RINGER LACTATE GRIFOLS SOLUTION FOR INFUSION

2. What you need to know before you start using Ringer Lactate Grifols

Do not use Ringer Lactate Grifols

• if you are allergic to the active substances or to any of the other components of this medicine (listed in section 6)

• in states of extracellular hyperhydration or hypervolemia (excess fluid in the body)
• if you have severe renal failure with oliguria or anuria (kidney failure with decreased or absent urine production)
• in case of uncompensated heart failure
• if your blood contains high levels of potassium, sodium, calcium, or chlorides
• if you have metabolic alkalosis
• in case of severe metabolic acidosis
• if you have lactic acidosis
• if you have severe hepatocellular failure (liver failure) or impaired lactate metabolism
• in situations of general edema or ascitic cirrhosis.

Warnings and Precautions

Consult your doctor or nurse before starting to use Ringer Lactate Grifols.

• If your kidneys, heart, and/or lungs do not function properly, the administration of large volumes of this solution should be performed under strict clinical control. The administration of large volumes will also require special monitoring if you are a patient with non-osmotic release of vasopressin (antidiuretic hormone) (including the syndrome of inappropriate secretion of antidiuretic hormone, SIADH), due to the risk of hospital hyponatremia (low sodium levels in the blood during hospitalization).

Hyponatremia:

If you are a patient with non-osmotic release of vasopressin (e.g., in critical states, pain, postoperative stress, infections, burns, and central nervous system diseases), if you have heart, liver, and kidney diseases, and if you are exposed to vasopressin agonists (see next subsection) you have a special risk of suffering from acute hyponatremia after the administration of hypotonic solutions.

Acute hyponatremia can cause acute hyponatremic encephalopathy (cerebral edema) characterized by headache, nausea, seizures, lethargy, and vomiting. Patients with cerebral edema have a special risk of suffering from severe, irreversible, and potentially fatal brain damage.

Children, women of childbearing age, and patients with reduced cerebral distensibility (e.g., in case of meningitis, intracranial hemorrhage, and cerebral contusion) have a special risk of suffering from severe and potentially fatal cerebral edema caused by acute hyponatremia.

• It is recommended that, during the administration of this solution, you undergo regular checks of your clinical condition and blood and urine tests (electrolytes in blood and urine, acid-base balance, hematocrit). You should undergo potassium checks in the blood if you are at risk of hyperkalemia (high potassium levels in the blood).

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

• Due to the presence of sodium: If you have high blood pressure (hypertension), heart failure, pulmonary edema, or edema in the ankles, feet, and legs, preeclampsia (a disease that occurs during pregnancy or postpartum that is characterized by high blood pressure), aldosteronism (a disease associated with increased 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 levels in the blood, such as renal or adrenal 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 calcium accumulation or diseases associated with high levels of vitamin D, such as sarcoidosis.

• Due to the presence of lactate ions: If Ringer Lactate solution is administered in large quantities, it can cause metabolic alkalosis.

• If you have severe potassium deficiency. Although 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 does not function properly, Ringer Lactate solution may not produce its effect, since lactate metabolism may be impaired.

• 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 Ringer Lactate solution should be performed with caution (see section "Use with other medicines").

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.

Other Medicines and Ringer Lactate Grifols

Tell your doctor if you are using, have recently used, or may need to use any other medicine.

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

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

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

• Medicines that may interact with any of the electrolytes present in 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 (medicines with renal toxicity)
• 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, dextroamphetamine)

• Medicines that increase the effect of antidiuretic hormone (such as chlorpropamide, clofibrate, carbamazepine, vincristine, selective serotonin reuptake inhibitors, 3,4-methylenedioxymethamphetamine, ifosfamide, antipsychotics, narcotics, nonsteroidal anti-inflammatory drugs, cyclophosphamide, desmopressin, oxytocin, vasopressin, terlipressin). These medicines reduce water excretion in urine and increase the risk of hospital hyponatremia after receiving insufficiently balanced treatment with intravenous infusion solutions (see previous subsection and sections 3 and 4)
• Diuretics in general and antiepileptics such as oxcarbazepine, which increase the risk of hyponatremia.

Pregnancy and Breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

If the administration of Ringer Lactate solution is performed correctly and controlled, no adverse effects are expected during pregnancy or breastfeeding.

This medicine 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 (see previous subsections and section 4).

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

Driving and Using Machines

There is no indication that this medicine may affect the ability to drive or use machines.

3. How to Use Ringer Lactate Grifols

This medicine is presented as a solution for intravenous administration.

Ringer Lactate Grifols will be used in a hospital by the corresponding healthcare personnel.

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

The dose may vary according to medical criteria. The volume and rate of administration will be adjusted to the clinical need of each patient based on age, weight, clinical condition (e.g., burns, surgery, head injury, infections), fluid balance, electrolytes, and acid-base balance.

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.

It may be necessary to monitor your fluid balance, serum electrolytes, and acid-base balance before and during administration, with special attention to serum sodium levels if you have an increased release of non-osmotic vasopressin (SIADH) and if you receive simultaneous medication with vasopressin agonists, due to the risk of hospital hyponatremia (see sections 2 and 4). Monitoring of serum sodium levels is especially important with hypotonic solutions (this medicine is considered slightly hypotonic).

Your doctor will decide on the need for simultaneous treatment (see sections 2 and 4).

When the Ringer Lactate solution is used as a vehicle for administering other medicines, the dose and rate of infusion will be determined by the nature and dosage regimen of the prescribed medicine.

If You Receive More Ringer Lactate Grifols Than You Should

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

• hyperhydration (edema, hypervolemia), electrolyte imbalance, 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 performed. 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 production), kidney stones, and, in severe cases, cardiac arrhythmias and coma, as well as a taste of calcium, 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 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 signs and symptoms related to the administered medication. If necessary, symptomatic and supportive measures should be taken.

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 medicine, ask your doctor or nurse.

4. Possible Side Effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

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

In patients with non-osmotic release of vasopressin, in patients with heart, liver, and kidney diseases, and in patients treated with vasopressin agonists, the risk of acute hyponatremia after the administration of hypotonic solutions increases. Hospital hyponatremia can cause irreversible and potentially fatal brain damage due to the development of cerebral edema (see sections 2 and 3).

Possible side effects are:

• Electrolyte disturbances, hospital hyponatremia
• Cerebral edema
• Venous thrombosis (clots), phlebitis (inflammation of the vein) (associated with intravenous administration)
• Nasal congestion, cough, sneezing, difficulty breathing during the administration of the solution, chest pain with altered heart rhythm
• Allergic reactions such as urticaria, skin rash, 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).

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

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

Reporting of Side Effects

If you experience any side effects, consult your doctor or nurse, even if they are not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Ringer Lactate Grifols

No special storage conditions are required.

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

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

Do not use this medicine after the expiration date stated on the container.

Do not use this medicine if the solution is not transparent or if precipitates are observed.

Medicines should not be disposed of via wastewater or household waste. Dispose of the containers and medicines you no longer need in the SIGRE (SIGRE symbol) collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and medicines you no longer need. This will help protect the environment.

6. Container Content and Additional Information

Composition ofRinger Lactate Grifols

The active ingredients are sodium chloride, potassium chloride, calcium chloride, and sodium lactate. Each 100 ml of solution contains 600 mg of sodium chloride, 40 mg of potassium chloride, 20.4 mg of calcium chloride (as dihydrate) and 305 mg of sodium lactate (as a 50% solution).

The other components (excipients) are: hydrochloric acid or sodium hydroxide (for pH adjustment) and water for injectable preparations.

Appearance of the Product and Container Content

Ringer Lactate Grifols is a clear and colorless solution for perfusion, presented in 500 and 1000 ml glass bottles; and in flexible polypropylene bags (Fleboflex) of 500 and 1000 ml.

Marketing Authorization Holder

LABORATORIOS GRIFOLS, S.A.

Can Guasch, 2

08150 Parets del Vallès, Barcelona (SPAIN)

Manufacturer

LABORATORIOS GRIFOLS, S.A.

Polígono Industrial Autopista. Passeig Fluvial, 24

08150 Parets del Vallès, Barcelona (SPAIN)

LABORATORIOS GRIFOLS, S.A.

Polígono Industrial Los Llanos. C/ Marte, 4

30565 Las Torres de Cotillas, Murcia (SPAIN)

Date of the Last Revision of this Prospectus:June 2018

Other Sources of Information

Detailed 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 healthcare professionals:

Ringer Lactate Grifols will be administered by perfusion.

The content of each container of this medication is for single perfusion. Once the container 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.

Fleboflex Bag:

• Check for the absence of small leaks by pressing the bag firmly. If leaks are detected, discard the product.
• To connect the perfusion equipment, separate the protective tab from the infusion port, exposing the access membrane to the bag.

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 Ringer Lactate Grifols, 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 causing the formation of clots. These clots could be perfused directly into the circulation and cause an embolism.