Cifoban

Package Leaflet: Information for the User

Cifoban, 136 mmol/L, Solution for Infusion

Sodium Citrate

Read the package leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you experience any side effects, talk to your doctor or nurse. See section 4.

Table of Contents of the Package Leaflet

• 1. What is Cifoban and what is it 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 is Cifoban and what is it used for

Cifoban is a solution for infusion, whose active substance is sodium citrate.
For extracorporeal use only (outside the patient's body).
This medicine is used as an anticoagulant (causing blood thinning) during local 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

Warnings and precautions

Before starting treatment with Cifoban, discuss it with your doctor.
Your doctor will:

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

Children

This medicine is not recommended for premature infants, as experience in this patient group is insufficient.

Cifoban and other medicines

Tell your doctor about all medicines you are taking or have recently taken, as well as any medicines you plan to take.
The following interactions may occur with medicines that contain:

• Calcium, which may reduce the anticoagulant effect of citrate if administered at the wrong site in the extracorporeal circuit (outside the patient's body).
• Sodium-containing products, which may increase the risk of hypernatremia (high sodium levels in the blood)
• Bicarbonate (or precursors, such as acetate), which may increase the risk of metabolic alkalosis (high bicarbonate levels in the blood)
• Blood products that are another source of citrate, which may increase the risk of hypocalcemia (low ionized calcium levels in the blood) and metabolic acidosis (high acid levels in the blood) when citrate is not adequately metabolized, or may increase the risk of metabolic alkalosis (high bicarbonate levels in the blood) when citrate is metabolized to bicarbonate.

This medicine must not be mixed with other medicines, as there are no sufficient data on compatibility.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.
There are no clinical data available on the use of Cifoban in pregnancy and breastfeeding, so it should only be used during pregnancy and breastfeeding if your doctor considers it necessary.

3. How to use Cifoban

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

This medicine must be administered using an appropriate device for extracorporeal blood purification, using an appropriate anticoagulation protocol, and, if possible, an appropriate choice of dialysis fluids and volume replacement.

Dose

The dose of Cifoban will be determined by your doctor. In general, Cifoban is administered in a specified dose to the blood flow in the extracorporeal circuit to cause a locally very low ionized calcium concentration for blood thinning (local citrate anticoagulation). The blood flow rate and dose of this medicine will depend on the patient's condition and procedure. More information on dosing can be found in the information intended for healthcare professionals below.
This medicine is administered in hospitals only by trained medical personnel and may be used in an intensive care unit, where it will be administered under close medical supervision.

Use in children

The equipment used must be suitable for procedures in children and must allow for low blood flow rates when used in neonates. Your doctor will ensure that a low blood flow rate is selected in relation to the child's body weight and will prescribe a reduced dose of Cifoban accordingly. This medicine is prescribed by a doctor only if they have experience with the prescribed renal replacement therapy or plasma exchange therapy in children.

Overdose

Since Cifoban will be administered only by a doctor, it is unlikely that a patient will receive too much or too little of the medicine. However, if you think you have received too much of the medicine, tell your doctor or nurse.
Signs of overdose may include symptoms of low calcium levels (such as muscle cramps, muscle spasms, irregular heartbeat) and symptoms of changes in acid-base and sodium balance (such as disorientation, dizziness, headache, vomiting).
If you experience any of these symptoms, seek medical attention immediately.
If you have any other questions about using this medicine, ask your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following more common side effects may occur:

• disturbances in electrolyte balance in the blood (e.g., low calcium levels, low magnesium levels, high sodium levels)
• disturbances in acid-base balance (abnormal pH blood levels)

The following less common side effects may occur (frequency not known):

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

Reporting side effects

If you experience any side effects, talk to your doctor or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring 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.
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cifoban

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label after: “Expiry Date (EXP)”. The expiry date refers to the last day of the month.
Do not store in a refrigerator or freeze.
Store the bags in the outer packaging – 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 should be disposed of.

6. Contents of the pack and other information

What Cifoban contains

• The active substance of Cifoban is sodium citrate. Each 1000 mL solution contains 40.0 g sodium citrate, corresponding to 408 mmol sodium and 136 mmol citrate.
• The other ingredients are water for injection and 25% hydrochloric acid.

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 and colorless, practically free from particles.
Each bag is equipped with a connecting tube and connector. Two bags are placed in a protective bag and connected by a perforated seam, which allows them to be completely separated.
Cifoban is supplied in the following connector systems and pack sizes:
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization 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 medicine has been authorized in the Member States of the European Economic Area and in 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

Date of last revision of the package leaflet:

Further information on this medicine 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 for healthcare professionals only:

1000 mL solution contains:

Sodium citrate 40.0 g

Na 408 mmol

Citrate 136 mmol

Theoretical osmolality:
544 mOsm/L
pH: 7.1 – 7.5

Dosing

Extracorporeal dosing of Cifoban should be adjusted proportionally to the blood flow in the extracorporeal circuit (e.g., 4 mmol citrate per liter of blood flow), to achieve sufficient suppression of ionized calcium, while generally aiming for a concentration of 0.3-0.35 mmol/L 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 the goals of therapy but maintained at a low level to avoid unnecessary citrate infusion and promote citrate clearance in the used filter. In renal replacement therapies and plasma exchange therapies, the composition and administered volumes of other solutions must take into account the administration of Cifoban. Further recommendations and restrictions apply in the case of patients with citrate metabolism disorders and in the elderly population and children and adolescents. Detailed information is contained in the Summary of Product Characteristics.

Method of administration

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

Infusion only via an integrated pump of the extracorporeal blood purification device, which is intended by the manufacturer for infusion of concentrated citrate solution into the arterial blood line segment (“blood access line”), which is located before the pump.
Special warnings and precautions contained in the Summary of Product Characteristics must be observed.
Additionally:

• Cifoban must be used only in accordance with the appropriate protocol for local citrate anticoagulation (Regional Citrate Anticoagulation, RCA). It should be used by, or under the supervision of, a doctor competent in the use of RCA and by trained medical personnel sufficiently trained in the indicated therapies and in the use of related products.
• The instructions for use provided by the manufacturer of the extracorporeal blood purification device and the tubing set must be observed.
• Cifoban may be used for RCA in an intensive care unit or similar setting, where it requires close medical supervision and continuous monitoring.

Disposal

The solution is for single use only. Any unused solution and any damaged container should be disposed of.

Instructions for use

The bags with solution are equipped with a SecuNect connectoror a Safe●Lock connector.
Before using the bag with solution, observe the following:

• 1. Separate the two bags at the perforated seam, without damaging the integrity of the outer packaging.
• 2. Remove the outer packaging only immediately before using the solution. Check the bag with solution (label, expiry date, solution clarity, absence of damage to the bag and outer packaging). Plastic containers may sometimes be damaged during transport from the manufacturer to the dialysis center or hospital clinic or in the clinic itself. This may lead to contamination and growth of bacteria or fungi in the solution. Therefore, it is essential to carefully check the bag and solution before use. Particular attention should be paid to even minor damage to the bag closure, welded seams, and bag corners. The solution may only be used if it is colorless and clear, and if the bag and connector are undamaged and intact.
• 3. Place the bag on the designated additional element, using its hanging hole.
• 4. Remove the protective cap from the SecuNect connector with a green ringand connect the connector to the corresponding part of the same color to prevent incorrect connection. Do not touch any internal parts, especially the connector ends. The internal part of the connector is supplied in a sterile state and is not intended for subsequent treatment with chemical disinfectants. Connect the bag connector manually with a twisting motion to the connector of the blood line, overcoming a certain force, until a audible “click” is heard, which confirms the connection.
• 5. Before starting the procedure and when changing the bag, break the fragile spike of the bag connector and ensure that the spike is completely broken.
• 6. In the subsequent steps, follow the protocol for local citrate anticoagulation used in the procedure.

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

• 1. Separate the two bags at the perforated seam, without damaging the integrity of the outer packaging.
• 2. Remove the outer packaging only immediately before using the solution. Check the bag with solution (label, expiry date, solution clarity, absence of damage to the bag and outer packaging). Plastic containers may sometimes be damaged during transport from the manufacturer to the dialysis center or hospital clinic or in the clinic itself. This may lead to contamination and growth of bacteria or fungi in the solution. Therefore, it is essential to carefully check the bag and solution before use. Particular attention should be paid to even minor damage to the bag closure, welded seams, and bag corners. The solution may only be used if it is colorless and clear, and if the bag and connector are undamaged and intact.
• 3. Place the bag on the designated additional element, using its hanging hole.
• 4. Remove the protective cap from the clear Safe●Lock connectorand connect the connector to the corresponding part of the same color to prevent incorrect connection. Do not touch any internal parts, especially the connector ends. The internal part of the connector is supplied in a sterile state and is not intended for subsequent treatment with chemical disinfectants. Connect the bag connector to the corresponding part and twist together.
• 5. Before starting the procedure and when changing the bag, break the fragile spike of the bag connector and ensure that the spike is completely broken.
• 6. In the subsequent steps, follow the protocol for local citrate anticoagulation used in the procedure.

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