Freeflex Ringer lactate solution for infusion

Package leaflet: Information for the user

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

Contents of this leaflet:

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

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

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

Freeflex Ringer Lactate solution belongs to the group of medicines known as infusion solutions.

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

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

As a vehicle for the administration of compatible medications.

2. What you need to know before using 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 diagnosed with excess fluid in the body (hyperhydration or hypervolemia) and this causes swelling (edema).
• if you suffer from high blood pressure problems.
• if you have excess potassium, sodium, calcium, or chloride in your body.
• if the fluids in your body are too alkaline (metabolic alkalosis).
• if the fluids in your body are excessively acidic (severe metabolic acidosis).
• if you have been diagnosed with high levels of lactic acid in the blood.
• if you suffer from severe kidney or liver disease.
• if you suffer from 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.

Take special care with Freeflex Ringer Lactate:

• If your kidney, heart, and/or lungs are not functioning properly. In such cases, administration of large volumes of this solution must be carried out under strict clinical monitoring.

• It is advisable that during administration of this solution, regular monitoring of your clinical condition and blood and urine tests (electrolytes in blood and urine, acid-base balance, hematocrit) are performed. Blood potassium levels should be monitored if you are at risk of hyperkalemia (high potassium levels in blood).

If you have any of the following conditions, this medicine will be administered with special caution and you may require additional tests to determine whether you can receive the medicine:

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

• Due to the presence of potassium: If you suffer from heart diseases or other conditions that may cause elevated blood potassium levels, such as renal or adrenocortical insufficiency, acute dehydration, or massive tissue destruction, as occurs in extensive burns.

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

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

• If you have severe potassium deficiency. Although Freeflex Ringer Lactate solution has a potassium concentration similar to plasma, this concentration is insufficient to produce a beneficial effect in such situations.

• If your liver is not functioning properly, Freeflex Ringer Lactate solution may not exert its intended effect, as lactate metabolism may be impaired.

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

Large-volume infusions require special monitoring in patients with cardiac or pulmonary insufficiency and in patients with non-osmotic release of vasopressin (including SIADH), due to the risk of hospital-acquired hyponatremia.

Hyponatremia:

Patients with non-osmotic release of vasopressin (e.g., in critical conditions, pain, postoperative stress, infections, burns, and CNS disorders), patients with heart, liver, or kidney diseases, and patients exposed to vasopressin agonists are at particular risk of developing acute hyponatremia following infusion of hypotonic solutions.

Acute hyponatremia may cause acute hyponatremic encephalopathy (cerebral edema), characterized by headache, nausea, seizures, lethargy, and vomiting. Patients with cerebral edema are at particular risk of suffering severe, irreversible, and potentially fatal brain damage.

Children, women of childbearing age, and patients with reduced cerebral compliance (e.g., in cases of meningitis, intracranial hemorrhage, cerebral contusion, and cerebral edema) are at particular risk of 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.

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

Use of Freeflex Ringer Lactate with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Certain medicines may interact with Ringer's Lactate solution. In such cases, it may be necessary to adjust the dose or discontinue treatment with one of the medicines.

In general, concomitant administration of Freeflex Ringer Lactate solution with any medicine that has or may have renal toxicity should be avoided, as it may lead to fluid and electrolyte retention.

It is important that you inform your doctor if you are taking any of the following medicines, as they may interact with the electrolytes present in 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)
• Cardiotonic digitalis glycosides (digoxin, methyldigoxin)
• Thiazide diuretics (hydrochlorothiazide, altizide, mebutizide, bendroflumethiazide) or vitamin D
• Acidic medicines such as salicylates and/or barbiturates
• Alkaline medicines such as sympathomimetics (ephedrine, pseudoephedrine) and/or stimulants (amphetamine, dexamphetamine)
• Medicines that enhance the effect of vasopressin:

The following medicines increase the effect of vasopressin, thereby reducing renal excretion of electrolyte-free water and increasing the risk of hospital-acquired hyponatremia when receiving inadequately balanced infusion therapy.

• Medicines that stimulate vasopressin release; include, among others:

chlorpropamide, clofibrate, carbamazepine, vincristine, selective serotonin reuptake inhibitors, 3,4-methylenedioxy-N-methamphetamine (MDMA), ifosfamide, antipsychotics, narcotics

• Medicines that potentiate the action of vasopressin; include, among others:

chlorpropamide, NSAIDs, cyclophosphamide

• Vasopressin analogs; include, among others:

desmopressin, oxytocin, vasopressin, terlipressin

• Other medicines known to increase the risk of hyponatremia include diuretics in general and antiepileptic drugs such as oxcarbazepine.

Use of Freeflex Ringer Lactate with food and drink

No interaction with food or drink 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 labor, and special monitoring of serum sodium is 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 machinery.

3. How to use Freeflex Ringer Lactate

Follow exactly the administration instructions for this medicine as given by your doctor or pharmacist. If 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 dose administered.

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

The recommended dose is 500–2,500 ml/day, at a rate of 40–60 drops/minute. Your doctor will determine the duration of treatment with Freeflex Ringer Lactate.

Use in children

Children will receive lower doses, adjusted according to body weight.

If you use more Freeflex Ringer Lactate than you should

In case of overdose or administration that is too rapid, the following symptoms may occur:

• Hyperhydration (edema, hypervolemia), disturbances in electrolyte balance and/or induction of metabolic alkalosis, especially in patients with impaired renal function. In such cases, administration will be reduced or discontinued, and symptomatic treatment will be initiated. If renal function is compromised, dialysis may be necessary.

• Water and sodium overload with risk of edema, particularly when there is defective renal sodium excretion.

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

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

Excessive administration of sodium lactate may lead to hypokalemia and metabolic alkalosis. Symptoms may include changes in behavior, fatigue, respiratory insufficiency, muscle weakness, and irregular heartbeat. Particularly in hypocalcemic patients, increased muscle tone, muscle spasms, and tetany (neuromuscular hyperexcitability) may develop. Treatment of metabolic alkalosis associated with bicarbonate overdose primarily involves appropriate correction of fluid and electrolyte balance.

When overdose is related to medication added to the infused solution, signs and symptoms of over-infusion may be related to the nature of the added medication. In case of accidental overdose, treatment should be discontinued immediately and the patient should be observed for symptoms and signs related to the administered drug. If necessary, appropriate symptomatic and supportive measures should be taken.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number 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 adverse effects

Like all medicines, this medicine may produce adverse effects, although not everyone experiences them.

The most commonly reported adverse effects are fluid overload (oedema) and electrolyte disturbances (mainly after administration of a large volume of Freeflex Ringer Lactate solution), as well as allergic reactions.

Possible adverse effects include:

• Electrolyte disturbances
• Hospital-acquired hyponatraemia*
• Acute hyponatraemic encephalopathy*
• Venous thrombosis (blood clots), phlebitis (vein inflammation) (associated with intravenous administration)
• Nasal congestion, cough, sneezing, breathing difficulty during administration of the solution, chest pain with alteration of heart rhythm
• Allergic reactions such as urticaria, skin rashes, skin redness, itching, swelling, fluid accumulation in tissues
• Fluid overload (oedema)
• Fever, injection site infection, local reaction or local pain (associated with intravenous administration)

*Hospital-acquired hyponatraemia may cause irreversible brain damage and death due to the development of acute hyponatraemic encephalopathy, frequency not known.

When Freeflex Ringer Lactate is used as a vehicle to administer other medicines, adverse effects may be related to the added medicines.

If any adverse effects occur, the infusion should be stopped immediately.

If you consider any of the adverse effects you experience to be severe, or if you notice any adverse effects not listed in this leaflet, inform your doctor or pharmacist.

Reporting of adverse effects

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

5. Storage of Freeflex Ringer's Lactate

Store below 25°C.

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

Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date is the last day of the month indicated.

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

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

6. Contents of the pack and other information

Composition of FreeflexRinger Lactate

• The active substances 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.

• Other components are: hydrochloric acid and/or sodium hydroxide (for pH adjustment) and water for injections.

Appearance of the product and contents of the pack

Freeflex Ringer Lactate is an intravenous infusion solution, transparent, colourless and free from visible particles, contained in freeflex® bags of 50 ml, 100 ml, 250 ml, 500 ml and 1000 ml, with an overpouch.

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 the most recent review of this summary: January 2020

Detailed information on this medicine is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/

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This information is intended exclusively for doctors or healthcare professionals:

This medicine is administered by infusion.

The contents of each vial are for single use only. Once the container has been opened, the solution must be administered immediately and any unused portion must be discarded.

The solution must be clear and free from precipitates. Do not administer if otherwise.

To administer the solution and when adding medications, maximum asepsis must be maintained. It is advisable to disinfect the rubber stopper before piercing it with the injection device. From a microbiological standpoint, when the solution is used as a vehicle for other medicines, it should be used immediately unless dilution has been carried out under controlled, aseptic, and validated conditions. If not used immediately, the conditions and duration of storage during use are the responsibility of the user.

Compatibility tables should be consulted before adding medications to Freeflex Ringer Lactate solution or administering it simultaneously with other medicines. The package leaflet of the added medicines should be reviewed, and solubility and stability in aqueous solution at the pH of Freeflex Ringer Lactate (pH 5.0–7.0) should be verified.

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

Freeflex Ringer Lactate solution must not be used as a vehicle for medicines containing ions capable of causing the formation of insoluble calcium salts.

It is recommended not to mix or administer Freeflex Ringer Lactate solution simultaneously in the same infusion set with whole blood or blood components preserved with a citrate-containing anticoagulant (such as CPD), because the calcium ions present in this solution may exceed the chelating capacity of citrate, potentially leading to clot formation. These clots could be infused directly into the circulation and cause embolism.

General advice

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

Monitoring of serum sodium is particularly important with hypotonic solutions.

Tonicity of Freeflex Ringer Lactate: 280 mOsmol/L.

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

INSTRUCTIONS FOR CORRECT ADMINISTRATION OF THE MEDICINE

Visual inspection

1. Do not remove the freeflex® from its overpouch until immediately before use.
2. Check the composition, batch number, and expiration date.
3. Inspect the unit to verify the integrity of the primary packaging. Do not use if the container is not intact.

Removal of the overpouch

Some freeflex® units have an overpouch for protection during storage. The overpouch, with a “peel” opening system, can be removed as follows:

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

Preparation for administration

Freeflex® bags are designed for administration without air entry. If an infusion set with air entry is used, ensure it remains closed at all times.

1. Squeeze the freeflex® to ensure there are no leaks and examine the solution for visible particles or precipitates. DO NOT ADMINISTER IF THE SOLUTION IS NOT CLEAR AND/OR THE CONTAINER IS NOT INTACT.
2. Using an aseptic technique, prepare the infusion set with the flow regulator closed.
3. Identify the administration port (blue), arrow-shaped, indicating the outlet from the bag.
4. Remove the protective plug from the administration port of the freeflex® by firmly holding the lower wings with one hand and breaking off the arrow-shaped plug with a steady twisting motion.
5. Hold the base of the administration port, placing fingers behind the protector, and firmly insert the spike of the administration set into the port. A slight resistance should be felt as the port membrane is punctured. To prevent leakage, insert the spike fully into the administration port.
6. Hang the bag on the stand and prime the administration set according to the manufacturer's instructions. Perform venipuncture and immediately connect the administration set to the intravenous cannula. Adjust the flow regulator to achieve the desired drip rate.
7. Freeflex® bags are calibrated to indicate the approximate infused volume. The scale should be read by stretching the bag and reading the volume at the upper surface of the liquid. For more accurate measurement of fluid volume, an administration set with a measuring chamber should be used.

To add medication

Freeflex® bags have a separate medication addition port with a self-sealing stopper. Since the port is protected by a hermetically sealed protective plug, disinfection of the medication addition site is not necessary before first use.

Additions using syringes

1. Identify the medication addition port (white), arrow-shaped, indicating inflow into the bag.
2. Using an aseptic technique, prepare a syringe with the medication using a 20–22 G needle.
3. Remove the protective plug from the medication addition port of the bag by firmly holding the lower wings with one hand and breaking off the arrow-shaped plug with a steady twisting motion.
4. Hold the medication addition port, placing fingers behind the protector, and fully insert the needle so that it pierces both the outer stopper and the inner membrane. Its rigid construction prevents the needle from penetrating the sides of the port.
5. Add the medication and withdraw the needle. To prevent aerosol formation, a sterile swab should be held around the stopper.

The following maximum addition volumes are recommended:

| Freeflex® size (ml) | Maximum recommended addition (ml) | |---------------------|-----------------------------------| | 100 | 70 | | 250 | 50 | | 500 | 75 | | 1000 | 150 | | 3000 | 150 |

NOTE: Additives may be incompatible; therefore, expert advice should be sought before adding medication to freeflex®. If the physician decides to add medication, an aseptic technique must be used. It is recommended that 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 complete mixing of the medication. With dense medications such as potassium chloride, it is advisable to squeeze both ports while the bag is in vertical position and invert the bag several times.
2. If necessary, a protective plug may be placed over the medication addition port to prevent further additions.

Additions using reconstitution devices

1. Identify the medication addition port (white), arrow-shaped, indicating inflow into the bag.
2. Remove the protective plug from the medication addition port of the bag by firmly holding the lower wings with one hand and breaking off the arrow-shaped plug with a steady twisting motion.
3. Using an aseptic technique, remove the reconstitution device from its packaging and push the narrow end onto the medication addition port so that the wings of the port align with the slots of the reconstitution device. Stop when the upper surface of the wings reaches the first stop in the slot. In this position, the tip of the reconstitution device needle is positioned between the stopper and the inner membrane, preventing fluid from escaping the freeflex®.
4. Using an aseptic technique, prepare the medication vial and connect it to the open end of the reconstitution device.
5. Connect the medication to the intravenous solution by rotating the reconstitution device so that the wings of the port align with the inner slot, and push the vial and reconstitution device together until the upper surface of the wings reaches the second stop.
6. With the vial inverted, squeeze and release the freeflex® several times to transfer solution into the medication vial. Shake to dissolve the medication. Note: If the medication is a liquid, step 6 may 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, allowing sterile air to push the liquid out of the vial.
8. If the medication has low solubility, steps 6 and 7 may need to be repeated.
9. Once transfer is complete, remove the reconstitution device from the freeflex® and safely discard the vial and reconstitution device. The reconstitution device is designed for single use and must not be reused for subsequent additions to this or another freeflex®.

NOTE: Additives may be incompatible; therefore, expert advice should be sought before adding medication to freeflex®. If the physician decides to add medication, an aseptic technique must be used. It is recommended that 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 complete mixing of the medication. With dense medications such as potassium chloride, it is advisable to squeeze both ports while the bag is in vertical position and invert the bag several times.
2. If necessary, a protective plug may be placed over the medication addition port to prevent further additions.

Warnings:

1. Do not vent
2. Do not administer if the solution is not clear and the freeflex® is not intact
3. If adverse reactions occur, stop the infusion
4. It is recommended that infusion sets be changed at least once every 24 hours

Partially used freeflex® units must be discarded