Ringer lactate S.A.L.F.

Patient Information Leaflet: Information for the User

RINGER LATTATE S.A.L.F. 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, as it may be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What RINGER LATTATO S.A.L.F. is and what it is used for

RINGER LATTATO S.A.L.F. is an infusion solution intended for direct intravenous injection, containing a combination of active substances: natrii chloridum, kalii chloridum, calcii chloridi dihydricus and natrii lactas.
This medicinal product is indicated:

• to supply 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 restore normal blood pH when mild or moderate acidosis (increased acidity) occurs;
• to restore normal blood pressure following shock caused by severe blood loss (mild or moderate haemorrhagic shock).

2. What you should know before using RINGER LACTATE S.A.L.F.

Do not use RINGER LACTATE S.A.L.F.

• 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 excess of other electrolytes (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 blood calcium levels (hypercalcemia);
• if you have circulatory problems due to increased tendency of blood to clot (hypercoagulability);
• if you are taking heart medications called cardioactive glycosides (see section “Other medicines and RINGER LACTATE S.A.L.F.”);
• 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 neonate (under 28 days of age), RINGER LACTATE S.A.L.F. (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 neonate's bloodstream. During blood transfusions, this solution must not be administered 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 S.A.L.F.
This medicine must be administered via very slow infusion, as rapid administration may cause potassium intoxication leading to cardiac dysfunction (cardiac depression), cardiac arrhythmias, and potentially fatal cardiac arrest (see section “How to use RINGER LACTATE S.A.L.F.”).
If signs or symptoms of suspected hypersensitivity occur, the infusion must be stopped immediately.
This medicine must be administered cautiously and under specific monitoring due to the risk of reduced sodium concentration in plasma (hyponatremia) if:

• you have heart problems (heart failure) or lung problems (respiratory failure);
• you have liver and/or kidney disease (hepatopathy and/or nephropathy);
• you have non-osmotic release of antidiuretic hormone (vasopressin), including syndrome of inappropriate secretion of vasopressin (SIADH), or are undergoing treatment with vasopressin agonists. Acute hyponatremia may cause acute hyponatremic encephalopathy (cerebral edema), characterized by headache, nausea, seizures, lethargy, and vomiting. Patients with cerebral edema are particularly at risk of severe, irreversible, and life-threatening brain injury. Children, women of childbearing age, and patients with reduced cerebral compliance (e.g., meningitis, intracranial hemorrhage, and cerebral contusion) are particularly at risk of severe, life-threatening cerebral fluid accumulation (cerebral edema) caused by acute hyponatremia.

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

• if you have heart problems (congestive heart failure, heart failure);
• if you have kidney problems (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 (cardiotropic inotropic drugs), corticosteroid anti-inflammatory drugs, or hormonal medicines (corticotropic agents);
• if you have high blood pressure (hypertension);
• if you suffer from a condition called pre-eclampsia, characterized by high blood pressure, swelling due to fluid retention, and protein in the urine, or other conditions caused by sodium accumulation.

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

• if you have kidney problems (renal failure), as it may cause potassium retention;
• if you have heart problems (heart failure) and are taking other heart medications (digitalis);
• if you have an adrenal gland disorder (adrenal insufficiency);
• if you have liver problems (hepatic failure);
• if a family member suffers from a disorder characterized by sudden attacks 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 the presence of calcium, this medicine must be administered with great caution in the following cases:

• if you have kidney 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 diseases that may cause heart enlargement (cor pulmonale);
• if you have breathing difficulties (respiratory failure) or decreased blood pH (respiratory acidosis);
• if you have low body water levels (dehydration) or an electrolyte imbalance;
• if you have low blood pressure, as calcium chloride administration may cause vasodilation and further lower blood pressure;
• if you have a history of kidney stones. Calcium chloride solution is irritating and must not be administered via intramuscular, subcutaneous, or peri-vascular injection, as tissue damage and death (necrosis) may occur.

Due to the presence of lactate, the medicine must be used cautiously if:

• you suffer from lactic acidosis or impaired oxidative processes preventing lactate utilization (e.g., shock, hypoxemia);
• you have type 2 diabetes;
• you have an abnormal blood lactate level (e.g., in case of severe liver failure). In such cases, RINGER LACTATE S.A.L.F. may only be administered if deemed necessary by the physician;
• you have a blood pH disorder characterized by bicarbonate accumulation, known as 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, such as primary hyperaldosteronism, secondary hyperaldosteronism, or pre-eclampsia;
• if you have conditions that may cause potassium accumulation, such as severe kidney damage, adrenocortical insufficiency, severe dehydration, extensive tissue damage, or heart failure. In these cases, RINGER LACTATE S.A.L.F. may only be administered if deemed necessary by the physician.

During treatment with this medicine, your doctor should periodically monitor heart function via serial electrocardiograms and check electrolyte concentrations—particularly sodium, as hospital-acquired hyponatremia (sodium deficiency) may develop—as well as fluid balance, blood 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 blood calcium levels (hypercalcemia).
This medicine must 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.
Any unused portion must not be retained.

Children
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 neonates (under 28 days of age) due to the risk of fatal precipitation of ceftriaxone-calcium salt in the neonate's bloodstream (see section “Possible side effects”).

Other medicines and RINGER LACTATE S.A.L.F.
Inform your doctor if you are currently using, have recently used, or might use any other medicines.
This medicine must not be administered together with the following medicines:

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

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

• blood pressure-lowering medicines such as potassium-sparing diuretics, ACE inhibitors (which reduce aldosterone levels), angiotensin II receptor antagonists, and immunosuppressive agents (e.g., tacrolimus and cyclosporine), as they may increase blood potassium levels (hyperkalemia); in such cases, close monitoring of serum potassium levels is required;
• corticosteroid anti-inflammatory drugs, which may cause sodium and water retention, leading to fluid accumulation (edema) and increased blood pressure (hypertension);
• medicines such as thiazide diuretics (used to treat high blood pressure) and vitamin D, which may increase blood calcium levels (hypercalcemia) due to reduced renal calcium excretion;
• magnesium-containing medicines, as they may increase the risk of elevated calcium (hypercalcemia) or magnesium (hypermagnesemia), especially in patients with kidney disorders;
• medicines that enhance the effect of vasopressin hormone, e.g., chlorpropamide, clofibrate, carbamazepine, vincristine, selective serotonin reuptake inhibitors, 3,4-methylenedioxymethamphetamine (MDMA), ifosfamide, antipsychotics, narcotics, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclophosphamide, desmopressin, oxytocin, vasopressin, and terlipressin;
• diuretics in general and antiepileptic drugs (e.g., oxcarbazepine), as they may increase the risk of hyponatremia.

Due to the alkalizing effect of lactate (bicarbonate formation), the medicine may interfere with the elimination of acidic drugs such as salicylates, barbiturates, and lithium (increasing renal clearance), and basic drugs such as sympathomimetics (e.g., ephedrine, pseudoephedrine), dexamfetamine sulfate, and fenfluramine hydrochloride (decreasing renal clearance).

Due to the presence of calcium chloride, RINGER LACTATE S.A.L.F. may interact with the following medicines:

• 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 hypercalcemia or hypermagnesemia, particularly in patients with kidney disorders;
• neuromuscular blocking agents, as calcium salts may counteract the effects of non-depolarizing blockers; in some cases, an increased and prolonged effect of tubocurarine has 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 a pregnancy, or breastfeeding, consult your doctor before receiving this medicine.
RINGER LACTATE S.A.L.F. must be administered with particular caution in pregnant women during labor, especially regarding blood sodium levels, when administered concomitantly with a medicine called oxytocin.
This medicine must not be used during pregnancy or breastfeeding unless strictly necessary.

Driving and using machines
This medicine does not affect the ability to drive or operate machinery.

3. How to use RINGER LATTATO S.A.L.F.

This medicinal product will be prepared by a doctor, pharmacist, or nurse and must not be mixed or administered simultaneously with injections containing ceftriaxone or other incompatible medicinal products.
Monitoring of electrolyte balance, serum electrolytes, and acid-base balance may be necessary before and during administration, with particular attention to serum sodium if you suffer from the syndrome of inappropriate antidiuretic hormone secretion (SIADH), or if you are receiving concomitant therapy with vasopressin agonists, due to the risk of hospital-acquired hyponatremia.
Monitoring of serum sodium is particularly important for hypotonic solutions.
This medicinal product must be administered directly into a vein (intravenous infusion) by trained medical personnel using clean, contamination-free equipment (sterile and pyrogen-free). It must not be injected via other routes of administration (intramuscular, subcutaneous, or into perivascular tissues).
This medicinal product 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 medicinal product, remain lying down for a short period.
The dose, volume of solution, and frequency of administration will depend on your age, weight, health status, concomitant treatment with other medicinal products, and your response to treatment with this medicinal product.
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 your needs.
Administration must be stopped if you experience pain or redness at the injection site, as this could be due to leakage of the medicinal product from the vein (drug extravasation).

Preparation of the medicinal product: Use the solution immediately after opening the container. The container is intended for single, uninterrupted administration and any remaining solution must not be reused.
Shake well before administration. Do not use the medicinal product if the solution is not clear and colourless, or if it contains particles.
Ensure that all precautions are taken to maintain sterility before and during intravenous infusion.
During treatment with this medicinal product, you will need to have blood levels of electrolytes monitored, especially sodium.

If you use more RINGER LATTATO S.A.L.F. than you should
This medicinal product will be administered by a doctor or trained medical personnel; therefore, it is unlikely that you will receive an excessive dose. However, if you think that you have been given an excessive dose of RINGER LATTATO S.A.L.F., inform your doctor immediately or go to the nearest hospital.
Following administration of an excessive dose of this medicinal product, the following may occur:

• increase in potassium levels in the blood (hyperkalemia), which may lead to death due to heart damage (cardiac depression, arrhythmias, or arrest);
• increase in sodium levels (hypernatremia) and in blood volume (hypervolemia). If sodium levels in the blood rise too much, loss of fluids from internal organs (dehydration) may occur, especially from the brain, and fluid accumulation may affect the cerebral, pulmonary, and peripheral circulation, leading to fluid buildup around the lung (pulmonary edema) or swelling in the legs and ankles (peripheral edema);
• increase in chloride levels leading to a reduction in blood pH (acidosis) due to decreased bicarbonate ion concentration;
• increase in calcium levels in the blood (hypercalcemia) 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 LATTATO S.A.L.F., 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”):

Not known (frequency cannot be estimated from the available data):
Gastrointestinal disorders:

• stomach and intestinal (gastrointestinal) disturbances and irritation, nausea, vomiting, diarrhoea, abdominal pain, constipation, thirst, reduced salivation, metallic taste, chalky taste;

Nervous system disorders:

• 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, acute hyponatraemic encephalopathy*;

Psychiatric disorders:

• drowsiness, confusion, mental disturbances;

Cardiac 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;

Vascular disorders:

• decrease or increase in blood pressure (hypotension, hypertension), swelling of limbs (peripheral oedema), vasodilation, flushing;

Disorders of water and electrolyte balance:

• increased levels of sodium (hypernatraemia), chloride (hyperchloraemia) and blood volume (hypovolaemia);

Respiratory, thoracic and mediastinal disorders:

• breathing difficulties (dyspnoea, respiratory arrest);
• accumulation of fluid in the lungs (pulmonary oedema) and air around the lung (pneumothorax);

Eye disorders:

• reduced tear production;

Renal and urinary disorders:

• kidney problems (renal failure), increased urine production (polyuria);

Metabolism and nutrition disorders:

• 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;
• hospital-acquired hyponatraemia*;

Musculoskeletal and connective tissue disorders:

• muscle weakness;

General disorders and administration site conditions:

• fever, infection and inflammation at the infusion site, local pain or reaction, redness, rash, burning, itching, swelling at the infusion site, circulation problems due to blood clot formation in veins (thrombosis), inflammation of veins at the infusion site (phlebitis), leakage of medicine into surrounding tissues (extravasation), tissue damage and death (tissue necrosis), abscess formation, and calcium deposits in the skin (cutaneous calcification);

Immune system disorders:

• hypersensitivity reactions to infusion, including anaphylactic/anaphylactoid reactions;

Calcium-ceftriaxone salt precipitation:

• kidney problems caused by calcium-ceftriaxone deposits. Pain during urination or reduced urine output may occur.

* Hospital-acquired hyponatraemia can cause irreversible brain damage and death due to the development of acute 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 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 LACTATE S.A.L.F.

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 refrigerate or freeze.
Do not dispose of medicines 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 S.A.L.F. 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, 5.46 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 component is water for injections.

Description of the appearance of RINGER LACTATE S.A.L.F. and contents of the pack
Pack containing one 100 ml or 500 ml glass infusion bottle;
Pack containing one 500 ml polypropylene (PP) infusion bottle;
Pack containing one 500 ml, 1000 ml or 3000 ml PVC infusion bag;
Pack containing 15 PVC infusion bags of 500 ml;
Pack containing 10 PVC infusion bags of 1000 ml.

Marketing Authorisation Holder and Manufacturer
S.A.L.F. S.p.A. Laboratorio Farmacologico – Via Marconi, 2 – Cenate Sotto (BG) – Italy.

The following information is intended exclusively for physicians or healthcare professionals

RINGER LACTATE S.A.L.F. infusion solution
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 Precautions for use).
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 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; 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 medicinal products, consult a pharmacist, if available, before adding any drug; 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 of calcium chloride have been reported with:

• 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 flocculate;
• Sodium heparin;
• Indomethacin: due to precipitate formation;
• Sodium nitrofurantoin;
• Promethazine: due to precipitate formation;
• Propofol: due to precipitate formation;
• Streptomycin: 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, calcium-containing solutions must not be administered within 48 hours following ceftriaxone administration.

Interactions
Medicinal products that may increase the risk of hospital-acquired hyponatremia due to inadequately balanced intravenous fluid therapy include:

• Medicinal products stimulating vasopressin release, e.g.: chlorpropamide, clofibrate, carbamazepine, vincristine, selective serotonin reuptake inhibitors, 3,4-methylenedioxy-N-methamphetamine, ifosfamide, antipsychotics, narcotics;
• Medicinal products enhancing vasopressin action, e.g.: chlorpropamide, NSAIDs, cyclophosphamide;
• Vasopressin analogues: desmopressin, oxytocin, vasopressin, terlipressin.

Other medicinal products increasing the risk of hyponatremia include diuretics in general and antiepileptic agents such as oxcarbazepine.

Warnings and precautions
Serum sodium monitoring is particularly important when administering physiologically hypotonic solutions.
Ringer Lactate S.A.L.F. may become markedly hypotonic after administration.

Patients with non-osmotic vasopressin release (e.g., during acute illness, pain, postoperative stress, infections, burns, and central nervous system disorders), patients with cardiac, hepatic or renal disease, and patients receiving vasopressin agonists are at particularly high risk of developing hyponatremia following infusion of hypotonic solutions. Acute hyponatremia may lead to acute hyponatremic encephalopathy (cerebral edema), characterized by headache, nausea, seizures, lethargy, and vomiting. Patients with cerebral edema are at particularly high risk of severe, irreversible, and life-threatening brain injury.

Children, women of childbearing age, and patients with reduced cerebral compliance (e.g., meningitis, intracranial hemorrhage, and cerebral contusion) are particularly at risk of severe, life-threatening cerebral edema caused by acute hyponatremia.

Pregnancy
Ringer Lactate S.A.L.F. should be administered with particular caution to pregnant women during labor, especially when administered concomitantly with oxytocin, due to the risk of hyponatremia.

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