ELECTROLYTE REHYDRATING SOLUTION WITH MONOHYDRATE GLUCOSE
Infusion Solution III
PHARMACOTHERAPEUTIC CATEGORY
Solutions affecting electrolyte balance, electrolytes associated with carbohydrates.

THERAPEUTIC INDICATIONS
Replenishment of fluids and electrolytes in conditions where a caloric intake must also be ensured.
Treatment of mild or moderate, but not severe, metabolic acidosis.

CONTRAINDICATIONS

Hypersensitivity to the active substances or to any of the excipients;
hypercalcemia, hypercalciuria;
severe renal failure;
hypernatremia;
hydro-saline plethoric states;
hyperkalemia or in cases of potassium retention;
ventricular fibrillation (calcium chloride may increase the risk of arrhythmias);
severe hepatic insufficiency (inability to metabolize acetate ion);
respiratory or metabolic alkalosis;
renal calculi (may be exacerbated by calcium administration);
sarcoidosis (may potentiate the typical hypercalcemia of this condition);
hypercoagulability;
concomitant therapy with cardioactive glycosides (see Interactions);
anuria;
spinal or intracranial hemorrhage;
severe dehydration;
delirium tremens (especially if these patients are already dehydrated);
untreated Addison's disease;
coma;
heat cramps;
concomitant treatment with ceftriaxone in neonates (≤ 28 days of age), even when using separate infusion lines. See sections Interactions with other medicinal products and other forms of interaction, Undesirable effects, and Incompatibilities.

When blood transfusions are performed, this solution must not be administered through the same infusion catheter as whole blood due to the possible risk of pseudoagglutination.

PRECAUTIONS FOR USE
Due to the presence of sodium, use with caution in patients with congestive heart failure, severe renal failure, and clinical conditions associated with edema and salt retention; in patients receiving inotropic cardiac drugs or corticosteroid or corticotropin drugs.

Sodium salts should be administered with caution in patients with hypertension, heart failure, peripheral or pulmonary edema, reduced renal function, pre-eclampsia, or other conditions associated with sodium retention (see Interactions).

Due to the presence of potassium, administration should be guided by serial electrocardiograms; serum potassium levels are not indicative of intracellular potassium concentrations.

High plasma potassium concentrations may cause death due to cardiac depression, arrhythmias, or cardiac arrest. To prevent potassium intoxication, the infusion must be slow.

The medicinal product must be administered with caution in patients:

with renal insufficiency (administration of potassium-containing solutions in patients with impaired renal function may cause potassium retention);
with heart failure, especially if digitalized;
with adrenal insufficiency;
with hepatic insufficiency;
with familial periodic paralysis;
with congenital myotonia;
in the early postoperative phase.

Due to the presence of calcium, the medicinal product must be used with great caution in patients:

with renal disorders;
with cardiac disorders;
who have received a blood transfusion, as calcium ion concentrations may differ from expected values.

Since calcium chloride is acidifying, caution is required when administering it in conditions such as renal disease, cor pulmonale, respiratory acidosis, or respiratory insufficiency, where acidification may worsen the clinical picture. Additionally, caution is advised in conditions where there may be an increased risk of hypercalcemia, such as chronic renal failure, dehydration, or electrolyte imbalance.

Since calcium salts may increase the risk of arrhythmias, care must be taken when prolonging calcium chloride administration in patients with cardiac disorders. Administration of calcium chloride may cause vasodilation with consequent lowering of blood pressure.

Calcium chloride solution is irritating and must not be administered intramuscularly, subcutaneously, or into peri-vascular tissue, as tissue necrosis may occur. Plasma calcium concentrations and urinary calcium levels should be monitored frequently to prevent hypercalciuria, as hypercalciuria may progress to hypercalcemia.

Due to the presence of magnesium, the medicinal product must be administered with caution in patients:

with renal insufficiency;
with heart failure, especially if digitalized;
with myasthenia gravis;
receiving central nervous system depressants or neuromuscular blocking agents.

Due to the presence of glucose, the medicinal product must be administered with caution in patients with overt or subclinical diabetes mellitus or with any form of glucose intolerance. One gram of glucose provides approximately 3.74 kcal (about 15.6 kJ). To minimize the risk of hyperglycemia and consequent glycosuria, blood and urine glucose levels should be monitored, and insulin administered if required. During prolonged use of glucose solutions, fluid overload, congestive state, and electrolyte deficits may occur. Particular attention should be paid when administering glucose to patients receiving corticosteroids or corticotropin (see Interactions).

In pediatric patients, particularly neonates and children with low body weight, glucose administration may increase the risk of hyperglycemia. Moreover, in low-weight children, rapid or excessive infusion may cause increased serum osmolarity and intracerebral hemorrhage.

Due to the presence of acetate, use with caution in patients with metabolic or respiratory alkalosis and in conditions where there is increased level or insufficient utilization of this ion, such as in mild to moderate hepatic insufficiency.

During infusion of the medicinal product, continuous monitoring of the electrocardiographic trace is essential. It is good practice to monitor fluid balance, electrolytes, plasma osmolarity, blood pressure, acid-base balance, osteotendinous reflexes (to monitor for possible respiratory paralysis), and blood glucose. Serum magnesium levels should be closely monitored during therapy to ensure they do not exceed normal limits. Plasma calcium concentrations and urinary calcium levels should be monitored frequently to avoid hypercalciuria, as hypercalciuria may progress to hypercalcemia.

INTERACTIONS
Inform your doctor or pharmacist if you have recently taken any other medicinal products, including those without
prescription.

The use of potassium-sparing diuretics may increase the risk of hyperkalemia, particularly in the presence of renal dysfunction. Therefore, in such cases, serum potassium levels must be closely monitored.

The use of drugs such as ACE inhibitors, which cause a decrease in aldosterone levels, may lead to potassium retention. Therefore, serum potassium levels must be closely monitored.

Corticosteroids are associated with sodium and water retention, leading to edema and hypertension: therefore, caution is required when administering sodium salts concomitantly with corticosteroids (see Precautions for use).

Calcium chloride solution may interact with the following medicinal products:

thiazide diuretics, as hypercalcemia may occur due to reduced renal calcium excretion;
cardioactive glycosides (digitalis), digoxin, and digitoxin, as concomitant use may increase the risk of arrhythmias, since inotropic and toxic effects are synergistic;
verapamil (and other calcium channel blockers), as concomitant use may reduce the antihypertensive effect of verapamil;
medicinal products containing magnesium, as this may increase the risk of hypercalcemia or hypermagnesemia, especially in patients with renal disorders;
neuromuscular blockers: calcium salts may antagonize the action of non-depolarizing blockers; in some cases, an increase and prolongation of the action of tubocurarine has also been observed.

As with other calcium-containing solutions, concomitant treatment with ceftriaxone is contraindicated in neonates (≤ 28 days of age), even when using separate infusion lines (risk of fatal precipitation of ceftriaxone-calcium salt in the neonate's bloodstream; see section Undesirable effects). In patients older than 28 days (including adults), ceftriaxone must not be administered concomitantly with intravenous solutions containing calcium, including Elettrolitica Reidratante MONICO - Infusion Solution III with Glucose, through the same infusion line (e.g., via a Y-connector). If the same line is used for sequential administration, the line must be flushed with a compatible fluid between infusions.

Magnesium chloride may interact with the following medicinal products:

central nervous system depressants: when barbiturates, narcotics, or other hypnotics (or systemic anesthetics) or other drugs that depress the central nervous system are administered concomitantly with magnesium, their dosage must be carefully adjusted due to the additive central nervous system depressant effect of magnesium. Central nervous system and peripheral transmission depression caused by magnesium may be antagonized by calcium;
cardioactive glycosides (digitalis), digoxin, and digitoxin: magnesium chloride must be administered with extreme caution in patients receiving digitalis due to changes in cardiac conduction that may evolve into cardiac arrhythmia, especially if calcium administration becomes necessary to treat magnesium intoxication;
competitive and depolarizing neuromuscular blockers: parenteral administration of magnesium chloride potentiates the effect of competitive and depolarizing neuromuscular blockers;
aminoglycoside antibiotics: the effect on neuromuscular blockade of parenterally administered magnesium and aminoglycoside antibiotics may be additive;
eltrombopag: administration of products containing aluminum, calcium, or magnesium may reduce plasma concentrations of eltrombopag;
rocuronium: concomitant administration of rocuronium and magnesium may increase the risk of rocuronium toxicity (prolonged neuromuscular blockade, respiratory depression, and apnea);
labetalol: concomitant administration of labetalol and magnesium may cause bradycardia and reduced cardiac output (labored breathing, dizziness, or fainting);
calcium antagonists (isradipine, felodipine, nicardipine, and nifedipine): concomitant administration of magnesium with a calcium antagonist may result in hypotension.

Since corticosteroids and corticotropin are associated with decreased carbohydrate tolerance and possible manifestation of latent diabetes mellitus, patients must be closely monitored when glucose is administered concomitantly.

SPECIAL WARNINGS
Use immediately after opening the container. The solution must be clear, colorless or slightly straw-yellow, and free from visible particles. It is intended for single, uninterrupted administration and any residual solution must not be used.

Pregnancy and lactation
No data are available on possible adverse effects of the medicinal product when administered during pregnancy or lactation or on reproductive capacity.
Therefore, the medicinal product must not be used during pregnancy or lactation unless absolutely necessary and only after careful assessment of the risk-benefit ratio.
Avoid use of magnesium 2 hours before delivery. If magnesium chloride is administered (especially for more than 24 hours before delivery) to control seizures in mothers with toxemia of pregnancy, newborns may show signs of magnesium toxicity, including neuromuscular and respiratory depression.

Effects on ability to drive and use machines
The medicinal product does not affect the ability to drive or use machinery.

Important information on some excipients: the product contains sodium metabisulfite: this substance may cause allergic reactions and severe asthma attacks in sensitive individuals, particularly asthmatics.

DOSAGE, METHOD AND DURATION OF ADMINISTRATION
The solution is hypertonic with respect to blood and must be administered by intravenous infusion with caution and at a controlled infusion rate.
Shake well before administration.
Dosage depends on the patient's age, weight, and clinical condition.
The medicinal product must be administered only in patients with intact renal function and at a rate not exceeding 10 mEq potassium/hour and 0.4–0.8 g glucose per kg body weight per hour.

Adults
The usual dose is generally 3 liters/day, administered at a rate of approximately 500 ml–1 liter/hour.

Children
In children, the safety and efficacy of the medicinal product have not been established.
Glucose dosage and infusion rate must be selected according to the patient's age, weight, and clinical condition. Particular caution is required in pediatric patients, especially neonates or children with low body weight (see Precautions for use).

Do not inject intramuscularly, subcutaneously, or into perivascular tissues.
Infusion must be stopped if the patient experiences pain or redness at the injection site, as this may indicate extravasation of the drug.
Infusions that are too rapid may cause local pain, and the infusion rate must be adjusted according to tolerance.
It is advisable for the patient to remain lying down for a short period after administration.

Incompatibilities with Elettrolitica Reidratante with Glucose MONICO
Due to the presence of glucose, the medicinal product is incompatible with:

cyanocobalamin;
kanamycin sulfate;
novobiocin sodium;
warfarin sodium.

Additionally, there are conflicting opinions regarding the compatibility of glucose with hydroxyethyl starch (hetastarch). Ampicillin and amoxicillin remain stable in glucose solutions only for a short period.

Due to the presence of calcium chloride, it 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 cloudiness;
cefamandole: due to presence of sodium carbonate in cefamandole preparation;
ceftriaxone sodium: due to precipitate formation; therefore, calcium-containing solutions must not be administered within 48 hours after ceftriaxone administration;
cephalothin: due to physical incompatibility;
cefradine: due to presence of sodium carbonate in cefradine preparation;
chlorpheniramine: due to physical incompatibility;
dobutamine: due to development of cloudiness;
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: 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 Contraindications, Interactions with other medicinal products and other forms of interaction, and Undesirable effects).

Due to the presence of magnesium, the medicinal product is incompatible with solutions containing alcohol (at high concentrations), heavy metals, carbonates and bicarbonates, hydrocortisone sodium, succinates, phosphates, polymyxin B sulfate, procaine hydrochloride, calcium salicylate, clindamycin phosphate, tartrates, as precipitates may form.

Potential incompatibility is often influenced by changes in reactant concentrations and pH of the solutions.

Use immediately after opening the container. The container is intended for single, uninterrupted administration and any residual solution must not be used.
Shake well before administration. Do not use the medicinal product if the solution is not clear, colorless or slightly straw-yellow, or if it contains particles.
Adopt all usual precautions to maintain sterility before and during intravenous infusion.

OVERDOSE
Symptoms
High plasma potassium concentrations may cause death due to cardiac depression, arrhythmias, or cardiac arrest.
Excessive administration of sodium chloride may lead, depending on the patient's clinical condition, to hypernatremia and/or hypervolemia. Hypernatremia and excessive sodium retention, especially when renal sodium excretion is impaired, may cause dehydration of internal organs, particularly the brain, and accumulation of extracellular fluid with edema affecting cerebral, pulmonary, and peripheral circulation, leading to pulmonary and peripheral edema.

In case of excessive administration of magnesium chloride, the following symptoms of intoxication may occur: flushing, sweating, hypotension, flaccid paralysis, hypothermia, circulatory collapse, cardiac and central nervous system depression, potentially progressing to respiratory paralysis.
Magnesium intoxication manifests with a peak in blood pressure and respiratory paralysis.
Disappearance of the patellar reflex is a useful clinical sign indicating the onset of intoxication.

In case of excessive administration of calcium chloride, hypercalcemia may occur, especially in patients with renal disorders. Typical symptoms of hypercalcemia include: thirst, nausea, vomiting, constipation, polyuria, abdominal pain, muscle weakness, mental disturbances, and, in severe cases, cardiac arrhythmias and coma. Hypercalcemia is diagnosed when plasma calcium concentrations exceed 2.6 mmol/L; therefore, these concentrations must be continuously monitored.

Prolonged administration of glucose may lead to hyperhydration and solute overload.

Treatment
Immediately discontinue the infusion and initiate corrective therapy for hyperglycemia and reduce plasma levels of excess ions, restoring acid-base balance if necessary (see Precautions for use).
The patient should be closely observed for any signs and symptoms related to the administered drug, ensuring appropriate symptomatic and supportive measures as needed.

In case of elevated natremia, 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 involves immediate discontinuation of the infusion and 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 promote calcium excretion;
monitoring of plasma potassium and magnesium levels with immediate correction to normal values;
monitoring of cardiac function, use of beta-blockers to reduce the risk of cardiac arrhythmias;
possible recourse to hemodialysis.

In case of magnesium overdose, artificial respiration is required. To counteract the effects of hypermagnesemia, calcium must be administered intravenously (10–20 ml of a 5% solution). Subcutaneous administration of 0.5–1 mg of physostigmine may be helpful. Elevated plasma electrolyte levels may require dialysis.

In case of excessive glucose administration, reassess the patient's clinical condition and implement appropriate corrective measures.

In case of accidental ingestion/overdose of Elettrolitica Reidratante with Glucose MONICO, contact a doctor immediately or go to the nearest hospital.
If you have any doubts about the use of Elettrolitica Reidratante with Glucose MONICO, consult your doctor or pharmacist.

UNDESIRABLE EFFECTS
Like all medicinal products, Elettrolitica Reidratante with Glucose MONICO can cause undesirable effects, although not everyone experiences them.
The following undesirable effects of Elettrolitica Reidratante with Glucose are listed. There are insufficient data to establish the frequency of individual listed effects.

Immune system disorders
Hypersensitivity reactions, urticaria.

Gastrointestinal disorders
Gastrointestinal disturbances and irritation, thirst, reduced salivation, nausea, vomiting, diarrhea, abdominal pain, constipation, delayed intestinal transit, paralytic ileus, metallic taste, chalky taste.

Nervous system disorders
Neuromuscular disturbances, muscle rigidity, paresthesia, flaccid paralysis, weakness, mental confusion, headache, dizziness, restlessness, irritability, convulsions, coma, death.

Psychiatric disorders
Somnolence, confusion, mental disturbances.

Cardiac disorders
Arrhythmias, tachycardia, bradycardia, conduction disturbances, disappearance of P wave, QRS widening on electrocardiogram, syncope, ventricular fibrillation, cardiac arrest.

Vascular disorders
Hypotension, hypertension, peripheral edema, vasodilation, flushing, sweating, shock.

Fluid and electrolyte imbalance disorders
Hypernatremia, hypervolemia, hyperchloremia.

Respiratory, thoracic and mediastinal disorders
Dyspnea, respiratory arrest, pulmonary edema, pneumothorax.

Eye disorders
Reduced lacrimation.

Renal and urinary disorders
Renal failure, polyuria.

Metabolism and nutrition disorders
Hypercalcemia, Burnett syndrome (milk-alkali syndrome), hypocalcemia.

Musculoskeletal and connective tissue disorders
Muscle weakness.

Metabolism and nutrition disorders
Increased metabolic rate, hyperglycemia, hypoglycemia, increased insulin levels, increased adrenaline levels.

General disorders and administration site conditions
Feverish reactions, infusion site infection, pain or local reaction, redness, rash, venous irritation, thrombosis or phlebitis extending from the infusion site, extravasation, tissue necrosis, abscess formation, cutaneous calcification.

Precipitation of calcium-ceftriaxone salt
Rarely, serious and in some cases fatal adverse reactions have been reported in preterm and full-term neonates (age < 28 days) treated with intravenous ceftriaxone and calcium. Post-mortem findings revealed calcium-ceftriaxone salt precipitation in the lungs and kidneys. The high risk of precipitation in neonates is due to their low blood volume and longer ceftriaxone half-life compared to adults (see sections Contraindications and Interactions with other medicinal products and other forms of interaction).

Cases of renal precipitation have been reported, mainly in children over 3 years of age treated with high daily doses (e.g., ≥ 80 mg/kg/day) or total doses exceeding 10 grams, and who had other risk factors (e.g., fluid restriction, bedridden patients). The risk of precipitate formation increases in immobilized or dehydrated patients. This event may be symptomatic or asymptomatic, may cause renal failure and anuria, and is reversible upon discontinuation of administration.

Calcium-ceftriaxone salt precipitation in the gallbladder has been observed, mainly in patients treated with doses higher than the recommended standard dose. Prospective studies in children have shown variable incidence of precipitation with intravenous administration; in some studies, incidence exceeded 30%. This incidence appears lower when infusions are administered slowly (20–30 minutes). This effect is generally asymptomatic, but in rare cases precipitation has been associated with clinical symptoms such as pain, nausea, and vomiting. Symptomatic treatment is recommended in such cases. Precipitation is generally reversible upon discontinuation of administration.

Following the instructions in the package leaflet reduces the risk of undesirable effects.
If any of the undesirable effects worsens, or if you notice any undesirable effect not listed in this leaflet, inform your doctor or pharmacist.

EXPIRY DATE AND STORAGE
Expiry date: see the date on the packaging.
The expiry date refers to the product in intact, properly stored packaging.
Caution: do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions
Store in the original packaging and in a tightly closed container. Do not refrigerate or freeze.
Medicinal products must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of unused medicines. This helps protect the environment.
Keep the medicinal product out of the reach and sight of children.

COMPOSITION
1000 ml contains
Active substances: sodium chloride 5.0 g
potassium chloride 0.75 g
calcium chloride dihydrate 0.35 g
magnesium chloride hexahydrate 0.31 g
sodium acetate trihydrate 6.4 g
sodium citrate 0.75 g
glucose monohydrate 55.0 g
equivalent to glucose 50 g
mEq/liter: Na 140
K 10
Ca 5
Mg 3
Cl 103
Acetate 47
Citrate 8
mmol/liter: glucose 278
theoretical osmolarity: (mOsm/liter) 585
pH: 5.0 ÷ 7.0
Excipients: water for injections, sodium metabisulfite, hydrochloric acid.

PHARMACEUTICAL FORM AND CONTENT
Sterile, pyrogen-free infusion solution.
Glass vials (pharmaceutical glass) of 50 – 100 – 250 – 500 – 1000 ml.
Plastic (polypropylene) bags of 100 – 250 – 500 – 1000 ml.

MARKETING AUTHORIZATION HOLDER
MONICO SPA, Via Ponte di Pietra 7 – VENEZIA / MESTRE

MANUFACTURER
MONICO SPA, Via Ponte di Pietra 7 – VENEZIA / MESTRE

Electrolyte rehydration solution with glucose Monico