Icalziss

Package leaflet: Information for the user

Icalziss 340 mmol/L solution for infusion

calcium
Please read all of this leaflet carefully before you start 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, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Icalziss is and what it is used for
2. What you need to know before you use Icalziss
3. How to use Icalziss
4. Possible side effects
5. How to store Icalziss
6. 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 for calcium replacement therapy during continuous renal replacement therapies (CRRT) and therapeutic plasma exchange (TPE), either as a single treatment or in combination, in adults and children of all ages (over 8 kg). This medicinal product allows maintenance of blood calcium levels within the desired range when using anticoagulant treatment with citrate.

2. What you need to know before using Icalziss

Do not use Icalziss:

• if you have high levels of calcium in your blood
• if you have high levels of chloride in your blood
• if you are allergic to the active substances or to any of the other ingredients (listed in section 6).
• in neonates being treated with ceftriaxone.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Icalziss.
Patients may experience irregular heartbeat, especially if digitalis glycosides are administered after treatment with this medicine. Excessive systemic calcium in the heart increases the risk of cardiac syncope, i.e. a brief loss of consciousness. Patients who are intoxicated or treated with digitalis glycosides may experience symptoms such as confusion, irregular pulse, and rapid heartbeat after using calcium-containing solutions.
It is recommended to administer small amounts of this medicine if intravenous calcium administration is required.
Your doctor will monitor and check your electrolyte levels and the acidity and alkalinity levels of your blood.
Before starting treatment, your doctor will correct your blood calcium and chloride levels.
During treatment, your doctor may increase or decrease the amount of calcium chloride administered, depending on your blood calcium levels.
If treatment is prolonged or repeated, your doctor will evaluate the levels of hormones produced by the body to regulate 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 the surrounding tissue. Your doctor will regularly examine the infusion site for any signs of coagulation. If coagulation is observed, your doctor will stop administration of this medicine.
The risks of complications due to excess or deficiency of calcium in the blood are increased in patients with conditions such as nephrocalcinosis, hypercalciuria, cancer, hyperparathyroidism, hypoparathyroidism, rhabdomyolysis, and liver failure.
A moderate reduction in body temperature to 30–34°C may lead to complications associated with high calcium levels in the blood (hypercalcemia).
If you are being treated with ceftriaxone, inform your doctor.
Use only if the solution is clear and free from visible particles.

Other medicines and Icalziss
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines, including those without a prescription. This is because during dialysis treatment, the concentration of other medicines may be reduced. Your doctor will decide whether adjustments to your medication dosage are needed.
Inform your doctor if you are taking vitamin D-containing medicines or vitamin D analogues, or other medicines containing calcium, calcium chloride, or calcium gluconate, as these may increase the risk of high calcium levels in the blood (hypercalcemia) and may reduce the anticoagulant effect.
Possible interactions may occur with:

• certain medicines containing vitamin D and other vitamin D analogues.
• certain medicines that reduce serum calcium levels (calcimimetics, such as etelcalcetide and cinacalcet).
• certain medicines used to increase urine production (thiazide diuretics).

Icalziss is incompatible with inorganic phosphate, carbonates, tetracycline antibiotics, ceftriaxone, and others.

Pregnancy and breastfeeding
Pregnancy and breastfeeding:
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor before this medicine is administered.
Icalziss should be used during pregnancy only if your doctor considers the treatment absolutely necessary.
Breastfeeding is possible if treatment with this medicine is required during this period.

Driving and using machines
It is not known that Icalziss impairs the ability to drive or use machinery.

3. How to use Icalziss

For intravenous use. Icalziss must be used in hospital settings and administered by medical personnel experienced in citrate anticoagulation, exclusively for the specific treatment with CRRT and/or TPE. The volume used, and therefore the dose of this medicinal product, will depend on your condition. The dosage will be determined by the physician.
Instructions for use
Icalziss will be administered to you in hospital. The physician will know how to use this medicinal product.
For instructions for use, see the end of this leaflet.
If you use more Icalziss than you should
Since Icalziss will be administered to you exclusively by a physician, it is unlikely that you will receive too little or too much. However, if you think you have been given too much of this medicinal product, inform your doctor or nurse immediately.
Signs of overdose may include symptoms of high levels of calcium in the blood, such as fatigue, tingling, lack of energy, disorientation, hyperreactive reflexes, nausea, vomiting, constipation, tendency to develop gastrointestinal ulcers, rapid heartbeat, slow heartbeat, and irregular heartbeat with possible cardiac arrest, high blood pressure, changes in electrocardiogram, fainting, increased urine production, thirst, loss of water without loss of electrolytes, calcium deposits in the kidneys, chalky taste, hot flushes, blood vessel dilation with low blood pressure.
In cases of very high calcium levels, also known as hypercalcemic crisis, the following symptoms may occur: vomiting, colic, lack of intestinal muscular tone, intestinal obstruction, generalized weakness, disturbances of consciousness, initially increased urine production, followed often by reduced or no urine output.
If you develop any of the symptoms listed above, inform your doctor or nurse immediately.
If you have any doubts about the use of this medicinal product, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Your doctor or nurse will regularly monitor your blood to detect possible side effects.
The use of Icalziss may cause:
Not known: frequency cannot be estimated from the available data

• excessive or insufficient amount of fluids in the body
• high or low levels of calcium in the blood
• increased acidity or increased alkalinity of the blood
• electrolyte imbalance (e.g. low levels of potassium or phosphate in the blood or excess chloride in the blood)
• low blood pressure
• low body temperature

In general, the following side effects may occur as a result of the treatment method:

• incorrect application may cause irritation at the infusion site, bleeding or fluid leakage into the tissue, which may lead to burning sensation, gangrene, tissue sloughing, cellulitis, and hardening of soft tissues

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please inform your doctor, pharmacist, or nurse.
You may also report side effects directly via the national reporting system at the following website: 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 Icalziss

Keep this medicine out of the sight and reach of children.
Do not freeze.
Once the outer packaging has been removed, Icalziss must be used within 72 hours. If not used according to the instructions for use, the user is responsible for the storage times 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 that month.
The contents should be used immediately after opening the bag.
Do not use this medicine if you notice any damage to the product or visible particles in the solution.
The solution is for single use only. Any unused solution and damaged containers must be discarded.
The solution may be disposed of via wastewater without harming the environment.

6. Contents of the pack 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
The other component is:
Water for injections

Description of the appearance of Icalziss and contents of the pack
Icalziss is a clear, colourless infusion solution packed in a single-compartment bag made of a multilayer film containing polypropylene (PP), polyamide (PA) and polyethylene (PE), with a high-density polyethylene (HDPE) administration port. The solution is sterile and free from visible particles. Each bag contains 500 mL of solution and is enclosed in a transparent film. Each carton contains 20 bags and a package leaflet.

Marketing Authorisation Holder
Vantive Belgium SRL
Boulevard d'Angleterre 2
1420 Braine-l'Alleud
Belgium

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

This medicinal product is authorised in the European Economic Area 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)

The following information is intended exclusively for healthcare professionals:

Do not use if the solution is not clear and colourless, or if the bag or connector are damaged. The
contents must be used immediately after opening. For single use only. Any unused solution must be
discarded.
Dosage
Icalziss must be administered according to the instructions of an experienced physician in citrate
anticoagulation for the specific treatment with CRRT and/or TPE.
This medicinal product is used as a calcium replacement solution and must be administered through a
separate central venous access line or through the return line of the extracorporeal blood circuit.
Do not add supplementary medicinal products.
The infusion rate must be adjusted to maintain systemic ionised calcium levels within the normal
physiological range of 1.0 to 1.3 mmol/L to avoid complications associated with hypocalcaemia or
hypercalcaemia. Systemic ionised calcium levels must not fall below 0.9 mmol/L.
Monitoring of post-filter blood ionised calcium (iCa), systemic blood iCa, and total blood calcium,
together with monitoring of other laboratory and clinical parameters, is essential to achieve an appropriate
medication dosage based on the desired level of anticoagulation during extracorporeal therapies with
RCA. Citrate accumulation occurs when the ratio between ionised calcium and total calcium exceeds 2.25.
Systemic ionised calcium levels should be assessed at baseline, during the first hour after starting therapy
or after dose adjustment until stable, and thereafter at least every 6 hours. Monitoring of systemic total
calcium levels is recommended every 12–24 hours.
The amount of calcium chloride required to maintain systemic ionised calcium levels within the desired
range depends on several factors, such as:

• The amount of calcium needed to compensate for the effects of citrate entering the systemic circulation and the patient's citrate metabolism
• The calcium concentration in the replacement fluid
• Any calcium present in other medications/infusions the patient is receiving (e.g. calcium in total parenteral nutrition)
• Any intentional modification of baseline systemic calcium concentration
• Any impact on the patient's ionised calcium concentration caused by other therapeutic interventions (e.g. chemotherapy, radiation therapy)
• Other medical conditions that may predispose the patient to hypocalcaemia or hypercalcaemia (e.g. hypoparathyroidism, hyperparathyroidism, neoplasms, hepatic failure, rhabdomyolysis, severe pancreatitis, tumour lysis syndrome, and toxic shock syndromes)

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

• Prescribed flow rates, particularly the effluent flow rate
• Adherence to a standardised protocol or algorithm, which simplifies and facilitates calcium replacement prescription and helps reduce errors and variability
• The filter membrane's permeability to calcium and calcium-citrate complexes

Dosage for adult and adolescent population:
In RCA-CRRT therapies, the typical calcium dose is 1.7 mmol per litre of effluent volume (4–6 mmol/h)
in adults and adolescents.
A maximum daily dose of 340 mmol calcium is recommended, equivalent to 1 L of Icalziss. This
medicinal product is not intended for chronic use.
Dosage in the paediatric population:
The recommended dosage of this medicinal product for neonates and children (from 0 to 11 years and
over 8 kg) is similar to that in adults and adolescents. The maximum hourly infusion rate of calcium on a
body weight basis is 0.3 mmol/h/kg, equivalent to a maximum hourly infusion rate of 0.88 mL/h/kg. Due
to generally lower effluent flow rates prescribed for children, the absolute flow rates of this medicinal
product will be correspondingly lower.
The weight limit of >8 kg stated in the indication does not depend on the safety or efficacy characteristics
of the medicinal product but is instead based on the characteristics of the monitoring devices provided by
the marketing authorisation holder.
Method of administration
Adjust or discontinue calcium infusion according to the physician's prescription when citrate
anticoagulation is discontinued.
Infuse only using an extracorporeal blood purification device intended for calcium chloride solution
infusion and which includes an appropriate balance of flow volumes.
Infuse only into the extracorporeal circuit or, if recommended in the instructions for use of the extracorporeal blood purification device, through a separate central venous access. Icalziss is not intended for intramuscular or subcutaneous use.
Follow the instructions for use provided by the manufacturer of the extracorporeal blood purification
device, the manufacturer of the extracorporeal circuit set, and the intravenous line.
Overdose
Rapid or excessive administration of this medicinal product may lead to hypercalcaemia (total plasma
concentration > 3 mmol/L, ionised calcium > 1.3 mmol/L, respectively), which must be medically corrected
appropriately.
Immediately suspend or reduce administration of this medicinal product if signs or symptoms of
hypercalcaemia are observed. In case of markedly elevated calcium levels, urgent reduction of calcium
levels is required. If adequate renal function is maintained, forced diuresis should be considered with
concomitant infusion of isotonic sodium chloride solution (9 mg/mL NaCl), with close monitoring of
fluid balance and plasma electrolyte concentrations. In patients with renal impairment, dialysis with
calcium-free dialysate may be considered.
Signs and symptoms of hypercalcaemia include:

• Nervous system disorders, e.g. lethargy, disorientation, hyporeflexia
• Cardiac disorders, e.g. tachycardia and tendency to develop cardiac arrhythmia, hypertension, changes in electrocardiogram (shortening of QT interval)
• Gastrointestinal disorders, e.g. nausea, vomiting, constipation, tendency to develop ulcers
• Renal and urinary disorders, e.g. increased diuresis, thirst, polyuria, deposition of calcium salts in the kidneys
• General disorders, e.g. fatigue.

Rapid administration of calcium salts may also cause chalky taste, tingling sensations, hot flushes,
peripheral vasodilation with hypotension, bradycardia, syncope, and arrhythmia with potential for cardiac
arrest.
Preparation and/or handling
The solution may be disposed of via wastewater without harming the environment.
Do not freeze.
Follow the instructions below for use:
During handling and administration to the patient, an aseptic technique must be used.
This medicinal product must be visually inspected for the presence of particles and colour changes prior
to administration. Do not administer if the solution is not clear and colourless or if the seal is not intact.
If damaged, the container must be discarded.
Remove the outer wrapper from the bag immediately before use. After removing the outer wrapper, this
medicinal product must be used within 72 hours. Squeeze the bag firmly to check for leaks. If leakage is
detected, immediately discard the solution as sterility can no longer be guaranteed. The solution must be
used immediately after opening the bag to avoid microbiological contamination.
Remove the plastic cap from the outlet port at the bottom of the container. Firmly hold the small tab on
the neck of the outlet port with one hand. With the other hand, grasp the large tab on the cap and rotate.
The cap will open.
Insert the spike through the rubber septum. See instructions provided with the administration set.
Ensure that the fluid flows freely.
Do not reconnect partially used containers. The solution is for single use only. Discard any unused portion.
If not used according to the instructions for use, the times and conditions of storage during use are the
responsibility of the user.