Ringer's acetate FKI

Package leaflet: Information for the user

RINGER ACETATO FRESENIUS KABI ITALIA infusion solution

Generic Medicine
Please read all of this leaflet carefully before you use this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

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

1. What RINGER ACETATO FRESENIUS KABI ITALIA is and what it is used for

RINGER ACETATO FRESENIUS KABI ITALIA is an infusion solution to be injected directly into a vein, containing a combination of active substances: sodium chloride, potassium chloride, calcium chloride dihydrate, and sodium acetate trihydrate.
This medicinal product is indicated to provide water and electrolytes to the body following losses of extracellular fluids and electrolytes, thereby restoring normal electrolyte levels necessary for proper body function, and to re-establish normal blood pH when mild or moderate acidosis (increased acidity) occurs.

2. What you should know before using RINGER ACETATE FRESENIUS KABI ITALIA

Take special care if:

• you suffer from acute illnesses, pain, postoperative stress, infections, burns, or diseases of the central nervous system;
• you have any type of heart, liver, or kidney disease;
• you have been treated with a medicine that enhances the effect of vasopressin (a hormone regulating water retention in the body), as this may increase the risk of hospitalization;
• you have low levels of sodium in the blood (hyponatremia).

Do not use RINGER ACETATE FRESENIUS KABI ITALIA

• if you are allergic to sodium chloride, potassium chloride, calcium chloride dihydrate, sodium acetate trihydrate, or any of the other ingredients of this medicine (listed in section 6);
• if you have severe kidney problems (renal failure);
• if you have high levels of calcium in the blood (hypercalcemia) or in the urine (hypercalciuria), or suffer from severe kidney diseases;
• if you have high levels of sodium in the blood (hypernatremia) or other mineral salts (water-salt overload);
• if you have high levels of potassium in the blood (hyperkalemia) or reduced ability to excrete potassium (potassium retention);
• if you have a heart rhythm disorder called ventricular fibrillation, because calcium chloride may increase the risk of heart rhythm irregularities (arrhythmias);
• if you have kidney stones, which may worsen with calcium administration;
• if you have a chronic systemic disease called sarcoidosis, which may exacerbate increased calcium levels in the blood (hypercalcemia);
• if you have severe liver problems (severe hepatic insufficiency);
• if you have circulatory problems due to high blood coagulability (hypercoagulability);
• if you are taking heart medications called cardioactive glycosides (see section "Other medicines and RINGER ACETATE FRESENIUS KABI ITALIA");
• if you have adrenal gland disease (Addison's disease) and are not receiving treatment for it;
• if you experience painful, short-duration muscle cramps (heat cramps);
• if the patient is a newborn (under 28 days of age), RINGER ACETATE FRESENIUS KABI ITALIA (or other calcium-containing solutions) must not be administered simultaneously with ceftriaxone (an antibiotic), even if separate infusion lines are used. There is a risk of fatal formation of particles in the newborn's bloodstream.

If you have recently received blood transfusions, this solution must not be administered through the same infusion catheter used for whole blood due to the possible risk of coagulation.

Warnings and precautions

Talk to your doctor or nurse before using RINGER ACETATE FRESENIUS KABI ITALIA.

This medicine must be administered via a very slow infusion, as potassium intoxication may occur, which can lead to death due to loss of heart function (cardiac depression), heart rhythm irregularities (arrhythmias), up to cardiac arrest (see section "How to use RINGER ACETATE FRESENIUS KABI ITALIA").

Due to the presence of sodium, this medicine must be administered with caution in the following cases:

• if you have heart problems (congestive heart failure, cardiac insufficiency) or kidney problems (severe renal failure, reduced kidney function);
• if you have fluid accumulation (edema with salt retention), either in the lungs (pulmonary edema) or associated with swelling of the ankles and legs (peripheral edema);
• if you are taking heart medications (cardiotropic inotropic drugs) or anti-inflammatory corticosteroid drugs or hormonal medications (corticotropin-related);
• if you have high blood pressure (hypertension);
• if you have a condition called pre-eclampsia, characterized by high blood pressure, swelling due to fluid retention, and presence of protein in the urine, or other conditions caused by sodium accumulation.

Due to the presence of potassium, this medicine must be administered with caution in the following cases:

• if you have severe kidney problems (renal failure), as it may cause potassium retention;
• if you have heart problems (cardiac insufficiency) and are taking other heart medications (digitalis);
• if you have adrenal gland disease (adrenal insufficiency);
• if you have severe liver problems (hepatic insufficiency);
• if someone in your family suffers from a disorder characterized by sudden episodes of muscle weakness (familial periodic paralysis);
• if you have a condition characterized by muscle stiffness (congenital myotonia);
• if you have recently undergone surgery (early postoperative phase).

Due to the presence of calcium, this medicine must be administered with great caution in the following cases:

• if you have kidney (renal failure) or heart problems, as it may increase the risk of heart rhythm irregularities (arrhythmias);
• if you have received a blood transfusion, as calcium ion concentrations may differ from expected levels;
• if you have lung problems that may cause heart enlargement (pulmonary heart disease);
• if you have breathing difficulties (respiratory failure) or a decreased blood pH (respiratory acidosis);
• if you have low body water levels (dehydration) or an electrolyte imbalance (electrolyte imbalance);
• if you have low blood pressure, because administration of calcium chloride may cause vasodilation leading to further lowering of blood pressure. Calcium chloride solution is irritating and therefore must not be administered by intramuscular injection, subcutaneous injection, or into tissue surrounding blood vessels (peri-vascular), as tissue damage and tissue death (necrosis) may occur.

Due to the presence of acetate, the medicine must be used cautiously in individuals with increased pH (metabolic and respiratory alkalosis) or elevated blood acetate levels, such as in individuals with liver problems (mild or moderate hepatic insufficiency).

The infusion must be stopped immediately if signs or symptoms of suspected hypersensitivity develop.

During treatment with this medicine, your doctor must periodically monitor heart function via electrocardiograms and monitor blood levels of electrolytes, fluids, osmolarity, and pH.

Blood and urine calcium levels must be frequently monitored to prevent hypercalciuria (elevated calcium levels in urine), which may lead to increased calcium levels in the blood (hypercalcemia).

All patients must be closely monitored. In cases where normal regulation of blood water content is affected due to increased vasopressin secretion (also known as antidiuretic hormone), infusion of fluids with low sodium chloride concentration (hypotonic fluids) may lead to low sodium levels in the blood (hyponatremia). This may result in headache, nausea, seizures, lethargy, coma, brain swelling (cerebral edema), and death. Consequently, these symptoms (acute symptomatic hyponatremic encephalopathy) are considered a medical emergency (see also section "Possible side effects").

Children, women of childbearing age, and patients with brain diseases such as meningitis, cerebral hemorrhage, cerebral contusion, and cerebral edema are particularly at risk of life-threatening cerebral edema caused by acute hyponatremia.

This medicine must be used immediately after opening the container. The solution must be clear, colorless, and free from visible particles and is intended for single, uninterrupted administration. Any remaining solution must not be reused.

Children and adolescents

As with other calcium-containing solutions, concomitant treatment with ceftriaxone is contraindicated in newborns (under 28 days of age) due to the risk of fatal precipitation of ceftriaxone-calcium salt in the newborn's bloodstream (see section "Possible unwanted effects").

Children are particularly at risk of life-threatening cerebral edema caused by acute hyponatremia.

Other medicines and RINGER ACETATE FRESENIUS KABI ITALIA

Inform your doctor if you are taking, have recently taken, or might take any other medicines, especially if you are taking:

• medicines that stimulate vasopressin release: chlorpropamide, clofibrate, carbamazepine, vincristine, selective serotonin reuptake inhibitors, 3,4-methylenedioxymethamphetamine (MDMA), ifosfamide, antipsychotics, narcotics;
• medicines that enhance vasopressin action: chlorpropamide, NSAIDs, cyclophosphamide;
• vasopressin analogs: desmopressin, oxytocin, vasopressin, terlipressin;
• other medicines that increase the risk of hyponatremia, including diuretics in general and antiepileptics such as oxcarbazepine.

This medicine must be administered with caution if you are taking:

• angiotensin II receptor antagonists;
• immunosuppressants such as tacrolimus and cyclosporine;
• medicines used to lower blood pressure such as potassium-sparing diuretics, ACE inhibitors, or other medicines causing decreased aldosterone levels, as they may lead to increased potassium in the blood (hyperkalemia); in such cases, blood potassium levels must be closely monitored;
• anti-inflammatory steroid medicines (corticosteroids) that may cause sodium and water retention, leading to fluid accumulation (edema) and increased blood pressure (hypertension).

Due to the presence of calcium chloride, RINGER ACETATE FRESENIUS KABI ITALIA may interact with the following medicines:

• thiazide diuretics, used to treat high blood pressure, as they may cause increased calcium levels in the blood (hypercalcemia) due to reduced renal calcium excretion;
• cardioactive glycosides (digitalis), digoxin and digitoxin, used for heart problems, as concomitant use may increase the risk of heart rhythm irregularities (arrhythmias), considering that inotropic and toxic effects are synergistic;
• verapamil (and other calcium channel blockers), used to treat high blood pressure, as concomitant use may reduce verapamil's antihypertensive effect;
• magnesium-containing medicines, as they may increase the risk of elevated calcium (hypercalcemia) or magnesium (hypermagnesemia) levels, especially in patients with kidney disorders;
• neuromuscular blockers, as calcium salts may counteract the effect of non-depolarizing blockers; in some cases, increased and prolonged action of tubocurarine has also been observed;
• ceftriaxone (an antibiotic) due to the risk of particle formation.

Pregnancy and breastfeeding

If you are pregnant, suspect you may be pregnant, planning pregnancy, or breastfeeding, consult your doctor before this medicine is administered.

Ringer Acetate Fresenius Kabi Italia must be administered with particular caution in pregnant women during labor, especially if administered in combination with oxytocin (a hormone that may induce labor and control bleeding), due to the risk of hyponatremia.

This medicine must not be used during pregnancy or breastfeeding unless absolutely necessary.

Driving and using machines

This medicine does not affect the ability to drive or operate machinery.

3. How to use RINGER ACETATO FRESENIUS KABI ITALIA

This medicine will be prepared by a doctor, pharmacist, or nurse and will not be mixed or administered simultaneously with injections containing ceftriaxone.
This medicine must be administered directly into a vein (intravenous infusion) by trained medical personnel. It must not be injected via other routes of administration (intramuscular, subcutaneous, or into perivascular tissues).
This medicine must be administered only if your kidney function is intact and at a rate not exceeding 10 mEq of potassium per hour.
After administration of the medicine, remain lying down for a short period.
The dose will be adjusted according to your age, body weight, and clinical condition.
The recommended dose in adults is approximately 20–30 ml of solution per kg of body weight per day, which may be increased up to a maximum of 40 ml of solution per kg of body weight per day.
Infusions that are too rapid may cause local pain; the infusion rate must be adjusted according to tolerance.
Administration must be stopped if you experience pain or redness at the injection site, as this may be due to leakage of the medicine from the vein (drug extravasation).
Preparation of the medicine: Use the solution immediately after opening the container. The container is intended for single, uninterrupted administration, and any remaining solution must not be used.
Shake well before administration. Do not use the medicine if the solution is not clear and colourless or if it contains particles.
Ensure all precautions are taken to maintain sterility before and during intravenous infusion.
If you use more RINGER ACETATO FRESENIUS KABI ITALIA than you should
This medicine will be administered by a doctor or trained healthcare professional; therefore, it is unlikely that you will receive an excessive dose. However, if you think you have been given too much RINGER ACETATO FRESENIUS KABI ITALIA, inform your doctor or another healthcare professional immediately.
Following administration of an excessive dose of this medicine, the following may occur:

• increased levels of potassium in the blood (hyperkalaemia), which may lead to death due to heart damage (cardiac depression, arrhythmias, or arrest);
• increased levels of sodium (hypernatraemia) and increased blood volume (hypervolaemia). If sodium levels in the blood rise too much, fluid loss from internal organs (dehydration), particularly from the brain, may occur, as well as fluid accumulation affecting the cerebral, pulmonary, and peripheral circulation, leading to fluid buildup around the lung (pulmonary oedema) or swelling in the legs and ankles (peripheral oedema);
• increased levels of chloride causing a decrease in blood pH (acidosis) due to reduced bicarbonate ion concentration;
• increased levels of calcium in the blood (hypercalcaemia), resulting in thirst, nausea, vomiting, constipation, increased urine production (polyuria), abdominal pain, muscle weakness, mental disturbances, and in severe cases, heart problems (cardiac arrhythmia) and coma.

If you have any doubts about how to use RINGER ACETATO FRESENIUS KABI ITALIA, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
The following side effects may occur, especially in case of inadequate administration or administration that is too rapid (see section "Warnings and precautions").
The following adverse reactions may occur:
Not known (frequency cannot be estimated from the available data):

• gastrointestinal disturbances and irritation, nausea, vomiting, diarrhoea, abdominal pain, constipation;
• thirst, reduced salivation, metallic taste, chalky taste;
• neuromuscular disturbances, muscle stiffness, altered sensation in limbs (paraesthesia), loss of muscle tone (flaccid paralysis), weakness;
• mental confusion, headache, dizziness, restlessness, irritability;
• seizures, coma, death;
• drowsiness, confusional states, psychiatric disorders;
• irregular heartbeat (arrhythmias), tachycardia, bradycardia, conduction disturbances, disappearance of the P wave, widening of the QRS complex on the electrocardiogram, syncope, ventricular fibrillation, cardiac arrest;
• reduction or increase in blood pressure (hypotension, hypertension), swelling of limbs (peripheral oedema), vasodilation, hot flushes;
• increased or decreased levels of sodium (hypernatraemia/hyponatraemia), chloride (hyperchloraemia), and blood volume (hypervolaemia);
• breathing difficulties (dyspnoea, respiratory arrest);
• fluid accumulation in the lungs (pulmonary oedema) and air around the lung (pneumothorax), chest tightness, chest pain;
• reduced tear production;
• kidney problems (renal failure), increased urine production (polyuria);
• increased levels of calcium in the blood (hypercalcaemia);
• Burnett's syndrome (also known as milk-alkali syndrome), a condition caused by excessive intake of milk or alkaline compounds, characterised by symptoms such as nausea, vomiting, headache, muscle weakness;
• overhydration, electrolyte imbalances;
• muscle weakness;
• fever, infection at the infusion site, pain or local reaction, redness, rash;
• circulatory problems due to blood clot formation in veins (thrombosis);
• inflammation of veins at the infusion site (phlebitis);
• leakage of medicine into surrounding tissues at the injection site (extravasation);
• tissue damage and death (tissue necrosis);
• abscess formation and calcium deposits in the skin (cutaneous calcification);
• kidney problems caused by calcium-ceftriaxone deposits. Pain during urination or reduced urine output may occur;
• hypersensitivity reactions to the infusion, including anaphylactic/anaphylactoid reactions;
• localized or generalized urticaria;
• headache, nausea, convulsive seizures, lethargy, and vomiting. This may be caused by low sodium levels in the blood. When blood sodium levels become very low, water enters brain cells and causes them to swell. This leads to increased intracranial pressure and results in hyponatraemic encephalopathy.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at the following website: http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store RINGER ACETATE FRESENIUS KABI ITALIA

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 refers to the last day of that month.
Store in the original packaging and in a tightly closed container. Do not freeze.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What RINGER ACETATE FRESENIUS KABI ITALIA contains

• The active substances are: sodium chloride, potassium chloride, calcium chloride dihydrate, sodium acetate trihydrate. 1000 ml of solution contain 6.0 g of sodium chloride, 0.3 g of potassium chloride, 0.22 g of calcium chloride dihydrate, 4.0 g of sodium acetate trihydrate (Each liter of solution contains 132 mEq of sodium, 4 mEq of potassium, 3 mEq of calcium, 110 mEq of chloride and 29 mEq of acetate). pH: 6.0 - 7.0
• The other components are water for injections and hydrochloric acid for pH adjustment.

Description of the appearance of RINGER ACETATE FRESENIUS KABI ITALIA and contents of the
package
Glass vial of 50 ml, 100 ml, 250 ml, 500 ml, 20x500 ml and 1000 ml.
Flexible bag of 100 ml, 250 ml, 500 ml and 1000 ml.
Plastic vial of 250 ml, 500 ml, 24x500 ml.
PE vial of 250 ml, 20x250 ml, 30x250 ml, 500 ml, 10x500 ml and 20x500 ml.
Marketing Authorization Holder
Fresenius Kabi Italia S.r.l.
Via Camagre, 41
37063 Isola della Scala (VR)
Italy
Manufacturer
Fresenius Kabi Italia S.r.l. Via Camagre, 41 – 37063 Isola della Scala (VR) – Italy
Fresenius Kabi Deutschland GmbH – Freseniusstrasse 1 - 61169 Friedberg – Germany
Fresenius Kabi France – 6, rue du Rempart BP 611 – 27400 Louviers Cedex – France
Fresenius Kabi Polska Sp. z o.o – ul. Sienkiewicza 25 – 99-300 Kutno – Poland
Fresenius Kabi España s.a. – Dr Ferran, 12 – Vilassar de Dalt – E-08339 Barcelona - Spain
S.M. Farmaceutici S.r.l. – Zona Industriale – 85050 Tito (PZ) – Italy

The following information is intended exclusively for physicians or healthcare professionals

Dosage and administration
The solution is isotonic with blood and must be administered cautiously by intravenous infusion at a controlled infusion rate.
Electrolyte balance, serum electrolytes, and acid-base status should be monitored before and during administration, with particular attention to serum sodium in patients with non-osmotic vasopressin release (syndrome of inappropriate antidiuretic hormone secretion, SIADH) and in patients receiving concomitant therapy with vasopressin agonists, due to the risk of hospital-acquired hyponatremia (see sections 4.4, 4.5, and 4.8 of the Summary of Product Characteristics).
Monitoring of serum sodium is particularly important for physiologically hypotonic solutions.
Tonicity of Ringer Acetate Fresenius Kabi Italia: 277 mOsm/L.
The infusion rate and volume depend on age, body weight, and clinical condition (e.g., burns, surgical procedures, head injuries, infections).
For pediatric patients, the dose and rate of administration must be determined by a physician experienced in pediatric intravenous fluid therapy. Concomitant therapy must be determined by a physician experienced in pediatric intravenous solutions (see sections 4.4 and 4.8).

Management of overdose
Immediately discontinue the infusion and initiate corrective therapy to reduce plasma levels of excess ions and, if necessary, restore acid-base balance (see section Warnings and Precautions).
The patient should be closely observed for the onset of any signs and symptoms related to the administered drug, with appropriate symptomatic and supportive measures provided as needed.
In cases of severe hypernatremia, loop diuretics may be used.
In cases of hyperkalemia, intravenous glucose (with or without insulin) or sodium bicarbonate may be administered.
In cases of mild calcium chloride overdose, treatment includes immediate discontinuation of the infusion and of any other calcium-containing medications. In cases of severe overdose (plasma concentrations >2.9 mmol/L), the following measures should be taken:

• Rehydration by administration of 0.9% sodium chloride solution;
• Use of non-thiazide diuretics to enhance calcium excretion;
• Monitoring of plasma potassium and calcium levels, with immediate correction to normal values;
• Monitoring of cardiac function and use of beta-blockers to reduce the risk of cardiac arrhythmias;
• Hemodialysis if necessary. Elevated plasma electrolyte levels may require dialysis.

Incompatibilities
If used to dilute medications, consult a pharmacist, if available, before adding any medicinal products; always consider the characteristics of the products to be added; use aseptic techniques.
Due to the presence of calcium chloride, the medicinal product is incompatible with:

• Magnesium sulfate: formation of a precipitate;
• Medicinal products containing phosphate: formation of calcium phosphate precipitate;
• Medicinal products containing carbonate: formation of calcium carbonate precipitate;
• Medicinal products containing tartrate: formation of calcium tartrate precipitate.

Incompatibilities of calcium chloride have been observed with:

• Aminophylline: due to precipitate formation;
• Amphotericin B: due to cloudiness development;
• Cefamandole: due to presence of sodium carbonate in the cefamandole preparation;
• Cephalothin: due to physical incompatibility;
• Cefradine: due to presence of sodium carbonate in the cefradine preparation;
• Ceftriaxone sodium: due to precipitate formation; therefore, calcium-containing solutions must not be administered within 48 hours following ceftriaxone administration;
• Chlorpheniramine: due to physical incompatibility;
• Dobutamine: due to cloudiness development;
• Fat emulsion: due to flocculation;
• Sodium heparin;
• Indomethacin: due to precipitate formation;
• Sodium nitrofurantoin;
• Promethazine: due to precipitate formation;
• Propofol: due to precipitate formation;
• Streptomycin: because calcium may inhibit streptomycin activity;
• Tetracyclines: calcium salts may complex with tetracyclines. Calcium salts may form complexes with many drugs, potentially leading to precipitate formation.

For further information, refer to the Summary of Product Characteristics.