FREEFLEX RINGER LACTATE SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Freeflex Ringer Lactate Solution for Infusion

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

1. What Freeflex Ringer Lactate is and what it is used for
2. What you need to know before you use Freeflex Ringer Lactate
3. How to use Freeflex Ringer Lactate
4. Possible side effects
5. Storage of Freeflex Ringer Lactate
6. Contents of the pack and further information

1. What Freeflex Ringer Lactate is and what it is used for

Freeflex Ringer Lactate is a solution for infusion that provides a supplement of mineral salts and water for hydration.

The Freeflex Ringer Lactate solution is included in the group of medicines called solutions for infusion.

This medicine will be administered intravenously by specialized personnel and is indicated in the following cases:

• When there is dehydration with high losses of salts and water, such as when there are vomiting, diarrhea, fistulas, or severe burns.
• When the body fluids are too acidic (mild or moderate metabolic acidosis).
• When there is a significant decrease in blood volume, in the case of hemorrhages, burns, shock, etc.
• During or after a surgical operation to prevent a drop in blood pressure.

As a vehicle for administering other compatible medicines.

2. What you need to know before you use Freeflex Ringer Lactate

Do not use Freeflex Ringer Lactate

• if you are allergic to the active substances or to any of the other components of this medicine (listed in section 6).
• if you have been detected with an excess of fluids in the body (hyperhydration or hypervolemia) and if this causes swelling (edema)
• if you have high blood pressure problems.
• if you have an excess of potassium, sodium, calcium, or chlorine in the body
• if the body fluids are too alkaline (metabolic alkalosis)
• if the body fluids are excessively acidic (severe metabolic acidosis)
• if you have been detected with high levels of lactic acid in the blood.
• if you have severe kidney or liver disease.
• if you have severe heart disease.
• if you are undergoing prolonged treatment with steroids or with a hormone called ACTH.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Freeflex Ringer Lactate.

Be especially careful with Freeflex Ringer Lactate:

• If the kidney, heart, and/or lungs are not functioning correctly. In these cases, the administration of large volumes of this solution should be performed under strict clinical control.

• It is recommended that, during the administration of this solution, regular checks of your clinical condition and analyzes of both blood and urine (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 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, 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 suffer from 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 accumulation of calcium or diseases associated with high concentrations of vitamin D, such as sarcoidosis.

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

• If you have severe potassium deficiency. Although the Freeflex 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 correctly, the Freeflex Ringer Lactate solution may not produce its effect, since lactate metabolism may be impaired.

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

The perfusion of large volumes will require special monitoring in patients with heart or lung failure and in patients with non-osmotic release of vasopressin (including SIADH), due to the risk of hospital hyponatremia.

Hyponatremia:

Patients with non-osmotic release of vasopressin (e.g., in critical states, pain, postoperative stress, infections, burns, and CNS diseases), patients with heart, liver, and kidney diseases, and patients exposed to vasopressin agonists have a special risk of experiencing acute hyponatremia after perfusion 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 severe, irreversible, and potentially fatal brain damage.

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

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.

Use of Freeflex Ringer Lactate with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Certain medicines may interact with the Ringer Lactate solution. 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 the Freeflex Ringer Lactate solution with any medicine that presents or may present renal toxicity, as it may cause fluid and electrolyte retention.

It is important to inform your doctor if you use any of the following medicines, as they may interact with any of the electrolytes present in the Freeflex 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 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 insufficiently balanced treatment with infusion solutions.

• Medicines that stimulate the release of vasopressin; these include:

chlorpropamide, clofibrate, carbamazepine, vincristine, selective serotonin reuptake inhibitors, 3,4-methylenedioxymethamphetamine, ifosfamide, antipsychotics, narcotics

• Medicines that potentiate the action of vasopressin; these include:

chlorpropamide, non-steroidal anti-inflammatory drugs, cyclophosphamide

• Vasopressin analogs; these include:

desmopressin, oxytocin, vasopressin, terlipressin

• Other medicines that are known to increase the risk of hyponatremia are diuretics in general and antiepileptics such as oxcarbazepine.

Use of Freeflex Ringer Lactate with food and drinks

No interaction with food and drinks is known.

Pregnancy and breastfeeding

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.

Freeflex Ringer Lactate should be administered with special caution in pregnant women during childbirth, and special monitoring of serum sodium will be required if it is administered in combination with oxytocin.

Driving and using machines

Freeflex Ringer Lactate does not affect the ability to drive or use machines.

3. How to use Freeflex Ringer Lactate

Follow exactly the administration instructions of this medicine indicated by your doctor or pharmacist. If you are in doubt, consult your doctor or pharmacist again.

Freeflex Ringer Lactate will always be administered under the direct supervision of your doctor, who will closely monitor the administered dose.

Freeflex Ringer Lactate is administered by slow injection into a vein (intravenous infusion). The speed and amount administered will depend on your needs and the disorder being treated.

The recommended dose is 500-2500 ml/day, at a speed of 40-60 drops/minute. Your doctor will indicate the duration of treatment with Freeflex Ringer Lactate.

Use in children

Children will be administered lower doses, proportional to their weight.

If you use more Freeflex Ringer Lactate than you should

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

• hyperhydration (edema, hypervolemia), disorders in the electrolyte balance 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.

• fluid 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 of 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 taste of calcium, burning, 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 used. 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 your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medicine and the amount ingested.

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

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 administration of a large volume of Freeflex Ringer Lactate solution), as well as allergic reactions.

Possible side effects are:

• Electrolyte disturbances
• Hospital hyponatremia*
• Acute hyponatremic encephalopathy*
• 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 urticaria, 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).

*Hospital hyponatremia can cause irreversible and potentially fatal brain damage due to the occurrence of acute hyponatremic encephalopathy, frequency not known.

When Freeflex Ringer Lactate 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.

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

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Freeflex Ringer Lactate

Store below 25°C.

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

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

Do not use this medicine if you notice that the solution is not transparent, free of particles, or the packaging is damaged.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Container Content and Additional Information

Freeflex CompositionRinger Lactate

• The active ingredients are: sodium lactate, sodium chloride, potassium chloride, and calcium chloride dihydrate. Each 100 ml of solution contains 317 mg of sodium lactate, 600 mg of sodium chloride, 40 mg of potassium chloride, and 27 mg of calcium chloride dihydrate.

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

Product Appearance and Container Content

Freeflex Ringer Lactate is an intravenous perfusion solution, transparent, colorless, and without visible particles, contained in freeflex? bags of 50 ml, 100 ml, 250 ml, 500 ml, and 1000 ml, with an overbag.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Fresenius Kabi España S.A.U.

Marina 16-18,

08005 – Barcelona

Spain

Manufacturer

Fresenius Kabi Deutschland GmbH

Freseniusstraße 1

61169, Friedberg

Germany

Or

HP Halden Pharma AS

Svinesundsveien 80

1788 Halden

Norway

Or

Fresenius Kabi France

6, Rue du Rempart B.P. 611

27400 Louviers Cedex

France

Date of Last Revision of this Prospectus: January 2020

Detailed information about 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 doctors or healthcare professionals:

This medication is administered by perfusion.

The content of each vial is for a 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.

To administer the solution and in case of addition of medications, maximum asepsis must be maintained. It is recommended to disinfect the rubber stopper before puncturing it with the injection equipment. 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 in 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 Freeflex Ringer Lactate solution or administering them simultaneously with other medications. It is recommended to consult the prospectus of the added medications, as well as verify if they are soluble and stable in aqueous solution at the pH of the Freeflex Ringer Lactate solution (pH 5.0 - 7.0).

When compatible medication is added, the solution must be administered immediately.

The Freeflex 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 Freeflex 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, which may cause the formation of clots. These clots could be perfused directly into the circulation and cause an embolism.

General Advice

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

Monitoring of serum sodium is especially important with hypotonic solutions.

Tonicity of Freeflex Ringer Lactate: 280 mOsmol/l.

The perfusion rate and volume depend on age, weight, and clinical picture (e.g., burns, surgery, head injury, infections); the responsible physician, with experience in pediatric treatments with perfusion solutions, must decide on the need for concomitant treatment.

INSTRUCTIONS FOR THE CORRECT ADMINISTRATION OF THE MEDICATION

Visual Inspection

1. Do not remove the freeflex? from its overbag until immediately before use.
2. Check the composition, batch number, and expiration date.
3. Inspect the set by checking the integrity of the primary container. Do not use if this container is not intact.

Removal of the Overbag

Some freeflex? bags have an overbag as protection during storage. The overbag, with a "peel" opening system, can be removed as follows:

1. Locate the tabs at the end where the bag ports are.
2. Separate the two halves of the overbag, leaving the bag on a clean surface.

Preparation for Administration

The freeflex? bags are designed for air-free administration. If a perfusion equipment with air entry is to be used, ensure that it is always closed.

1. Squeeze the freeflex? to ensure it does not have leaks and examine the solution to observe the presence of visible particles or precipitates. DO NOT ADMINISTER IF THE SOLUTION IS NOT TRANSPARENT AND/OR THE CONTAINER IS NOT INTACT.
2. Using an aseptic technique, prepare the perfusion equipment with the flow regulator closed.
3. Identify the administration port (blue) in the shape of an arrow indicating the exit of the bag.
4. Remove the protective cap from the administration port of the freeflex?, holding the lower fins firmly with one hand and breaking the cap in the shape of an arrow by means of a sustained twisting action.
5. Hold the base of the administration port by placing the fingers behind the protector and push the spike of the administration equipment firmly into the port. A slight resistance should be felt when the port membrane breaks. To prevent leaks, insert the spike to the bottom of the administration port.
6. Suspend the bag on the hanger and purge the administration equipment according to the manufacturer's instructions. Perform the venipuncture and immediately connect the administration equipment to the intravenous cannula. Adjust the flow regulator to achieve the desired drip rate.
7. The freeflex? bags are calibrated to indicate the approximate volume that has been infused. The scale should be read by stretching the bag and reading the volume on the upper surface of the liquid. For a more accurate measurement of the fluid volume, a administration equipment with a measuring chamber should be used.

To Add Medication

The freeflex? bags have a medication addition port that is independent and has a self-closing cap. Since the port is protected by a hermetically sealed protective cap, it is not necessary to disinfect the medication addition site before its first use.

Additions using Syringes

1. Identify the medication addition port (white) in the shape of an arrow indicating an entry flow to the bag.
2. Using an aseptic technique, prepare a syringe with the medication, using a 20-22 G needle.
3. Remove the protective cap from the medication addition port of the bag by holding the lower fins firmly with one hand and breaking the cap in the shape of an arrow by means of a sustained twisting action.
4. Hold the medication addition port by placing the fingers behind the protector and insert the needle completely, so that it pierces the outer cap and the inner membrane. Its rigid construction prevents any possibility of the needle penetrating the sides of the port.
5. Add the medication and withdraw the needle. To prevent any aerosol formation, a sterile swab should be kept around the cap.

The following maximum addition volumes are recommended:

Size of the freeflex? (ml) Maximum recommended addition (ml)

1. 70

1. 50

1. 75

1. 150

1. 150

NOTE: Additives may be incompatible, so expert advice should be sought before adding medication to freeflex?. If the physician decides to add medication, an aseptic technique should be used. It is recommended that the medication be added only under the supervision of a pharmacist. Do not store solutions to which medication has been added.

1. Shake and squeeze the freeflex? to ensure a complete mixture of the medication. With dense medications such as potassium chloride, it is advisable to squeeze both ports while the bag is in a vertical position and invert the bag several times.
2. If necessary, a protective cap can be placed over the medication addition port to prevent subsequent additions.

Additions using Reconstitution Equipment

1. Identify the medication addition port (white) in the shape of an arrow indicating an entry flow to the bag.
2. Remove the protective cap from the medication addition port of the bag by holding the lower fins firmly with one hand and breaking the cap in the shape of an arrow by means of a sustained twisting action.
3. Using an aseptic technique, remove the reconstitution equipment from its packaging and push the narrow end over the medication addition port of the bag so that the port fins fit with the grooves of the reconstitution equipment. Stop when the upper surface of the fins reaches the first stop of the groove. In this position, the upper part of the needle of the reconstitution equipment is between the cap and the inner membrane, so that fluid cannot escape from the freeflex?.
4. Using an aseptic technique, prepare the vial of the medication and connect it to the open end of the reconstitution equipment.
5. Connect the medication to the intravenous solution by turning the reconstitution equipment so that the port fins fit with the inner groove and pushing the vial and the reconstitution equipment until the upper surface of the fins reaches the second stop.
6. With the vial inverted, squeeze and release the freeflex? several times to transfer solution to the medication vial. Shake to dissolve the medication. NOTE:If the medication is a liquid, this step 6 can be omitted.
7. Invert the freeflex? so that the vial is above the bag and transfer the medication to the bag by squeezing and releasing the bag several times so that the sterile air pushes the liquid out of the vial.
8. If the solubility of the medication is low, it may be necessary to repeat steps 6 and 7.
9. When the transfer is complete, remove the reconstitution equipment from the freeflex? and discard the vial and the reconstitution equipment in a safe place. The reconstitution equipment is designed for single use and should not be used for subsequent additions to this or another freeflex?.

NOTE: Additives may be incompatible, so expert advice should be sought before adding medication to freeflex?. If the physician decides to add medication, an aseptic technique should be used. It is recommended that the medication be added only under the supervision of a pharmacist. Do not store solutions to which medication has been added.

1. Shake and squeeze the freeflex? to ensure a complete mixture of the medication. With dense medications such as potassium chloride, it is advisable to squeeze both ports while the bag is in a vertical position and invert the bag several times.
2. If necessary, a protective cap can be placed over the medication addition port to prevent subsequent additions.

Warnings:

1. Do not vent
2. Do not administer if the solution is not transparent and the freeflex?is not intact
3. If adverse reactions appear, stop the perfusion
4. It is recommended that perfusion equipment be changed at least every 24 hours

Partially used freeflex?bags must be discarded