KABIPAC GLUCOSE 10% SOLUTION FOR INFUSION

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

Do not use KabiPac 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 hyperglycemia states (high blood glucose levels).
• In hyperhydration states (excess water in the body), or edema due to fluid accumulation in tissues.
• If you have severe renal insufficiency (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 coma.
• In case of hypotonic dehydration (with salt loss), if not administered simultaneously with electrolytes.
• If you have untreated diabetes.
• Within the first 24 hours after a head injury.

Warnings and precautions

Consult your doctor or pharmacist before starting to use KabiPac 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 ischemic brain 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 checks 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 checks 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 KabiPac 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 KabiPac Glucose 10%

Use of KabiPac 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 KabiPac 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 administration of glucose in patients treated with these medicines may lead to a reduction in their therapeutic efficacy (antagonistic action).

- Corticosteroids: Intravenous administration of glucose 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 administration of glucose 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 hypokalemia that may be caused by glucose administration if potassium is not added to the solution.

Electrolyte-free glucose solutions should not be administered with the same infusion equipment, simultaneously, before, or after blood administration, 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-methylenedioxy-N-methamphetamine, ifosfamide, antipsychotics, narcotics.

• Medicines that potentiate the action of vasopressin; e.g., chlorpropamide, 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 plan to become pregnant, consult your doctor or pharmacist before using this medicine.

KabiPac 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 glucose 10%, as it should be used with caution in this case.

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

There is no evidence to suggest that KabiPac 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 KabiPac Glucose 10% solution may affect the ability to drive or use machines.

3. How to use KabiPac Glucose 10%

Follow exactly the administration instructions of this medicine indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

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

KabiPac Glucose 10% is administered intravenously by infusion.

Your doctor will indicate the duration of your treatment with KabiPac 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 the doctor indicates otherwise, 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 of glucose/kg body weight/day) that 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 of 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 insufficiency, for example, during post-stress metabolism, hypoxia conditions (lack of oxygen), or organ failure, the daily dose should be reduced to 200-300 g of 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 dose of glucose in premature infants should be 11.5 g per kg of body weight on the first day of life. From the second day of life, the maximum daily dose of glucose should not exceed 17.3 g per kg of body weight. In newborns, the maximum dose of glucose should be 7.2 g per kg of body weight on the first day of life. From the second day of life, the maximum daily dose of glucose should not exceed 17.3 g per kg of body weight.

Infants and children

The maximum dose of glucose depends on the body weight of the infant/child 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 doses of glucose in g per kg of body weight per day are listed in the following table according to the phase of the illness:

Recommended maximum daily dose of glucose

Monitoring of blood glucose levels 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 KabiPac 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 suspended, and symptomatic treatment will be performed. In the event of increased glycemia, insulin will be administered.

In case of presenting capillary 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 other questions about the use of this product, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, KabiPac Glucose 10% can cause 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 technique of intravenous administration.

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 place of insertion of the catheter periodically (24-48 hours).

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

The hypoglycemia resulting from rapid perfusion or excessive volume should be especially 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 medicines, the nature of the added medicines will determine the probability 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 an increase in 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 does not appear 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 medicine.

5. Conservation of KabiPac Glucose 10%

Keep this medicine out of sight and reach of children.

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

Medicines should not be thrown away through drains or into the trash. Ask your pharmacist how to dispose of packaging and medicines 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 KabiPac Glucose 10%

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

Appearance of the Product and Package Contents

KabiPac Glucose 10% is a transparent solution packaged in a closed polyethylene vial. It is available in package sizes of 250, 500, and 1000 ml.

Clinical packaging is also available in the following presentations:

20 vials with 250 ml

10 vials with 500 ml

20 vials with 500 ml

10 vials with 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

Labesfal – Laboratórios Almiro, S.A

Zona Industrial do Lagedo

3465-157 Santiago de Besteiros

Portugal

or

Fresenius Kabi España, S.A.U.

C/ Dr. Ferran, 12

Vilassar de Dalt (Barcelona)

08339 - Spain

Date of the Last Revision of this Prospectus:March 2021.

Detailed and updated information on this medicine 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

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

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

The contents of each vial of KabiPac Glucose 10% are for a single perfusion.

Once the package 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 otherwise.

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

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

However, before making mixtures for parenteral nutrition or adding medicines to the solution or administering them simultaneously with other medicines, 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, α-erythropoietin, erythromycin lactobionate, sodium heparin, imipenem-cilastatin sodium, indomethacin sodium, meropenem, and sodium thiopental.

However, some of these medicines 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 medicine in the solution (sodium heparin), or the period of time that elapses between dissolution and administration (imipenem-cilastatin sodium, meropenem).

Similarly, samples of incompatibility have been observed when some medicines are diluted in solutions that contain 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 medicines, such as amrinone lactate or amoxicillin sodium/clavulanic acid, can be injected directly into the injection point while these perfusion solutions are being administered.

Glucose solutions free of 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 release of non-osmotic vasopressin (inappropriate antidiuretic hormone secretion syndrome, 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. KabiPac Glucose 10% can become extremely hypotonic after administration due to the metabolism of glucose in the body (see sections 2 and 4).