Cifoban

Package leaflet: Information for the user

Cifoban, 136 mmol/L, infusion solution
Natrii citras
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or nurse.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or nurse immediately. See section 4.

Contents of the leaflet

1. What Cifoban is and what it is used for
2. Important information before using Cifoban
3. How to use Cifoban
4. Possible side effects
5. How to store Cifoban
6. Contents of the pack and other information

1. What Cifoban is and what it is used for

Cifoban is an infusion solution whose active substance is sodium citrate.
For extracorporeal administration only (outside the patient's body).
This medicine is used as an anticoagulant (blood thinner) during regional citrate anticoagulation in the following renal replacement therapies and plasma exchange therapies:

• Continuous veno-venous hemodialysis (CVVHD)
• Continuous veno-venous hemodiafiltration (CVVHDF)
• Slow low-efficiency daily dialysis (SLEDD)
• Therapeutic plasma exchange (TPE) (removes and replaces the patient's plasma).

This medicine is intended for use in adults and children of all age groups (except premature infants).

2. Important information before using Cifoban

When not to use Cifoban

• if the patient is allergic to sodium citrate
• if recent treatment with Cifoban has been discontinued because the patient's body was unable to metabolize the required dose of Cifoban, resulting in accumulation of citrate in the blood.

Warnings and precautions
Before starting treatment with Cifoban, discuss this with the doctor.
The doctor will:

• ensure that any existing liver function impairment, reduced blood oxygen levels, or impaired oxygen utilization in tissues are known before starting treatment, and if necessary, initiate therapy with an adjusted dose or an alternative anticoagulation method.
• ensure that any existing hypocalcemia (low ionized calcium levels in blood) is treated prior to starting therapy.
• ensure that calcium, sodium, and magnesium levels, as well as acid-base balance (pH deviations in blood), are normal and closely monitored during treatment.
• ensure that anticoagulant effect is monitored during treatment and that any unexpected clotting in the filter is detected.
• ensure that, if the patient has been immobilized for a prolonged period, any unusual changes in calcium dosing are noted and that calcium and other bone mineral status (bone mass) are monitored.
• discontinue, if necessary, regional citrate anticoagulation with Cifoban in case of citrate accumulation in the patient.

Children
This medicine is not recommended for preterm neonates, as experience in this patient group is insufficient.

Cifoban and other medicines
Inform the doctor about all medicines currently or recently taken by the patient, as well as any medicines the patient plans to take.
The following interactions may occur with medicines containing:

• Calcium, which may reduce the anticoagulant effect of citrate if administered at an incorrect site in the extracorporeal circuit (outside the patient's body).
• Sodium-enriched products, which may increase the risk of hypernatremia (high sodium levels in blood).
• Bicarbonate (or precursors such as acetate), which may increase the risk of metabolic alkalosis (high bicarbonate levels in blood).
• Blood products that are another source of citrate, which may increase the risk of hypocalcemia (low ionized calcium levels in blood) and metabolic acidosis (high levels of citric acid in blood) when citrate is inadequately metabolized, or may increase the risk of metabolic alkalosis (high bicarbonate levels in blood) when citrate is metabolized to bicarbonate.

This medicine must not be mixed with other medicines, as sufficient compatibility data are not available.

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.
There are no documented clinical data on the use of Cifoban during pregnancy and breastfeeding; therefore, it should be used during pregnancy and breastfeeding only if the doctor considers the treatment necessary.

3. How to use Cifoban

Parenteral administration. Exclusively for infusion into the extracorporeal blood circuit (outside
the patient's body).
This medicine must be administered using an appropriate device for extracorporeal (outside the
patient's body) blood purification, employing an appropriate anticoagulation protocol and, if possible,
appropriate selection of dialysis and volume-replacement fluids.
Dosage
The dose of Cifoban will be determined by the physician. Generally, Cifoban is administered at a specific
rate into the blood flow of the extracorporeal circuit (outside the patient's body) to achieve locally very low
ionized calcium concentration for blood thinning (regional citrate anticoagulation). The blood flow rate and
dosage of this medicine will depend on the patient's condition and the procedure. More information on
dosing can be found in the information provided below for healthcare professionals.
This medicine is administered in hospitals exclusively by trained medical personnel and may be used in
intensive care units, where it will be given under strict medical supervision.
Use in children
The equipment used must be suitable for pediatric procedures and should allow low blood flow rates when
treatment is required in newborns. The physician will ensure that a low blood flow rate relative to the child's
body weight is selected and will prescribe a correspondingly reduced dose of Cifoban. This medicine is
prescribed by a physician only if he or she has experience with recommended renal replacement therapy or
plasma exchange therapy in children.
Administration of a higher than recommended dose
Since Cifoban will be administered exclusively by a physician, it is unlikely that the patient will receive too
low or too high a dose. However, if the patient believes they have received too high a dose, they should
inform their doctor or nurse immediately.
Signs of overdose may include symptoms of low calcium levels (such as muscle cramps, muscle twitching,
irregular or uncoordinated heartbeat) and symptoms of acid-base and sodium imbalance (such as
disorientation, dizziness, headache, vomiting).
If the patient experiences any of the above symptoms, they should seek immediate advice from their doctor
or nurse.
If the patient has any other questions regarding the use of this medicine, they should consult their doctor or
nurse.

4. Possible adverse reactions

Like all medicinal products, this medicine can cause adverse reactions, although not everyone will experience them.

The following more common adverse reactions may occur:

• electrolyte imbalance in the blood (e.g. low calcium levels in blood, low magnesium levels in blood, high sodium levels in blood)
• acid-base imbalance (excessively high or low blood pH)

The following less common adverse reactions may occur (exact frequency is not known):

• allergic reactions leading, for example, to low blood pressure, nausea, back and abdominal pain, local reactions (itching, rash, skin redness)
• excessive fluid accumulation in the body
• headache, seizures, unconsciousness
• irregular heartbeat, cardiac arrest
• pulmonary edema (fluid in the lungs)
• low blood pressure
• breathing difficulties, respiratory arrest
• abnormally rapid breathing
• vomiting
• muscle cramps, muscle twitching

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181 C, PL-02-222 Warsaw, Tel.: + 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 Cifoban

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label following: “Expiry date (EXP)”. The expiry date refers to the last day of the stated month.
Do not store in the refrigerator and do not freeze.
Store the bags in their outer packaging – the cardboard box – to protect from light.
The contents of the bag should be used immediately after opening.
The solution is for single use only. Any unused solution and any damaged container must be discarded.

6. Contents of the pack and other information

What Cifoban contains

• The active substance is sodium citrate. Each 1000 mL of solution contains 40.0 g of sodium citrate, corresponding to 408 mmol sodium and 136 mmol citrate.
• Other components of the medicine are water for injections and hydrochloric acid 25%.

What Cifoban looks like and contents of the pack
Cifoban is supplied in a bag containing 1500 mL of ready-to-use solution.
The solution is clear, colourless, and practically free from particles.
Each bag is equipped with a connecting tube and connector. Two bags are placed in a protective overwrap and connected by a perforated seam allowing complete separation.
Cifoban is supplied in the following connector systems and pack sizes:

Not all types of packaging must be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Fresenius Medical Care Deutschland GmbH
Else-Kröner-Strasse 1
61352 Bad Homburg v.d.H.
Germany
Tel. +48 61 8392 600
Manufacturer
Fresenius Medical Care Deutschland GmbH
Frankfurter Strasse 6-8
66606 Sankt Wendel
Germany
This medicinal product has been authorised in the Member States of the European Economic Area and the United Kingdom (Northern Ireland) under the following names:
AT, BG, CY, DK, EL, ES, FI, HU, IE, IT, LT, MT, NL, NO, PL, PT, RO, SK, UK(NI): Cifoban
FR, HR, LV, SE: Civaron
BE, DE, LU: Cibastyn
CZ, EE, SI: Cigenta
Detailed information on this medicinal product is available on the website of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products (website: https://smz.ezdrowie.gov.pl).

Information intended exclusively for healthcare professionals:

1000 mL of solution contains:
Sodium citrate 40.0 g
Na 408 mmol
Citrate 136 mmol
Theoretical osmolarity: 544 mOsm/L
pH: 7.1 – 7.5

Dosage
Extracorporeal administration of Cifoban should be proportionally adjusted according to the extracorporeal blood flow rate (e.g., 4 mmol of citrate per liter of flowing blood) in order to achieve adequate suppression of ionized calcium, generally aiming for a concentration of 0.3–0.35 mmol/L of ionized calcium post-filter. In adult patients, the administered volume should not exceed 10.4 liters per day. The extracorporeal blood flow should be sufficient to achieve therapeutic goals, but maintained at the lowest possible level to avoid unnecessary citrate infusion and to promote citrate clearance through the filter used. In renal replacement therapies and plasma exchange, the composition and volumes of other solutions used must take into account the administration of Cifoban. Additional recommendations and limitations apply to patients with citrate metabolism disorders, elderly patients, and pediatric and adolescent populations. Detailed information is provided in the Summary of Product Characteristics.

Route of administration
Extracorporeal administration. For infusion into the extracorporeal blood circuit only.
Infusion must be performed exclusively via the integrated pump of the extracorporeal blood purification device, as intended by the manufacturer, for infusion of concentrated citrate solution into the access drainage segment ("access blood line"), located before the pump.

Special warnings and precautions described in the Summary of Product Characteristics must be observed.

Additionally:

• Cifoban must be used strictly in accordance with an appropriate local citrate anticoagulation (LCA) protocol. It should be administered by, or under the supervision of, a physician experienced in the use of LCA, and by healthcare professionals adequately trained in the indicated therapies and the use of associated products.
• The manufacturer's instructions for use of the extracorporeal blood purification device and drainage set must be followed.
• Cifoban may be used for LCA in intensive care units or similar settings requiring close medical supervision and continuous monitoring.

Disposal
The solution is for single use only. Any unused solution and any damaged container must be discarded.

Instructions for use
Bags containing the solution are equipped with either a SecuNect connector or a Safe●Lock connector.

Prior to using the solution bag, the following instructions must be observed:
Aseptic techniques must be followed when administering the medicinal product to the patient. The solution should be used immediately after opening to avoid microbiological contamination.

Extracorporeal administration. For infusion into the extracorporeal blood circuit only.

For solution bags equipped with a SecuNect connector (transparent with green ring):

1. Separate the two bags at the tear-off seal without damaging the integrity of the outer packaging.
2. Remove the outer packaging only immediately before use. Inspect the solution bag (label, expiry date, clarity of solution, absence of damage to the bag and outer packaging). Plastic containers may occasionally be damaged during transport from the manufacturer to the dialysis center or hospital clinic, or within the clinic itself. This may lead to contamination and growth of bacteria or fungi in the solution. Therefore, careful inspection of the bag and solution before use is essential. Particular attention should be paid to even minor damage to the closure, sealed seams, and corners of the bag. The solution may only be used if it is colorless and clear, and the bag and connector are undamaged and intact.
3. Hang the bag on the designated accessory using its hanger hole.
4. Remove the protective cap from the SecuNect connector with green ring and connect it to the corresponding part of the same color to prevent incorrect connection. Do not touch any internal parts, especially the tip of the connector. The internal part of the connector is supplied sterile and is not intended for subsequent treatment with chemical disinfectants. Connect the bag’s connector manually by twisting until an audible "click" confirms secure connection.
5. Before starting the procedure and when replacing the bag, break the brittle spike of the bag’s connector and ensure it is completely broken.
6. Proceed with the next steps according to the local citrate anticoagulation protocol used in the procedure.

For solution bags equipped with a Safe●Lock connector (transparent):

1. Separate the two bags at the tear-off seal without damaging the integrity of the outer packaging.
2. Remove the outer packaging only immediately before use. Inspect the solution bag (label, expiry date, clarity of solution, absence of damage to the bag and outer packaging). Plastic containers may occasionally be damaged during transport from the manufacturer to the dialysis center or hospital clinic, or within the clinic itself. This may lead to contamination and growth of bacteria or fungi in the solution. Therefore, careful inspection of the bag and solution before use is essential. Particular attention should be paid to even minor damage to the closure, sealed seams, and corners of the bag. The solution may only be used if it is colorless and clear, and the bag and connector are undamaged and intact.
3. Hang the bag on the designated accessory using its hanger hole.
4. Remove the protective cap from the transparent Safe●Lock connector and connect it to the corresponding part of the same color to prevent incorrect connection. Do not touch any internal parts, especially the tip of the connector. The internal part of the connector is supplied sterile and is not intended for subsequent treatment with chemical disinfectants. Connect the bag’s connector to the corresponding part and twist together securely.
5. Before starting the procedure and when replacing the bag, break the brittle spike of the bag’s connector and ensure it is completely broken.
6. Proceed with the next steps according to the local citrate anticoagulation protocol used in the procedure.

The solution is not intended for use as an additive to other medicinal products.