a medicinal product

CALCIUM GLUCONATE-DARNITSA (STABILIZED)

Qualitative and quantitative composition:

active substances: саlcium gluconate;

1 ml of solution contains calcium gluconate 95.5 mg;

excipients: calcium saccharate, sodium hydroxide, water for injection.

1 ml of medicinal product contains 8,95 mg of total calcium (Са2+), which is equivalent to 100 mg/ml in terms of the theoretical content of calcium gluconate.

Pharmaceutical form. Solution for injection.

Basic physical and chemical properties: transparent colorless liquid.

Pharmacotherapeutic group.

Calcium. Cаlcium gluconate. ATC code А12А А03.

Solutions affecting the electrolyte balance. Electrolytes. ATC code B05B B01.

Pharmacological properties.

Pharmacodynamic properties.

Calcium gluconate (stabilized) – is an agent that regulates metabolic processes, compensates for calcium deficiency in the body, has a hemostatic, anti-allergic effect and reduces capillary permeability.

Calcium ions are involved in the transmission of nerve impulses, contraction of smooth and striated muscles, myocardial function, blood coagulation; they are necessary for the formation of bone tissue, the functioning of other systems and organs. The concentration of calcium ions in the blood decreases in many pathological processes; severe hypocalcemia contributes to the occurrence of tetany. In addition to eliminating hypocalcemia, calcium compounds reduce vascular permeability, have anti-allergic, anti-inflammatory, hemostatic effects.

Pharmacokinetic properties.

After parenteral administration, the medicinal product is evenly distributed in all organs and tissues. In blood plasma, calcium is in an ionized state. Passes through the placental barrier, is excreted in breast milk. It is excreted from the body, mainly by the kidneys.

Clinical particulars.

Therapeutic indications.

To be used in case of insufficiency of the function of the parathyroid glands; increased excretion of calcium from the body (especially with prolonged dehydration); as an auxiliary agent for allergic diseases (serum disease, urticaria, angioedema) and allergic complications of drug therapy; to reduce vascular permeability in pathological processes of any genesis (exudative phase of the inflammatory process, hemorrhagic vasculitis, radiation sickness); with parenchymal hepatitis; toxic liver damage; nephritis; eclampsia; hyperkalemia; hyperkalemic form of paroxysmal myoplegia; skin diseases (skin itching, eczema, psoriasis); as a hemostatic agent; as an antidote for poisoning with magnesium salts, oxalic acid or its soluble salts, soluble salts of fluoric acid.

Contraindications.

Hypersensitivity to the components of the medicinal product; tendency to thrombosis; hypercalcemia (for example, with hyperparathyroidism, hypervitaminosis D, tumor diseases with bone decalcification, sarcoidosis, immobilization osteoporosis, milk-alkali syndrome); serious hypercalciuria; severe atherosclerosis; increased blood coagulation; severe renal failure; simultaneous use with cardiac glycosides.

Aluminum oxide can be washed out of glass vials with calcium gluconate, therefore, in order to limit the effect of aluminum on patients, especially patients with impaired kidney function and children, calcium gluconate must not be used for the preparation of total parenteral nutrition.

Repeated and long-term treatment of children (under the age of 18) and people with impaired kidney function (due to the risk of exposure to aluminum on the body) is contraindicated.

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

• premature newborns aged ≤ 41 weeks, taking into account the period of intrauterine development (gestational age + age after birth);
• term newborns (age ≤ 28 days).

Interaction with other medicinal products and other forms of interaction.

When ethyl alcohol interacts with calcium gluconate, the latter precipitates.

Simultaneous administration of calcium and epinephrine attenuates the β-adrenergic effect of epinephrine in patients after cardiac surgery.

It is not recommended to prescribe together with other calcium preparations.

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

When used simultaneously with nifedipine, calcium medicinal products reduce its effectiveness.

The combination with thiazide diuretics can cause the development of hypercalcemia, since these medicinal products reduce the excretion of calcium by the kidneys.

When used simultaneously with quinidine, it is possible to slow down intraventricular conduction and increase the toxicity of quinidine.

During treatment with cardiac glycosides, parenteral use of calcium gluconate is not recommended due to increased cardiotoxicity. The effect of digoxin and other cardiac glycosides is enhanced in the presence of calcium.

Calcium gluconate eliminates inhibition of neuromuscular transmission caused by the use of antibiotics of a number of aminoglycosides.

Magnesium and calcium have a mutual antagonistic effect.

Special warnings and precautions for use.

Calcium salts should be used with caution in patients with impaired renal function, heart disease, sarcoidosis, patients prescribed adrenaline, and the elderly patients.

Calcium salts are an irritant, so the injection site must be constantly monitored to prevent extravasal damage.

Patients with a tendency to the formation of calculi in the urinary tract during treatment are recommended to increase the amount of fluid consumed.

It is necessary to monitor the level of calcium in the blood and the excretion of calcium, especially in children, patients with chronic с or nephrolithiasis. If the level of calcium in the blood plasma exceeds 2.75 mmol/l or the daily excretion of calcium in the urine exceeds 5 mg/kg, treatment must be stopped immediately because of the risk of cardiac arrhythmias.

Calcium gluconate is physically incompatible with many compounds (see section "Incompatibilities"), so care must be taken when administering medicinal products to avoid the combined use of incompatible components or their interaction after separate administration.

Before filling the syringe with a solution of calcium gluconate, it is necessary to make sure that there are no residues of ethyl alcohol in it, because as a result of interaction with calcium alcohol, gluconate precipitates.

Serious complications, including those with a fatal outcome, developed after microcrystallization of insoluble calcium salts in the body after separate administration of physically incompatible solutions or solutions of complete parenteral nutrition containing calcium and phosphates.

Aluminum oxide can be washed out of the glass vials with calcium gluconate, therefore, in order to limit the effect of aluminum, especially on patients with impaired kidney function and children (under the age of 18), calcium gluconate should not be used to prepare total parenteral nutrition.

Cases of fatal reactions due to the formation of ceftriaxone-calcium precipitates in the lungs and kidneys of premature and full-term newborns under the age of 1 month have been described. At least one of them received ceftriaxone and calcium at different times.

In the available scientific data, there is no confirmation of the formation of intravascular ceftriaxone - calcium complexes in patients of other age categories. In vitro studies have shown that neonates have an increased risk of ceftriaxone-calcium precipitation compared to other age groups.

Ceftriaxone should not be mixed or administered simultaneously with intravenous solutions containing calcium, even through different injection systems or at different injection sites.

Sequential infusions of ceftriaxone and calcium-containing drugs should be avoided in cases of hypovolemia.

However, in patients 28 days of age or older, ceftriaxone and calcium-containing solutions can be administered sequentially one after the other if the infusion is done at different sites or if the infusion system is changed to avoid precipitation.

In patients taking calcium salts, it is necessary to carefully check the correctness of ensuring the balance of calcium without the formation of its tissue accumulations.

The patient should avoid taking large doses of vitamin D.

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

Intravenous injections should be accompanied by heart rate (HR) or ECG monitoring due to the risk of bradycardia, vasodilatation, or arrhythmia in case of ultra-rapid administration. With parenteral administration of large doses of calcium, it is necessary to monitor its level in the plasma and excretion of calcium in the urine.

Fertility, pregnancy and lactation.

Calcium penetrates through the placenta, its concentration in the body of the fetus is higher than in the blood of the mother. The use of the medicinal product during pregnancy or period of breast feeding is possible, taking into account the ratio of benefit to the mother / risk to the fetus (child).

The prescribed dose must be carefully calculated. Serum calcium levels should be monitored regularly to avoid hypercalcemia, which can be harmful to the fetus.

Calcium passes into breast milk. The decision to refuse breast feeding or to stop using the prescribed calcium gluconate should be made taking into account the benefit of feeding for the child and the benefit of treatment for the woman.

Effects on ability to drive and use machines.

There is no data on the negative impact of medicinal product on the reaction rate when driving vehicles or working with other mechanisms.

Posology and method of administration.

Use intravenously or intramuscularly.

The ampoule with the solution is heated to body temperature before administration. The solution is introduced slowly.

The rate of intravenous administration should not exceed 2 ml (0.45 mmol calcium) per minute. The patient should be supine and closely monitored during the injection (monitoring should include heart rate or ECG monitoring).

Dilution in a solution containing bicarbonate, phosphate or sulfate should be avoided.

To administer a solution in the amount of less than 1 ml, a single dose of the medicinal product is brought to the appropriate volume (syringe volume) with 0.9% sodium chloride solution or 5% glucose solution.

Doses and route of administration should be reviewed according to updated safety data. A normal plasma calcium concentration is between 2.25 and 2.75 mmol, or 4.5 and 5.5 mEq, per liter. Treatment should be aimed at restoring or maintaining this level.

Adults and children over the age of 14 are injected with 5–10 ml of the medicinal product "Calcium gluconate-Darnitsa (stabilized)" daily or after 1–2 days, depending on the course of the disease and the patient's condition.

For children under 14 years of age, the medicinal product is used only intravenously. Depending on age, 10% calcium gluconate solution is administered in the following doses: children under the age of 6 months - 0.1-1 ml, 6-12 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.

Elderly patients. Although there is no evidence that tolerance to calcium gluconate injection is directly affected by advanced age, factors that can sometimes be associated with aging, such as renal impairment and poor diet, may indirectly affect tolerance and may require dosage reduction. Renal function declines with age, therefore, when prescribing this medicinal product to elderly patients, it should be considered, that calcium gluconate injection is contraindicated (see section "Contraindications") for repeated or long-term use in patients with impaired renal function.

During therapy, the level of calcium in the blood serum should be carefully monitored.

Children.

This medicinal product should not be a routine remedy in the treatment of children (under the age of 18).

For children under 14 years of age, it is not recommended to administer the medicinal product intramuscularly due to the possibility of necrosis.

Overdose.

Symptoms: possible development of hypercalcemia, manifested by anorexia, nausea, vomiting, constipation, abdominal pain, muscle weakness, polydipsia, dehydration, bone pain, mental disorders, nephrocalcinosis, nephrolithiasis, drowsiness, confusion of consciousness, hypertension, and in severe cases – cardiac arrhythmia, cardiac arrest, coma. If the intravenous injection is too rapid, symptoms of hypercalcemia may occur, as well as a chalky taste, hot flushes, and hypotension.

Treatment: the goal of treatment is to reduce hypercalcemia. Infusion of sodium chloride to increase the volume of intracellular fluid followed by furosemide may increase calcium excretion, but thiazide diuretics should be avoided because they may increase renal reabsorption of calcium.

In case of a severe overdose (calcium concentration in the blood serum is more than 2.9 mmol/l), calcitonin is administered parenterally at a dose of 5–10 IU/kg of body weight per day (diluting it in 500 ml of 0.9% sodium chloride solution), intravenous drip within 6 hours. It is possible to inject slowly intravenously 2-4 times a day. Non-thiazide diuretics are used; monitor the concentration of potassium and magnesium in the serum, if necessary, administer potassium and magnesium preparations; control of the function of the cardiovascular system is carried out, β-adrenoblockers are administered to prevent arrhythmias.

Hemodialysis or peritoneal dialysis may be considered if other measures have failed and the patient remains acutely symptomatic.

Undesirable effects.

Adverse events have been ranked under headings of frequency using the following convention: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, <1/100); rare (≥ 1/10000, <1/1000); very rare (<1/10000), not known (cannot be estimated from the available data).

Systemic adverse effects and cardiovascular system adverse effects are likely to occur as symptoms of acute hypercalcemia with intravenous overdose or with ultra-rapid administration. Their appearance and frequency directly depend on the frequency of administration and dose.

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

Cardiovascular system: not known: bradycardia, arrhythmias, hypotension, vasodilatation, circulatory collapse (possibly fatal), flushing, mostly after rapid administration.

General disorders and administration site conditions: very rare: allergic and anaphylactic reactions, up to anaphylactic shock; not known: hot flushes, sweating.

Ceftriaxone-calcium precipitation.

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

Postmortal, ceftriaxone-calcium precipitate was found in the lungs and kidneys. The high risk of precipitation in newborns is a consequence of their small blood volume and the long half-life of ceftriaxone compared to adults (see sections "Contraindications", "Special warnings and precautions for use").

Undesirable effects due to incorrect administration technique.

Not known: Calcification of the skin has been reported, followed by possible detachment and necrosis as a result of extravasation. Skin redness, burning sensation or pain during injection may indicate an accidental extravascular injection, which may lead to tissue necrosis.

Reported suspected adverse reactions.

Reporting suspected adverse reactions after registration of a medicinal product is an important procedure. This allows for continued monitoring of the benefit/risk ratio for the respective drug. Healthcare providers should be informed of any suspected adverse reactions through the national alert system.

Shelf life. 3 years.

Special precautions for storage.

Store in the original package at a temperature not above 25°C. Do not freeze.

Keep out of the reach of children.

Incompatibilities.

Pharmaceutically incompatible with ethyl alcohol, oxidizing agents, citric acid, carbonates, bicarbonates, phosphates, salicylates, sulfates, tartrates.

Physical incompatibility with amphotericin, cephalotin solution, cefamandole, ceftriaxone, novobiocin sodium, dobutamine hydrochloride, prochlorpyrazine, tetracycline.

Nature and contents of container.

5 ml in an ampoule; 5 ampoules in a contour honeycomb package; 2 contour honeycomb packages in a pack; 10 ml in an ampoule; 5 ampoules in a contour honeycomb package; 2 contour honeycomb packages in a pack.

Category of release. Prescription only medicinal product.

Manufacturer. PrJSC “Pharmaceutical firm “Darnitsa”.

The manufacturer's location and address of the place of business.

13, Boryspilska Street, Kyiv, 02093, Ukraine.

Date of last revision. 09.11.2021.