Calcium chloride S.A.L.F.

Patient Information Leaflet: Information for the User

CALCIUM CHLORIDE S.A.L.F. 1 g/10 ml concentrate for solution for infusion

Calcium chloride dihydrate
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

1. What CALCIO CLORURO S.A.L.F. is and what it is used for
2. What you need to know before you are given CALCIO CLORURO S.A.L.F.
3. How CALCIO CLORURO S.A.L.F. is given to you
4. Possible side effects
5. How to store CALCIO CLORURO S.A.L.F.
6. Contents of the pack and other information

1. What CALCIO CLORURO S.A.L.F. is and what it is used for

CALCIO CLORURO S.A.L.F. contains the active substance calcium chloride, which is a calcium salt. Calcium is an important element for bones and for many functions of the human body.
This medicine is indicated:

• for the treatment of calcium deficiency (hypocalcemia);
• for the treatment of certain conditions in which it is necessary to rapidly increase calcium concentrations in the blood, such as in case of kidney problems (renal failure) or parathyroid gland disorders (hypoparathyroidism), if you suffer from a muscle disorder (tetany, including neonatal tetany), if your vitamin D levels are low, or if blood acidity is too low (alkalosis);
• for treating elevated potassium levels in the blood (hyperkalemia), a condition that may cause heart problems (cardiac toxicity);
• for treating magnesium intoxication;
• in cardiac resuscitation, used in cases of severe disturbances of heart rhythm, or when the heart shows weak or inadequate contraction even after defibrillation (a medical technique used to correct heart beat and rhythm) or after administration of adrenaline (a medicine used in cases of absent or insufficient heart activity).

2. What you need to know before you are given CALCIO CLORURO S.A.L.F.

Do not be administered CALCIO CLORURO S.A.L.F.

• if you are allergic to calcium chloride or to any of the other ingredients of this medicine (listed in section 6);
• if you have high levels of calcium in your blood (hypercalcemia) or in your urine (hypercalciuria);
• if you have severe kidney problems;
• if you have a heart rhythm disorder (ventricular fibrillation), because calcium increases the risk of heart rhythm disturbances (arrhythmias);
• if you suffer from kidney stones;
• if you have a disease called sarcoidosis, characterized by cough associated with bleeding and difficulty breathing;
• if you have an increased tendency of the blood to form clots (hypercoagulability);
• if you are taking medicines used to treat heart problems (cardiac glycosides);
• if the patient is a neonate (≤ 28 days of age) receiving ceftriaxone (an antibiotic), even if administered through separate infusion lines. Indeed, the simultaneous administration of CALCIO CLORURO S.A.L.F. (or other calcium-containing solutions) and ceftriaxone in such patients carries a fatal risk of forming ceftriaxone-calcium salts in the neonate's bloodstream. This medicine must not be administered through muscle or under the skin (intramuscular or subcutaneous route).

Warnings and precautions
Talk to your doctor or nurse before using CALCIO CLORURO S.A.L.F.
This medicine should be administered to you with particular caution if:

• you suffer from kidney disorders (renal diseases), especially if your kidneys are poorly functioning (chronic renal failure);
• you suffer from heart disorders; this medicine may increase the risk of heart rhythm disturbances (arrhythmias), particularly during prolonged treatment;
• you have received a blood transfusion;
• you suffer from lung disorders that may cause enlargement of the heart (pulmonary heart disease); if you have an increase in acidic substances in the blood (respiratory acidosis) or suffer from severe breathing difficulty (respiratory failure); in all these cases, the use of calcium may increase the acidity level of the blood;
• you are predisposed to high levels of calcium in the blood (hypercalcemia), severe fluid loss (dehydration), or disturbances in blood electrolyte levels (electrolyte imbalance).

During treatment with CALCIO CLORURO S.A.L.F., your doctor should monitor:

• your heart activity (electrocardiogram);
• the amount of fluids and electrolytes in your blood;
• calcium levels in your blood (to prevent excess, hypercalcemia) and in your urine (to prevent excess, hypercalciuria).

This medicine must not be administered as supplied (in concentrated solution), but only after appropriate dilution and through a large vein, and not via other routes of administration (intramuscular, subcutaneous, intracardiac, or perivascular tissues), as administration via other routes may cause tissue necrosis due to the irritant nature of calcium chloride solution. This medicine should only be administered if the solution is clear, colorless, and free from particles. Slow administration is recommended (not exceeding 0.35–7.0 mmol/min), as too rapid administration may cause damage to veins, heart problems, and fainting with loss of consciousness (syncope). Inform your doctor if you experience pain or redness at the injection site during administration (see section How to use CALCIO CLORURO S.A.L.F.).
A drop in blood pressure may occur during administration of this medicine.
Children
The safety and efficacy of CALCIO CLORURO S.A.L.F. in children have not been established. Therefore, its use in children is not recommended except in cases of absolute necessity, such as cardiac resuscitation.
Other medicines and CALCIO CLORURO S.A.L.F.
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
Pay particular attention and consult your doctor if you are taking:

• medicines used to promote fluid elimination (thiazide diuretics), as excessive increase in blood calcium levels (hypercalcemia) may occur due to reduced calcium excretion through the kidneys;
• medicines used to treat heart problems (cardiac glycosides, digoxin and digitoxin, see section “Do not use CALCIO CLORURO S.A.L.F.”), as the risk of heart rhythm disturbances (arrhythmias) is higher when these medicines are taken together with CALCIO CLORURO S.A.L.F.;
• medicines used to treat high blood pressure (verapamil and other calcium channel blockers), because CALCIO CLORURO S.A.L.F. may reduce their antihypertensive effect;
• medicines containing magnesium, as increased levels of calcium (hypercalcemia) and magnesium (hypermagnesemia) in the blood may occur, especially if you have kidney problems (renal disorders);
• medicines used to reduce muscle contractions (non-depolarizing neuromuscular blockers), as CALCIO CLORURO S.A.L.F. may increase or decrease their effectiveness;
• ceftriaxone (an antibiotic) due to the risk of formation of calcium-ceftriaxone salt particles.

Fertility, Pregnancy and Breast-feeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breast-feeding, ask your doctor for advice before using this medicine.
This medicine should not be administered during pregnancy or breast-feeding, except in cases of absolute necessity.
Driving and using machines
The effects of this medicine on the ability to drive and use machines are unknown.

3. How CALCIO CLORURO S.A.L.F. is administered to you

The medicine must be administered by a doctor or nurse, immediately after opening the vial and after appropriate dilution in a compatible solution (5% glucose and 0.9% sodium chloride), via a single, uninterrupted administration.
Any unused medicine must be discarded.
The dose and rate of infusion will be determined by the doctor according to your age, body weight, and health condition. The recommended dose is provided in the information intended exclusively for doctors or healthcare professionals.
It is recommended, however, that the medicine be administered slowly (rate not exceeding 0.35–7.0 mmol/min; see section “Warnings and precautions”), except in emergency situations.
If you experience pain or redness at the injection site during administration, treatment must be stopped immediately, as leakage of the injected solution from the vein (extravasation) may occur (see section “Possible side effects”). After administration of this medicine, remain lying down.
Since the safety and efficacy of CALCIO CLORURO S.A.L.F. in children have not been established, use of this medicine in pediatric patients is recommended only in cases of absolute necessity, such as cardiac resuscitation.

If you are given more CALCIO CLORURO S.A.L.F. than you should
This medicine will be administered by a doctor or trained medical personnel; therefore, it is unlikely that you will receive an excessive dose. However, if you think you have been given too much CALCIO CLORURO S.A.L.F., inform your doctor or another healthcare professional immediately.
In case of overdose, an increase in blood calcium levels (hypercalcaemia, when calcium levels exceed 2.6 mmol/l) may occur, especially if you have kidney disorders. For this reason, during treatment with this medicine, your doctor should monitor your blood calcium levels (see section “Warnings and precautions”).
Symptoms of overdose include:

• thirst;
• nausea, vomiting, constipation;
• increased need to urinate (polyuria);
• abdominal pain;
• muscle weakness;
• mental disturbances;
• changes in heartbeat (arrhythmia) and coma in severe cases.

In case of mild overdose, treatment with this medicine and other calcium-containing medicines must be stopped immediately. In more severe cases of overdose (when calcium levels exceed 2.9 mmol/l), the doctor will take the most appropriate necessary measures (as described in the information intended exclusively for doctors or healthcare professionals).

If you miss a dose of CALCIO CLORURO S.A.L.F.
Since this medicine will be administered under close medical supervision, it is unlikely that a dose will be missed. However, inform your doctor if you think a dose has been missed.
If you have any doubts about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
The following side effects may occur, especially in case of improper administration (administration route other than intravenous) or too rapid administration (see section “Warnings and precautions”):
Frequency not known (frequency cannot be estimated from the available data)

• dilation of veins and arteries (vasodilation),
• decrease in blood pressure (hypotension);
• slowing of heart rate (bradycardia) or irregular heartbeat (arrhythmias, ventricular fibrillation);
• fainting associated with loss of consciousness (syncope);
• cessation of heart activity (cardiac arrest);
• sudden sensation of warmth (flushing);
• increase in blood pressure (hypertension);
• damage to the vein where the medicine is administered (extravasation);
• fever, skin redness, skin irritations (rash), pain and infection at the infusion site, calcium deposits in tissues (cutaneous calcification), inflammation due to pus accumulation (abscesses), formation of blood clots in veins (venous thrombosis), inflammation of veins (venous phlebitis) even in areas near the infusion site, leakage of the injected solution from the vein (extravasation), tissue damage and tissue death (tissue necrosis);
• increased levels of calcium in the blood and/or decreased blood acidity (hypercalcemia, Burnett syndrome);
• irritation of the stomach and intestines, nausea, vomiting, constipation, altered taste (metallic and chalky taste);
• abdominal pain, accumulation of air in the abdomen (pneumoperitoneum);
• increased need to urinate (polyuria);
• mental disturbances;
• muscle weakness;
• kidney problems caused by calcium-ceftriaxone deposits. Pain during urination or reduced urine output may occur.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please consult your doctor or pharmacist. You may also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store CALCIO CLORURO S.A.L.F.

Keep this medicine out of the sight and reach of children.
This medicine must not be used after the expiry date stated on the packaging after "Exp.". The expiry date refers to the last day of that month.
This medicine should be stored in its original packaging, protected from light. No special temperature requirements apply for storage. This medicine must not be frozen.
This medicine must not be administered to you if the solution is not clear and colourless or if it contains particles.
Each vial is intended for single and uninterrupted administration; any remaining medicine must be discarded.
Medicines must not be disposed of via wastewater or household waste. It is important to ask your pharmacist how to dispose of medicines that are no longer required. This will help protect the environment.

6. Package contents and other information

What CALCIO CLORURO S.A.L.F. contains
CALCIO CLORURO S.A.L.F. 1 g/10 ml

• The active substance is calcium chloride dihydrate. Each vial contains 1 g of calcium chloride dihydrate, corresponding to 1,360 mEq/ml of Ca++ and 0.680 mmol/ml of Ca++.
• The other component is water for injections.

Description of the appearance of CALCIO CLORURO S.A.L.F. and package contents
Pack containing 5 vials of 10 ml.
Marketing Authorization Holder and Manufacturer
S.A.L.F. S.p.A. Laboratorio Farmacologico - Via Marconi, 2 - Cenate Sotto (BG) - Tel. 035 - 940097

The following information is intended exclusively for physicians or healthcare professionals:
Dosage
Acute hypocalcemia
Adults: the recommended initial dose is 3.5–7 mmol (7–14 mEq) of calcium. If necessary, repeat administration at intervals of 1–3 days.
Hypocalcemic tetany
Adults: the recommended initial dose is 2.25–8 mmol (4.5–16 mEq) of calcium. Repeat administration until response is achieved.
Hyperkalemia
Adults: the recommended initial dose is 1.12–7 mmol (2.25–14 mEq) of calcium. If necessary, the dose may be repeated after 1–2 minutes. ECG monitoring is required during administration.
Magnesium poisoning
Adults: the recommended dose is 3.5 mmol (7 mEq) of calcium, administered slowly. Repeat administration only if the clinical condition does not improve.
Cardiac resuscitation
Adults:
a) intravenous administration: the recommended dose of calcium is 0.054–0.109 mmol (0.109–0.218 mEq) per kg of body weight or 3.5–7 mmol (7–14 mEq) of calcium. If necessary, repeat administration at 10-minute intervals;
b) intraventricular administration: the recommended dose is 1.35–2.7 mmol (2.7–5.4 mEq) of calcium.
Children: the recommended dose of calcium is 0.136 mmol (0.272 mEq) per kg of body weight (calcium chloride provides better calcium bioavailability compared to calcium gluconate). Slow administration via a central vein is preferred; however, intraosseous administration is also considered acceptable.
Patients with renal impairment
In patients with severe renal impairment and creatinine clearance below 25 ml/min, dosage adjustments may be required based on serum calcium levels.

Overdose
In case of severe overdose (plasma concentrations > 2.9 mmol/l), the following measures should be taken:

• rehydration with 0.9% sodium chloride solution;
• use of non-thiazide diuretics to enhance calcium excretion;
• monitoring of plasma potassium and magnesium levels, with immediate correction to normal values;
• monitoring of cardiac function, and use of beta-blockers to reduce the risk of cardiac arrhythmias;
• hemodialysis if necessary.

Incompatibilities
Calcium chloride solution is incompatible with:

• magnesium sulfate: formation of a precipitate;
• medications containing phosphate: formation of calcium phosphate precipitate;
• medications containing carbonate: formation of calcium carbonate precipitate;
• medications containing tartrate: formation of calcium tartrate precipitate.

Incompatibilities have been reported between calcium chloride solution and the following:

• aminophylline: due to precipitate formation;
• amphotericin B: due to development of cloudiness;
• cefamandole: due to presence of sodium carbonate in cefamandole formulation;
• ceftriaxone sodium: due to precipitate formation; therefore, calcium solution must not be administered within 48 hours following ceftriaxone administration;
• cephalothin: due to physical incompatibility;
• cefradine: due to presence of sodium carbonate in cefradine formulation;
• chlorphenamine: due to physical incompatibility;
• dobutamine: due to development of cloudiness;
• fat emulsion: due to flocculation;
• sodium heparin;
• indomethacin: due to precipitate formation;
• sodium nitrofurantoin;
• promethazine: due to precipitate formation;
• propofol: due to precipitate formation;
• streptomycin: since calcium may inhibit streptomycin activity;
• tetracyclines: calcium salts may complex with tetracyclines.

Calcium salts may form complexes with many drugs, potentially leading to precipitate formation. Physical incompatibility has been reported with ceftriaxone (see sections 4.3, 4.5 and 4.8).