FREEFLEX GLUCOSA 10% SOLUTION FOR INFUSION

2. What you need to know before you use Freeflex Glucose 10%

Do not use Freeflex Glucose 10%

• If you are allergic to the active substance or to any of the other components of this medicine (listed in section 6).
• In states of hyperglycemia (high blood glucose levels).
• In states of hyperhydration (excess water in the body), or edema due to fluid accumulation in tissues.
• If you have severe renal failure (severe kidney dysfunction) or anuria (absence of urine production).
• In case of electrolyte depletion (loss of salts).
• If you have hyperlactatemia (presence of lactic acid in the blood).
• If you suffer from significant glucose tolerance alterations, including hyperosmolar conditions.
• In case of hypotonic dehydration (with salt loss), if electrolytes are not administered simultaneously.
• If you have untreated diabetes.
• During the first 24 hours after a head injury.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Freeflex Glucose 10%.

• Blood glucose levels should be carefully monitored during episodes of intracranial hypertension.
• In case of having suffered acute ischemic attacks (decreased or absent circulation in arteries), since hyperglycemia has been related to an increase in cerebral ischemic damage and difficulty in recovery.
• In case of shock and acid-base balance disorders, electrolytes should be administered according to individual requirements before starting the administration of glucose solutions. In case of sodium deficit, the administration of sodium-free solutions may cause peripheral circulatory collapse and decreased urine output.
• It is recommended that regular controls of serum electrolytes and water balance be performed, as frequent and massive administration of parenteral glucose solutions can cause significant ionic depletions. In this case, it will be necessary to administer electrolyte supplements.
• To avoid hypokalemia (decreased potassium in the blood) produced during prolonged parenteral nutrition with glucose, potassium may be added to the glucose solution as a safety measure.
• The possibility of hyperhydration can be avoided by maintaining a total balance of the fluid incorporated and lost.
• It is recommended that regular controls of blood glucose levels be performed, especially if you are diabetic. In this case, it may be necessary to modify insulin requirements. Similarly, these solutions should be used with caution if you have Addison's disease or carbohydrate intolerance.
• If you have malnutrition, as you may have a vitamin B1 deficiency. This vitamin is essential for glucose metabolism, so if necessary, this deficiency should be corrected first.
• If the 10% glucose solution is administered via peripheral vein, continuous administration at the same injection site should be avoided due to the risk of thrombophlebitis (inflammation of a vein associated with clot formation).
• Special attention should be paid if used in elderly patients, as they may have affected liver and/or kidney function.
• In prolonged treatments, insulin production may be reduced.
• If you suffer from critical conditions, pain, postoperative stress, infections, burns, or central nervous system diseases.
• You have any type of heart, liver, or kidney disease and are being treated with a medication that increases the effect of vasopressin (a hormone that regulates water retention in the body) because it may increase the risk of acquiring low sodium levels in the blood (hyponatremia) in the hospital (see section "Other medicines and Freeflex Glucose 10%").

All patients should be closely monitored. In cases where normal regulation of blood water content is altered due to increased vasopressin secretion, also known as Antidiuretic Hormone (ADH), perfusion of fluids with low sodium chloride concentration (hypotonic fluids) may result in low sodium levels in the blood (hyponatremia). This can cause headache, nausea, seizures, lethargy, coma, brain swelling (cerebral edema), and death; therefore, these symptoms (acute symptomatic hyponatremic encephalopathy) are considered a medical emergency. (See section 4, Possible side effects)

Children, women of childbearing age, and patients with brain diseases such as meningitis, cerebral hemorrhage, brain contusion, and cerebral edema have a special risk of suffering from severe and potentially fatal brain inflammation caused by acute hyponatremia.

Other medicines and Freeflex Glucose 10%

Use of Freeflex Glucose 10% with other medicines. Inform your doctor or pharmacist if you are using, have recently used, or may need to use any other medicine.

Certain medicines may interact with Freeflex Glucose 10%. In this case, it may be necessary to change the dose or interrupt treatment with one of the medicines.

It is important that you inform your doctor if you are using any of the following medicines:

- Insulin or oral antidiabetics (biguanides, sulfonylureas), as intravenous glucose administration in patients treated with these medicines may lead to a reduction in their therapeutic efficacy (antagonistic action).

- Corticosteroids: Intravenous glucose administration in patients treated with systemic corticosteroids with glucocorticoid activity (cortisol) may lead to a significant increase in plasma glucose levels due to the hyperglycemic action of these medicines. As for corticosteroids with mineralocorticoid activity, they should be administered with caution due to their ability to retain water and sodium.

- Digitalis glycosides (digoxin), as when intravenous glucose administration coincides with therapy with these medicines, an increase in digitalis activity may occur, with the risk of developing intoxication with these medicines. This is due to the hypokalemia that can be caused by glucose administration if potassium is not added to the solution.

Solutions of glucose free of electrolytes should not be administered with the same infusion equipment, simultaneously, before, or after the administration of blood, due to the possibility of pseudoagglutination.

Medicines that potentiate the effect of vasopressin

The following medicines increase the effect of vasopressin, which reduces renal excretion of water without electrolytes and increases the risk of hospital hyponatremia after inadequately balanced treatment with intravenous infusion solutions.

• Medicines that stimulate the release of vasopressin; e.g.,

chlorpropamide, clofibrate, carbamazepine, vincristine, selective serotonin reuptake inhibitors, 3,4-methylenedioxymethamphetamine, ifosfamide, antipsychotics, narcotics.

• Medicines that potentiate the action of vasopressin; e.g.,

chlorpropamide, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclophosphamide.

• Vasopressin analogs; e.g.,

desmopressin, oxytocin, vasopressin, terlipressin.

Other medicines that are known to increase the risk of hyponatremia are also diuretics in general and antiepileptics such as oxcarbazepine.

Pregnancy, breastfeeding, and fertility

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

Freeflex Glucose 10% should be administered with special caution in pregnant women during labor, especially if administered in combination with oxytocin, due to the risk of hyponatremia (see section 4).

In case of pregnancy, your doctor will decide the convenience of using a 10% glucose solution, as it should be used with caution in this case.

Excessive glucose administration during pregnancy may cause hyperglycemia (high blood glucose levels), hyperinsulinemia (high insulin levels in the blood), and fetal acidosis (increased acidity of fetal blood), and may be harmful to the newborn.

There is no evidence to suggest that Freeflex Glucose 10% solution may cause adverse effects during the breastfeeding period in the neonate. However, it is recommended to use with caution during this period.

Driving and using machines

There is no indication that Freeflex Glucose 10% solution may affect the ability to drive or use machines.

3. How to use Freeflex Glucose 10%

Follow exactly the administration instructions of this medicine indicated by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again.

Freeflex Glucose 10% comes in the form of a solution and will be administered to you in the hospital by the corresponding healthcare personnel.

Freeflex Glucose 10% is administered intravenously by infusion.

Your doctor will indicate the duration of your treatment with Freeflex Glucose 10%. The dose may vary according to medical criteria, depending on age, weight, clinical condition, fluid balance, electrolytes, and acid-base balance of the patient.

When used as a vehicle for the administration of other medicines, the volume will depend on the medicines administered.

For the rest of the indications and unless otherwise indicated by the doctor, the recommended dose is as follows:

Maximum daily dose

Adults

Maximum daily dose of 20 ml/kg body weight/day (equivalent to 2.0 g glucose/kg body weight/day), which should only be exceeded in exceptional cases up to 6.0 g/kg body weight/day.

Maximum infusion rate

2.5 ml/kg body weight/hour (equivalent to 0.25 g glucose/kg body weight/hour).

Due to the maximum metabolic oxidation rate of the body, carbohydrate intake should be restricted to 300-400 g/day under normal metabolic conditions.

In case of metabolic failure, for example, during post-stress metabolism, hypoxic conditions (lack of oxygen), or organ failure, the daily dose should be reduced to 200-300 g glucose (equivalent to 3 g/kg body weight per day) to avoid high blood sugar levels (hyperglycemia), insulin resistance, and morbidity. Adequate monitoring is required for personalized dose adaptation.

Use in children

Newborns and premature infants

The maximum glucose dose in premature infants should be 11.5 g per kg body weight on the first day of life. From the second day of life, the maximum daily glucose dose should not exceed 17.3 g per kg body weight. In newborns, the maximum glucose dose should be 7.2 g per kg body weight on the first day of life. From the second day of life, the maximum daily glucose dose should not exceed 17.3 g per kg body weight.

Infants and children

The maximum glucose dose depends on the body weight of the infants/children and the phase of the critical illness, which can be divided into acute, stable, and recovery phases. The acute phase is defined as the resuscitation phase when the patient requires vital organ support (sedation, mechanical ventilation, vasopressors, fluid resuscitation). The stable phase is defined as a stable or independent patient. The recovery phase is defined as a patient who is being mobilized. The maximum daily glucose doses in g per kg body weight per day are listed in the following table according to the phase of the illness:

Recommended maximum daily dose of glucose

Blood glucose level control is recommended during the administration of carbohydrate solutions.

To prevent overdose, the use of infusion pumps is recommended, especially for the infusion of high-concentration glucose solutions.

Method of administration

Peripheral infusion (administration through a small vein) or central intravenous infusion (administration through a large vein).

If you use more Freeflex Glucose 10% than you should

Given the nature of the product, if its indication and administration are correct and controlled, there is no risk of intoxication.

If the administration of the solution is not performed correctly and under control, some of the following signs of overdose may appear: hyperglycemia, glucosuria, fatty liver, hyperhydration, or electrolyte disorders. In these cases, administration will be discontinued, and symptomatic treatment will be initiated. In the event of increased glycemia, insulin will be administered.

In case of presenting capillary blood glucose values above 200 mg/dl, insulin administration will be resorted to. Similarly, in cases where glucose administration is used as a non-protein energy source in parenteral nutrition, the composition of the nutrition mixture should be modified (increasing lipid intake and reducing glucose intake).

In case of overdose or accidental ingestion, consult the Toxicology Information Service. Phone: 915 620 420.

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

4. Possible Adverse Effects

Like all medications, Freeflex Glucose 10% can produce adverse effects, although not all people suffer from them.

If the administration of the solution is carried out correctly and controlled, the possible complications are those derived from the intravenous administration technique.

If administration is carried out through a central vein, the main complications will be due to the implantation and maintenance of the catheter or complications due to infections.

If administration is carried out through a peripheral vein, there is a risk of suffering from thrombophlebitis (inflammation of a vein associated with the formation of a clot), especially when administration is prolonged. In these cases, it is recommended to vary the insertion site of the catheter periodically (24-48 hours).

Hyperglycemia, glucosuria (glucose in urine), or alterations in fluid or electrolyte balance may occur if the solution is administered too quickly or if the fluid volume is excessive, or in cases of metabolic insufficiency.

The hyperglycemia resulting from rapid perfusion or excessive volume should be closely monitored in severe cases of diabetes mellitus, and can be avoided by decreasing the dose and perfusion rate or by administering insulin.

The following adverse reactions have been described:

Metabolic and nutritional disorders:

• Hyperglycemia
• Electrolyte imbalance
• Fluid imbalance

General disorders and administration site conditions:

• Edema at the perfusion site
• Pyrexia
• Extravasation at the injection site
• Infection at the injection site
• Reaction at the injection site
• Pain at the injection site

Renal and urinary disorders:

• Glucosuria

Vascular disorders:

• Thrombophlebitis

If used as a vehicle for the administration of other medications, the nature of the added medications will determine the likelihood of other adverse reactions.

Hyponatremia:

Headache, nausea, convulsions, lethargy. This can be caused by a low level of sodium in the blood. When blood sodium levels drop significantly, water enters the brain cells and causes them to swell. This results in increased cranial pressure and causes hyponatremic encephalopathy.

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Freeflex Glucose 10%

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Medications should not be thrown away through drains or trash. Ask your pharmacist how to dispose of packaging and medications that are no longer needed. This will help protect the environment.

No special storage conditions are required.

6. Package Contents and Additional Information

Composition of Freeflex Glucose 10%

• The active ingredient is glucose. Each 100 ml of solution contains 10 g of anhydrous glucose (equivalent to 11 g of glucose monohydrate).
• The other components are water for injectable preparations and hydrochloric acid and sodium hydroxide (for pH adjustment).

Appearance of the Product and Package Contents

Freeflex Glucose 10% is a transparent solution packaged in a sealed plastic bag, known as a Freeflex bag. It is available in the following package sizes:

1 bag of 500 ml

1 bag of 1000 ml

20 bags of 500 ml

10 bags of 1000 ml

Not all package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Fresenius Kabi España S.A.U.

Torre Mapfre-Vila Olímpica

C/ Marina 16-18

08005-Barcelona (Spain)

Manufacturer

Fresenius Kabi España S.A.U.

Dr. Ferran, 4

Vilassar de Dalt

08339 Spain

Date of Last Revision of this Prospectus:March 2021.

Detailed and updated information on 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 doctors or healthcare professionals

Freeflex Glucose 10% will be administered by perfusion, through a central or peripheral vein.

Healthcare personnel must ensure the proper placement of the needle in the vein, as this is a hypertonic solution, and its extravasation produces significant tissue irritation.

The contents of each Freeflex Glucose 10% bag are for single perfusion.

Once the packaging is opened, the solution must be administered immediately. The unused fraction must be discarded.

The solution must be transparent and not contain precipitates. Do not administer if this is not the case.

When administering the solution and in the case of preparing mixtures or adding medications, maximum asepsis must be maintained.

Within the framework of parenteral nutrition, Freeflex Glucose 10% can be administered with other nutritional preparations together in a single bag or separately.

However, before making mixtures for parenteral nutrition or adding medications to the solution or administering them simultaneously with other medications, it must be checked that there are no incompatibilities.

Various studies have described signs of incompatibility for 10% glucose solutions with: sodium ampicillin, disodium calcium edetate, alpha-erythropoietin, erythromycin lactobionate, sodium heparin, imipenem-cilastatin sodium, indomethacin sodium, meropenem, and sodium thiopental.

However, some of these medications may be compatible with this perfusion solution depending on different factors such as the pH of the solution (as is the case with sodium heparin and erythromycin lactobionate), the concentration of the medication in the solution (sodium heparin), or the time period between dissolution and administration (imipenem-cilastatin sodium, meropenem).

Similarly, samples of incompatibility have been observed when certain medications are diluted in solutions containing glucose, including: amrinone lactate, cisplatin, interferon alpha-2b, procainamide hydrochloride, amoxicillin sodium/clavulanic acid, teicoplanin, bleomycin sulfate, cladribine, melphalan hydrochloride, phenytoin sodium, mecloretamine hydrochloride, mitomycin, amoxicillin sodium, rifampicin, trimethoprim-sulfamethoxazole. However, it should be noted that some of these medications, such as amrinone lactate or amoxicillin sodium/clavulanic acid, can be injected directly into the injection site while these perfusion solutions are being administered.

Glucose solutions without electrolytes should not be administered with the same perfusion equipment, simultaneously, before, or after the administration of blood, due to the possibility of pseudoagglutination.

General Advice

It may be necessary to monitor fluid balance, serum glucose, serum sodium, and other electrolytes before and during administration, especially in patients with increased non-osmotic release of vasopressin (syndrome of inappropriate secretion of antidiuretic hormone, SIADH) and in patients receiving concomitant medication with vasopressin agonists due to the risk of hyponatremia.

Monitoring of serum sodium is especially important when administering physiologically hypotonic solutions. Freeflex Glucose 10% can become extremely hypotonic after administration due to the metabolism of glucose in the body (see sections 2 and 4).

INSTRUCTIONS FOR THE CORRECT ADMINISTRATION OF THE MEDICATION

Visual Inspection

1. Do not remove the freeflex from its overbag until immediately before use.
2. Check the composition, batch number, and expiration date.
3. Inspect the assembly by checking the integrity of the primary packaging. Do not use if this packaging is not intact.

Removal of the Overbag

Some freeflex bags have an overbag as protection during storage. The overbag, with a "peel" opening system, can be removed as follows:

1. Locate the tabs at the end where the ports of the bag are.
2. Separate the two halves of the overbag, leaving the bag on a clean surface.

Preparation for Administration

The freeflex bags are designed for air-free administration. If a perfusion equipment with air entry is to be used, ensure that it is always closed.

1. Squeeze the freeflex to ensure it has no leaks and examine the solution to observe the presence of visible particles or precipitates. DO NOT ADMINISTER IF THE SOLUTION IS NOT TRANSPARENT AND/OR THE BAG IS NOT INTACT.
2. Using an aseptic technique, prepare the perfusion equipment with the flow regulator closed.
3. Identify the administration port (blue) in the shape of an arrow indicating the exit of the bag.
4. Remove the protective cap from the administration port of the freeflex, holding the lower fins firmly with one hand and breaking the cap in the shape of an arrow by means of a sustained twisting action.
5. Hold the base of the administration port, placing the fingers behind the protector, and push the perfusion equipment's spike firmly into the port. A slight resistance should be felt when the port membrane breaks. To prevent leaks, insert the spike to the bottom of the administration port.
6. Hang the bag on the hanger and purge the administration equipment according to the manufacturer's instructions. Perform the venipuncture and immediately connect the administration equipment to the intravenous cannula. Adjust the flow regulator to achieve the desired drip rate.
7. The freeflex bags are calibrated to indicate the approximate volume that has been perfused. The scale should be read by stretching the bag and reading the volume on the upper surface of the liquid. For a more exact measurement of the fluid volume, a perfusion equipment with a measuring chamber should be used.

To Add Medication

The freeflex bags have an independent medication addition port with a self-closing cap. Since the port is protected by a hermetically sealed cap, it is not necessary to disinfect the medication addition site before its first use.

Additions Using Syringes

1. Identify the medication addition port (white) in the shape of an arrow indicating an entry flow into the bag.
2. Using an aseptic technique, prepare a syringe with the medication, using a 20-22 G needle.
3. Remove the protective cap from the medication addition port of the bag, holding the lower fins firmly with one hand and breaking the cap in the shape of an arrow by means of a sustained twisting action.

1. Hold the medication addition port, placing the fingers behind the protector, and insert the needle completely so that it perforates the outer cap and the inner membrane. Its rigid construction prevents any possibility of the needle penetrating the sides of the port.
2. Add the medication and withdraw the needle. To prevent any aerosol formation, a sterile swab should be kept around the cap.

The following maximum addition volumes are recommended:

NOTE: Additives may be incompatible, so expert advice should be sought before adding medication to freeflex.If the doctor decides to add medication, an aseptic technique should be used. It is recommended that the medication be added only under the supervision of a pharmacist. Do not store solutions to which medication has been added.

1. Shake and squeeze the freeflex to ensure a complete mix of the medication. With dense medications such as potassium chloride, it is advisable to squeeze both ports while the bag is in a vertical position and invert the bag several times.
2. If necessary, a protective cap can be placed over the medication addition port to prevent subsequent additions.

Additions Using Reconstitution Equipment

1. Identify the medication addition port (white) in the shape of an arrow indicating an entry flow into the bag.
2. Remove the protective cap from the medication addition port of the bag, holding the lower fins firmly with one hand and breaking the cap in the shape of an arrow by means of a sustained twisting action.
3. Using an aseptic technique, remove the reconstitution equipment from its packaging and push the narrow end over the medication addition port of the bag so that the port fins fit with the equipment's grooves. Stop when the upper surface of the fins reaches the first stop of the groove. In this position, the upper part of the equipment's needle is between the cap and the inner membrane, so that no fluid can escape from the freeflex.
4. Using an aseptic technique, prepare the medication vial and connect it to the open end of the reconstitution equipment.
5. Connect the medication to the intravenous solution by turning the reconstitution equipment so that the port fins fit with the inner groove and pushing the vial and the reconstitution equipment until the upper surface of the fins reaches the second stop.
6. With the vial inverted, squeeze and release the freeflex several times to transfer solution to the medication vial. Shake to dissolve the medication. Note: If the medication is a liquid, this step 6 can be omitted.
7. Invert the freeflex so that the vial is above the bag and transfer the medication to the bag by squeezing and releasing the bag several times so that the sterile air pushes the liquid out of the vial.
8. If the solubility of the medication is low, it may be necessary to repeat steps 6 and 7.
9. When the transfer is complete, remove the reconstitution equipment from the freeflex and discard the vial and the reconstitution equipment in a safe place. The reconstitution equipment is designed for single use and should not be used for subsequent additions to this or another freeflex.

NOTE: Additives may be incompatible, so expert advice should be sought before adding medication to freeflex.If the doctor decides to add medication, an aseptic technique should be used. It is recommended that the medication be added only under the supervision of a pharmacist. Do not store solutions to which medication has been added.

1. Shake and squeeze the freeflex to ensure a complete mix of the medication. With dense medications such as potassium chloride, it is advisable to squeeze both ports while the bag is in a vertical position and invert the bag several times.
2. If necessary, a protective cap can be placed over the medication addition port to prevent subsequent additions.

Warnings:

1. Do not vent
2. Do not administer if the solution is not transparent and the freeflex is not intact
3. If adverse reactions appear, stop the perfusion
4. It is recommended that perfusion equipment be changed at least every 24 hours

Partially used freeflex bags must be discarded