RINGER ACETATO MONICO
infusion solution
ATC: B05BB01
PHARMACOTHERAPEUTIC CATEGORY
Electrolytes.

THERAPEUTIC INDICATIONS
Replacement therapy for extracellular fluid and electrolyte losses, when correction of mild to moderate, but not severe, acidotic states is required.

CONTRAINDICATIONS

Hypersensitivity to the active substances or to any of the excipients;
severe renal failure;
hypercalcemia, hypercalciuria, or severe renal diseases;
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 the acetate ion);
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);
untreated Addison's disease;
heat cramps;
treatment concomitant 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 administered, this solution must not be given through the same infusion catheter as whole blood due to the possible risk of coagulation.

PRECAUTIONS FOR USE
Due to its sodium content, 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 therapy.
Sodium salts should be administered cautiously in patients with hypertension, heart failure, peripheral or pulmonary edema, reduced renal function, pre-eclampsia, or other conditions associated with sodium retention (see Interactions).
The medicinal product should not be administered to:

patients with conditions that may cause sodium retention, fluid overload, and edema, such as patients with primary hyperaldosteronism, secondary hyperaldosteronism (associated, for example, with hypertension, congestive heart failure, renal artery stenosis, or nephrosclerosis), or pre-eclampsia; if strictly necessary, it should be administered with particular caution;
patients with conditions predisposing to hyperkalemia (such as severe renal damage or adrenocortical insufficiency, severe dehydration, or extensive tissue damage) and in patients with heart failure; if strictly necessary, it should be administered with particular caution. Due to its potassium content, administration should be guided by serial electrocardiograms; serum potassium levels do not reflect intracellular potassium concentrations. High plasma potassium concentrations may lead to death due to cardiac depression, arrhythmias, or arrest. To avoid potassium intoxication, the infusion must be administered at a controlled rate (see Dosage, method and duration of administration).

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 period.

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

with renal diseases;
with cardiac diseases;
who have received blood transfusions, as ionized calcium 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 failure, where acidification may worsen the clinical picture. Additionally, caution is advised in conditions where there is an increased risk of hypercalcemia, such as chronic renal failure, dehydration, or electrolyte imbalance. Calcium-containing solutions should be used carefully in patients with a history of renal calculi. Since calcium salts may increase the risk of arrhythmias, care should be taken when prolonging calcium chloride administration in patients with cardiac diseases. Administration of calcium chloride may cause vasodilation leading to a drop in blood pressure. Calcium chloride solution is irritating and must not be administered intramuscularly, subcutaneously, or into perivascular tissues, as tissue necrosis may occur. During infusion, continuous ECG monitoring is essential. It is good practice to monitor fluid balance, electrolytes, plasma osmolarity, and acid-base equilibrium. Plasma calcium levels and urinary calcium excretion should be monitored frequently to prevent hypercalciuria, which may progress to hypercalcemia.

Due to its acetate content, the medicinal product should be used with caution in patients with metabolic or respiratory alkalosis and in conditions where acetate levels are elevated or its utilization is impaired, such as in mild or moderate hepatic insufficiency.

Hypersensitivity
Infusion must be stopped immediately if signs or symptoms of suspected hypersensitivity occur. Appropriate therapeutic countermeasures should be instituted as clinically indicated.

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

Contraindicated combinations
Concomitant therapy with cardioactive glycosides (digitalis), digoxin, and digitoxin is contraindicated, as their combined use may increase the risk of arrhythmias due to synergistic inotropic and toxic effects (see Contraindications).

Combinations requiring caution
Angiotensin II receptor antagonists
Immunosuppressants such as tacrolimus and cyclosporine
Due to potassium content and the risk of hyperkalemia, administer with caution.

ACE inhibitors
Use of ACE inhibitors, which reduce aldosterone levels, may lead to potassium retention. Therefore, serum potassium levels must be closely monitored.

Potassium-sparing diuretics
Use of drugs such as potassium-sparing diuretics may increase the risk of hyperkalemia, especially in the presence of renal dysfunction. Therefore, serum potassium levels must be closely monitored in such cases.

Corticosteroids
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).

Thiazide diuretics, vitamin D
Hypercalcemia may occur due to reduced renal excretion of calcium.

Medicinal products containing magnesium
May increase the risk of hypercalcemia or hypermagnesemia, especially in patients with renal disorders.

Effects of Ringer Acetate on other medicinal products
Calcium chloride solution may interact with the following medicinal products:

Verapamil (and other calcium channel blockers), as concomitant use may reduce the antihypertensive effect of verapamil;
Neuromuscular blocking agents, as calcium salts may reverse the action of non-depolarizing blockers; in some cases, an increased and prolonged effect 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 Ringer Acetato MONICO, 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. It is intended for single, uninterrupted administration; any residual solution must not be used.

Fertility, pregnancy and lactation
Consult your doctor or pharmacist before taking any medicine.
There are no available data 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.

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

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, using sterile and pyrogen-free equipment.
Shake well before administration.
Dosage depends on age, body weight, clinical condition, concomitant therapy, and the patient’s clinical and laboratory response to treatment.
The medicinal product must be administered only in patients with intact renal function and at a rate not exceeding 10 mEq potassium/hour.

Adults
Daily dose is approximately 20–30 ml of solution/kg body weight, up to a maximum of 40 ml of solution/kg body weight.
Care must be taken in selecting volume/infusion rate in relation to underlying diseases and concomitant therapies (see Precautions for use and Interactions).

Children
In children, the safety and efficacy of the medicinal product have not been established.
Infusions that are too rapid may cause local pain; infusion rate must be adjusted according to tolerance.
Do not inject intramuscularly, subcutaneously, or into perivascular tissues.
Administration must be discontinued if the patient experiences pain or redness at the injection site, as this may indicate extravasation.
It is advisable for the patient to remain lying down for a short period after administration.

Incompatibilities with Ringer Acetato MONICO
Due to the presence of calcium chloride, the medicinal product is incompatible with:

magnesium sulfate: precipitate formation;
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.

Calcium salts may form complexes with many drugs, 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). Incompatibilities of calcium chloride have been observed with:

aminophylline: due to precipitate formation;
amphotericin B: due to 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;
cephalothin: due to physical incompatibility;
cefradine: due to presence of sodium carbonate in cefradine preparation;
chlorphenamine: due to physical incompatibility;
dobutamine: due to 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: calcium may inhibit streptomycin activity;
tetracyclines: calcium salts may complex with tetracyclines.

Use the solution immediately after opening the container. The container is intended for single, uninterrupted administration; any residual solution must not be used.
Shake well before administration. Do not use the medicinal product if the solution is not clear and colorless or if it contains particles.
Adopt all standard 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, especially when renal sodium excretion is impaired, may cause dehydration of internal organs, particularly the brain, and accumulation of extracellular fluid leading to edema affecting the cerebral, pulmonary, and peripheral circulation, including pulmonary and peripheral edema.
Accumulation of chloride ions reduces bicarbonate concentration, leading to acidosis.
Excessive administration of calcium chloride may cause hypercalcemia, especially in patients with renal diseases. 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, plasma levels 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 Precautions for use).
The patient should be closely monitored for any signs and symptoms related to the administered drug, with appropriate symptomatic and supportive measures provided as needed.
In cases of severe hypernatremia, loop diuretics may be used.
In cases of hyperkalemia, intravenous glucose (with or without insulin) or sodium bicarbonate may be administered.
In cases of mild calcium chloride overdose, treatment includes immediate discontinuation of the infusion and any other calcium-containing medication. In cases of severe overdose (plasma concentrations > 2.9 mmol/L), the following measures should be taken:

rehydration with 0.9% sodium chloride solution;
use of non-thiazide diuretics to enhance calcium excretion;
monitoring of plasma potassium and calcium levels, with immediate correction to normal values;
cardiac function monitoring, use of beta-blockers to reduce the risk of cardiac arrhythmias;
hemodialysis if necessary.
Elevated plasma electrolyte levels may require dialysis.

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

UNDESIRABLE EFFECTS
Like all medicinal products, Ringer Acetato may cause adverse effects, although not everyone experiences them.
The following adverse effects of Ringer Acetato are reported. There are insufficient data to determine the frequency of individual listed effects.

Gastrointestinal disorders
Gastrointestinal disturbances and irritation, thirst, reduced salivation, nausea, vomiting, diarrhea, abdominal pain, constipation, 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 disorders, disappearance of P wave, QRS widening on ECG, syncope, ventricular fibrillation, cardiac arrest.

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

Disorders of water and electrolyte balance
Hypernatremia, hypervolemia, hyperchloremia.

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

Eye disorders
Reduced lacrimation.

Renal and urinary disorders
Renal failure, polyuria.

Metabolism and nutrition disorders
Hypercalcemia, Burnett syndrome (milk-alkali syndrome), hyperhydration, electrolyte imbalances.

Musculoskeletal and connective tissue disorders
Muscle weakness.

General disorders and administration site conditions
Pyrexia, 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.

Immune system disorders
Infusion-related hypersensitivity reactions, including anaphylactic/anaphylactoid reactions.

Skin and subcutaneous tissue disorders
Localized or generalized urticaria.

Precipitation of calcium-ceftriaxone salt
Rarely, serious and sometimes 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 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).

Cases of renal precipitation have been reported, mainly in children over 3 years of age receiving 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 exceeding the recommended standard dose. Prospective studies in children have shown a 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. In such cases, symptomatic treatment is recommended. Precipitation is generally reversible upon discontinuation of administration.

Following the instructions in the leaflet reduces the risk of undesirable effects.

EXPIRY DATE AND STORAGE
Expiry date: see the date on the packaging.
The expiry date refers to the product in its original, unopened packaging, stored correctly.
Caution: Do not use the medicinal product after the expiry date stated on the packaging.
Do not refrigerate or freeze.
Medicinal products must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This helps protect the environment.
Keep the medicinal product out of the sight and reach of children.

COMPOSITION
1000 ml contains
Active substances: sodium chloride 6.0 g
potassium chloride 0.3 g
calcium chloride dihydrate 0.22 g
sodium acetate trihydrate 4.0 g
Excipients: water for injections, hydrochloric acid q.s.
mEq/liter: Na 132
K 4
Ca 3
Cl 110
Acetate as HCO₃⁻ 29
theoretical osmolarity: (mOsm/liter) 277
pH: 6.0 ÷ 7.0

PHARMACEUTICAL FORM AND CONTENT
Infusion solution, sterile and pyrogen-free.
Glass vials of 50 – 100 – 250 – 500 – 1000 ml.
Polypropylene bags of 50 – 100 – 250 – 500 – 1000 ml.

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

Ringer acetate Monico