Product Information: information for the user

Apiroserum Normaion Restaurador solution for perfusion

Active ingredients: sodium chloride, potassium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate, sodium acetate trihydrate, sodium citrate dihydrate, glucose monohydrate

Read this entire prospectus carefully before starting to use this medication because it contains important information for you.

• Keep this prospectus, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you and should not be given to other people, even if they present the same symptoms of the disease, as it may harm them.
• If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they do not appear in this prospectus. See section 4.

1.What isApiroserum Normaion Restauradorand what it is used for

2.What you need to know before starting to useApiroserum Normaion Restaurador

3.How to useApiroserum Normaion Restaurador

4.Possible adverse effects

5.Storage ofApiroserum Normaion Restaurador

6.Contents of the package and additional information

Apiroserum Normaion Restaurador is a polielectrolyte solution, with a content of chloride and sodium ions very similar to that of extracellular fluid. It also contains potassium ions and sodium acetate and trisodium citrate, precursors of bicarbonate, which confer an alkalizing effect.

Therefore, Apiroserum Normaion Restaurador is indicated in the treatment of moderate electrolyte losses and with a tendency to acidosis, whereas it is contraindicated when it comes to repairing predominant water losses, since its osmolarity does not yield water.

Apiroserum Normaion Restaurador is indicated in extracellular hydroelectrolyte disorders produced by:

• Fluid loss in surgical patients. Deficit of fluid in the extracellular space in the pre and postoperative period. Intestinal obstruction. Inflammation of the peritoneum (peritonitis). Intestinal, biliary, and pancreatic fistulas. Gastric or intestinal fluid aspiration (endodigestive). Blood loss (hemorrhages). Extensive burns. Postoperative collapse. Shock.
• Digestive losses. Diarrhea and vomiting. Digestive system disorders (gastrointestinal) in infants (gastroenteritis, enteric colitis, etc.). Nausea and vomiting during pregnancy (hyperemesis gravidarum).
• Metabolic losses. Diabetic acidosis.
• Skin losses. Abundant sweating in case of infectious and febrile diseases.

No use Apiroserum Normaion Restaurador

• If you are allergic to the active ingredients or any of the other components of this medication (listed in section 6)
• If you have hyperkalemia (excess of potassium in the blood)
• If you have fluid overload (hyperhydration), such as in cases of edema (fluid retention), pulmonary edema, congestive heart failure (or other types of cardiac decompensation) and ascitic cirrhosis
• If you have renal insufficiency (kidney failure)
• If you have severe liver disease
• If you have hypertension (high blood pressure)
• If you have significant extracellular fluid loss with important water loss
• If you have metabolic alkalosis
• If you have hypernatremia (excess of sodium)
• If you have hypercalcemia (excess of calcium)
• If you have hypermagnesemia (excess of magnesium)
• If you have hyperchloremia (excess of chloride)
• If you have hyperglycemia (excess of glucose)
• During the first 24 hours after a head trauma

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting to use Apiroserum Normaion Restaurador.

Be especially careful with Apiroserum Normaion Restaurador:

- If you have kidney, heart or lung impairment. In these cases, the administration of large volumes of this solution should be carried out under strict medical control.

- If you have hypertension (high blood pressure), heart failure (the heart does not function well), peripheral or pulmonary edema (fluid retention in general or in the lungs), preeclampsia, aldosteronism or have impaired renal function or other conditions associated with sodium retention. In these situations, the administration of the solution should be carried out with caution since it contains sodium chloride.

- If you have heart disease or conditions that predispose to hyperkalemia (excess of potassium), such as renal insufficiency or adrenocortical insufficiency, acute dehydration or massive tissue destruction, such as in severe burns. In these situations, the administration of the solution should be carried out with caution since it contains potassium salts.

- It is recommended that regular clinical and analytical controls (blood and urine electrolytes, acid-base balance, hematocrit) be performed during the administration of this solution. Particular attention should be paid to potassium serum controls if you are at risk of developing hyperkalemia (excess of potassium).

- If you have severe potassium deficiency. Although the Apiroserum Normaion Restaurador solution has a potassium concentration similar to that of plasma, it is insufficient to produce a beneficial effect in these situations.

- If you have impaired renal function or have had or have kidney stones of calcium or diseases associated with high amounts of vitamin D such as sarcoidosis. In these situations, the administration of the solution should be carried out with caution since it contains calcium salts.

- Solutions containing magnesium salts should be used with caution in patients with renal insufficiency, severe arrhythmia and in patients with myasthenia gravis. Patients should be monitored for signs of magnesium excess, especially when being treated for eclampsia. Administration in the postoperative period after a neuromuscular blockade should be carried out with caution since magnesium salts can lead to recurarization.

- If the Apiroserum Normaion Restaurador solution is administered in large quantities, metabolic alkalosis may occur due to the presence of acetate and citrate ions in the solution.

- If your liver does not function well, the Apiroserum Normaion Restaurador solution may not produce its effect, since the metabolism of acetate and citrate may be impaired.

- Special attention should be paid to elderly patients, as they may have impaired liver, kidney and heart function.

- The solution should be administered with caution if you are at risk of developing cerebral edema or intracranial hypertension.

- If you are being treated with corticosteroids, adrenocorticotropic hormone or digitalis medications, the administration of the Apiroserum Normaion Restaurador solution should be carried out with caution (see section Use of other medications).

- Administration in the same location should be avoided due to the risk of thrombophlebitis.

- Regular glucose monitoring is recommended, especially in diabetic patients. In this case, insulin requirements may need to be modified.

- Similarly, caution should be exercised in patients who have had acute ischemic attacks (decreased or absent circulation in arteries), as hyperglycemia has been related to an increase in ischemic brain damage and difficulty in recovery.

- Vitamin B1 is essential for glucose metabolism. Special caution should be exercised in patients at risk of vitamin B1 deficiency (e.g. malnourished or alcoholic patients) and, if necessary, this deficiency should be corrected first.

- Due to the presence of glucose, this solution should not be administered through the same infusion equipment used for blood transfusions, as it may cause agglutination of blood cells.

In patients with compromised renal function, or in the immediate postoperative period, it should not be administered without prior control of potassium levels, due to its potassium content.

All patients should be closely monitored.

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

Children, fertile women and patients with brain diseases such as meningitis, cerebral hemorrhage, head trauma and cerebral edema have a special risk of developing severe and potentially fatal brain inflammation caused by acute hyponatremia.

Interaction of Apiroserum Normaion Restaurador with other medications

Inform your doctor or pharmacist if you are using or have recently used any other medication, especially:

• Medications that lead to an increase in vasopressin effect (see section Warnings and precautions), for example:

- Medications that stimulate the release of vasopressin (e.g. antipsychotics, narcotics)

- Medications that potentiate the action of vasopressin (e.g. non-steroidal anti-inflammatory drugs)

- Medications that act like vasopressin, called vasopressin analogs

- Other medications that increase the risk of hyponatremia, including diuretics in general and antiepileptic drugs.

• Corticosteroids/steroids or ACTH (adrenocorticotropic hormone)
• Lithium carbonate
• Amiloride, spironolactone, triamterene (potassium-sparing diuretics), alone or in combination
• Captopril or enalapril (angiotensin-converting enzyme inhibitors) candesartan, telmisartan, eprosartan, irbesartan, losartan and valsartan (angiotensin II receptor antagonists)
• Tacrolimus and cyclosporine (immunosuppressants), due to the potential risk of hyperkalemia
• Digoxin and methyldigoxin (cardiotonic digitalis glycosides) as the effects of these drugs may be potentiated by an increase in blood calcium levels, potentially leading to serious or fatal cardiac arrhythmia due to digitalis intoxication
• Hydrochlorothiazide, altizide, mebutizide, bendroflumethiazide (thiazide diuretics) or vitamin D
• Decamethonium, succinylcholine (depolarizing neuromuscular blockers) and atracurium, mivacurium, rocuronium, doxacurium, pancuronium, vecuronium
• Insulin or oral antidiabetic drugs (biguanides, sulfonylureas): may lead to a reduction in the therapeutic efficacy of the latter (antagonistic action)
• Systemic corticosteroids with glucocorticoid activity (such as cortisol)

The following contraindications have been reported with solutions of a similar type to the one presented:

1. Nitrofurantoin sodium.
2. Thiopental sodium.
3. Warfarin sodium.

Caution should be exercised in cases of alkalization of the urine by bicarbonate, as it will increase the elimination of certain medications (such as salicylates, lithium) and decrease the elimination of alkaline medications such as sympathomimetics (e.g. amphetamines).

In the case of multiple mixtures, other incompatibilities may occur.

Pregnancy and lactation

If you are pregnant or breastfeeding, or think you may be pregnant or intend to become pregnant, consult your doctor or pharmacist before using this medication.

If Apiroserum Normaion Restaurador is administered correctly and under control, no adverse effects should be expected during pregnancy or during lactation.

In the case of pregnancy, your doctor will decide whether to use Apiroserum Normaion Restaurador, as it should be used with caution in this case.

Excessive glucose administration during pregnancy may cause hyperglycemia, hyperinsulinemia and fetal acidosis, and may be harmful to the newborn.

Apiroserum Normaion Restaurador should be administered with special caution in pregnant women during delivery and close monitoring of serum sodium levels will be required if it is administered in combination with oxytocin.

There is no evidence to suggest that Apiroserum Normaion Restaurador may cause adverse effects during lactation in the neonate. However, it is recommended to use with caution during lactation.

Driving and operating machinery

There is no indication that Apiroserum Normaion Restaurador may affect the ability to drive or operate machinery.

Apiroserum Normaion Restaurador contains 17 mg of sodium metabisulfite per 100 ml of solutionwhich may cause rare severe hypersensitivity reactions and bronchospasm in susceptible patients, especially those with a history of asthma.

Follow exactly the administration instructions for this medication as indicated by your doctor. Consult your doctor or pharmacist if you have any doubts.

The recommended dose is 1 to 4 liters (as prescribed by your doctor)via slow intravenous infusiondrop by drop, at an approximate rate of 40 to 60 drops per minute.

Use in children and adolescents

In children, the dose will be 50 to 150 ml/kg and the infusion rate will be proportionally lower.

If you have any other questions about the use of this medication, ask your doctor or pharmacist or nurse.

Like all medications,ApiroserumNormaion Restaurador may cause side effects, although not everyone will experience them.

The frequency of the possible side effects listed below is defined as follows:

Very common (affects more than 1 in 10 patients)

Common (affects between 1 and 10 in 100 patients)

Uncommon (affects between 1 and 10 in 1,000 patients)

Rare (affects between 1 and 10 in 10,000 patients)

Very rare (affects less than 1 in 10,000 patients)

Unknown (cannot be evaluated with available data)

Some side effects may be severe

As rare adverse reactions, allergic reactions may occur. The signs of an allergic reaction may include:

•Hives

•Difficulty breathing

•Inflammation of the face, lips, throat

Other side effects include:

Very common (affects more than 1 in 10 patients)

•Pain at the injection site,

•Edema (inflammation),

•Flebitis at the infusion site,

•Infection at the injection site,

•Fever (high fever accompanied by sweating),

•Local reaction,

•Pruritus (itching),

•Induration (appearance of hard nodules),

•Erythema (redness and inflammation of the skin),

•Inflammation with painful nodules,

•Venous irritation.

Uncommon (affects less than 1 in 100 patients)

•Necrosis and ulceration at the injection site

Unknown (cannot be evaluated with available data)

•Electrolyte imbalance,

•Hyperglycemia (high blood sugar levels),

•Bradycardia (slow heart rate),

•Chest pain,

•Tachycardia (rapid heart rate),

•Thrombosis, bronchospasm, nasal congestion, difficulty breathing, dyspnea, sneezing, cough,

•Angioedema, facial edema, laryngeal edema, periorbital edema, erythema, rash, skin swelling, pruritus,

•Glucosuria (high sugar levels in urine).

•Hypotonic hospitalization*

•Acute hypotonic encephalopathy*

*Hypotonic hospitalization may cause irreversible brain damage and death due to acute hypotonic encephalopathy, unknown frequency.

Given the nature of the product, if its indication and administration are correct and controlled, there is no risk of intoxication. In the event that these requirements are not met, and any symptoms related to side effects appear, administration will be suspended and symptomatic treatment will be sought.

If you experience side effects, consult your doctor or nurse, even if they are side effects that do not appear in this prospectus.

General advice

You may need to monitor fluid balance, serum glucose, serum sodium, and other electrolytes before and during administration, especially in patients with increased non-osmotic vasopressin release (SIADH syndrome) and patients receiving concomitant medication with vasopressin agonists due to the risk of hypotonicity. Serum sodium monitoring is especially important when administering products with a lower sodium concentration compared to serum sodium. After perfusion of Apiroserum Normaion Restaurador, a rapid and active transport of glucose to the body's cells occurs. This condition promotes an effect that can be considered as a free water supply and may lead to severe hypotonicity.

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

Store below 25°C.

Do not use this medicationafter the expiration date that appears on the packaging afterCAD. The expiration date is the last day of the month indicated.

Do not use this medication if the solution is not transparent and/or if particles are observed.

In case of mixtures with medications, it must be stored in maximum asepsis during the addition of medications to intravenous liquid use, and use these mixtures within 6 hours of preparation.

-

Composition ofApiroserum Normaion Restaurador

- The active principles are,

Content per 100 ml:

Sodium chloride 0.490 g

Potassium chloride 0.075 g

Calcium chloride (2 H2O) 0.028 g

Magnesium chloride (6 H2O) 0.014 g

Sodium acetate (3 H2O) 0.385 g

Trisodium citrate 2 H2O 0.057 g

Glucose (H2O) 5.000 g

- The excipients are: Sodium metabisulphite and water for injection preparations.

Milliequivalents/litre:

Osmolarity: 579 mOsmol/litre

Calories: 200 kcal/litre.

Appearance of the product and contents of the container

Apiroserum Normaion Restaurador is a transparent solutionexempt from visible particles.

It is presented in bottles with 250, 500 and 1,000 ml.

Clinical packaging of 12 bottles of 500 and 10 bottles of 1,000 ml.

Only some sizes of packaging may be commercially marketed.

Holder of the marketing authorization

Fresenius Kabi España S.A.U

Marina 16-18, 08005-Barcelona

Spain

Responsible for manufacturing

Fresenius Kabi Italia S.R.L.

Via Camagre, 41/43

37063 Isola della Scala (VR)

Italy

This leaflet has been approved in[pending]

“Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.es/”

-----------------------------------------------------------------------------------------------------------------

This information is intended solely for doctors or healthcare professionals:

Apiroserum Normaion Restaurador must be injected, either totally or partially, once the injector equipment is connected to the bottle, to prevent possible contaminations.

Do not administer by intramuscular route.

In the case of multiple mixtures, maximum asepsis must be maintained during the addition of the medications to the intravenous liquids, and these mixtures must be used within 6 hours of preparation.

-