Package leaflet: Information for the user

Icalziss, 340 mmol/l, solution for infusion
calcium
Please read all of this leaflet carefully before using this medicine, because it contains
important information for you.

Keep this leaflet, as you may need to read it again.
If you have any further questions, ask your doctor, pharmacist, or nurse.
If you get any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

What Icalziss is and what it is used for
What you need to know before you use Icalziss
How to use Icalziss
Possible side effects
How to store Icalziss
Contents of the pack and other information

1. What Icalziss is and what it is used for

Icalziss is an infusion solution containing calcium chloride dihydrate. It is used to
replenish calcium during continuous renal replacement therapy (CRRT) and therapeutic plasma exchange (TPE), as monotherapy or in combination with other treatments, in adults and children of all ages (with body weight above 8 kg). This medicine helps maintain blood calcium levels within the desired range when citrate is used as an anticoagulant in the therapy.

2. Important information before using Icalziss

When not to use Icalziss:

if the patient has high levels of calcium in the blood;
if the patient has high levels of chlorides in the blood;
if the patient is allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6);
in newborns treated with ceftriaxone.

Warnings and precautions
Before starting treatment with Icalziss, discuss this with your doctor, pharmacist, or nurse.
Patients may experience irregular heartbeat, especially if cardiac glycosides have been administered after treatment with this medicine. Excess systemic calcium in the heart increases the risk of cardiac syncope, i.e. brief loss of consciousness. In patients with cardiac glycoside intoxication or those treated with cardiac glycosides, administration of calcium-containing solutions may result in symptoms such as disorientation, irregular pulse, and rapid heartbeat. If intravenous calcium administration is necessary, it is recommended to administer small doses of this medicine.
The doctor will monitor and control electrolyte levels as well as blood acidity and alkalinity. The doctor will correct calcium and chloride levels in the blood before starting treatment.
During treatment, the doctor may increase or decrease the amount of calcium chloride administered depending on the calcium concentration in the blood.
If the duration of treatment is prolonged or treatment is repeated multiple times, the doctor will assess the levels of hormones produced by the patient's body to monitor calcium levels in the blood and the bones' ability to release or reabsorb calcium.
Administration of calcium chloride may increase the risk of kidney stone formation.
Intravenous administration of calcium salts may cause leakage of blood or fluid into tissues. The doctor will regularly check the infusion site for signs of thrombosis. If thrombosis is observed, the doctor will discontinue administration of this medicine.
The risk of complications due to excess or deficiency of calcium in the blood increases in patients with conditions such as nephrocalcinosis, hypercalciuria, cancer, hyperparathyroidism, hypoparathyroidism, rhabdomyolysis, and liver failure.
Moderate reduction of body temperature to 30–34°C may lead to complications associated with high calcium levels in the blood (hypercalcemia).
Inform the doctor if ceftriaxone is being used.
Use only if the solution is clear and does not contain visible solid particles.

Icalziss and other medicines
Tell your doctor, pharmacist, or nurse about all medicines currently taken or recently used, as well as any medicines planned for future use, including over-the-counter medicines.
This is necessary because dialysis may reduce the concentration of other medicines.
The doctor will decide whether any dosage adjustments are needed for medicines taken by the patient.
Inform the doctor if taking medicines containing vitamin D or its analogs, or other medicines containing calcium, calcium chloride, or calcium gluconate, as this may increase the risk of excessive calcium levels in the blood (hypercalcemia) and may reduce anticoagulant effectiveness.
Possible interactions may occur with:

certain medicines containing vitamin D and other vitamin D analogs;
certain medicines that lower serum calcium levels (calcimimetics such as etelcalcetide and cinacalcet);
certain medicines used to increase urine production (thiazide diuretics).

Icalziss is incompatible with inorganic phosphates, carbonates, tetracycline antibiotics, ceftriaxone, and other medicines.

Pregnancy and breastfeeding
Pregnancy and breastfeeding:
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor before using this medicine.
Icalziss may be used during pregnancy only if the doctor considers treatment absolutely necessary.
Breastfeeding is possible if the patient requires treatment with Icalziss during this period.

Driving and operating machinery
No effects of Icalziss on the ability to drive vehicles or operate machinery have been observed.

3. How to use Icalziss

For intravenous administration. Icalziss is intended for use in hospitals and must be administered by
qualified medical personnel experienced in anticoagulant management using citrate, exclusively within
the specific treatment of CRRT or TPE. The volume administered, and thus the dose of this medicinal
product, will depend on the patient's condition. The dose is determined by the physician.
Instructions for use
Icalziss is administered to the patient in a hospital setting. The physician knows how to use this medicinal
product.
Instructions for use are provided at the end of the leaflet.
If you receive more Icalziss than you should
Since Icalziss is always administered by a physician, it is unlikely that too small or too large a dose will be
given. However, if the patient believes they have received too high a dose of this medicinal product, this
should be reported immediately to the physician or nurse.
Signs of overdose may include symptoms of high calcium levels in the blood, such as fatigue, tingling, lack
of energy, disorientation, increased reflexes, nausea, vomiting, constipation, tendency to develop
gastrointestinal ulcers, rapid heartbeat, slow heartbeat, and irregular heartbeat with potential cardiac
arrest, high blood pressure, changes in electrocardiogram recording, fainting, increased urine output,
thirst, loss of water without loss of electrolytes, calcium deposition in the kidneys, chalky taste, hot
flushes, vasodilation with low blood pressure.
In cases of very high calcium levels, also known as hypercalcemic crisis, the following symptoms may
occur: vomiting, colic, loss of intestinal muscle tone, intestinal obstruction, general weakness,
disturbances in consciousness, initially increased urine output, followed by frequent passage of smaller
amounts of urine or absence of urine output.
If any of the above symptoms occur, inform the physician or nurse immediately.
If you have any further doubts regarding the use of this medicinal product, consult your physician or
nurse.

4. Possible adverse reactions

Like all medicines, this medicine may cause adverse reactions, although not everyone will experience them. Your doctor or nurse will perform regular blood tests to detect any possible adverse reactions. Use of Icalziss may cause the following adverse reactions:

Frequency unknown: frequency cannot be estimated from the available data

excess or insufficient fluid in the body;
high or low blood calcium levels;
high blood acidity or alkalinity;
electrolyte imbalance (e.g. low blood potassium or phosphate levels, or excess chlorides in the blood);
low blood pressure;
low body temperature.

The following adverse reactions may occur as a result of the method of administration:

incorrect administration may cause irritation at the infusion site, leakage of blood or fluid into surrounding tissues, leading to burning sensation, necrosis, tissue sloughing, connective tissue inflammation or soft tissue sclerosis.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Icalziss

Keep the medicine out of the sight and reach of children.
Do not freeze.
After removing the protective packaging, Icalziss must be used within 72 hours. If the medicine is not
handled according to the instructions for use, the user is responsible for the storage time and conditions during use.
Do not use this medicine after the expiry date stated on the label and packaging. The expiry date refers to the last day of the stated month.
The contents should be used immediately after opening the bag.
Do not use this medicine if any damage to the product is observed or if visible solid particles are present in the solution.
The solution is intended for single use only. Any unused solution and damaged packaging must be discarded.
The solution may be disposed of via the sewer system without harm to the natural environment.

6. Contents of the packaging and other information

What Icalziss contains
Composition:
Calcium chloride dihydrate 50 g/l
Calcium, Ca 340 mmol/l
Chloride, Cl 680 mmol/l
Theoretical osmolarity: 1020 mOsm/l
pH ≈ 5.5–7.5
Other ingredients:
Water for injections

What Icalziss looks like and contents of the pack
Icalziss is a clear, colourless infusion solution packed in a single-chamber bag made of multilayer film containing polypropylene (PP), polyamide (PA) and polyethylene (PE), with a port made of high-density polyethylene (HDPE). The solution is sterile and contains no visible particles. Each bag contains 500 ml of solution and is placed in a protective overwrap made of transparent film. Each carton contains 20 bags and one package leaflet.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Vantive Belgium SRL
Boulevard d’Angleterre 2
1420 Braine-l’Alleud
Belgium
[email protected]

Manufacturer
Bieffe Medital S.A.
Ctra de Biescas – Senegüé
22666 Sabiñánigo (Huesca)
Spain

This medicinal product is authorised for sale in the European Economic Area (EEA) countries
under the following names:
Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden: Icalziss
France, Lithuania: Icoziss
Bulgaria: Icalziss (Икалзис)

Information intended exclusively for healthcare professionals:

Do not use if the solution is not clear and colourless or if the bag or closure is damaged. The contents
should be used immediately after opening. For single use only. Any unused solution should be discarded.
Dosage
The medicinal product Icalziss should be administered according to the recommendations of a physician experienced in the use of citrate anticoagulation in the context of specific CRRT and/or TPE therapy.
This medicinal product is used as a calcium replacement solution and must be administered via a separate central venous access line or through the return line of the extracorporeal blood circulation circuit.
Additional medicinal products should not be administered.
The infusion rate must be adjusted to maintain systemic ionized calcium concentration within the normal physiological range of 1.0–1.3 mmol/L to avoid complications related to hypocalcemia or hypercalcemia. Systemic ionized calcium concentration should not fall below 0.9 mmol/L.
Monitoring of ionized calcium (iCa) concentration in blood post-filter, systemic blood iCa concentration, and total blood calcium concentration, in conjunction with other laboratory and clinical parameters, is essential to determine the appropriate dosage of the medicinal product based on the desired anticoagulant level during extracorporeal therapies using RCA. Citrate accumulation occurs when the ratio of ionized to total calcium exceeds 2.25.
Systemic ionized calcium concentration should be assessed at the beginning of therapy, within the first hour after initiation or dose adjustment until stabilization is achieved, and thereafter at least every 6 hours. Monitoring of systemic total calcium concentration is recommended every 12 to 24 hours.
The amount of calcium chloride required to maintain systemic ionized calcium concentration within the desired range depends on several factors, such as:

The amount of calcium needed to compensate for the effects of citrate entering systemic circulation and citrate metabolism in the patient
Calcium concentrations in the replacement fluid
Any calcium present in other medicinal products/infusions administered to the patient (e.g., calcium in total parenteral nutrition)
Any intended change in initial systemic calcium concentration
Potential impact of other medical interventions (e.g., chemotherapy, radiotherapy) on the patient's ionized calcium concentration
Other conditions predisposing the patient to hypocalcemia or hypercalcemia (e.g., hypoparathyroidism, hyperparathyroidism, malignancy, liver failure, rhabdomyolysis, severe pancreatitis, tumor lysis syndrome, toxic shock syndrome)

When determining the appropriate amount of calcium replacement during CRRT, several factors should be considered, such as:

Recommended flow rates, especially the rate of effluent fluid flow
Adherence to a standard protocol or algorithm, which simplifies and facilitates calcium replacement therapy orders and helps reduce errors and variability
Membrane permeability of the filter for calcium and calcium-citrate complexes

Dosage in adults and adolescents:
For RCA-CRRT, the typical calcium dose is 1.7 mmol per litre of effluent fluid volume (4–6 mmol/hour) in adults and adolescents.
The recommended maximum daily calcium dose is 340 mmol, equivalent to 1 litre of the medicinal product Icalziss. This medicinal product is not intended for chronic use.
Dosage in children and adolescents:
The recommended dose of the medicinal product in infants and children (from 0 to 11 years and above 8 kg) is similar to that used in adults and adolescents. The maximum hourly calcium infusion rate per body weight is 0.3 mmol/hour/kg, corresponding to a maximum hourly infusion rate of 0.88 ml/hour/kg body weight. Due to generally lower recommended effluent fluid flow rates in children, the absolute flow rates of the medicinal product will be proportionally lower.
The body weight limit of >8 kg in the indication does not result from the safety or efficacy profile of the medicinal product, but from characteristics of monitoring devices offered by the marketing authorization holder.
Method of administration
If citrate anticoagulation is interrupted, calcium infusion should be adjusted or stopped according to the physician's recommendations.
Infusion must be performed exclusively using an extracorporeal blood purification device designed for calcium chloride solution infusion and equipped with appropriate fluid flow volume control functionality.
Administer exclusively into the extracorporeal circuit or, if specified by the extracorporeal blood purification device user manual, via a separate central venous access. The medicinal product Icalziss is not intended for intramuscular or subcutaneous administration.
Follow the instructions for use provided by the manufacturer of the extracorporeal blood purification device, the extracorporeal circuit set, and the intravenous line.
Overdose
Rapid or excessive administration of this medicinal product may lead to hypercalcemia (serum total calcium > 3 mmol/L, ionized calcium > 1.3 mmol/L), which should be appropriately managed medically.
Administration of this medicinal product should be immediately discontinued or the dose reduced if objective or subjective symptoms of hypercalcemia occur. In cases of significantly elevated calcium levels, immediate measures should be taken to rapidly reduce calcium concentration. If renal function is preserved, forced diuresis should be considered with concurrent infusion of physiological sodium chloride solution (NaCl 9 mg/mL), with strict monitoring of fluid balance and serum electrolyte concentrations. In patients with impaired renal function, dialysis using calcium-free dialysate may be considered.
Objective and subjective symptoms of hypercalcemia include:

Neurological disturbances, e.g., lethargy, disorientation, hyporeflexia
Cardiac disturbances, e.g., tachycardia and tendency to cardiac arrhythmias, hypertension, ECG changes (shortened QT interval)
Gastrointestinal disturbances, e.g., nausea, vomiting, constipation, tendency to ulcer formation
Renal and urinary tract disturbances, e.g., polyuria, thirst, aquaresis, calcium salt deposition in the kidneys
General disturbances, e.g., fatigue

Rapid administration of calcium salts may also cause chalky taste, tingling sensations, hot flashes, peripheral vasodilation with hypotension, bradycardia, syncope, and arrhythmia with potential cardiac arrest.
Preparation and handling of the medicinal product
The solution may be disposed of into the sewage system without harm to the natural environment.
Do not freeze.
Follow the instructions below for use:
Aseptic technique must be maintained throughout the entire process of preparation and administration of the medicinal product.
Visually inspect the medicinal product for particulate matter and discoloration before administration. Use only if the solution is clear and colourless and the seal is intact. Discard if the packaging is damaged.
Remove the protective overwrap from the bag only immediately before use. After removal of the protective overwrap, this medicinal product should be used within 72 hours. Squeeze the bag firmly to check for leakage. If leakage is detected, discard the solution immediately, as sterility cannot be guaranteed. The solution should be used immediately after opening the packaging to avoid microbiological contamination.
Remove the plastic cover from the outlet port at the bottom of the bag. With one hand, grasp the small wing on the port neck. With the other hand, grasp the large wing on the cap and twist. The cap will pop off.
Insert the spike through the rubber septum. Refer to the set instructions for connection. Check that fluid flows freely.
Do not reconnect partially used bags. The solution is intended for single use only. Any unused solution should be discarded. If the product is not used according to the instructions for use, the user is responsible for the time and conditions of storage during use.