APIROSERUM RINGER-LACTATE SOLUTION FOR INFUSION

2. BEFORE USING APIROSERUM RINGER LACTATE

It is recommended to monitor the hydroelectrolytic balance.

Do not use Apiroserum Ringer Lactate in case of:

• Allergy to the active principles or to any of the other components of Apiroserum Ringer Lactate
• Extracellular hyperhydration or hypervolemia (excess of fluids in the body)
• Severe renal failure with oliguria or anuria (kidney failure with decreased or absent urine production)
• Uncompensated heart failure
• If your blood contains a high level of potassium, sodium, calcium, or chlorides - Metabolic alkalosis
• Severe metabolic acidosis
• Lactic acidosis
• Severe hepatocellular failure (liver failure) or impaired lactate metabolism
• General edema (excessive accumulation of fluids) or ascitic cirrhosis.

Warnings and precautions

Be particularly careful with Apiroserum Ringer Lactate

• If your kidneys, heart, and/or lungs are not functioning properly. In these cases, the administration of large volumes of this solution should be carried out under strict clinical control.
• It is recommended that, during the administration of this solution, regular checks of your clinical condition and blood and urine analyses (electrolytes in blood and urine, acid-base balance, hematocrit) be performed. Potassium checks in the blood should be performed if you are at risk of hyperpotasemia (high potassium levels in the blood).

If you have any of the following diseases, this medication will be administered with special caution and it is likely that additional tests will be performed to determine if you can receive the medication:

• Due to the presence of sodium: If you have high blood pressure (hypertension), heart failure, edema in the lungs or in the ankles, feet, and legs, preeclampsia (a disease that occurs during pregnancy or postpartum that is characterized by an increase in blood pressure), aldosteronism (a disease associated with an increase in the secretion of a hormone called aldosterone) or you have impaired renal function or other conditions associated with sodium retention.

Due to the presence of potassium: If you have heart diseases or other problems that can cause an increase in potassium in the blood, such as renal or adrenocortical insufficiency, acute dehydration, or massive tissue destruction, as occurs in large burns.

• Due to the presence of calcium: If you have impaired renal function or if you have or have had kidney stones produced by a calcium accumulation or diseases associated with elevated vitamin D levels, such as sarcoidosis.

Due to the presence of lactate ions: If the Ringer Lactate solution is administered in large quantities, metabolic alkalosis may occur.

• If you have severe potassium deficiency. Although the Ringer Lactate solution has a potassium concentration similar to that of plasma, it is insufficient to produce a beneficial effect in these situations.
• If your liver is not functioning properly, the Ringer Lactate solution may not produce its effect, since lactate metabolism may be impaired.

• The Ringer Lactate solution should be administered with caution if you are at risk of cerebral edema or intracranial hypertension.

• If you are being treated with corticosteroids, adrenocorticotropic hormone, or digitalis medications, the administration of the Ringer Lactate solution should be carried out with caution (see section on Use of other medications).

Special attention should be paid to elderly patients, as they may have impaired renal, hepatic, and/or cardiac function.

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

Be particularly careful:

• If you suffer from critical states, 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 on Other medications and Apiroserum Ringer Lactate)

All patients should be closely monitored. In cases where normal regulation of blood water content is altered due to increased vasopressin secretion, also called 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 inflammation (cerebral edema), and death; therefore, these symptoms (symptomatic acute 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 are at special risk of suffering from severe and potentially fatal brain inflammation caused by acute hyponatremia.

Children and adolescents

Children are at particular risk of suffering from severe and potentially fatal brain inflammation due to acute hyponatremia.

Other medications and Apiroserum Ringer Lactate

Tell your doctor or pharmacist if you are using or have recently used any other medications, including those purchased without a prescription.

Certain medications may interact with Apiroserum Ringer Lactate. In this case, it may be necessary to change the dose or interrupt treatment with one of the medications.

In general, it is recommended to avoid the concomitant administration of the Ringer Lactate solution with any medication that may have renal toxicity, as it may cause fluid and electrolyte retention.

It is essential to inform your doctor if you are using any of the following medications, as they may interact with some of the electrolytes present in the Ringer Lactate solution:

• Corticosteroids/steroids or adrenocorticotropic hormone
• Lithium carbonate
• Potassium-sparing diuretics (amiloride, spironolactone, triamterene) alone or in combination
• Angiotensin-converting enzyme inhibitors (ACE inhibitors) (captopril, enalapril) or angiotensin II receptor antagonists (candesartan, telmisartan, eprosartan, irbesartan, losartan, valsartan)
• Tacrolimus and cyclosporine (medications with renal toxicity) - Digitalis cardiac glycosides (digoxin, methyldigoxin)
• Thiazide diuretics (hydrochlorothiazide, altizide, mebutizide, bendroflumethiazide) or vitamin D
• Acidic medications such as salicylates and/or barbiturates
• Alkaline medications such as sympathomimetics (ephedrine, pseudoephedrine) and/or stimulants (amphetamine, dexamphetamine)

In particular, inform your doctor if you are taking:

Medications that lead to an increased effect of vasopressin (see section on Warnings and precautions), such as:

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

Pregnancy and breastfeeding

Consult your doctor or pharmacist before using any medication.

If the administration of the Ringer Lactate solution is carried out correctly and under control, no adverse effects are expected during pregnancy or breastfeeding.

During pregnancy and breastfeeding, the use of the Ringer Lactate solution as a vehicle for administering other medications should be assessed based on the nature of these medications.

This medication should be administered with special caution in pregnant women during labor, especially if it is administered in combination with oxytocin (a hormone that can be administered to induce labor and control bleeding) due to the risk of hyponatremia.

Driving and using machines

There is no indication that Apiroserum Ringer Lactate may affect the ability to drive or use machines.

3. HOW TO USE APIROSERUM RINGER LACTATE

Apiroserum Ringer Lactate comes in the form of a solution for intravenous administration. Apiroserum Ringer Lactate will be used in a hospital by the corresponding healthcare personnel.

Your doctor will indicate the duration of your treatment with Apiroserum Ringer Lactate.

The dose may vary according to medical criteria.

The amount of solution needed to restore normal blood volume is 3-4 times the volume of blood lost.

Recommended daily dose:

• Adults: between 500 and 3000 ml per day.
• Children: - up to 10 kg of weight: 100 ml per kg of weight and day.

between 10 and 20 kg of weight: 1000 ml + 50 ml additional per kg that exceeds 10 kg of weight, per day.

• over 20 kg of weight: 1500 ml + 20 ml additional per kg that exceeds 20 kg of weight, per day.

The perfusion rate should be adjusted to the patient's clinical need based on age, weight, clinical condition, fluid balance, electrolytes, and acid-base balance.

When the Ringer Lactate solution is used as a vehicle for administering other medications, the dose and perfusion rate will be defined by the nature and dosage regimen of the prescribed medication.

If you are given more Apiroserum Ringer Lactate than you should

In case of overdose or too rapid administration, the following symptoms may appear:

• Hyperhydration (edema, hypervolemia), electrolyte balance disorders, and/or induction of metabolic alkalosis, especially in patients with impaired renal function. In these cases, administration will be decreased or suspended, and symptomatic treatment will be initiated. If renal function is compromised, dialysis may be necessary.
• Water and sodium overload with a risk of edema, particularly when there is a defective renal excretion of sodium.

Excessive administration of potassium salts can lead to the development of hyperkalemia, especially in patients with impaired renal function. Symptoms include tingling, numbness, and/or burning sensation in hands and feet, muscle weakness, paralysis, cardiac arrhythmias, cardiac block, cardiac arrest, and mental confusion.

Excessive administration of calcium salts can lead to hypercalcemia. Symptoms of hypercalcemia may include anorexia, nausea, vomiting, constipation, abdominal pain, muscle weakness, mental changes, polydipsia (excessive thirst), polyuria (excessive urine volume), kidney stones, and, in severe cases, cardiac arrhythmias and coma, as well as a metallic taste, burning sensation, and peripheral vasodilation. Mild asymptomatic hypercalcemia will usually resolve by interrupting calcium administration and other contributing medications, such as vitamin D. If hypercalcemia is severe, urgent treatment is required (such as diuretic cycles, hemodialysis, calcitonin, bisphosphonates, disodium edetate).

Excessive administration of sodium lactate can lead to hypokalemia and metabolic alkalosis. Symptoms may include changes in character, fatigue, respiratory failure, muscle weakness, and irregular heartbeats. It can develop, especially in hypocalcemic patients, increased muscle tone, muscle spasms, and tetany (neuromuscular hyperexcitability). The treatment of metabolic alkalosis associated with bicarbonate overdose consists mainly of correcting fluid and electrolyte balance.

When the overdose is related to the medication added to the perfused solution, the signs and symptoms of overperfusion may be related to the nature of the added medication. In case of accidental overdose, treatment should be interrupted, and the patient should be observed for symptoms and signs related to the administered medication. If necessary, take appropriate symptomatic and supportive measures.

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

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

4. Possible side effects

Like all medications, Apiroserum Ringer Lactate can cause side effects, although not everyone will experience them.

The most commonly described side effects are hyperhydration (edema) and electrolyte disturbances (mainly after administration of a large volume of Ringer Lactate solution), as well as allergic reactions.

Possible side effects are:

• Electrolyte disturbances
• Venous thrombosis (clots), phlebitis (inflammation of the vein) (associated with intravenous administration)

Nasal congestion, cough, sneezing, difficulty breathing during administration of the solution, chest pain with altered heart rhythm

• Allergic reactions such as hives, skin rashes, skin redness, itching, swelling, fluid accumulation in tissues

Hyperhydration (edema)

• Fever, infection at the injection site, local reaction, or local pain (associated with intravenous administration)

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

When the Ringer Lactate solution is used as a vehicle for administering other medications, the side effects may be associated with the medications added to the solution.

In case of appearance of side effects, the perfusion should be interrupted.

If you think any of the side effects that you are suffering from are serious, or if you notice any side effects not mentioned in this leaflet, inform your doctor or pharmacist.

5. Storage of APIROSERUM RINGER LACTATE

No special storage conditions are required.

Once the container is opened, the solution should be used immediately.

Keep out of the reach and sight of children.

Do not use Apiroserum Ringer Lactate after the expiration date shown on the container.

Do not use Apiroserum Ringer Lactate if the solution is not transparent and contains precipitates.

Medications should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of containers and medications that are no longer needed. This will help protect the environment.

6. ADDITIONAL INFORMATION

Composition of Apiroserum Ringer Lactate

The active ingredients are:

Per 100ml, Sodium lactate 310 mg, Sodium chloride 600 mg, Potassium chloride 30 mg, Calcium chloride (dihydrate) 21.9 mg.

The other components (excipients) are: water for injectables.

Transparent and colorless solution, without visible particles, sterile and apyrogenic.

The electrolyte composition per 1000 ml is:

Calcium 1.5 mmol/l, 3.0 meq/l; Potassium 4.0 mmol/l, 4.0 meq/l; Sodium 130 mmol/l, 130 meq/l; Lactate 27 mmol/l, 27 meq/l; Chloride 110 mmol/l, 110 meq/l.

Theoretical osmolality: 273 mosm/l. pH: 5.0-7.0

Appearance of the product and packaging content

Apiroserum Ringer Lactate is a transparent and colorless solution, without visible particles. It is presented in glass bottles of 250 ml, 500 ml, and 1000 ml.

Marketing authorization holder

Fresenius Kabi España S.A.

C/ Marina 16-18, 17th floor

08005-Barcelona (Spain)

Manufacturing responsibles

Fresenius Kabi España, S.A.

C/ Marina, 16-18

08005 Barcelona (Spain)

Fresenius Kabi Italia S.R.L.

Via Camagre, 41/43

37063 Isola della Scala (VR) (Italy)

This leaflet was revised in

August 2018

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This information is intended only for doctors or healthcare professionalsApiroserum Ringer Lactate will be administered by perfusion.

The content of each bottle of Apiroserum Ringer Lactate is for single perfusion. Once the packaging is opened, the solution must be administered immediately and the unused fraction must be discarded.

The solution must be transparent and not contain precipitates. Do not administer otherwise.

To administer the solution and in case of addition of medications, maximum asepsis must be maintained. From a microbiological point of view, when the solution is used as a vehicle for other medications, it must be used immediately unless the dilution has been carried out under controlled and validated aseptic conditions. If it is not used immediately, the conditions and periods of conservation during use are the responsibility of the user.

It is recommended to consult compatibility tables before adding medications to the Ringer Lactate solution or administering them simultaneously with other medications. It is recommended to consult the prospectus of the added medications, as well as to verify if they are soluble and stable in aqueous solution at the pH of the Ringer Lactate solution (pH 5.0-7.0).

When compatible medication is added to Apiroserum Ringer Lactate, the solution must be administered immediately.

The Ringer Lactate solution should not be used as a vehicle for medications that contain ions capable of causing the formation of insoluble calcium salts.

It is recommended not to mix or administer simultaneously in the same perfusion equipment Ringer Lactate solution with whole blood or with blood components preserved with an anticoagulant that contains citrate (such as CPD), since the calcium ions present in this solution may exceed the chelating capacity of citrate, potentially producing clot formation. These clots could be perfused directly into the circulation and cause an embolism.

General advice

Hydration balance, serum electrolytes, and acid-base balance must be monitored before and during administration, with special attention to serum sodium in patients with increased release of non-osmotic vasopressin (syndrome of inappropriate secretion of antidiuretic hormone, SIADH) and in patients receiving concomitant medication with vasopressin agonists due to the risk of hospital hyponatremia.

Serum sodium monitoring is especially important with hypotonic physiological solutions.

For pediatric patients, the dose and administration rate must be determined by a doctor with experience in pediatric intravenous fluid therapy.