Ringer's lactate Monico

PACKAGE LEAFLET: INFORMATION FOR THE USER

RINGER LACTATE MONICO

Infusion solution
Sodium chloride, potassium chloride, calcium chloride dihydrate, sodium lactate
Equivalent medicine
Please read this leaflet carefully before using this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, 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 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 MONICO is and what it is used for
2. What you need to know before using RINGER LACTATE MONICO
3. How to use RINGER LACTATE MONICO
4. Possible side effects
5. How to store RINGER LACTATE MONICO
6. Contents of the pack and other information

1. What RINGER LACTATE MONICO is and what it is used for

RINGER LACTATE MONICO is an infusion solution for direct intravenous injection (intravenous infusion), containing a combination of active substances: sodium chloride, potassium chloride, calcium chloride dihydrate and sodium lactate.
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 there is increased acidity (mild or moderate, but not severe acidosis);
• to restore normal blood pressure following shock caused by significant blood loss (mild or moderate, but not severe hemorrhagic shock).

2. What you should know before using RINGER LATTATO MONICO

Do not use RINGER LATTATO MONICO

• 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 (severe renal insufficiency);
• 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 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, as calcium chloride may increase the risk of cardiac rhythm disturbances (arrhythmias);
• if you have kidney stones, which may worsen with calcium administration;
• if you suffer from a chronic systemic disease called sarcoidosis, which may enhance the increase in 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 LATTATO MONICO”);
• 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 (up to 28 days of age), RINGER LATTATO MONICO (or other calcium-containing solutions) must not be administered simultaneously with ceftriaxone (an antibiotic), even if separate infusion lines are used. There is a risk of fatal formation of particles in the newborn's bloodstream.

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 LATTATO MONICO.

This medicine must be administered by a very slow infusion, as potassium intoxication may occur, potentially leading to cardiac arrest due to loss of heart function (cardiac depression), cardiac rhythm disturbances (arrhythmias), and even death (see section “How to use RINGER LATTATO MONICO”).

If signs or symptoms of suspected hypersensitivity occur, the infusion must be stopped immediately.

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);
• if you have 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 agents), steroid anti-inflammatory drugs (corticosteroids), or hormonal medicines (corticotropins);
• 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 accumulation, and presence of protein in the urine, or other conditions associated with sodium retention.

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

• if you have kidney problems (renal insufficiency), as potassium retention may occur;
• if you have heart problems (cardiac insufficiency) and are taking other heart medications (digitalis);
• if you have adrenal gland problems (adrenal insufficiency);
• if you have 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 post-operative 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 problems (renal insufficiency) or lung problems with heart enlargement (pulmonary heart disease), if you have breathing difficulties (respiratory insufficiency), or if you have a decreased blood pH (respiratory acidosis), as in all these cases the administration of calcium chloride (acidifying agent) may worsen the clinical condition;
• if you have heart problems, as calcium salts may increase the risk of cardiac rhythm disturbances (arrhythmias);
• if you have received a blood transfusion, as calcium ion concentrations may differ from expected levels;
• if you have low body water levels (dehydration) or an electrolyte imbalance, or suffer from severe kidney problems (chronic renal failure), as this may increase the risk of elevated blood calcium levels (hypercalcemia);
• if you have low blood pressure, as calcium chloride administration may cause vasodilation leading to further blood pressure reduction.

Calcium chloride solution is irritating and therefore must not be administered by intramuscular injection, subcutaneous injection, or into the tissue surrounding blood vessels (peri-vascular tissue), as this may cause tissue damage and death (necrosis).

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

• you suffer from lactic acidosis or have impaired oxidative processes preventing lactate utilization (e.g., shock, hypoxemias);
• you have type 2 diabetes;
• you have altered blood lactate levels (e.g., if you suffer from severe liver insufficiency).

This medicine must not be administered in the following cases:

• if you suffer from diseases that may cause sodium accumulation, excess fluid, or swelling due to fluid accumulation, such as primary hyperaldosteronism, secondary hyperaldosteronism, or pre-eclampsia;
• if you suffer from conditions that may cause potassium accumulation, such as severe kidney damage, adrenocortical insufficiency, severe dehydration, extensive tissue damage, or heart failure. Inform your doctor if you are in any of the following conditions:
• you have an acute illness;
• you have pain;
• you have undergone surgery;
• you have infections or burns;
• you have brain diseases;
• you have liver, heart, or kidney diseases;
• you are being treated with vasopressin agonists. This may increase the risk of low sodium levels in the blood (hyponatremia), which may cause cerebral edema characterized by headache, nausea, seizures, drowsiness, vomiting, and potentially life-threatening complications. Cerebral edema is more likely to occur:
• in children;
• in women of childbearing age;
• in cases of meningitis, intracranial bleeding, or cerebral contusion and edema.

During treatment with this medicine, your doctor must periodically monitor heart function using serial electrocardiograms and check levels of mineral salts (electrolytes), fluids, osmolarity, and blood pH (acid-base balance). Blood and urine calcium levels must be frequently monitored 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 from visible particles. It is intended for single, uninterrupted administration, and any remaining solution must not be reused.

Children

In children, the safety and efficacy of this medicine have not been established. As with other calcium-containing solutions, concomitant treatment with ceftriaxone is contraindicated in newborns (up to 28 days of age), even when using separate infusion lines, due to the risk of fatal precipitation of ceftriaxone-calcium salt in the newborn's bloodstream (see sections “Do not use RINGER LATTATO MONICO” and “Possible side effects”).

Other medicines and RINGER LATTATO MONICO

Inform your doctor if you are taking, have recently taken, or might take any other medicine.

This medicine must not be administered if you are taking:

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

This medicine must 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, as they may lead to increased potassium levels in the blood (hyperkalemia) and potassium retention, especially in the presence of renal dysfunction; in such cases, blood potassium levels must be closely monitored;
• angiotensin II receptor antagonists and drugs used in organ transplantation such as tacrolimus and cyclosporine, as they may lead to increased potassium levels in the blood (hyperkalemia); in such cases, blood potassium levels must be closely monitored;

• thiazide diuretics, used to treat high blood pressure, and vitamin D, as they may cause increased blood calcium levels (hypercalcemia) due to reduced renal excretion of calcium;
• magnesium-containing medications, as they may increase the risk of elevated calcium (hypercalcemia) or magnesium (hypermagnesemia) levels in the blood, especially in patients with kidney disorders;
• steroid anti-inflammatory drugs (corticosteroids), which may cause sodium and water retention, leading to fluid accumulation (edema) and increased blood pressure (hypertension);
• drugs that enhance vasopressin effects: chlorpropamide, clofibrate, carbamazepine, vincristine, selective serotonin reuptake inhibitors, 3,4-methylenedioxy-N-methamphetamine, ifosfamide, antipsychotics, narcotics, NSAIDs, cyclophosphamide, desmopressin, oxytocin, vasopressin, terlipressin, diuretics in general, and oxcarbazepine.

Due to the alkalinizing effect of lactate (bicarbonate formation), the 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 phenfluramine hydrochloride (decreased renal clearance).

Due to the presence of calcium chloride, RINGER LATTATO MONICO 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 effects 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 in the blood (precipitation of calcium-ceftriaxone salt). 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 administrations, it must be flushed with a compatible fluid between infusions (see sections “Do not use RINGER LATTATO MONICO”, “Children”, and “Possible side effects”).

Pregnancy and breastfeeding

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

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

Driving and use of machines

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

3. How to use RINGER LATTATO MONICO

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 trained medical personnel. It must not be injected via other routes of administration (intramuscular, subcutaneous, or into perivascular tissues). This medicine should only be administered if your kidney function is normal and at a rate not exceeding 10 mEq of potassium per hour.
After administration, remain lying down for a short period.
The dose will be adjusted according to your age, body weight, and health condition. Your doctor will determine the dose and method of administration (e.g. volume and infusion rate) based on your health status and any other medicines you may be taking.
Before and during administration, your doctor will monitor your blood levels of electrolytes, fluids, osmolarity, and pH (acid-base balance).

The recommended dose in adults is approximately 20–30 ml of solution per kilogram of body weight per day, which may be increased up to a maximum of 40 ml of solution per kilogram of body weight per day.
Infusions that are too rapid may cause local pain; the infusion rate should 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 necessary precautions are taken to maintain sterility before and during intravenous infusion.

If you use more RINGER LATTATO MONICO 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 LATTATO MONICO, inform your doctor immediately or go to the nearest hospital.

Following an overdose of this medicine, the following may occur:

• increased potassium levels in the blood (hyperkalaemia), which may lead to cardiac damage (cardiac depression, arrhythmias) and potentially death;
• increased sodium levels (hypernatraemia) and increased blood volume (hypervolaemia); if sodium levels in the blood rise too much, fluid loss from internal organs (dehydration) may occur, particularly from the brain, and fluid accumulation may affect the cerebral, pulmonary, and peripheral circulation,

leading to fluid accumulation around the lung (pulmonary oedema) or swelling in the legs and ankles (peripheral oedema);

• increased chloride ion levels causing a decrease in blood pH (acidosis) due to reduced bicarbonate ion concentration;
• increased calcium levels in the blood (hypercalcaemia), especially in patients with kidney disease, resulting in symptoms such as thirst, nausea, vomiting, constipation, increased urine production (polyuria), abdominal pain, muscle weakness, mental disturbances, and in severe cases, cardiac problems (cardiac arrhythmia) and coma. Therefore, plasma calcium concentrations must be monitored continuously to ensure they do not exceed 2.6 mmol/l.

In case of overdose, stop the infusion immediately and initiate corrective therapy to reduce plasma levels of excess ions and, if necessary, restore acid-base balance.
If you have any doubts about the use of RINGER LATTATO MONICO, 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 established from the available data):

• stomach and intestinal disturbances and irritation (gastrointestinal disorders), nausea, vomiting, diarrhoea, abdominal pain, constipation;
• thirst, reduced salivation, metallic taste, chalky taste;
• muscle and nerve disturbances (neuromuscular disorders), muscle stiffness, altered limb sensation (paraesthesia), loss of muscle tone (flaccid paralysis), weakness;
• confusion, headache, dizziness, restlessness, irritability;
• seizures, coma, death;
• drowsiness, confusional states, mental disorders;
• irregular heartbeat (arrhythmias), increased heart rate (tachycardia), decreased heart rate (bradycardia), conduction disturbances, disappearance of the P wave, widening of the QRS complex on the electrocardiogram, syncope, ventricular fibrillation, cardiac arrest;
• decreased or increased blood pressure (hypotension or hypertension), swelling of the limbs (peripheral oedema), vasodilation, flushing;
• 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 in the membrane surrounding the lung (pneumothorax);
• reduced tear production;
• kidney problems (renal failure), increased urine production (polyuria);
• increased levels of calcium in the blood (hypercalcaemia);
• Burnett's syndrome (also known as milk-alkali syndrome), a condition caused by excessive intake of milk or alkaline compounds;

• 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 the veins (thrombosis);
• inflammation of the veins extending from the infusion site (phlebitis);
• leakage of the medicine into the surrounding tissues at the injection site (extravasation);
• tissue damage and death (tissue necrosis);
• abscess formation and calcium deposits on 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 neonates under 28 days of age, serious reactions, including death, may occur if calcium is administered together with ceftriaxone;
• allergic reactions at the time of infusion, including anaphylactic/anaphylactoid reactions;
• low levels of sodium in the blood (hyponatraemia, which may be hospital-acquired);
• cerebral oedema which may lead to brain damage (hyponatraemic encephalopathy).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at the following website:
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 MONICO

Keep this medicine out of the reach and sight of children.
Do not use this medicine after the expiry date which is 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 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 MONICO contains

• The active substances are: sodium chloride, potassium chloride, calcium chloride dihydrate and sodium lactate. 1000 ml of solution contain: 6.0 g of sodium chloride, 0.4 g of potassium chloride, 0.27 g of calcium chloride dihydrate, 5.419 g of sodium lactate. 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 MONICO and contents of the pack

Glass vials of 50, 100, 250, 500, 1000 ml of infusion solution.
Plastic bags of 50, 100, 250, 500, 1000 ml of infusion solution.
Marketing Authorisation Holder and Manufacturer
MONICO SPA – Via Ponte di Pietra 7, 30173 – VENEZIA / MESTRE – Italy.

The following information is intended exclusively for healthcare professionals

Warnings and precautions
The infusion of large volumes should be used under specific monitoring conditions in
patients with cardiac or pulmonary insufficiency and in patients with non-osmotic release of
vasopressin (including SIADH), due to the risk of hospital-acquired hyponatremia (see below).

Hyponatremia
Patients with non-osmotic vasopressin release (e.g. in the acute phase of illness, pain, post-operative stress, infections, burns, and central nervous system disorders), patients with cardiac, hepatic, or renal disease, and patients treated with vasopressin agonists are particularly at risk of acute hyponatremia following infusion of hypotonic solutions. Acute hyponatremia may cause 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, contusion, and cerebral edema) are particularly at risk of severe and life-threatening cerebral edema caused by acute hyponatremia.

Interactions
The following list includes medicinal products that enhance the effect of vasopressin, causing reduced renal excretion of electrolyte-free water and increasing the risk of hospital-acquired hyponatremia during inadequately balanced intravenous fluid therapy:

• 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 potentiating the action of vasopressin, e.g.: chlorpropamide, NSAIDs, cyclophosphamide;
• Vasopressin analogues: desmopressin, oxytocin, vasopressin, terlipressin. Other medicinal products that also increase the risk of hyponatremia include diuretics in general and antiepileptic drugs such as oxcarbazepine.

Pregnancy
RINGER LACTATE MONICO must be administered with particular caution to pregnant women during labor, especially when administered concomitantly with oxytocin, due to the risk of hyponatremia.

Incompatibilities
Due to the presence of calcium chloride, RINGER LACTATE MONICO 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;
• Ceftriaxone sodium: due to precipitate formation; therefore, calcium-containing solutions must not be administered within 48 hours following ceftriaxone administration;
• 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: as 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.
Physical incompatibility has been reported with ceftriaxone (see sections “Do not use RINGER LACTATE MONICO”, “Children”, and “Possible side effects”).

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