PHARMACOTHERAPEUTIC CATEGORY
Electrolytes
THERAPEUTIC INDICATIONS
Rehydration and electrolyte replacement.
Treatment of mild or moderate, but not severe, metabolic acidosis.
CONTRAINDICATIONS

Hypersensitivity to the active substance or to any of the excipients;
hypercalcemia, hypercalciuria;
severe renal failure;
hypernatremia;
hydro-saline plethora;
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);
metabolic and respiratory 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 section 4.5);
untreated Addison's disease;
acute dehydration;
heat cramps. Concomitant treatment with ceftriaxone in neonates (≤28 days of age), even when using separate infusion lines. See sections Interactions, Undesirable effects, Incompatibilities

PRECAUTIONS FOR USE
Due to the presence of sodium, use with caution in patients with congestive heart failure, severe renal failure, and in 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 section 4.5).
Due to the presence of potassium, administration should be guided by serial electrocardiograms; serum potassium levels do not reflect intracellular potassium concentrations. High plasma potassium concentrations may cause death due to cardiac depression, arrhythmias, or arrest. To avoid potassium intoxication, the infusion must be slow.
The medicine should be administered with caution in patients:

with renal impairment (administration of potassium-containing solutions in patients with reduced 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 medicine 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 an acidifying agent, caution is required when administering it in conditions such as renal disease, cor pulmonale, respiratory acidosis, or respiratory failure, where acidification may worsen the clinical picture. Additionally, caution is required in conditions where there is an increased risk of hypercalcemia, such as chronic renal failure, dehydration, or electrolyte imbalance. Since calcium salts may increase the risk of arrhythmias, care should be taken when prolonging calcium chloride administration in patients with cardiac disorders. Administration of calcium chloride may cause vasodilation leading to a drop in blood pressure. Calcium chloride solution is irritating and therefore must not be administered intramuscularly, subcutaneously, or into peri-vascular tissue, as tissue necrosis may occur. Plasma calcium concentrations and urinary calcium excretion should be monitored frequently to avoid hypercalciuria, as hypercalciuria may progress to hypercalcemia. Due to the presence of magnesium, the medicine should be administered with caution in patients:
with renal impairment;
with heart failure, especially if digitalized;
with severe myasthenia gravis;
receiving central nervous system depressants and neuromuscular blocking agents.

Due to the presence of acetate, use with caution in patients with metabolic and respiratory alkalosis and in conditions where there is an elevated level or inadequate utilization of this ion, such as mild to moderate hepatic insufficiency.
During infusion of the medicine, continuous monitoring of the electrocardiographic trace is essential, and it is good practice to monitor fluid balance, electrolytes, plasma osmolarity, blood pressure, acid-base balance, and osteotendinous reflexes, the latter to monitor for possible respiratory paralysis.
Serum magnesium levels should be closely monitored during therapy to ensure they do not exceed normal limits.
INTERACTIONS
Inform your doctor or pharmacist if you have recently taken any other medicines, including those not requiring a 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 reduce 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 co-administering sodium salts and corticosteroids (see Precautions).
Calcium chloride solution may interact with the following medicines:

thiazide diuretics, as hypercalcemia may occur due to reduced renal excretion of calcium;
cardioactive glycosides (digitalis), digoxin and digitoxin, as concomitant use may increase the risk of arrhythmias due to synergistic inotropic and toxic effects;
verapamil (and other calcium channel blockers), as concomitant use may reduce the antihypertensive effect of verapamil;
medicines containing magnesium, as the risk of hypercalcemia or hypermagnesemia may increase, especially in patients with renal disorders;
neuromuscular blocking agents: 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. Magnesium chloride may interact with the following medicines:
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 CNS depressant effect of magnesium. CNS and peripheral transmission depression caused by magnesium can be antagonized by

calcium;

cardioactive glycosides (digitalis), digoxin and digitoxin: magnesium chloride must be administered with extreme caution in patients taking digitalis due to alterations in cardiac conduction that may progress to cardiac arrhythmia if calcium administration becomes necessary to treat magnesium intoxication;
competitive and depolarizing neuromuscular blockers: parenteral administration of magnesium chloride potentiates the effect of both competitive and depolarizing neuromuscular junction blockers;
aminoglycoside antibiotics: the neuromuscular blocking effect 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 drug may result in hypotension. 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 Undesirable effects). In patients older than 28 days (including adults), ceftriaxone must not be administered concomitantly with intravenous solutions containing calcium, including Elettrolitica reidratante Diaco, 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.

SPECIAL WARNINGS
Use immediately after opening the container. The solution must be clear, colorless, and free from visible particles.
For single, uninterrupted administration only; any residual solution must not be used.
Pregnancy and breastfeeding
No data are available on potential adverse effects of the medicine when administered during pregnancy or lactation or on reproductive capacity.
Therefore, the medicine must not be used during pregnancy or breastfeeding unless absolutely necessary and only after careful risk/benefit assessment.
Avoid the use of magnesium within 2 hours of delivery. If magnesium chloride is administered (especially for more than 24 hours before delivery) to control seizures in mothers with eclampsia, neonates may show signs of magnesium toxicity, including neuromuscular and respiratory depression.
Effects on ability to drive and use machines
The medicine does not affect the ability to drive vehicles or operate machinery.
Important information on some excipients: N/A
DOSAGE, METHOD AND DURATION OF ADMINISTRATION
The solution is isotonic with blood and must be administered cautiously by intravenous infusion at a controlled infusion rate.
Shake well before administration.
Dosage depends on the patient's age, weight, and clinical condition.
The medicine must be administered only in patients with intact renal function and at a rate not exceeding 10 mEq potassium/hour.
Adults
Generally, the dose is 3 liters/day, administered at an infusion rate of approximately 1 liter/hour.
Children
In children, the safety and efficacy of the medicine have not been established.
Dosage and infusion rate must be determined based on 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 discontinued if the patient experiences pain or redness at the injection site, as this may indicate extravasation.
Infusions that are too rapid may cause local pain, and the infusion rate should 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 Diaco
Due to the presence of calcium chloride, it is incompatible with:

magnesium sulfate: formation of a precipitate;
medicines containing phosphate: formation of calcium phosphate precipitate;
medicines containing carbonate: formation of calcium carbonate precipitate;
medicines containing tartrate: formation of calcium tartrate precipitate. Incompatibilities reported with calcium chloride include:
aminophylline: due to precipitate formation;
amphotericin B: due to development of turbidity;
cefamandole: due to presence of sodium carbonate in cefamandole preparation;
ceftriaxone sodium: due to precipitate formation; therefore, calcium solution administration must not occur 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 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: calcium may inhibit streptomycin activity;
tetracyclines: calcium salts may complex with tetracyclines. Due to the presence of magnesium, the medicine is incompatible with solutions containing alcohol (at high concentrations), heavy metals, carbonates and bicarbonates, sodium hydrocortisone, succinates, phosphates, polymyxin B sulfate, procaine hydrochloride, calcium salicylate, clindamycin phosphate, tartrates, as precipitates may form. Potential incompatibility is often influenced by changes in reagent concentration and solution pH. Calcium salts may form complexes with many drugs, leading to precipitate formation. Physical incompatibility has been reported with ceftriaxone (see sections Contraindications, Interactions, Undesirable effects). Use immediately after opening the container. The container is for single, uninterrupted administration only; any residual solution must not be used. Shake well before administration. Do not use the medicine if the solution is not clear, colorless or nearly colorless, or if it contains particles. Take 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 arrest.
Excessive administration of sodium chloride may lead to hypernatremia and/or hypervolemia, depending on the patient's clinical condition. Hypernatremia and excessive sodium retention, particularly when renal sodium excretion is impaired, may cause dehydration of internal organs, especially 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, hypertension, flaccid paralysis, hypothermia, circulatory collapse, cardiac and central nervous system depression, potentially progressing to respiratory paralysis.
Magnesium intoxication manifests with a peak in arterial pressure and respiratory paralysis.
Disappearance of the patellar reflex is a useful clinical sign to identify 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 defined as plasma calcium concentrations exceeding 2.6 mmol/l; therefore, such concentrations must be monitored continuously.
Treatment
Immediately discontinue the infusion and initiate corrective therapy to reduce plasma levels of excess ions and, if necessary, restore acid-base balance (see section 4.4).
The patient should be closely observed for the appearance of any signs and symptoms related to the administered drug, ensuring 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 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 calcium levels with immediate correction to normal values;
monitoring of cardiac function, use of beta-blockers to reduce the risk of cardiac arrhythmia;
hemodialysis if necessary. In case of magnesium overdose, artificial respiration is required. To counteract the effects of hypermagnesemia, intravenous calcium must be administered (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 accidental ingestion/overdose of Elettrolitica reidratante Diaco, contact a doctor immediately or go to the nearest hospital.
If you have any doubts about the use of Elettrolitica reidratante Diaco, consult your doctor or pharmacist.
UNDESIRABLE EFFECTS
Like all medicines, Elettrolitica reidratante III may cause undesirable effects, although not everyone experiences them.
Below are the undesirable effects of Elettrolitica reidratante III classified according to the MedDRA organ system classification. Sufficient data are not available to determine the frequency of individual listed effects.
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
Arrhythmia, tachycardia, bradycardia, conduction disorders, disappearance of P wave, widening of QRS complex on electrocardiogram, syncope, ventricular fibrillation, cardiac arrest.
Vascular disorders
Hypotension, hypertension, peripheral edema, vasodilation, flushing, sweating, shock.
Disorders of water and electrolyte balance
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's syndrome (milk-alkali syndrome), hypocalcemia.
Musculoskeletal and connective tissue disorders
Muscle weakness
General disorders and administration site conditions
Febrile 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 examination revealed precipitation of calcium-ceftriaxone salt 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 Contraindications and Interactions).
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 have 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 has been observed in the gallbladder, primarily in patients treated with doses exceeding the recommended standard dose. In children, prospective studies have shown variable incidence of precipitation with intravenous administration; in some studies, the incidence exceeded 30%. This incidence appears lower when infusions are administered slowly (20–30 minutes). This effect is generally asymptomatic, but in rare cases, precipitations have been associated with clinical symptoms such as pain, nausea, and vomiting. In such cases, symptomatic treatment is recommended. Precipitation is generally reversible upon discontinuation of administration.
Following the instructions in this 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 kept in its original packaging, stored correctly.
Warning: do not use the medicine 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.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.
Keep the medicine 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
mEq/liter
Na 140
K 10
Ca 5
Mg 3
Cl 103
Acetate 47
Citrate 8
Theoretical osmolarity (mOsm/liter) 307
pH: 5.0 – 7.0
PHARMACEUTICAL FORM AND CONTENT
Solution for infusion, sterile and pyrogen-free
MARKETING AUTHORIZATION HOLDER
Diaco Biofarmaceutici S.r.l.
Via Flavia n.124 - 34147 - Trieste (Italy)
MANUFACTURER
S.M. FARMACEUTICI SRL
Via Flavia n.124 - 34147 - Trieste (Italy)