Ringer lactate Galenica Senese

Package leaflet: Information for the patient

RINGER LACTATE GALENICA SENESE infusion solution

sodium chloride, potassium chloride, calcium chloride dihydrate, sodium lactate
Equivalent medicine
Please read this leaflet carefully before 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.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

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

RINGER LACTATE GALENICA SENESE is an infusion solution for direct intravenous injection, containing a combination of active substances: sodium chloride, potassium chloride, calcium chloride dihydrate, and sodium lactate.
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 occurs;
• to restore normal blood pressure following shock caused by significant blood loss (mild or moderate hemorrhagic shock).

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

Do not use RINGER LACTATE GALENICA SENESE

• if you are allergic to sodium chloride, potassium chloride, calcium chloride dihydrate, sodium lactate, or any of the other components 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 (hydrosaline overload);
• if you have high levels of potassium in the blood (hyperkalemia) or reduced ability to eliminate potassium (potassium retention);
• if you have a heart rhythm disorder called ventricular fibrillation, as calcium chloride may increase the risk of cardiac arrhythmias;
• if you have kidney stones, which may worsen with calcium administration;
• if you suffer from a chronic systemic disease called sarcoidosis, which may exacerbate increased calcium levels in the blood (hypercalcemia);
• if you have circulatory problems due to increased tendency of blood to clot (hypercoagulability);
• if you are taking medications for heart conditions called cardioactive glycosides (see section "Other medicines and RINGER LACTATE GALENICA SENESE");
• if you have an increased blood pH (metabolic and respiratory alkalosis);
• if you have a disease of the adrenal glands (Addison's disease) and are not receiving treatment for it;
• if you experience painful, brief muscle cramps (heat cramps);
• if the patient is a newborn (under 28 days of age), RINGER LACTATE GALENICA SENESE (or other calcium-containing solutions) must not be administered simultaneously with ceftriaxone (an antibiotic), even when using separate infusion lines. There is a fatal risk of particle formation in the newborn's bloodstream.

When administered concomitantly with blood transfusions, this solution must not be given through the same
infusion catheter as whole blood due to the possible risk of blood coagulation.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using RINGER LACTATE GALENICA SENESE.
This medicine must be administered by very slow infusion, as rapid administration may cause potassium intoxication, potentially leading to cardiac dysfunction (cardiac depression), cardiac rhythm disturbances (arrhythmias), and even cardiac arrest (see section “How to use RINGER LACTATE GALENICA SENESE”).
Infusion of large volumes should be used with specific monitoring 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).
Special attention should be paid in:

• Patients affected by 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 disease (cardiopathy), liver disease (hepatopathy), or kidney disease (nephropathy), and patients treated with drugs that enhance the activity of a hormone called vasopressin (vasopressin agonists) (see section 2);

These patients are particularly at risk of decreased sodium levels in the blood (acute hyponatremia) following infusion of hypotonic solutions.
Acute reduction in blood sodium levels (acute hyponatremia) may cause a condition called acute hyponatremic encephalopathy, characterized by fluid accumulation in the brain (cerebral edema), headache, nausea, seizures, drowsiness, and vomiting. These patients are particularly at risk of severe, life-threatening brain injury.
Children, women of childbearing age, and patients with impaired brain function (e.g., meningitis, intracranial hemorrhage, contusion (trauma), and cerebral edema) are particularly at risk of severe, life-threatening cerebral edema caused by low sodium levels in the blood (acute hyponatremia).
If signs or symptoms suggestive of hypersensitivity occur, the infusion must be stopped immediately.
Due to its sodium content, this medicine should be administered with caution in the following cases:

• if you have heart problems (congestive heart failure, cardiac insufficiency);
• if you have kidney problems (severe renal failure);
• 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 (cardiotonic drugs), corticosteroid anti-inflammatory drugs, or hormonal medications (corticotropins);
• if you have high blood pressure (hypertension);
• if you suffer from a condition called preeclampsia, characterized by high blood pressure, fluid retention-related swelling, and protein in the urine, or other conditions caused by sodium accumulation.

Due to its potassium content, this medicine should 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 someone in your family suffers from a disorder characterized by sudden episodes of muscle weakness (familial periodic paralysis);
• if you suffer from a condition characterized by muscle stiffness (congenital myotonia);
• if you have recently undergone surgery (early postoperative phase). This medicine must not be used to treat potassium deficiency.

Due to its calcium content, 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 cardiac arrhythmias;
• if you have received a blood transfusion, as calcium ion concentrations may differ from expected levels;
• if you suffer from lung disorders that may cause heart enlargement (pulmonary heart disease);
• if you have breathing difficulties (respiratory insufficiency) or reduced blood pH (respiratory acidosis);
• if you have low body water levels (dehydration) or electrolyte imbalance (electrolyte disturbance);
• if you have low blood pressure, as calcium chloride administration may cause vasodilation and further reduction in blood pressure;
• if you have a history of kidney stones.

Calcium chloride solution is irritating and must not be administered via intramuscular, subcutaneous, or
perivascular injection, as tissue damage and death (necrosis) may occur.
Due to its lactate content, the medicine should be used with caution if:

• you suffer from lactic acidosis or impaired oxidative processes that prevent lactate utilization (e.g., shock, hypoxemia);
• you have type 2 diabetes;
• you have altered lactate levels in the blood (e.g., in case of severe liver insufficiency). In such cases, RINGER LACTATE GALENICA SENESE may be administered only if deemed necessary by the physician;
• you have a blood pH disturbance characterized by bicarbonate accumulation called metabolic alkalosis.

This medicine must not be administered in the following cases:

• if you suffer from diseases that may cause sodium accumulation, excess fluid, or fluid retention-related swelling, such as primary hyperaldosteronism, secondary hyperaldosteronism, or preeclampsia;
• if you suffer from conditions that may cause potassium accumulation, such as severe kidney damage, adrenocortical insufficiency, severe dehydration, extensive tissue damage, or cardiac insufficiency.

In these cases, RINGER LACTATE GALENICA SENESE may be administered only if the physician considers it necessary.
During treatment with this medicine, your doctor should periodically monitor heart function via serial electrocardiograms and check electrolyte concentrations, fluid balance, osmolarity, and blood pH.
Serum and urinary calcium levels should be frequently monitored to prevent hypercalciuria, which may lead to increased blood calcium levels (hypercalcemia).
This medicine should be used immediately after opening the container. The solution must be clear, colorless, and free of visible particles, and is intended for single, uninterrupted administration only.
Any unused portion must not be reused.
If allergic reactions occur, infusion of this medicine must be stopped immediately.
Monitoring of electrolyte balance, serum electrolytes, and acid-base equilibrium before and during administration may be necessary, particularly serum sodium levels in patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH) and in patients taking medications that enhance the action of a hormone called vasopressin (vasopressin agonists), due to the risk of hospital-acquired hyponatremia (see sections 2 and 4).
Children and adolescents
The safety and efficacy of this medicine in children have not been established.
As with other calcium-containing solutions, concomitant treatment with ceftriaxone is contraindicated in newborns (under 28 days of age) due to the fatal risk of precipitation of ceftriaxone-calcium salt in the newborn's bloodstream (see sections “Do not use RINGER LACTATE GALENICA SENESE” and “Possible side effects”).
Children are particularly at risk of severe, life-threatening cerebral edema caused by low sodium levels in the blood (acute hyponatremia).
Concomitant therapy should be determined by a physician experienced in pediatric intravenous therapy, particularly considering the potential risk of reduced sodium levels (hyponatremia).
Other medicines and RINGER LACTATE GALENICA SENESE
Inform your doctor if you are currently using, have recently used, or might use any other medicines.
This medicine must not be administered if you are taking:

• cardioactive glycosides (digitalis), digoxin, or digitoxin, used for heart conditions, as concomitant use may increase the risk of cardiac arrhythmias, given the synergistic inotropic and toxic effects.

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

• medications used to lower blood pressure such as potassium-sparing diuretics, ACE inhibitors, or other drugs that reduce aldosterone levels, angiotensin II receptor antagonists, and organ transplant medications such as tacrolimus and cyclosporine, as they may lead to increased potassium levels in the blood (hyperkalemia); in such cases, serum potassium levels must be closely monitored;
• corticosteroid anti-inflammatory drugs (corticosteroids), which may cause sodium and water retention, resulting in fluid accumulation (edema) and increased blood pressure (hypertension);
• thiazide diuretics, used to treat high blood pressure, and vitamin D, as they may cause increased calcium levels in the blood (hypercalcemia) due to reduced renal calcium excretion;
• magnesium-containing medications, as they may increase the risk of elevated calcium (hypercalcemia) or magnesium (hypermagnesemia) levels, especially in patients with kidney disorders.

Due to the alkalinizing effect of lactate (bicarbonate formation), this medicine may interfere with the elimination of acidic drugs such as salicylates, barbiturates, and lithium (increased renal clearance) and basic drugs such as sympathomimetics (e.g., ephedrine, pseudoephedrine), dexamfetamine sulfate, and fenfluramine hydrochloride (decreased renal clearance).
The following medicines may increase the risk of hospital-acquired hyponatremia following inadequately balanced intravenous fluid therapy:

• drugs 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);
• drugs that potentiate the effect of a hormone called vasopressin (chlorpropamide, NSAIDs, cyclophosphamide);
• drugs similar to a hormone called vasopressin (desmopressin, oxytocin, vasopressin, terlipressin).

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

• verapamil (and other calcium channel blockers), used to treat high blood pressure, as concomitant use may reduce the antihypertensive effect of verapamil;
• neuromuscular blocking agents, as calcium salts may counteract the action of non-depolarizing blockers; in some cases, an increased and prolonged effect of tubocurarine has also been observed;
• ceftriaxone (an antibiotic) due to the risk of particle formation. This medicine must not be administered through the same infusion line as ceftriaxone (in individuals over 28 days of age). If the same line is used for sequential administration, it must be flushed with a compatible fluid between infusions (see sections “Do not use RINGER LACTATE GALENICA SENESE”, “Children”, and “Possible side effects”).

Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor before receiving this medicine.
This medicine should not be used during pregnancy or breastfeeding unless absolutely necessary.
Ringer Lactate Galenica Senese infusion solution should be administered with particular caution in pregnant women during labor, especially regarding serum sodium levels (serum sodium), when administered concomitantly with a hormone called oxytocin (see sections 2 and 4).
Driving and use of machines
This medicine does not affect the ability to drive vehicles or operate machinery.

3. How to use RINGER LACTATE 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 or other incompatible medicines.
This medicine must be administered directly into a vein (intravenous infusion) by specialized 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, frequency, and volume of infusion will be adjusted according to your age, weight, clinical condition (e.g., burns, surgical procedures, head injuries, infections), and concomitant therapy, which must be determined by a physician experienced in pediatric intravenous therapy (see sections 2 and 4). The physician will determine the dose and method of administration (e.g., volume and rate of infusion) based on your clinical condition and any other medicines you may be taking.
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; therefore, the infusion rate must be adjusted according to your needs.
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, 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 LACTATE 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 LACTATE GALENICA SENESE, inform your doctor immediately or go to the nearest hospital.
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, fluid loss from internal organs (dehydration), particularly from the brain, may occur, along with 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 chloride levels leading to a reduction in blood pH (acidosis) due to decreased 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 the use of RINGER LACTATE GALENICA SENESE, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets 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:
Frequency not known (frequency cannot be estimated from the available data):

• Stomach and intestinal (gastrointestinal) disturbances and irritation, nausea, vomiting, diarrhoea, abdominal pain, constipation;
• Thirst, reduced salivation, metallic taste, chalky taste;
• Neuromuscular disturbances, muscle stiffness, altered limb sensation (paraesthesia), loss of muscle tone (flaccid paralysis), weakness;
• Mental confusion, headache, dizziness, restlessness, irritability;
• Seizures, coma, death;
• Drowsiness, confusional states, psychiatric disorders;
• Irregular heartbeat such as arrhythmias, tachycardia, bradycardia, conduction disturbances, disappearance of the P wave, widening of the QRS complex on the electrocardiogram, syncope, ventricular fibrillation, cardiac arrest;
• Decrease or increase in blood pressure (hypotension, hypertension), swelling of the limbs (peripheral oedema), vasodilation, flushing;
• Increased levels of sodium (hypernatraemia), chloride (hyperchloraemia), and blood volume (hypovolaemia);
• Breathing difficulties (dyspnoea, respiratory arrest);
• Fluid accumulation in the lungs (pulmonary oedema) and air around the lung (pneumothorax);
• 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, characterised by symptoms such as nausea, vomiting, headache, muscle weakness;
• Muscle weakness;
• Fever, infection and inflammation at the infusion site, pain or local reaction, redness, rash, burning, itching, swelling at the infusion site;
• Circulatory problems due to blood clot formation in the veins (thrombosis);
• Inflammation of the veins at the infusion site (phlebitis);
• Leakage of the medicine into the surrounding tissues at the injection site (extravasation);
• Tissue damage and tissue death (tissue necrosis);
• Abscess formation and calcium deposits in the skin (cutaneous calcification);
• Kidney problems caused by calcium-ceftriaxone deposits, especially in children. Pain during urination or reduced urine output may occur. In preterm neonates and full-term infants under 28 days of age, serious reactions, including death, may occur when calcium is administered together with ceftriaxone;
• Allergic reactions at the time of infusion, including anaphylactic/anaphylactoid reactions;
• Decreased sodium levels in the blood following hospitalisation, known as hospital-acquired hyponatraemia*;
• A brain disorder called acute hyponatraemic encephalopathy*.

*Decreased sodium levels in the blood following hospitalisation (hospital-acquired hyponatraemia) may lead to irreversible cerebrovascular damage and death due to the development of acute hyponatraemic encephalopathy, with frequency not known (see sections 3 and 2).
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please inform your doctor or pharmacist. You may also report side effects directly via the national reporting system at http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store RINGER LACTATE 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 “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 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 LACTATE GALENICA SENESE contains

• The active substances are: sodium chloride, potassium chloride, calcium chloride dihydrate, sodium lactate 60% solution. 1000 ml of solution contain 6.0 g of sodium chloride, 0.4 g of potassium chloride, 0.27 g of calcium chloride dihydrate, and 5.416 g of sodium lactate 60% solution. (Each litre of solution contains 132 mEq of sodium, 5 mEq of potassium, 4 mEq of calcium, 112 mEq of chloride, and 29 mEq of lactate). (pH: 5.5–7.0).
• The other components are hydrochloric acid and water for injections.

Description of the appearance of RINGER LACTATE GALENICA SENESE and contents of the package
Pack containing one glass bottle of 50 ml, 100 ml, 250 ml, 500 ml or 1000 ml of solution for infusion.
Pack containing 1 or 20 polypropylene bottles of 500 ml of solution for infusion.
Pack containing one plastic bag of 50 ml, 100 ml, 250 ml, 500 ml, 1000 ml, 2000 ml, 3000 ml, and 5000 ml of solution for infusion.

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

The following information is intended exclusively for physicians or healthcare professionals

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

• rehydration with 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;
• dialysis, if necessary.

Elevated plasma levels of electrolytes may require dialysis.
Incompatibilities
If used to dilute medications, 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 have been reported:

• aminophylline: due to precipitate formation;
• amphotericin B: due to development of turbidity;
• cefamandole: due to presence of sodium carbonate in cefamandole formulation;
• cephalothin: due to physical incompatibility;
• cefradine: due to presence of sodium carbonate in cefradine formulation;
• chlorphenamine: due to physical incompatibility;
• dobutamine: due to development of turbidity;
• 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: since calcium may inhibit streptomycin activity;
• tetracyclines: calcium salts may form complexes 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 ceftriaxone administration.

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