APIROSERUM NORMAION RESTAURADOR

Introduction

Leaflet:information for the user

Apiroserum Normaion Restaurador solution for infusion

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

Read the entire leaflet carefully before starting to use this medicine because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed to you only, and you should not give it to others, even if they have the same symptoms of the disease, as it may harm them.
• If you experience side effects, consult your doctor, pharmacist, or nurse, even if they are side effects not listed in this leaflet. See section 4.

Contents of the leaflet:

1. What is Apiroserum Normaion Restaurador and what is it used for
2. What you need to know before starting to use Apiroserum Normaion Restaurador
3. How to use Apiroserum Normaion Restaurador
4. Possible side effects
5. Storage of Apiroserum Normaion Restaurador
6. Package contents and additional information

1. What is Apiroserum Normaion Restaurador and what is it used for

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

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

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

• Fluid loss in surgical patients. Lack of fluid in the extracellular space in the pre- and postoperative period. Intestinal occlusion. Peritonitis. Intestinal, biliary, and pancreatic fistulas. Aspirations of stomach or intestinal fluid (endodigestive). Blood losses (hemorrhages). Extensive burns. Postoperative collapse. Shock.
• Digestive losses. Diarrhea and vomiting. Disorders of the digestive system (dyspeptic) of the infant (gastroenteritis, enterocolitis, etc.). Nausea and vomiting during pregnancy (hyperemesis gravidarum).
• Metabolic losses. Diabetic acidosis.
• Cutaneous losses. Abundant sweating in case of infectious and febrile diseases.

2. What you need to know before starting to use Apiroserum Normaion Restaurador

Do not use Apiroserum Normaion Restaurador

• if you are allergic to the active ingredients or to any of the other components of this medicine (listed in section 6)
• if you suffer from hyperpotasemia (excess potassium in the blood)
• if you suffer from fluid overload (hyperhydration), such as in the case of edema (fluid retention), such as pulmonary edema, congestive heart failure (or other types of cardiac decompensation) and ascitic cirrhosis
• if you suffer from renal insufficiency (kidney failure)
• if you suffer from severe liver disease
• if you suffer from hypertension (high blood pressure)
• if you suffer from extracellular fluid loss with significant water loss
• if you suffer from metabolic alkalosis
• if you suffer from hypernatremia (excess sodium)
• if you suffer from hypercalcemia (excess calcium)
• if you suffer from hypermagnesemia (excess magnesium)
• if you suffer from hyperchloremia (excess chloride)
• if you suffer from hyperglycemia (excess 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 suffer from kidney, heart, or lung disorders. In these cases, the administration of large volumes of this solution should be done under strict medical control.

• If you suffer from hypertension (high blood pressure), heart failure (the heart does not work 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 done with caution since it contains sodium chloride.

• If you suffer from heart disease or conditions that predispose to hyperpotasemia (excess potassium), such as renal or adrenocortical insufficiency, acute dehydration, or massive tissue destruction, as occurs in large burns. In these situations, the administration of the solution should be done with caution since it contains potassium salts.

• It is recommended that regular checks of your clinical condition and analytical tests (electrolytes in blood and urine, acid-base balance, hematocrit) be performed during the administration of this solution. Particular care should be taken to monitor potassium levels in serum if you are at risk of developing hyperpotasemia (excess 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 kidney stones or diseases associated with high levels of vitamin D, such as sarcoidosis. In these situations, the administration of the solution should be done with caution since it contains calcium salts.

• Solutions containing magnesium salts should be used with caution in patients with renal insufficiency, severe heart rate disorders, and in patients with myasthenia gravis. Patients should be monitored for clinical signs of excess magnesium, especially when being treated for eclampsia. Administration in the postoperative period after neuromuscular blockade should be done with caution since magnesium salts can lead to a recurarizing effect.

• If the Apiroserum Normaion Restaurador solution is administered in large quantities, it can cause metabolic alkalosis due to the presence of acetate and citrate ions in the solution.

• If your liver does not work well, the Apiroserum Normaion Restaurador solution may not produce its effect, as 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 Apiroserum Normaion Restaurador 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 done with caution (see section on use with other medications).

• Continuous administration at the same injection site should be avoided due to the risk of developing thrombophlebitis.

• It is recommended that blood glucose levels be regularly monitored, especially in diabetic patients. In this case, it may be necessary to modify insulin requirements.

• Similarly, caution should be exercised in patients who have suffered acute ischemic attacks (decreased or absent circulation in arteries), as hyperglycemia has been associated with increased 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 can 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 potasemia, 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), perfusion of fluids with low sodium chloride concentration (hypotonic fluids) can 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, women of childbearing age, and patients with brain diseases such as meningitis, cerebral hemorrhage, contusion, and cerebral edema are at special risk of developing severe and potentially fatal cerebral inflammation caused by acute hyponatremia.

Interaction of Apiroserum Normaion Restaurador with other medications

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

• Medications that increase the effect of vasopressin (see section on warnings and precautions), such as:

• Medications that stimulate the release of vasopressin (e.g., antipsychotics, narcotics)
• Medications that enhance the action of vasopressin (e.g., non-steroidal anti-inflammatory medications)
• Medications that act like vasopressin, called vasopressin analogs
• Other medications that increase the risk of hyponatremia, including diuretics in general and antiepileptics.
• 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 (ACEIs)) candesartan, telmisartan, eprosartan, irbesartan, losartan, and valsartan (angiotensin II receptor antagonists)
• Tacrolimus and cyclosporine (immunosuppressants), due to the risk of potentially fatal hyperpotasemia
• Digoxin and methyldigoxin (cardiac glycosides) as the effects of these medications can be enhanced by increased blood calcium levels, potentially leading to serious or fatal cardiac arrhythmia due to digitalis toxicity
• Hydrochlorothiazide, altizide, mebutizide, bendroflumethiazide (thiazide diuretics) or vitamin D
• Decamethonium, succinylcholine (depolarizing neuromuscular blockers) and atracurium, mivacurium, rocuronium, doxacurium, pancuronium, vecuronium
• Insulin or oral antidiabetics (biguanides, sulfonylureas): may lead to a reduction in the therapeutic efficacy of these medications (antagonistic action)
• Systemic corticosteroids with glucocorticoid activity (such as cortisol)

With solutions of a similar type to the one presented, the following contraindications have been reported:

1. Sodium nitrofurantoin.
2. Sodium thiopental.
3. Sodium warfarin.

Precautions should be taken in cases of urine alkalization by bicarbonate, as this 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 plan to become pregnant, consult your doctor or pharmacist before using this medicine.

If the administration of Apiroserum Normaion Restaurador is done correctly and under control, no adverse effects are expected during pregnancy or breastfeeding.

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 administration of glucose during pregnancy can 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 labor and will require special monitoring of serum sodium levels if administered in combination with oxytocin.

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

Driving and using machines

There is no indication that Apiroserum Normaion Restaurador can affect the ability to drive or use machines.

Apiroserum Normaion Restaurador contains 17 mg of sodium metabisulfite per 100 mlof solution, which can rarely cause severe hypersensitivity reactions and bronchospasm in susceptible patients, especially those with a history of asthma.

3. How to use Apiroserum Normaion Restaurador

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

The recommended dose is 1 to 4 liters (according to medical prescription) by slow intravenous injection, drop 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 drip rate will be proportionally lower.

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

4. Possible side effects

Like all medicines, Apiroserum Normaion Restaurador can cause side effects, although not everyone gets them.

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

Very common (affect more than 1 in 10 patients)

Common (affect between 1 and 10 in 100 patients)

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

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

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

Unknown (cannot be estimated from the available data)

Some side effects can be serious

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

•Rash

•Difficulty breathing

•Swelling of the face, lips, throat

Other side effects include:

Very common (affect more than 1 in 10 patients)

• pain at the injection site,
• edema (inflammation),
• phlebitis at the infusion site,
• infection at the injection site,
• pyrexia (high fever with sweating),
• local reaction,
• pruritus (itching),
• induration (appearance of hard nodules),
• erythema (redness and inflammation of the skin),
• irritation of the vein.

Uncommon (affect less than 1 in 100 patients)

• necrosis and ulceration at the injection site

Unknown (cannot be estimated from the available data)

• electrolyte imbalance,
• hyperglycemia (excessive sugar levels in the blood),
• bradycardia (slow heart rate),
• chest pain,
• tachycardia (fast heart rate),
• venous thrombosis,
• bronchospasm, nasal congestion, respiratory difficulty, dyspnea, sneezing, cough,
• angioedema, facial edema, laryngeal edema, periorbital edema, erythema, rash, skin swelling, pruritus,
• glucosuria (elevated sugar levels in urine).
• Hospital hyponatremia*
• Acute symptomatic hyponatremic encephalopathy*

*Hospital hyponatremia can cause irreversible brain damage and death due to the development of acute symptomatic hyponatremic encephalopathy, frequency not known.

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, due to non-compliance with these requirements, any symptoms derived from side effects occur, administration will be suspended and symptomatic treatment will be initiated.

If you experience side effects, consult your doctor or nurse, even if they are side effects not listed in this leaflet.

General advice

It may be necessary to monitor fluid balance, blood 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 products with a lower sodium concentration compared to serum sodium concentration. After infusion of Apiroserum Normaion Restaurador, there is a rapid and active transport of glucose to the body's cells. This condition promotes an effect that can be considered as a supply of free water and can lead to severe hyponatremia.

5. Storage of Apiroserum Normaion Restaurador

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

Store below 25°C.

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

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

In the case of mixtures with medications, maximum asepsis should be maintained during the addition of medications to intravenous fluids, and such mixtures should be used within 6 hours of preparation.

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6. Package Contents and Additional Information

Composition ofApiroserum Normaion Restaurador

• The active ingredients 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 metabisulfite and water for injectable preparations.

Millequivalents/liter:

Osmolality: 579 mOsmol/liter

Calories: 200 kcal/liter.

Appearance of the Product and Package Contents

Apiroserum Normaion Restaurador is a transparent solution and free of visible particles.

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

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

Only some package sizes may be marketed.

Marketing Authorization Holder

Fresenius Kabi España S.A.U

Marina 16-18, 08005-Barcelona

Spain

Manufacturer

Fresenius Kabi Italia S.R.L.

Via Camagre, 41/43

37063 Isola della Scala (VR)

Italy

This leaflet was approved on[pending]

“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.es/”

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This information is intended only for doctors or healthcare professionals:

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

Do not administer intramuscularly.

In the case of multiple mixtures, maximum asepsis should be maintained during the addition of medications to intravenous fluids, and such mixtures should be used within 6 hours of preparation.

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