Cifoban

Package leaflet: Information for the patient

Cifoban 136 mmol/l solution for infusion

sodium citrate
Read this entire leaflet carefully before this medicine is administered to you
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 or nurse.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor or nurse. See section 4.

Contents of this leaflet:

1. What Cifoban is and what it is used for
2. What you must know before being administered Cifoban
3. How Cifoban is administered
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 containing the active substance sodium citrate.
For exclusive use in the extracorporeal circuit (outside the body).
This medicinal product is used as an anticoagulant (to make the blood less likely to clot) during
regional citrate anticoagulation in the following renal replacement and plasma exchange therapies:

• continuous veno-venous haemodialysis (CVVHD)
• continuous veno-venous haemodiafiltration (CVVHDF)
• sustained low-efficiency daily dialysis (SLEDD)
• therapeutic plasma exchange (TPE) (removes and replaces the plasma in the patient's blood).

This medicinal product is intended for use in adults and children of all age groups (except premature neonates).

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

Do not be administered Cifoban

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

Warnings and precautions
Consult your doctor before you are administered Cifoban.
The doctor:

• will ensure to check for possible impaired liver function, reduced oxygen levels in the blood, or abnormal oxygen utilization in body tissues before starting treatment, and, if necessary, will initiate treatment with an adjusted dose or with another anticoagulant method.
• will ensure that any existing hypocalcemia (low ionized calcium concentration in the blood) is treated before starting therapy.
• will ensure that calcium, sodium, and magnesium levels, as well as acid-base balance (deviation in blood pH), are corrected and closely monitored during treatment.
• will ensure that the anticoagulant effect is monitored during treatment and that any unexpected clotting in the filter is detected.
• if you are immobilized for a prolonged period, will ensure that any unusual changes in calcium dosage are recorded and that calcium and other mineral status in the bones (bone mass) are monitored.
• if necessary, will discontinue regional anticoagulation with citrate if you develop citrate accumulation.

Children
This medicine is not recommended in premature neonates, as there is insufficient experience in this patient group.
Other medicines and Cifoban
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
The following interactions are possible with medicines containing:

• Calcium administered at an incorrect position in the extracorporeal circuit (outside the body), which may reduce the anticoagulant effect of citrate.
• Sodium-enriched products, which may increase the risk of hypernatremia (high sodium concentration in the blood).
• Bicarbonate (or precursors such as acetate), which may increase the risk of metabolic alkalosis (high bicarbonate concentration in the blood).
• Blood-derived medicinal products, 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 acid (citrate) 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 has been metabolized into bicarbonate.

This medicine must not be mixed with other medicines, as available compatibility data are insufficient.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor before starting treatment with this medicine.
There are no documented clinical data on the use of Cifoban during pregnancy and breastfeeding.
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. Exclusively for infusion into the extracorporeal (outside the body) blood circuit.
This medicine must be administered using a dedicated extracorporeal (outside the body) device for blood purification, an appropriate anticoagulation protocol, and, if possible, in combination with dialysis using fluids for volume replacement.

Dosage
The dose of Cifoban will be determined by your doctor. Briefly, Cifoban is administered at a specific dose into the blood flow of the extracorporeal (outside the body) circuit to locally induce very low levels of ionized calcium, thereby making the blood less prone to clotting (regional anticoagulation with citrate). The blood flow rate used and the dosage of this medicine will depend on your clinical condition and treatment. Further information on dosing is provided in the section below intended for healthcare professionals.

This medicine is administered in a hospital setting and must be given exclusively by qualified healthcare professionals. It may be used in an intensive care environment under close medical supervision.

Use in children
The equipment used must be suitable for pediatric treatment and capable of supporting low blood flow rates when neonatal use is intended. The doctor 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 will only be prescribed by a doctor experienced in renal replacement therapy or plasma exchange therapy in children.

If you have been given more Cifoban than you should have received
Since Cifoban will be administered exclusively 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 dose of this medicine, inform your doctor or nurse immediately.

Signs of overdose may include symptoms of low calcium levels (such as muscle cramps and spasms, abnormal or irregular heartbeat) and symptoms related to disturbances in acid-base balance and sodium levels (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 doubts about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
The following more common adverse reactions may occur:

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

The following less common adverse reactions may occur (exact frequency unknown):

• allergic reactions leading, for example, to low blood pressure, feeling unwell, back and abdominal pain, local reaction (itching, skin rash, skin redness)
• fluid overload in the body
• headache, seizures, unconsciousness
• abnormal heart rate, cardiac arrest
• fluid accumulation in the lungs
• low blood pressure
• breathing difficulties, respiratory arrest
• abnormally rapid breathing
• vomiting (feeling sick)
• muscle cramps, muscle spasms

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, tell your doctor or nurse. You can also report side effects directly via the national reporting system at 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 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 refers to the last day of that month.
Do not refrigerate or freeze.
Keep the bags in the outer packaging to protect the medicine from light.
The contents of the bag must be used immediately after opening.
The solution is for single use only. Any unused solution and any damaged container must be discarded.

6. Package contents and other information

What Cifoban contains

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

Description of the appearance of Cifoban and contents of the pack
Cifoban is supplied in a 1500 ml bag containing ready-to-use solution.
The solution is clear, colourless and practically free from particles.
Each bag is equipped with a connection cannula and connector, and is covered by a protective overwrap.
Cifoban is available in the following connection systems and pack sizes:

It is possible that not all pack sizes are 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 Italia S.p.A.
Tel: + 39 0373 974 1
This medicinal product is authorized in the European Economic Area Member States 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
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The following information is intended exclusively for physicians or healthcare professionals:
1000 ml of solution contain:
Sodium citrate 40.0 g
Na 408 mmol
Citrate 136 mmol
Theoretical osmolarity: 544 mOsm/l
pH: 7.1 – 7.5
Dosage
The extracorporeal administration of Cifoban must be titrated proportionally to the blood flow rate of the extracorporeal circuit (e.g., 4 mmol of citrate per liter of blood treated) to achieve adequate suppression of ionized calcium, with a target generally being a post-filter ionized calcium concentration below 0.3–0.35 mmol/l. The volume administered in adult patients must not exceed 10.4 l/day. The extracorporeal blood flow rate must be sufficient to achieve therapeutic goals but kept sufficiently low to avoid unnecessary citrate infusion and to favor citrate clearance within the applied filter. In renal replacement therapies or plasma exchange therapies, the composition and volumes of other solutions must be taken into account when prescribing Cifoban. Additional recommendations and restrictions apply to use in patients with impaired citrate metabolism and in geriatric and pediatric populations. For details, refer to the Summary of Product Characteristics.
Method of Administration
For extracorporeal use only. For intravenous infusion into the extracorporeal blood circuit only.
For infusion exclusively via a pump integrated into a device for extracorporeal blood purification, as intended by the manufacturer for the infusion of a concentrated citrate solution into the pre-pump segment of the vascular access catheter system (“arterial blood line”).
Observe the special warnings and precautions described in the Summary of Product Characteristics.
In addition:

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

Disposal
The solution is for single use only. Unused solution and damaged containers must be discarded.
Handling
Solution bags are equipped with a SecuNect connector or a Safe●Lock connector.
Before using the solution, the following points must be considered:
Throughout the entire administration period to the patient, aseptic technique must be maintained. The solution must be used immediately after opening to avoid microbiological contamination.
For extracorporeal use only. For intravenous infusion into the extracorporeal blood circuit only.
For solution bags equipped with a SecuNect connector (transparent with green ring) :

1. Separate the two bags along the connecting line without damaging the integrity of the 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 packaging). Occasionally, plastic containers may be damaged during transport from the manufacturer to the dialysis or hospital facility, or within the facility itself. This may lead to contamination and bacterial or fungal growth 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, welds, and corners of the bag. The solution must only be used if it is colorless and clear, and if the bag and connector are intact and undamaged.
3. Place the bag in the dedicated holder in the drip chamber pole holder.
4. Remove the protective cap from the SecuNect connector with its green ring and connect it only to its corresponding counterpart of the same color to prevent incorrect connections. Do not touch any internal parts, especially the upper part of the connector. The internal part of the connector is supplied sterile and is not intended to be treated further with chemical disinfectants. Manually connect the bag connector to the catheter connector by rotating until a “click” is heard and a secure connection is established.
5. Before starting treatment and when changing bags, break the breakable tip of the bag connector and ensure it is completely broken.
6. Proceed with subsequent steps as indicated in the RCA protocol applied to the treatment.

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

1. Separate the two bags along the connecting line without damaging the integrity of the 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 packaging). Occasionally, plastic containers may be damaged during transport from the manufacturer to the dialysis or hospital facility, or within the facility itself. This may lead to contamination and bacterial or fungal growth 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, welds, and corners of the bag. The solution must only be used if it is colorless and clear, and if the bag and connector are intact and undamaged.
3. Place the bag in the dedicated holder in the drip chamber pole holder.
4. Remove the protective cap from the transparent Safe●Lock connector and connect it only to its corresponding counterpart to prevent incorrect connections. Do not touch any internal parts, especially the upper part of the connector. The internal part of the connector is supplied sterile and is not intended to be treated further with chemical disinfectants. Connect the bag connector to the corresponding counterpart and rotate together.
5. Before starting treatment and when changing bags, break the breakable tip of the bag connector and ensure it is completely broken.
6. Proceed with subsequent steps as indicated in the RCA protocol applied to the treatment.

The solution is not intended for use as a vehicle for adding medicinal products.