Ringer's acetate Galenica Senese

Package leaflet: Information for the user

RINGER ACETATO GALENICA SENESE infusion solution

Sodium chloride, potassium chloride, calcium chloride dihydrate, sodium acetate trihydrate
Generic medicine
Please 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 questions, ask your doctor, pharmacist, or nurse.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any side effects not listed in this leaflet. See section 4.

What is in this leaflet:

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

1. What RINGER ACETATE GALENICA SENESE is and what it is used for

RINGER ACETATE GALENICA SENESE 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, in order to restore normal electrolyte levels necessary for proper body function, and to re-establish normal blood pH when increased acidity occurs (mild or moderate acidosis).

2. What you need to know before using RINGER ACETATE GALENICA SENESE

Do not use RINGER ACETATE GALENICA SENESE

• 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 electrolytes (hydrosaline 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 irregular heartbeat (arrhythmias);
• if you have kidney stones, which may worsen with calcium administration;
• if you have a chronic systemic disease called sarcoidosis, which may enhance the increase in blood calcium levels (hypercalcemia);
• if you have severe liver problems (severe hepatic insufficiency);
• if you have circulatory problems due to a high tendency of blood to clot (hypercoagulability);
• if you are taking medicines for heart conditions called cardioactive glycosides (see section "Other medicines and RINGER ACETATE GALENICA SENESE");
• if you have a disease of the adrenal glands (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 (less than 28 days of age), RINGER ACETATE GALENICA SENESE (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 particle formation in the newborn's bloodstream.

If you have recently received blood transfusions, this solution must not be administered through the same
infusion catheter as whole blood due to the possible risk of coagulation.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using RINGER ACETATE GALENICA SENESE.
This medicine must be administered via very slow infusion, as potassium intoxication may occur, which can lead to cardiac death due to loss of heart function (cardiac depression), irregular heartbeat (arrhythmias), and even cardiac arrest (see section "How to use RINGER ACETATE GALENICA SENESE").
Infusion of large volumes should be used under specific monitoring conditions in patients with heart or lung failure and in patients affected by a condition called syndrome of inappropriate antidiuretic hormone secretion (SIADH), due to the risk of reduced sodium levels in the blood following hospitalization (hospital-acquired hyponatremia) (see below).
Low levels of sodium in the blood (Hyponatremia)
Patients affected by a condition called syndrome of inappropriate antidiuretic hormone secretion (SIADH) (e.g., during the acute phase of illness, pain, postoperative stress, infections, burns, and central nervous system disorders), patients with heart (cardiac), liver (hepatic), or kidney (renal) diseases, and patients treated with medicines that enhance the action of vasopressin (vasopressin agonists) (see section 2) are particularly at risk of acute reduction in blood sodium levels (acute hyponatremia) following infusion of hypotonic solutions.
Acute reduction in blood sodium levels (acute hyponatremia) may cause a condition called acute hyponatremic encephalopathy, which involves increased fluid in the brain (cerebral edema), characterized by headache, nausea, seizures, drowsiness, and vomiting. These patients are particularly at risk of severe, irreversible, and life-threatening brain damage.
Children, women of childbearing age, and patients with impaired brain function (e.g., meningitis, intracranial hemorrhage, contusion, and cerebral edema) are particularly at risk of severe and life-threatening cerebral edema caused by low sodium levels in the blood (acute hyponatremia).
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 corticosteroids or hormonal medicines (corticotropins);
• if you have high blood pressure (hypertension);
• if you have a condition called pre-eclampsia, characterized by high blood pressure, swelling due to fluid accumulation, 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 an adrenal gland disorder (adrenal insufficiency);
• if you have severe liver problems (hepatic insufficiency);
• if a family member suffers from a disorder characterized by sudden attacks 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 insufficiency) or heart problems, as it may increase the risk of irregular heartbeat (arrhythmias);
• if you have received a blood transfusion, as calcium ion concentrations may differ from expected levels;
• if you suffer from lung problems that may cause heart enlargement (pulmonary heart disease);
• if you have breathing difficulties (respiratory insufficiency) 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, as calcium chloride administration may cause vasodilation, leading to further reduction in blood pressure. Calcium chloride solution is irritating and therefore must not be administered by intramuscular injection, subcutaneous injection, or peri-vascular injection, as tissue damage and death (necrosis) may occur. Due to the presence of acetate, the medicine must be used with caution 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).

During treatment with this medicine, your doctor should periodically monitor heart function via electrocardiograms and check electrolyte concentrations, fluid levels, osmolarity, and blood pH.
Frequent monitoring of calcium levels in blood and urine is required to prevent hypercalciuria (high calcium levels in urine), which may lead to increased calcium levels in blood (hypercalcemia).
Monitoring of electrolyte balance, serum electrolytes, and acid-base equilibrium may be necessary before and during administration, with particular attention to serum sodium levels in patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH) and in patients taking medicines that enhance the action of a hormone called vasopressin (vasopressin agonists), due to the risk of reduced sodium levels in blood following hospitalization (hospital-acquired hyponatremia) (see sections 2 and 4).
Infusion must be stopped immediately if signs or symptoms of suspected hypersensitivity occur.
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 only.
Any unused residue must not be reused.
Children
As with other calcium-containing solutions, concomitant treatment with ceftriaxone is contraindicated in newborns (less than 28 days of age) due to the risk of fatal precipitation of ceftriaxone-calcium salt in the newborn's bloodstream (see section "Possible side effects").
Other medicines and RINGER ACETATE GALENICA SENESE
Inform your doctor if you are currently using, have recently used, or might use any other medicines.
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 levels in blood (hyperkalemia); in such cases, blood potassium levels must be closely monitored;
• steroid anti-inflammatory medicines (corticosteroids), which may cause sodium and water retention, resulting in fluid accumulation (edema) and increased blood pressure (hypertension).

The following medicines may increase the risk of reduced sodium levels in blood following hospitalization (hospital-acquired hyponatremia) after inadequately balanced intravenous solution treatment:

• medicines that stimulate the release of a hormone called vasopressin (chlorpropamide, clofibrate, carbamazepine, vincristine, selective serotonin reuptake inhibitors, 3,4-methylenedioxy-N-methamphetamine, ifosfamide, antipsychotics, narcotics);
• medicines that enhance the effect of a hormone called vasopressin (chlorpropamide, NSAIDs, cyclophosphamide);
• medicines similar to a hormone called vasopressin (desmopressin, oxytocin, vasopressin, terlipressin).

Other medicines that increase the risk of reduced sodium levels in blood (hyponatremia) include medicines that increase urine production (diuretics in general) and antiepileptic medicines such as oxcarbazepine.
Due to the presence of calcium chloride, RINGER ACETATE GALENICA SENESE may interact with the following medicines:

• thiazide diuretics, used to treat high blood pressure, as they may cause increased calcium levels in 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 irregular heartbeat (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 the antihypertensive effect of verapamil;
• medicines containing magnesium, 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 action 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.

Fertility, pregnancy, and breastfeeding
If you are pregnant, suspect you may be pregnant, planning pregnancy, or breastfeeding, consult your doctor before receiving this medicine.
This medicine must not be used during pregnancy and breastfeeding unless absolutely necessary.
Ringer Acetate Galenica Senese infusion solution must be administered with particular caution in pregnant women during labor, especially regarding serum sodium levels, if administered in combination with a hormone called oxytocin (see sections 2 and 4).
Driving and using machines
This medicine does not impair the ability to drive or operate machinery.

3. How to use RINGER ACETATO GALENICA SENESE

This medicine will be prepared by a doctor, pharmacist, or nurse and must 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 normal 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, infusion frequency, and volume will be adjusted according to your age, body weight, clinical condition (e.g. burns, surgery, head injuries, infections), and concomitant therapy, and must be determined by a physician experienced in pediatric intravenous fluid therapy (see sections 2 and 4).
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.
In children, the safety and efficacy of this medicine have not been established.
Infusions that are too rapid may cause local pain; the infusion rate should be adjusted according to tolerance.
Administration must be discontinued 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 and 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 necessary precautions are taken to maintain sterility before and during intravenous infusion.
If you use more RINGER ACETATO GALENICA SENESE 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 GALENICA SENESE, inform your doctor or another healthcare professional immediately.
Following administration of an excessive dose of this medicine, the following may occur:

• increased potassium levels in the blood (hyperkalaemia), which may lead to death due to heart damage (cardiac depression, arrhythmias, or arrest);
• increased sodium levels (hypernatraemia) and increased blood volume (hypervolaemia). If sodium levels in the blood rise too much, loss of fluids from internal organs (dehydration), particularly from the brain, may occur, and fluid accumulation may affect 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 chloride levels leading to a decrease in blood pH (acidosis) due to reduced bicarbonate ion concentration;
• increased calcium levels 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 GALENICA SENESE, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
The following side effects may occur, especially in case of inappropriate administration or administration that is too rapid (See section “Warnings and precautions”):
The following side effects may occur:
Not known (frequency cannot be established 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 limb sensation (paraesthesiae), loss of muscle tone (flaccid paralysis), weakness;
• Mental confusion, headache, dizziness, restlessness, irritability;
• Seizures, coma, death;
• Drowsiness, confusional states, mental disorders;
• Irregular heartbeat (arrhythmias, tachycardia, bradycardia, conduction disturbances, disappearance of the P wave, widening of the QRS complex on electrocardiogram, syncope, ventricular fibrillation, cardiac arrest);
• Decrease or increase in blood pressure (hypotension, hypertension), swelling of the limbs (peripheral oedema), vasodilation, hot flushes;
• Increased levels of sodium (hypernatraemia), 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 calcium levels in the blood (hypercalcaemia);
• Burnett’s syndrome (also known as milk-alkali syndrome), a condition caused by excessive intake of milk or alkaline compounds, characterized by symptoms such as nausea, vomiting, headache, muscle weakness, hyperhydration, and electrolyte imbalances;
• Muscle weakness;
• Fever, infection at the infusion site, pain or local reaction, redness, rash, venous irritation;
• Circulatory problems due to blood clot formation in veins (thrombosis);
• Inflammation of the vein at the infusion site (phlebitis);
• Leakage of the medicine into surrounding tissues at the injection site (extravasation);
• Tissue damage and tissue death (tissue necrosis);
• Abscess formation and calcium deposits on the skin (cutaneous calcification);
• Hypersensitivity reactions to the infusion, including anaphylactic/anaphylactoid reactions;
• Localized or generalized urticaria;
• Kidney problems caused by calcium-ceftriaxone deposits. Pain during urination or reduced urine output may occur;
• Decreased sodium levels in the blood following hospitalization as hospital-acquired hyponatraemia*;
• A brain disorder called acute hyponatraemic encephalopathy*.

*Decreased sodium levels in the blood following hospitalization (hospital-acquired hyponatraemia) may lead to irreversible brain damage and death due to the development of acute hyponatraemic encephalopathy, frequency not known (see sections 3 and 2).
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 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 ACETATO GALENICA SENESE

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 “Expiry”.
The expiry date refers to the last day of that month.
Store the vials in the original packaging and in a tightly closed container. Do not refrigerate or
freeze.
Store the bags at a temperature not exceeding 30°C, in the original packaging and in a tightly closed container. Do not refrigerate or
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 GALENICA SENESE 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 GALENICA SENESE and package contents
Glass vial of 50 ml, 100 ml, 250 ml, 500 ml and 1000 ml of infusion solution.
1 vial or 20 polypropylene vials of 500 ml of infusion solution.
Plastic bag containing 50 ml, 100 ml, 250 ml, 500 ml and 1000 ml of infusion solution.

Marketing Authorization Holder and Manufacturer
Industria Farmaceutica Galenica Senese S.r.l.
Via Cassia Nord, 351
53014 Monteroni D’Arbia (SI)
Italy

Package leaflet: information for the physician

RINGER ACETATO GALENICA SENESE infusion solution

The following information is intended exclusively for physicians or healthcare professionals
CLINICAL INFORMATION
Dosage and method of administration
The solution is isotonic with blood and must be administered cautiously by intravenous infusion at a controlled infusion rate.

Overdose
Treatment
Immediately discontinue the infusion and initiate corrective therapy to reduce plasma levels of the ions in excess and, if necessary, restore acid-base balance (see section 4.4).
The patient should be closely monitored for the appearance of any signs and symptoms related to the administered drug, providing appropriate symptomatic and supportive measures as needed.

In case of severe hypernatremia, loop diuretics may be used.
In case of hyperkalemia, intravenous glucose (with or without insulin) or sodium bicarbonate may be administered.

In case of mild calcium chloride overdose, treatment includes immediate discontinuation of the infusion and of any other calcium-containing medications. In case 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 arrhythmia;
• Hemodialysis, if necessary. Elevated plasma electrolyte levels may require dialysis.

Incompatibilities
If used to dilute medicinal products, consult a pharmacist, if available, before adding any additive drugs; always consider the characteristics of the products to be added; use aseptic techniques.

Due to the presence of calcium chloride, this 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 between calcium chloride and the following medicinal products have been reported:

• Aminophylline: due to precipitate formation;
• Amphotericin B: due to development of turbidity;
• Cefamandole: due to presence of sodium carbonate in the cefamandole formulation;
• Cephalothin: due to physical incompatibility;
• Cefradine: due to presence of sodium carbonate in the cefradine formulation;
• Chlorpheniramine: due to physical incompatibility;
• Dobutamine: due to development of turbidity;
• Fat emulsion: due to presence of flocculation;
• Sodium heparin;
• Indomethacin: due to precipitate formation;
• Sodium nitrofurantoin;
• Promethazine: due to precipitate formation;
• Propofol: due to precipitate formation;
• Streptomycin: since 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;
• Sodium ceftriaxone: due to precipitate formation; therefore, administration of calcium-containing solutions must not occur within 48 hours following administration of ceftriaxone.

For further information, please consult the Summary of Product Characteristics.