PACKAGE LEAFLET: INFORMATION FOR THE USER

RINGER LATTATE B.BRAUN solution for infusion

Sodium chloride, potassium chloride, calcium chloride, lactic acid and sodium hydroxide
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.
This medicine has been prescribed for you only. Do not pass it on to other people, even if their symptoms are the same as yours, as it may 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:

What RINGER LATTATE B.BRAUN is and what it is used for
What you need to know before using RINGER LATTATE B.BRAUN
How to use RINGER LATTATE B.BRAUN
Possible side effects
How to store RINGER LATTATE B.BRAUN
Contents of the pack and other information

1. What RINGER LACTATE B.BRAUN is and what it is used for

RINGER LACTATE B.BRAUN is an infusion solution for direct intravenous injection containing a combination of active substances: sodium chloride, potassium chloride, calcium chloride, lactic acid and sodium hydroxide.
This medicinal product is indicated:

to provide water and electrolytes to the body following loss of extracellular fluids and electrolytes, in order to restore normal electrolyte levels necessary for proper body function, and to restore normal blood pH when mild or moderate acidosis (increased blood acidity) occurs;

2. What you need to know before using RINGER LACTATE B.BRAUN

Do not use RINGER LACTATE B.BRAUN

if you are allergic to sodium chloride, potassium chloride, calcium chloride, lactic acid, sodium hydroxide, or any of the other components of this medicine (listed in section 6);
if you have impaired lactate metabolism and have high levels of lactate in the blood (hyperlactatemia);
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 of other mineral salts (water-salt 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, 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 enhance the increase in blood calcium levels (hypercalcemia);
if you have circulatory problems due to a high tendency of blood to clot (hypercoagulability);
if you are taking medicines for heart conditions called cardiac glycosides (see section "Other medicines and RINGER LACTATE B.BRAUN");
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, short-lived muscle cramps (heat cramps);
if the patient is a newborn (under 28 days of age), RINGER LACTATE B.BRAUN (or other calcium-containing solutions) must not be administered simultaneously with ceftriaxone (an antibiotic), even if separate infusion lines are used. There is a fatal risk of particle formation in the newborn'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 B.BRAUN.

This medicine must be administered by very slow infusion, as potassium intoxication may occur, potentially leading to cardiac dysfunction (cardiac depression), heart rhythm irregularities (arrhythmias), and even cardiac arrest (see section "How to use RINGER LACTATE B.BRAUN").

If signs or symptoms of suspected 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 inotropic drugs), anti-inflammatory medicines (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 retention;
if you have non-osmotic release of antidiuretic hormone (vasopressin), including the 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 damage.
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 and life-threatening cerebral fluid accumulation (cerebral edema) caused by acute hyponatremia.

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 a disease of the adrenal glands (adrenal insufficiency);
if you have severe liver problems (hepatic insufficiency);
if a family member 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 post-operative phase).

Due to its calcium content, this medicine must be administered with particular caution in the following cases:

if you have kidney problems (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 (cor pulmonale);
if you have breathing difficulties (respiratory insufficiency) or decreased blood pH (respiratory acidosis);
if you have low body water levels (dehydration) or an electrolyte imbalance (electrolyte disturbance);
if you have low blood pressure, as administration of calcium chloride may cause vasodilation and further lower blood pressure;
if you have previously suffered from kidney stones.

Calcium chloride solution is irritating and therefore must not be administered by intramuscular injection, subcutaneous injection, or perivascular injection, as tissue damage and tissue death (necrosis) may occur.

Due to its lactate content, this medicine should be used with caution in the following cases:

if you are at risk of increased blood pH (alkalosis), as lactate is metabolized into bicarbonate and may cause or worsen metabolic alkalosis;
if you have type 2 diabetes, as lactate activates a metabolic process that produces glucose by converting a non-carbohydrate compound into glucose (gluconeogenesis).

During treatment with this medicine, your doctor should periodically monitor heart function using serial electrocardiograms (repeated over time) and check electrolyte concentrations, fluid balance, osmolarity, and blood pH.

Serum and urine calcium levels should be frequently monitored to prevent hypercalciuria (high calcium levels in urine), which may lead to increased calcium levels in the blood (hypercalcemia).

Children

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 section "Possible side effects").

In children, the safety and efficacy of this medicine have not been established.

Other medicines and RINGER LACTATE B.BRAUN

Inform your doctor if you are using, have recently used, or might use any other medicine.

This medicine must not be administered if you are taking:

cardiac glycosides (digitalis), digoxin, and digitoxin, used for heart conditions, as concomitant use may increase the risk of heart rhythm irregularities (arrhythmias), since the inotropic and toxic effects are synergistic.

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

medicines used to lower blood pressure such as potassium-sparing diuretics, ACE inhibitors that reduce aldosterone levels, angiotensin II receptor antagonists, and medicines that suppress the immune response such as immunosuppressants (e.g., 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 medicines, 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, as they may lead to increased calcium levels in the blood (hypercalcemia) due to reduced renal excretion of calcium;
medicines containing magnesium, as they may increase the risk of elevated calcium (hypercalcemia) or magnesium (hypermagnesemia) levels, 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-methylenedioxy-N-methamphetamine, ifosfamide, antipsychotics, narcotics, chlorpropamide, NSAIDs, cyclophosphamide, desmopressin, oxytocin, vasopressin, terlipressin;
diuretics in general and antiepileptic medicines (e.g., oxcarbazepine), as they may increase the risk of hyponatremia.

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 (increasing renal clearance) and basic drugs such as sympathomimetics (e.g., ephedrine, pseudoephedrine), dextroamphetamine sulfate, and fenfluramine hydrochloride (decreasing renal clearance).

Due to the presence of calcium chloride, RINGER LACTATE B.BRAUN 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 blockers, as calcium salts may counteract the effect 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 (see sections "Do not use RINGER LACTATE B.BRAUN" and "Possible side effects").

Pregnancy and breastfeeding

If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor before this medicine is administered to you.

If you are pregnant, this medicine should be administered with particular caution during labor, especially regarding serum sodium levels, if administered together with a medicine inducing labor (oxytocin).

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

Driving and using machines

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

3. How to use RINGER LACTATE B.BRAUN

This medicinal product will be prepared by a doctor, pharmacist, or nurse and will not be mixed or administered simultaneously with injections containing ceftriaxone or other incompatible medicines.
Electrolyte balance, serum electrolytes, and acid-base balance may need to be monitored before and during administration, with particular attention to serum sodium levels 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 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.
The dose will be adjusted according to your age, body weight, health condition, concomitant therapy, and your clinical and laboratory response to treatment.
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 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 B.BRAUN than you should
Since this medicine will be administered by a doctor or trained healthcare professional, it is unlikely that you will receive an excessive dose. However, if you think you have been given too much RINGER LACTATE B.BRAUN, 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 (hyperkalemia), which may lead to death due to heart damage (cardiac depression, arrhythmias, or arrest);
increased sodium levels (hypernatremia) and increased blood volume (hypervolemia). If sodium levels in the blood rise too much, loss of fluids 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 lungs (pulmonary edema) or swelling in the legs and ankles (peripheral edema);
increased chloride levels leading to a reduction in blood pH (acidosis) due to decreased bicarbonate ion concentration;
increased calcium levels in the blood (hypercalcemia), especially in people with kidney problems, 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 B.BRAUN, consult your doctor or pharmacist.

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 inadequate administration or administration that is too rapid (see section “Warnings and precautions”).
Not known (frequency cannot be established from available data):

Stomach and intestinal (gastrointestinal) disturbances and irritation, nausea, vomiting, diarrhoea, abdominal pain, constipation, thirst, reduced salivation, metallic taste, chalky taste;
Muscle and nerve (neuromuscular) disturbances, muscle stiffness, altered sensation in limbs (paraesthesias), loss of muscle tone (flaccid paralysis), weakness, mental confusion, headache, dizziness, restlessness, irritability, seizures, coma, death;
Drowsiness, confusional states, mental disorders;
Irregular heartbeat such as arrhythmias, tachycardia, bradycardia, conduction disorders, 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 limbs (peripheral oedema), vasodilation, hot flushes;
Increased levels of sodium (hypernatraemia), chloride (hyperchloraemia), and blood volume (hypervolaemia);
Breathing problems (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, and 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, 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 tissue death (tissue necrosis), abscess formation, and calcium deposits in the skin (cutaneous calcification);
Kidney problems caused by calcium-ceftriaxone deposits. This may cause pain when urinating or reduced urine output.
Presence of calcium-ceftriaxone deposits in the gallbladder, which may lead to pain, nausea, and vomiting;
Low levels of sodium in the blood (hospital-acquired hyponatraemia*);
Acute cerebral oedema (acute hyponatraemic encephalopathy*). *Hospital-acquired hyponatraemia may 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, please inform 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 LATTATE B. BRAUN

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. Store at a temperature not exceeding 25°C. 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. Contents of the pack and other information

What RINGER LACTATE B. BRAUN contains

The active substances are: sodium chloride, potassium chloride, calcium chloride, lactic acid and sodium hydroxide. 1000 ml of solution contain 6.0 g of sodium chloride, 0.4 g of potassium chloride, 0.27 g of calcium chloride, 2.60 g of lactic acid and 1.17 g of sodium hydroxide. 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 B. BRAUN and contents of the pack
Sterile, pyrogen-free isotonic solution with blood, in packs of 1 or 10 low-density polyethylene flasks of 500 ml and 1000 ml.
Marketing Authorization Holder
B. Braun Melsungen AG – Carl-Braun-Strasse, 1 – D-34209 Melsungen – Germany.
Representative in Italy
B. Braun Milano S.p.A. – Via Vincenzo da Seregno, 14 – 20161 Milano – Italy.
Manufacturer
B. Braun Melsungen AG – Carl-Braun-Strasse, 1 – D-34209 Melsungen – Germany.
B. Braun Medical SA – Carretera de Terrassa, 121 – 08191 Rubi – Barcelona – Spain.

The following information is intended exclusively for physicians or healthcare professionals

Overdose
Treatment
Immediately discontinue the infusion and initiate corrective therapy to reduce plasma levels of ions present 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, with appropriate symptomatic and supportive measures provided as required.
In case of marked 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 consists of 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 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; use of beta-blockers to reduce the risk of cardiac arrhythmias;
Hemodialysis if necessary. Elevated plasma electrolyte levels may require dialysis.

Incompatibilities
When used to dilute medications, consult the 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 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;
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: 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.
Sodium ceftriaxone: due to precipitate formation; therefore, administration of calcium-containing solutions must not occur within 48 hours following ceftriaxone administration.

Interactions
Medicinal products that may increase the risk of hospital-acquired hyponatremia following 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 (MDMA), 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 drugs such as oxcarbazepine.

Warnings and Precautions
Monitoring of serum sodium is particularly important for physiologically hypotonic solutions.
Ringer Lactate B. Braun may become markedly hypotonic after administration.
Patients with non-osmotic vasopressin release (e.g. in the acute phase of illness, pain, postoperative stress, infections, burns, and central nervous system disorders), patients with cardiac, hepatic, or renal disease, and patients receiving vasopressin agonists are particularly at risk of acute 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 particular 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, cerebral contusion) are particularly at risk of severe, life-threatening cerebral edema caused by acute hyponatremia.
Pregnancy
Ringer Lactate B. Braun 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 refer to the Summary of Product Characteristics.

Ringer's lactate B. Braun