Calcium gluconate Bioindustria L.I.M.

BIOINDUSTRIA Italian Medicinal Laboratory S.p.A.

ILLUSTRATED LEAFLET

Calcium Gluconate Bioindustria L.I.M. 500 mg/5 ml infusion solution, 1000 mg/10 ml infusion solution

PHARMACOTHERAPEUTIC CATEGORY
Mineral supplements

THERAPEUTIC INDICATIONS
Treatment of hypocalcemic conditions.
Adjuvant in antianaphylactic therapy, for controlling increased capillary permeability in allergic conditions and in non-thrombocytopenic purpura.

CONTRAINDICATIONS

• Hypersensitivity to the active substance or to any of the excipients;
• Pathologies and/or conditions associated with hypercalcemia (e.g., hyperparathyroidism, hypervitaminosis D, neoplastic disease with bone demineralization);
• Severe hypercalciuria;
• Severe renal insufficiency;
• Ventricular fibrillation;
• Patients receiving cardiac glycosides;
• Concomitant treatment with ceftriaxone in neonates (≤28 days of age), even when using separate infusion lines. See sections Interactions, Undesirable Effects, and Dosage, Method and Duration of Administration.

PRECAUTIONS FOR USE
Subcutaneous and intramuscular administration must be avoided, as calcium salts are irritant and may cause local abscesses and necrosis. Patients should therefore be regularly monitored at the infusion site to prevent local extravasation of the solution.
Serum calcium levels and urinary excretion should be monitored, particularly in children, in cases of chronic renal insufficiency, or in the presence of urinary tract stones.
If plasma calcium levels exceed 2.75 mmol/l or if 24-hour urinary calcium excretion exceeds 5 mg/kg, treatment must be immediately discontinued, as cardiac arrhythmias may occur.
Calcium salts should be administered with caution in patients with impaired renal function, nephrocalcinosis, and in patients with cardiac disease.
Calcium gluconate is physically incompatible with several substances (see Dosage, Method and Duration of Administration). Avoid mixing calcium gluconate solutions in the same infusion set with incompatible drugs, or even administering them sequentially through the same line.
Serious, potentially fatal complications may occur following the simultaneous administration of physically incompatible solutions or total parenteral nutrition solutions containing calcium and phosphate, due to microcrystallization of insoluble calcium salts within the body.
Concomitant use of calcium gluconate and ceftriaxone should be avoided, as precipitation of calcium-ceftriaxone complexes may occur.

BIOINDUSTRIA Laboratorio Italiano Medicinali S.p.A.

INTERACTIONS
Inform your doctor or pharmacist if you have recently taken any other medicines, including those not requiring a prescription.

Cardiac glycosides/digitalis: Potentiation of effects. The combination increases the risk of digitalis toxicity.
Verapamil: Concomitant systemic use of verapamil and calcium gluconate may reverse the hypotensive effect.
Thiazide diuretics: Concomitant use of thiazide diuretics with calcium gluconate increases the risk of hypercalcemia.

Laboratory tests
Calcium gluconate may cause false negative results in laboratory tests for serum and urinary magnesium. The mechanism of this interaction is unknown.

Physical incompatibilities
See Precautions for Use and Dosage, Method and Duration of Administration.
As with other calcium-containing solutions, concomitant use with ceftriaxone is contraindicated in neonates (≤28 days of age), even when separate infusion lines are used (risk of fatal precipitation of calcium-ceftriaxone salt in the neonate’s bloodstream; see section Undesirable Effects).
In patients older than 28 days (including adults), ceftriaxone must not be administered concomitantly with intravenous calcium-containing solutions, including Calcium Gluconate Bioindustria L.I.M., through the same infusion line (e.g., via a Y-connector).
If the same line is used for sequential administration, the line must be flushed with a compatible fluid between infusions.

SPECIAL WARNINGS
Pregnancy and breastfeeding
Consult your doctor or pharmacist before taking any medicine.
Calcium gluconate should be used during pregnancy only if considered essential by the physician.
Calcium is excreted in breast milk. This should be taken into account when prescribing calcium to women who are breastfeeding.

Effects on ability to drive and use machines
Calcium gluconate does not affect the ability to drive vehicles or operate machinery.

Important information about certain excipients: None

DOSAGE, METHOD AND DURATION OF ADMINISTRATION
Normal plasma calcium concentration generally ranges between 2.25–2.75 mmol or 4.5–5.5 mEq/l. Treatment with calcium gluconate aims to restore or maintain these levels.
However, the exact amount of calcium required in specific clinical situations is difficult to determine and may vary widely. During therapy, serum calcium levels must therefore be closely monitored.
Calcium gluconate must not be administered subcutaneously or intramuscularly (see Precautions for Use).
Calcium Gluconate Bioindustria L.I.M. is a hypertonic solution and must be used with caution and at a controlled infusion rate. Administration must be performed via slow intravenous infusion. Infusion rates should not exceed 1.5 ml per minute.

BIOINDUSTRIA Laboratorio Italiano Medicinali S.p.A.

The following dosage recommendations for calcium gluconate are provided as a guide:

Adults
500 mg – 2000 mg (5 – 20 ml of solution)

Children
200 mg – 500 mg (2 – 5 ml of solution)

Infants
Not more than 200 mg (not more than 2 ml of solution)

Elderly patients
Although there is no evidence that tolerance to calcium gluconate is directly affected by advanced age, certain factors or clinical conditions—such as poor diet and impaired renal function—may negatively affect drug tolerance and therefore may require dosage reduction.

Do not use if the solution is not clear; any precipitate may be redissolved by gentle warming in warm water.

Calcium gluconate for intravenous use may be diluted with 5% glucose or 0.9% sodium chloride solutions. Dilution in solutions containing bicarbonates, phosphates, or sulfates must be avoided.

Calcium salts may form complexes with many substances, leading to precipitate formation. Calcium salts are incompatible with oxidizing agents, citrates, soluble carbonates, bicarbonate, phosphates, tartrates, and sulfates.

Additionally, incompatibility has been reported with ceftriaxone (see Precautions for Use), amphotericin, sodium cefalotin, sodium cefazolin, cefamandole nafate, sodium novobiocin, dobutamine hydrochloride, prochlorperazine, tetracyclines, methylprednisolone sodium succinate, prochlorperazine edisylate, metoclopramide hydrochloride, fluconazole, indomethacin, and meropenem.

The medicinal product must not be mixed with intravenous nutritional emulsions.

Calcium salts may form complexes with many drugs, potentially leading to precipitate formation. Physical incompatibility has been reported with ceftriaxone (see sections Contraindications, Interactions, and Undesirable Effects).

OVERDOSE
Excessive administration of calcium salts leads to hypercalcemia. Symptoms of hypercalcemia may include: anorexia, nausea, vomiting, constipation, abdominal pain, muscle weakness, polydipsia, polyuria, mental disturbances, bone pain, nephrocalcinosis, kidney stones, and, in severe cases, cardiac arrhythmias and coma.

Treatment of overdose
Severe hypercalcemia is treated with infusion of a sodium chloride solution to increase extracellular fluid volume. Furosemide may then be used, either concurrently or subsequently, to further enhance calcium excretion. If this treatment is ineffective, other drugs such as calcitonin, bisphosphonates, disodium edetate, and phosphates may be used.
Hemodialysis may be considered as a last resort.
During overdose management, serum electrolyte levels must be closely monitored.
In case of accidental ingestion/overdose of Calcium Gluconate Bioindustria L.I.M., contact a doctor immediately or go to the nearest hospital.
If you have any doubts about the use of Calcium Gluconate Bioindustria L.I.M., consult your doctor or pharmacist.

BIOINDUSTRIA Laboratorio Italiano Medicinali S.p.A.

UNDESIRABLE EFFECTS
Like all medicines, Calcium Gluconate Bioindustria L.I.M. can cause adverse effects, although not everyone experiences them.
Listed below are the adverse effects associated with calcium gluconate. There are insufficient data to determine the frequency of individual listed effects.
Many of the adverse effects are due to excessively rapid infusion rates. This may cause vasodilation, with sweating, nausea, vomiting, hot flushes, hypotension, bradycardia, arrhythmias, and even syncope and vasomotor collapse, which may be fatal.
Local extravasation of the solution may lead to soft tissue calcification, abscess formation, and necrosis.
Some adverse effects may result from overdosage, including nephrolithiasis due to hypercalcemia and hypercalciuria.

Precipitation of calcium-ceftriaxone salt
Serious, and in some cases fatal, adverse reactions have rarely been reported in preterm and full-term neonates (age < 28 days) treated with intravenous ceftriaxone and calcium. Post-mortem findings revealed precipitation of calcium-ceftriaxone salt in the lungs and kidneys. The high risk of precipitation in neonates is due to their low blood volume and longer ceftriaxone half-life compared to adults (see sections Contraindications and Interactions).

Cases of renal precipitation have been reported, primarily in children over 3 years of age treated with high daily doses (e.g., ≥ 80 mg/kg/day) or total doses exceeding 10 grams, and who had other risk factors (e.g., fluid restriction, bedridden patients). The risk of precipitate formation increases in immobilized or dehydrated patients. This event may be symptomatic or asymptomatic, may cause renal failure and anuria, and is reversible upon discontinuation of the drug.

Calcium-ceftriaxone salt precipitation in the gallbladder has been observed, primarily in patients treated with doses exceeding the recommended standard dose. Prospective studies in children have shown variable incidence of precipitation with intravenous administration; in some studies, incidence exceeded 30%. This incidence appears lower when infusions are administered slowly (20–30 minutes). This effect is generally asymptomatic, but in rare cases, precipitation has been associated with clinical symptoms such as pain, nausea, and vomiting. Symptomatic treatment is recommended in such cases. Precipitation is generally reversible upon discontinuation of treatment.

Following the instructions in this leaflet reduces the risk of adverse effects.
If any of the adverse effects worsens, or if you notice any adverse effect not listed in this leaflet, inform your doctor or pharmacist.

EXPIRY DATE AND STORAGE
Expiry date: see date on the packaging
The expiry date refers to the product stored unopened and under proper storage conditions.

Warning: Do not use the medicine after the expiry date stated on the packaging.

Storage conditions
Store in the original packaging. Do not freeze.
Do not use if the solution is not clear; any precipitate may be redissolved by gentle warming in warm water.

BIOINDUSTRIA Laboratorio Italiano Medicinali S.p.A.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This helps protect the environment.

Keep the medicine out of the reach and sight of children.

COMPOSITION
Calcium Gluconate Bioindustria L.I.M. 500 mg/5 ml infusion solution
1 vial contains:
Active substance: calcium gluconate 475 mg
Excipient: calcium D-saccharate 18 mg
(equivalent to mEq/l Ca 446)
Excipients: calcium D-saccharate, water for injections

Calcium Gluconate Bioindustria L.I.M. 1000 mg/10 ml infusion solution
1 vial contains:
Active substance: calcium gluconate 950 mg
Excipient: calcium D-saccharate 36 mg
(equivalent to mEq/l Ca 446)
Excipients: calcium D-saccharate, water for injections

PHARMACEUTICAL FORM AND CONTENT
Infusion solution
10 vials of 5 ml and 10 vials of 10 ml.

MARKETING AUTHORIZATION HOLDER
BIOINDUSTRIA Laboratorio Italiano Medicinali S.p.A.
Via De Ambrosiis, 2 – 15067 Novi Ligure (AL)

MANUFACTURER
BIOINDUSTRIA Laboratorio Italiano Medicinali S.p.A.
Via De Ambrosiis, 2 – 15067 Novi Ligure (AL)

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