Calcium and magnesium chloride Bioindustria L.I.M.: detailed information

CALCIUM AND MAGNESIUM CHLORIDE BIOINDUSTRIA L.I.M. 4 mEq Ca /10 ml / 6 mEq Mg /10 ml
CONCENTRATE FOR INFUSION SOLUTION

PHARMACOTHERAPEUTIC CATEGORY
Electrolyte solutions – combinations of electrolytes.

THERAPEUTIC INDICATIONS
Treatment of pathological conditions requiring the combined administration of calcium ions and magnesium ions.

CONTRAINDICATIONS

Hypersensitivity to the active substances or to any of the excipients;
Ventricular fibrillation;
Signs of digitalis intoxication;
Hypercalcemia, hypercalciuria;
Severe oliguric renal failure;
Severe myocardial pathology;
Cardiac arrhythmias or myocardial damage;
Respiratory rate below 16 breaths/minute;
Renal calculi (the medicinal product may exacerbate this condition);
Sarcoidosis (the medicinal product may enhance the typical hypercalcemia of this condition);
Hypercoagulability;
Patients undergoing treatment with cardiac glycosides (see Interactions);
Comatose patients.

PRECAUTIONS FOR USE
The medicinal product must be administered with caution in patients:

With renal impairment;
With heart failure, particularly if digitalized;
With myasthenia gravis;
Receiving treatment with central nervous system depressants and neuromuscular blocking agents.

Since calcium chloride is acidifying, caution is required when administering it in conditions such as renal disease, cor pulmonale, respiratory acidosis, or respiratory insufficiency, where acidification may worsen the clinical picture. Furthermore, caution is advised in conditions where there may be an increased risk of hypercalcemia, dehydration, or electrolyte imbalance. In patients who have received transfusions of citrated blood, calcium ion concentration may differ from expected values. During infusion, it is advisable to monitor fluid balance, electrolytes, blood pressure, electrocardiographic trace, and osteotendinous reflexes—latterly to monitor for possible respiratory paralysis. Serum calcium and magnesium levels should be closely monitored during therapy to ensure they do not exceed normal limits. Urinary calcium concentrations should also be monitored to prevent hypercalciuria, as hypercalciuria may progress to hypercalcemia.

INTERACTIONS
Inform your doctor or pharmacist if you have recently taken any other medicines, including those without a prescription.

Calcium chloride may interact with the following medicinal products:

Thiazide diuretics, as hypercalcemia may occur due to reduced renal excretion of calcium;
Cardiac glycosides (digitalis), digoxin and digitoxin, as concomitant use may increase the risk of arrhythmias due to synergistic inotropic and toxic effects;
Verapamil (and other calcium channel blockers), as concomitant use may reduce the antihypertensive effect of verapamil;
Medicinal products containing magnesium, as this may increase the risk of hypercalcemia or hypermagnesemia, especially in patients with renal disorders;
Neuromuscular blocking agents: calcium salts may counteract the action of non-depolarizing blockers; in some cases, an increase and prolongation of the effect of tubocurarine has also been observed.

Magnesium chloride may interact with the following medicinal products:

Medicinal products that depress the central nervous system: when barbiturates, narcotics, or other hypnotics (or systemic anesthetics) or other drugs that depress the central nervous system are administered concurrently with magnesium, their dosage must be carefully adjusted due to the additive depressant effect of magnesium on the central nervous system. Central nervous system and peripheral transmission depression caused by magnesium can be antagonized by calcium;
Cardiac glycosides (digitalis), digoxin and digitoxin: magnesium chloride must be administered with extreme caution in patients taking digitalis due to alterations in cardiac conduction that may evolve into cardiac arrhythmia if calcium administration becomes necessary to treat magnesium intoxication;
Competitive and depolarizing neuromuscular blockers: parenteral administration of magnesium chloride potentiates the effect of competitive and depolarizing neuromuscular junction blockers;
Aminoglycoside antibiotics: the effect on neuromuscular blockade of parenterally administered magnesium and aminoglycoside antibiotics may be additive;
Eltrombopag: magnesium may decrease plasma concentrations of eltrombopag;
Rocuronium: simultaneous administration of rocuronium and magnesium may increase the risk of rocuronium toxicity (prolonged neuromuscular blockade, respiratory depression, and apnea);
Labetalol: simultaneous administration of labetalol and magnesium may cause bradycardia and reduced cardiac output (labored breathing, dizziness, or fainting);
Calcium antagonists (isradipine, felodipine, nicardipine, and nifedipine): concomitant administration of magnesium with a calcium antagonist may lead to hypotension.

SPECIAL WARNINGS
Use immediately after opening the container. The solution must be clear, colorless, and free from visible particles. The container is intended for single, uninterrupted administration and any residual solution must not be used.

Pregnancy and breastfeeding
Consult your doctor or pharmacist before taking any medicine.
There are no available data on possible adverse effects of the medicinal product when administered during pregnancy or breastfeeding or on reproductive capacity.
Therefore, the medicinal product should not be used during pregnancy or breastfeeding unless absolutely necessary and only after careful assessment of the risk/benefit ratio.
Avoid using magnesium within 2 hours before delivery. If magnesium chloride is administered (especially for more than 24 hours before delivery) to control seizures in mothers affected by pregnancy toxemia, newborns may show signs of magnesium toxicity, including neuromuscular and respiratory depression.

Effects on ability to drive and use machines
The medicinal product does not affect the ability to drive vehicles or operate machinery.

DOSAGE, METHOD AND DURATION OF ADMINISTRATION
The medicinal product must be administered by intravenous infusion after appropriate dilution with 5% glucose solution, 0.9% sodium chloride solution, or other compatible solutions (see end of this section).
Do not inject intramuscularly, subcutaneously, or into perivascular tissues.
The dosage depends on the patient's age, weight, and clinical condition; it is advisable not to exceed an infusion rate of 3 ml/min, starting with 250 ml of a solution with a concentration of approximately 1.5% magnesium chloride and 0.8% calcium chloride (obtained by diluting the contents of 7 vials in 250 ml of diluent).
In children, the safety and efficacy of the medicinal product have not been established.
Administration must be discontinued if the patient experiences pain or redness at the injection site, as this may indicate drug extravasation.
It is advisable for the patient to remain lying down for a short period after administration.

INCOMPATIBILITIES WITH CALCIO E MAGNESIO CLORURO BIOINDUSTRIA L.I.M.
Due to the presence of calcium chloride, the medicinal product is incompatible with:

Magnesium sulfate: formation of a precipitate;
Medicinal products containing phosphate: formation of calcium phosphate precipitate;
Medicinal products containing carbonate: formation of calcium carbonate precipitate;
Medicinal products containing tartrate: formation of calcium tartrate precipitate;
Aminophylline: due to precipitate formation;
Amphotericin B: due to development of cloudiness;
Cefamandole: due to presence of sodium carbonate in cefamandole preparation;
Ceftriaxone sodium: due to precipitate formation; therefore, calcium-containing solutions must not be administered within 48 hours after ceftriaxone administration;
Cephalothin: due to physical incompatibility;
Cefradine: due to presence of sodium carbonate in cefradine preparation;
Chlorpheniramine: due to physical incompatibility;
Dobutamine: due to development of cloudiness;
Fat emulsion: due to presence of flocculate;
Sodium heparin;
Indomethacin: due to precipitate formation;
Sodium nitrofurantoin;
Promethazine: due to precipitate formation;
Propofol: due to precipitate formation;
Streptomycin: calcium may inhibit streptomycin activity;
Tetracyclines: calcium salts may complex with tetracyclines.

Due to the presence of magnesium, the medicinal product is incompatible with solutions containing alcohol (at high concentrations), heavy metals, carbonates and bicarbonates, sodium hydrocortisone, succinates, phosphates, polymyxin B sulfate, procaine hydrochloride, calcium salicylate, clindamycin phosphate, tartrates, as precipitates may form. Potential incompatibility is often influenced by changes in reagent concentrations and solution pH.

SOLUTIONS TO BE USED FOR DILUTION OF CALCIO E MAGNESIO CLORURO BIOINDUSTRIA L.I.M.
Dilute the solution immediately after opening the container; the diluted solution must be used immediately.
The solution must be clear, colorless, and free from visible particles. It is intended for single, uninterrupted administration and any residual solution must not be used.
Shake well during dilution preparation and before administration. Do not use the medicinal product if the solution is not clear and colorless or contains particles.
Adopt all standard precautions to maintain sterility before and during intravenous infusion.

OVERDOSE
In case of administration of high doses of calcium chloride, hypercalcemia may occur, especially in patients with renal disease. Typical symptoms of hypercalcemia include: sensation of thirst, nausea, vomiting, constipation, polyuria, abdominal pain, muscle weakness, mental disturbances, and in severe cases, cardiac arrhythmia and coma. Hypercalcemia is defined as plasma calcium concentrations exceeding 2.6 mmol/l; therefore, such concentrations must be constantly monitored.
In case of mild overdose, treatment involves immediate discontinuation of calcium chloride and any other calcium-containing medication.
In case of severe overdose (plasma concentrations > 2.9 mmol/l), the following measures should be taken:

Rehydration via administration of 0.9% sodium chloride solution;
Use of non-thiazide diuretics to promote calcium excretion;
Monitoring of plasma potassium and magnesium levels, with immediate restoration to normal values;
Monitoring of cardiac function, use of beta-blockers to reduce the risk of cardiac arrhythmia;
Possible recourse to hemodialysis.

In case of administration of high doses of magnesium chloride, the following symptoms of intoxication may occur: flushing, sweating, hypotension, flaccid paralysis, hypothermia, circulatory collapse, cardiac and central nervous system depression, which may progress to respiratory paralysis. Magnesium intoxication manifests with a peak in blood pressure and respiratory paralysis. Disappearance of the patellar reflex is a useful clinical sign to identify the onset of intoxication. Artificial respiration must be initiated. To counteract the effects of hypermagnesemia, calcium must be administered intravenously (10–20 ml of a 5% solution). Subcutaneous administration of 0.5–1 mg of physostigmine may be helpful.

In case of accidental ingestion/overdose of Calcio e Magnesio Cloruro Bioindustria L.I.M., contact a doctor immediately or go to the nearest hospital.
If you have any doubts about the use of Calcio e Magnesio Cloruro Bioindustria L.I.M., consult your doctor or pharmacist.

UNDESIRABLE EFFECTS
Like all medicines, Calcio e Magnesio Cloruro may cause undesirable effects, although not everyone experiences them.
Listed below are the undesirable effects of Calcio e Magnesio Cloruro. There are insufficient data to determine the frequency of individual listed effects.

Nervous system disorders
Mental disorders, coma.

Respiratory, thoracic and mediastinal disorders
Respiratory depression, pneumothorax.

Cardiac disorders
Arrhythmia, ventricular fibrillation, bradycardia, syncope, cardiac arrest.

Vascular disorders
Vasodilation, sweating, hypotension, hypertension, shock, flushing.

Metabolism and nutrition disorders
Hypercalcemia, Burnett syndrome (milk-alkali syndrome), metabolic acidosis.

Gastrointestinal disorders
Gastrointestinal irritation, constipation, delayed intestinal transit, paralytic ileus, metallic taste, chalky taste, nausea, vomiting, abdominal pain.

Renal and urinary disorders
Polyuria.

Musculoskeletal and connective tissue disorders
Muscle weakness.

Fluid and electrolyte imbalance disorders
Hypervolemia.

Systemic disorders and administration site conditions
Febrile reactions, redness, rash, pain and infection at infusion site, cutaneous calcification, abscess formation, venous thrombosis, venous phlebitis extending from the infusion site, extravasation with possible subsequent tissue necrosis.

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

EXPIRY DATE AND STORAGE
Expiry date: see the date on the packaging.
The expiry date refers to the product in intact packaging, correctly stored.
Warning: do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions
Store in the original packaging to protect the medicinal product from light.
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 medicinal product out of the reach and sight of children.

COMPOSITION
10 ml contain:
Active substances: Calcium chloride dihydrate 290 mg
Magnesium chloride hexahydrate 610 mg
mEq/10 ml: Ca 4
Mg 6
Cl 10
pH: 5.5 – 6.5
Excipients: water for injections

PHARMACEUTICAL FORM AND CONTENT
Concentrate for infusion solution, sterile and pyrogen-free.
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)

REVISION OF THE PACKAGE LEAFLET BY THE ITALIAN MEDICINES AGENCY (AIFA):
Italian Medicines Agency (AIFA) Decision of 20/02/2013.