SODIUM CITRATE GRIFOLS 136 mmol/L ANTICOAGULANT AND PRESERVATIVE SOLUTION FOR BLOOD

2. What you need to know before you start using Sodium Citrate Grifols 136 mmol/l

Do not useSodium Citrate Grifols 136 mmol/l

• if you are allergic to sodium citrate or any of the other components of this medicinal product (listed in section 6).
• if you are a donor at risk of suffering from a citrate metabolism disorder (your body is unable to break down the necessary dose of Sodium Citrate Grifols 136 mmol/l and as a result, citrate accumulates in your blood) (e.g. liver failure).
• if you suffer from a severe citrate metabolism disorder.

Warnings and precautions

Consult your doctor or nurse before starting treatment with Sodium Citrate Grifols 136 mmol/l.

• Sodium Citrate Grifols 136 mmol/l is not for direct intravenous infusion.
• The solution should only be administered if it is transparent and the seal is intact.

Your doctor will take into account the following:

• In donation apheresis, an excess of citrate may produce mild hypocalcaemia (low ionised calcium concentration in the blood), with mild symptoms of citrate toxicity. Your doctor may then slow down the blood flow, the rate of citrate infusion or the rate of reinfusion during the apheresis session. You may be given oral calcium supplements. The session should be suspended if more severe symptoms develop.
• In therapeutic apheresis, inadequate infusion of too large an amount of citrate causes acute hypocalcaemia (low ionised calcium concentration in the blood) and metabolic alkalosis (high bicarbonate concentration in the blood), and may expose you to neurological and cardiac complications. Your doctor may interrupt the citrate infusion and proceed to calcium infusion.
• Ensure that the anticoagulant effect is controlled during treatment and that any unexpected coagulation of the filter is detected.
• Your doctor will monitor, before and during treatment, how the blood flows through your blood vessels, fluid balance, glucose levels, electrolytes (a type of substances present in the blood) and acid/base balance (deviation in blood pH).
• Ensure that any reduced liver function, decreased oxygen in the blood or altered oxygen use in body tissues is known before starting treatment and treatment will be started with an adapted dose or another anticoagulation method, if necessary.
• Citrate metabolism (to bicarbonate) may be altered in patients with liver failure, leading to citrate accumulation. If this medicinal product is administered to patients with mild to moderate liver failure, it is essential to frequently monitor pH, electrolytes, total calcium/ionised calcium ratio and systemic ionised calcium to avoid electrolyte and/or acid-base imbalances. This medicinal product should not be used in patients with severe liver failure.
• If other solutions are used in regional citrate anticoagulation (RCA), imbalances may occur in your blood, such as metabolic acidosis (high acid concentration in the blood) and hyponatraemia (low sodium concentration in the blood). Your doctor will treat these imbalances with the appropriate protocol.
• Prolonged immobilised patients may suffer from unusual changes in body calcium levels, resulting in calcium loss in the bones. The calcium and other mineral status in the bones of immobilised patients for more than 2 weeks or those with progressively reduced calcium infusion rates should be closely monitored.
• Ensure that the anticoagulant effect is controlled in patients with suspected hypercoagulable state.
• Patient with known severe mitochondrial dysfunction (e.g. paracetamol and metformin intoxications) may be preferably treated with an alternative anticoagulant protocol to mitigate the risk of citrate accumulation.
• Ensure that any existing hypocalcaemia (low ionised calcium concentration in the blood) is treated before starting therapy.
• Citrate binds calcium and magnesium ions which, by subsequent elimination in the filter or in the centrifugation procedure, may cause hypocalcaemia (low ionised calcium concentration in the blood) and/or hypomagnesaemia (low magnesium concentration in the blood). Calcium supplementation to compensate for losses is usually a common practice and magnesium supplementation may also be necessary.
• Blood plasma-derived products containing citrate may increase the risk of citrate accumulation and overload.

Children

This medicinal product is not recommended in premature babies because there is not enough experience in this patient group.

Other medicines andSodium Citrate Grifols 136 mmol/l

Tell your doctor if you are using, have recently used or might use any other medicines.

The following interactions are possible with medicines that contain:

• calcium, which may increase the risk of hypercalcaemia (high ionised calcium concentration in the blood) and may reduce the anticoagulant effect of citrate.
• sodium-enriched products, which may increase the risk of hypernatraemia (high sodium concentration in the blood).
• sodium bicarbonate, which may increase the risk of high hydrogen carbonate concentration in the blood (metabolic alkalosis).
• haemoderivatives, which are another source of citrate, may increase the risk of high citrate concentration in the blood or high hydrogen carbonate concentration in the blood.

This medicinal product should not be mixed with other medicines, as there are not enough data on compatibility.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before using this medicine.

There are not enough clinical data on the use of Sodium Citrate Grifols 136 mmol/l in pregnant and breast-feeding women. Therefore, this medicinal product should only be used during pregnancy and breast-feeding if your doctor considers that the treatment is necessary.

There are no data on the effect of sodium and citrate on fertility, but no side effects are expected.

Driving and using machines

Not applicable.

3. How to use Sodium Citrate Grifols 136 mmol/l

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

This medicinal product should be used and handled under the supervision of qualified personnel in accordance with a pre-defined protocol as part of the automated apheresis procedure. For hospital use only.

Dose

This medicinal product is administered in healthcare facilities and is administered only by trained medical professionals.

Sodium Citrate Grifols 136 mmol/l solution should be prescribed and its administration (dose, infusion rate and accumulated volume) established only by expert physicians. In summary, Sodium Citrate Grifols 136 mmol/l is administered in a specific dose through the blood flow in the extracorporeal circuit (outside the body) to induce very low local ionised calcium levels, to dilute blood (regional citrate anticoagulation). The blood flow used and the dose of this medicinal product will depend on the patient's condition and treatment. You can find more information on dosing in the information for healthcare professionals below.

Use in children

Sodium Citrate Grifols 136 mmol/l is intended for the paediatric population only for therapeutic apheresis procedures. The equipment used must support treatment in children and low blood flows when neonatal application is desired. Your doctor will ensure that a low blood flow is selected in relation to your child's weight and will prescribe a reduced dose of Sodium Citrate Grifols 136 mmol/l accordingly. This medicinal product will be prescribed by your doctor only if your doctor has experience in renal replacement therapy or plasma exchange therapy prescribed in children.

Intensive monitoring is required to prevent the development of citrate overload and citrate accumulation in neonates and small children, and is recommended in children and adolescents.

If you are given more Sodium Citrate Grifols 136 mmol/l than you should

Since Sodium Citrate Grifols 136 mmol/l will only be administered to you by a doctor, it is unlikely that you will receive more or less than the required amount. However, if you think you have been given too much of this medicinal product, tell your doctor or nurse or call the Toxicology Information Service, telephone 91 562 04 20.

Signs of an overdose may be symptoms of low calcium levels (such as muscle cramps and spasms, and abnormal or irregular heartbeats) and symptoms of changes in acid/base balance and sodium balance (such as confusion, dizziness, headache, vomiting).

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

If you have any further questions on the use of this medicinal product, ask your doctor or nurse.

4. Possible side effects

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

In therapeutic apheresis,the following side effects are the most common:

• imbalances in electrolyte levels in the blood (low calcium level in blood, high sodium level in blood)
• disorders in the acid/base state of the blood (blood pH too high or too low)
• very low calcium level in the blood
• paraesthesia (tingling or burning sensation that is usually felt in the hands, arms, legs or feet, but can also occur in other parts of the body)
• oral hypoesthesia (reduced sensitivity or numbness in the oral cavity)
• anaesthesia (loss of sensation)
• low blood pressure

In therapeutic apheresis, the following side effects may occur (the exact frequency is unknown):

• flushing
• allergic reactions
• severe disorders in the acid/base state of the blood (blood pH too high)
• imbalances in electrolyte levels in the blood (low magnesium level in blood, low phosphate level in blood)
• high lactate level in the blood
• headache
• muscle spasms

Patient who receive blood components containing citrate have a higher risk of both citrate accumulation and citrate overload and, therefore, a higher risk of related side effects (hypocalcaemia, metabolic acidosis, metabolic alkalosis).

In donation apheresis,the following side effects are the most common:

• low blood pressure

In donation apheresis, the following side effects are less common:

• thrombosis (formation of a blood clot in a blood vessel)
• infection
• arrhythmia

In donation apheresis, the following side effects may occur (the exact frequency is unknown):

• paraesthesia (tingling or burning sensation that is usually felt in the hands, arms, legs or feet, but can also occur in other parts of the body)
• oral hypoesthesia (reduced sensitivity or numbness in the oral cavity)
• convulsion
• tetany (involuntary muscle contractions or spasms)
• nausea
• vomiting

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. You can also report side effects directly to the Spanish Medicines Monitoring Centre at www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicinal product.

5. Storage of Sodium Citrate Grifols 136 mmol/l

Keep this medicinal product out of the sight and reach of children.

Do not use this medicinal product after the expiry date which is stated on the carton. The expiry date is the last day of the month stated.

This medicinal product does not require any special storage conditions. Do not freeze.

Use the solution immediately once the container is opened.

Do not use this medicinal product if the solution is cloudy or if the container is damaged.

The solution is for single use only. Discard any unused portion.

6. Container Contents and Additional Information

Composition of Sodium Citrate Grifols136 mmol/l

The active ingredient is sodium citrate. Each 1000 ml of solution contains 40 g of sodium citrate corresponding to 408 mmol of sodium and 136 mmol of citrate.

The other components (excipients) are water for injectable preparations and citric acid monohydrate.

Appearance of the Product and Container Contents

Sodium Citrate Grifols 136 mmol/l is presented in a bag with 250 ml of solution. The solution is transparent and colorless.

This medication is supplied in flexible polypropylene bags of 250 ml (in boxes containing 30 bags) in two distinct presentations:

• Flexible polypropylene bag with a tube closed by a twist-off port.
• Flexible polypropylene bag with a tube closed by a correct connect port.

Only some package sizes may be marketed.

Marketing Authorization Holder

Grifols Laboratories, S.A.

Can Guasch, 2

08150 Parets del Vallès, Barcelona (SPAIN)

Manufacturer

LABORATORIOS GRIFOLS, S.A.

Polígono Autopista. Passeig Fluvial, 24

08150 Parets del Vallès, Barcelona (SPAIN)

This medication is authorized in the Member States of the European Economic Area under the following names:

Date of the Last Revision of this Prospectus:February 2025

Other Sources of Information

Detailed information about this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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This information is intended only for healthcare professionals:

1000 ml of solution contains:

Sodium citrate 40.0 g

Na+ 408 mmol

Citrate3- 136 mmol

Theoretical osmolality 544 mOsm/l

pH: 6.4-7.5

Posology

In general, in centrifugal apheresis and membrane filtration apheresis, the infusion rate of Sodium Citrate Grifols 136 mmol/l in the inlet line of the apheresis circuit should be assessed proportionally to the blood flow of the extracorporeal circuit to achieve sufficient suppression of ionized calcium in the blood within the circuit. In general, a concentration of ionized calcium of the order of 0.25 to 0.35 mmol/l should be achieved in the extracorporeal circuit, which is usually achieved with a dosage of 3-4 mmol of citrate per liter of treated blood.

• Donation apheresis

The dose of Sodium Citrate Grifols 136 mmol/l to be administered depends on the total blood volume of the donor and the parameters of the procedure configured in the apheresis circuit. Infusion rates of up to 1.1 mg/kg/min of citrate have been described as safe in apheresis procedures lasting up to 90 minutes.

After the initiation phase, donors should be monitored to detect early signs of citrate toxicity, including tingling in the fingers and around the mouth, chills, hot flashes, abdominal cramps, headaches, nervousness, irritability, dizziness, chest discomfort, nausea, and vomiting. Reducing the total blood processing rate, inlet pump rate, citrate infusion rate, or reinfusion rate during the apheresis session has immediate effects and is often sufficient to mitigate mild symptoms. Oral calcium supplements have been shown to be effective in treating mild symptomatic hypocalcemia. If more severe symptoms develop, the procedure should be discontinued.

• Therapeutic apheresis

After the initiation phase, regular monitoring of systemic and total blood calcium levels should be performed in the return line. The systemic calcium concentration should be maintained within the normal physiological range, which usually requires the administration of calcium supplements. Adjust or discontinue calcium supplementation as medically prescribed when anticoagulation is interrupted.

The application volume in adult patients should not exceed 10.4 liters/day. The extracorporeal blood flow should be sufficient to achieve the objectives of therapy but kept low enough to avoid unnecessary infusion of citrate and promote citrate elimination within the applied filter. In renal replacement therapy and plasma exchange, the composition and volumes applied of other solutions should be considered with the prescription of Sodium Citrate Grifols 136 mmol/l. More recommendations and posological limitations apply when using other solutions in therapeutic apheresis, for use in special populations, patients with altered citrate metabolism, as well as in geriatric and pediatric populations. For more information, consult the Technical Data Sheet or Summary of Product Characteristics.

The solution is for single use. Discard any unused portion.

Do not use if the solution is turbid or if leaks are detected.

Do not remove the overbag until use. The primary bag maintains the product's sterility.

Use aseptic methodology. Once the protective bag is opened, the solution must be used immediately to avoid microbiological contamination.

Extracorporeal use. For perfusion in extracorporeal blood circuit only.

Follow these instructions for use:

For solution bags equipped with a twist-off port:

1. Inspect the product container.
2. Peel off the corner of the protective bag to open it and remove the container.
3. Inspect the container once the protective bag is removed to detect damage or leaks. Do not use the solution bag if there are leaks or if the access port or hanger is damaged/loose.
4. Inspect the solution.
5. Verify that the product's expiration date has not been exceeded.
6. Place the bag in the specific accessory for its hole to hang.
7. Open the access port of the bag by breaking it.

1. Connect the bag aseptically to the anticoagulant line of the apheresis set. Insert the tube's spike of the apheresis set completely through the port until it stops. To insert the spike, make a rotational movement for better ergonomics.

1. Once inserted, do not move the spike back and forth.
2. Carry out the apheresis procedure according to the detailed instructions of the apheresis machine manufacturer.

For solution bags equipped with a correct connect port:

1. Inspect the product container.
2. Peel off the corner of the protective bag to open it and remove the container.
3. Inspect the container once the protective bag is removed to detect damage or leaks. Do not use the solution bag if there are leaks or if the access port or hanger is damaged/loose.
4. Inspect the solution.
5. Verify that the product's expiration date has not been exceeded.
6. Place the bag in the specific accessory for its hole to hang.
7. Unscrew the cap of the port (a) and connect directly to the apheresis kit used (b) through the connector (see figure 1).
8. Break the breakable valve by making a 90° movement in both directions until a "click" is heard. Then, bend the tube in both directions (see figure 2) to slide the separable part of the breakable piece inside the flexible tube, separating it from the connector to ensure correct flow (see figure 3).

1. Carry out the apheresis procedure according to the detailed instructions of the apheresis machine manufacturer.

Any unused medication or waste material must be disposed of in accordance with local regulations.