Cifoban 136 mmol/l solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Cifoban 136 mmol/l solution for infusion

sodium citrate

Read all of this leaflet carefully before you are given this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you experience any side effects, talk to your doctor or nurse, even if it is not a side effect listed in this leaflet. See section 4.

Contents of this leaflet

1. What Cifoban is and what it is used for

2. What you need to know before you are given Cifoban

3. How Cifoban is administered

4. Possible side effects

5. Storage of Cifoban

6. Contents of the pack and other information

1. What Cifoban is and what it is used for

Cifoban is an infusion solution containing the active substance sodium citrate.

For use only in extracorporeal circuit (outside the body).

This medicine is used as an anticoagulant (to thin the blood) during regional citrate anticoagulation in the following kidney replacement therapies and plasma exchange therapies:

• continuous venovenous hemodialysis (CVVHD)
• continuous venovenous hemodiafiltration (CVVHDF)
• sustained low-efficiency dialysis (daily) (SLED)
• therapeutic plasma exchange (TPE) (removes and replaces a patient's blood plasma).

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

2. What you need to know before Cifoban is administered to you

Do not receive Cifoban

• if you are allergic to sodium citrate
• if a recent treatment with Cifoban was discontinued because your body was unable to sufficiently metabolize the required dose of Cifoban, resulting in citrate accumulation in your blood.

Warnings and precautions

Consult your doctor before starting treatment with Cifoban.

Your doctor will ensure:

• to be aware of any reduced liver function, decreased oxygen in the blood, or impaired oxygen utilization in body tissues before starting treatment, and will initiate treatment with an adjusted dose or an alternative anticoagulation method, if necessary.
• to treat any existing hypocalcemia (low ionized calcium concentration in the blood) prior to initiating therapy.
• that levels of calcium, sodium, and magnesium, as well as acid-base balance (deviation in blood pH), are correct and closely monitored during your treatment.
• to monitor the anticoagulant effect during treatment and to detect any unexpected clotting of the filter.
• in case of prolonged immobilization, to observe unusual changes in calcium dosage and to monitor the status of calcium and other minerals in your bone (bone mass).
• to discontinue, if necessary, regional citrate anticoagulation with Cifoban if citrate accumulation has developed.

Children

This medicine is not recommended in premature infants due to insufficient experience in this patient group.

Other medicines and Cifoban

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines.

The following interactions are possible with medications containing:

• Calcium administered at an incorrect position in the extracorporeal circuit, which may reduce the anticoagulant effect of citrate.
• Sodium-enriched products, which may increase the risk of hypernatremia (high sodium concentration in the blood).
• Sodium bicarbonate (or precursors such as acetate), which may increase the risk of metabolic alkalosis (high bicarbonate concentration in the blood).
• Blood derivatives, which are another source of citrate, may increase the risk of hypocalcemia (low ionized calcium concentration in the blood) and metabolic acidosis (high concentration of (citrate) acid in the blood) when citrate is not sufficiently metabolized, or may increase the risk of metabolic alkalosis (high bicarbonate concentration in the blood) once citrate is metabolized into bicarbonate.

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

There are insufficient clinical data on the use of Cifoban in pregnant and breastfeeding women. Therefore, this medicine should only be used during pregnancy and breastfeeding if your doctor considers the treatment necessary.

3. How Cifoban is administered

Extracorporeal use. For perfusion only in the extracorporeal blood circuit (outside the body).

This medicine must be administered using a specific extracorporeal blood purification device, an appropriate anticoagulation protocol, and, if possible, the corresponding dialysis and volume replacement fluids.

Dosage

Your doctor will determine the dose of Cifoban. Briefly, Cifoban is administered at a specific dose through the blood flow in the extracorporeal circuit (outside the body) to induce locally very low ionized calcium levels, thereby anticoagulating the blood (regional citrate anticoagulation). The blood flow rate used and the dose of this medicine will depend on your condition and treatment. You can find more information about dosing in the information for healthcare professionals below.

This medicine is administered in hospitals and is given only by trained medical professionals. It may be used in an intensive care setting where it will be administered under close medical supervision.

Use in children

The equipment used must support treatment in children and low blood flow rates when neonatal application is intended. Your doctor will ensure a low blood flow rate is selected relative to your child's weight and will prescribe a reduced dose of Cifoban accordingly. This medicine will be prescribed by your doctor only if your doctor has experience in kidney replacement therapy or plasma exchange therapy in children.

If you are given more Cifoban than you should

Since Cifoban will only be administered by a doctor, it is unlikely that you will receive too much or too little. However, if you think you have been given an excessive amount of this medicine, inform your doctor or nurse immediately, or call the Toxicology Information Service at 91 562 04 20, indicating the medicine and the amount administered.

Signs of an overdose may include symptoms of low calcium levels (such as muscle cramps and abnormal or irregular heartbeats) and symptoms related to disturbances in acid-base balance and sodium balance (such as confusion, dizziness, headache, vomiting).

If you experience any of the symptoms listed above, inform your doctor or nurse immediately.

If you have any further questions about the use of this medicine, ask your doctor or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

The following more frequent adverse effects that may occur are:

• imbalances in blood electrolyte levels (for example, low blood calcium levels, low blood magnesium levels, high blood sodium levels)
• disturbances in the acid-base balance of the blood (blood pH too high or too low)

The following less frequent adverse effects (exact frequency unknown) that may occur are:

• allergic reactions leading to, for example, low blood pressure, feeling unwell, back and abdominal pain, local reaction (itching, skin rash, skin redness)
• too much fluid in your body
• headache, seizures, unconscious state
• abnormal heartbeats, cardiac arrest
• excess fluid in the lungs
• low blood pressure
• difficulty breathing, respiratory arrest
• abnormally rapid breathing
• vomiting (being sick)
• muscle cramps

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system at www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Cifoban

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label after EXP. The expiry date is the last day of the month indicated.

Do not refrigerate or freeze.

Store the bags in the outer packaging to protect them from light.

The contents of the bag must be used immediately after opening.

The solution is for single use only. Any unused solution or solution from a damaged container must be discarded.

6. Contents of the pack and other information

Composition of Cifoban

• The active substance is sodium citrate. Each 1000 ml of solution contains 40.0 g of sodium citrate, corresponding to 408 mmol of sodium and 136 mmol of citrate.
• The other components are water for injections and hydrochloric acid.

Appearance of the product and contents of the pack

Cifoban is supplied as a bag containing 1500 ml of ready-to-use solution.

The solution is clear, colourless, and free from visible particles.

This medicine is supplied as two identical solution bags, which can be separated by a seam in the protective overwrap. Each bag is equipped with a connecting tube and a connector piece.

Cifoban is available in the following pack sizes and connector systems per carton:

Some pack sizes may not 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

Manufacturer

Fresenius Medical Care Deutschland GmbH,
Frankfurter Straße 6-8,
66606 St. Wendel,
Germany

Local Representative

Fresenius Medical Care España, S.A.,
C/ Ronda de Poniente, 8, planta baja, Parque Empresarial Euronova,
28760 Tres Cantos (Madrid),
Spain

This medicinal product is authorized in the European Economic Area member states and in the United Kingdom (Northern Ireland) under the following names:

AT: Citravyl
BE, LU, PT: Civastyn
BG: ???????
BG, CY, DK, EL, ES, FI, HU, IE, IT, NL, NO, PL, RO, SK, UK(XI): Cifoban
CZ, EE, LT, SI: Cigenta
DE, FR, HR, LV, SE: Civaron

Date of latest revision of this summary: 02/2023

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/.

This information is intended for healthcare professionals only:

1000 ml of solution contain:

Sodium citrate 40.0 g
Na+ 408 mmol Citr3- 136 mmol

Theoretical osmolarity: 544 mOsm/l
pH: 7.1 – 7.5

Dosage

The extracorporeal dosage of Cifoban should be proportionally adjusted to the blood flow rate of the extracorporeal circuit (e.g., 4 mmol of citrate per liter of blood processed) to achieve adequate suppression of ionized calcium, with post-filter ionized calcium concentrations generally maintained below 0.3–0.35 mmol/l. The administered volume in adult patients should not exceed 10.4 liters/day. The extracorporeal blood flow rate should be sufficient to meet therapeutic goals, but kept as low as possible to avoid unnecessary citrate infusion and to promote citrate clearance within the filter used. In renal replacement therapies and plasma exchange procedures, the composition and volumes of other solutions administered must be considered when prescribing Cifoban. Additional recommendations and limitations apply to its use in patients with impaired citrate metabolism, as well as in geriatric and pediatric populations. For further information, refer to the Summary of Product Characteristics.

Method of administration

Extracorporeal use only. For perfusion into the extracorporeal blood circuit only.

For perfusion exclusively via an integrated pump within the extracorporeal blood purification device, designed by its manufacturer for the infusion of concentrated citrate solution into the pre-pump segment of the access tubing set ("blood access line").

Refer to warnings and special precautions in the Summary of Product Characteristics.

Additionally:

• Cifoban must only be used according to an appropriate protocol for regional citrate anticoagulation (RCA). It must only be administered by, or under the supervision of, a physician experienced in RCA, and by healthcare professionals adequately trained in the indicated therapies and use of the products involved.
• The handling instructions provided by the manufacturer for the extracorporeal blood purification device and tubing set must be followed.
• Cifoban may be used for RCA in intensive care units or similar settings, where it must be administered under close medical supervision and continuous monitoring.

Disposal

The solution is for single use only. Any unused solution or solution from a damaged container must be discarded.

Handling

Solution bags are equipped with a SecuNect or Safe?Lock connector.

The following points must be observed before using the solution bag:

Aseptic technique must be maintained throughout administration to the patient. The solution should be used immediately after opening to prevent microbiological contamination.

Extracorporeal use only. For perfusion into the extracorporeal blood circuit only.

The solution is not intended for addition of any medicinal products.

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

1. Separate the two bags along the tear seam without damaging the integrity of the packaging.
2. Remove the outer packaging immediately before use. Check the solution bag (label, expiry date, clarity of solution, bag and packaging for damage).

Plastic containers may occasionally be damaged during transport from the manufacturing site to the dialysis clinic, 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 must be paid to even minor damage to the bag closure, welded seams, and bag corners. The solution should only be used if it is colorless and clear, and if the bag and connector are undamaged and intact.

3. Hang the bag on the designated holder using its hanging hole.
4. Remove the protective cap from the SecuNect connector with its green ring and connect it only to its corresponding mating component of the same color to prevent connection errors. Do not touch any internal parts, especially the top of the connector. The interior of the connector is supplied sterile and must not be treated with chemical disinfectants. Connect the bag connector to the tubing connector by hand with a twisting motion, overcoming the safety force until an audible "click" is heard and the connection is secured.
5. Before starting treatment and when changing bags, break the frangible plug in the bag connector and ensure it is completely broken.
6. Proceed with the next steps as specified in the applied RCA treatment protocol.

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

1. Separate the two bags along the tear seam without damaging the integrity of the packaging.
2. Remove the outer packaging immediately before use. Check the solution bag (label, expiry date, clarity of solution, bag and packaging for damage).

Plastic containers may occasionally be damaged during transport from the manufacturing site to the dialysis clinic, 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 must be paid to even minor damage to the bag closure, welded seams, and bag corners. The solution should only be used if it is colorless and clear, and if the bag and connector are undamaged and intact.

3. Hang the bag on the designated holder using its hanging hole.
4. Remove the protective cap from the transparent Safe?Lock connector and connect it only to its corresponding mating component to prevent connection errors. Do not touch any internal parts, especially the top of the connector. The interior of the connector is supplied sterile and must not be treated with chemical disinfectants. Connect the bag connector to the corresponding component and twist them together.
5. Before starting treatment and when changing bags, break the frangible plug in the bag connector and ensure it is completely broken.
6. Proceed with the next steps as specified in the applied RCA treatment protocol.