Ringer Galenica Senese: detailed information

PACKAGE LEAFLET

Ringer Galenica Senese infusion solution

THERAPEUTIC PHARMACOLOGICAL CATEGORY
Electrolytes.
THERAPEUTIC INDICATIONS
Replacement therapy for extracellular fluid and electrolyte losses.
CONTRAINDICATIONS

Hypersensitivity to the active substances or to any of the excipients;
severe renal insufficiency;
hypercalcemia, hypercalciuria, or severe renal disorders;
hypernatremia;
hydro-saline plethora.
hyperkalemia or in cases of potassium retention;
ventricular fibrillation (calcium chloride may increase the risk of arrhythmias);
renal calculi (may be exacerbated by calcium administration);
sarcoidosis (may potentiate the typical hypercalcemia of this condition);
hypercoagulability;
concomitant therapy with cardiac glycosides (see section 4.5).
untreated Addison's disease;
heat cramps;
concomitant administration with ceftriaxone in neonates (≤ 28 days of age), even when using separate infusion lines. See sections Interactions, Undesirable effects, and Dosage, route and duration of administration.

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 the presence of sodium, use with caution in patients with congestive heart failure, severe renal insufficiency, and clinical conditions associated with edema and salt retention; in patients receiving cardiac inotropic drugs or corticosteroid or corticotropin medications.
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).
Due to the presence of potassium, administration should be guided by serial electrocardiograms; serum potassium levels do not necessarily reflect intracellular potassium concentrations. High plasma potassium concentrations may cause death due to cardiac depression, arrhythmias, or cardiac arrest. To avoid potassium intoxication, the infusion must be administered at a controlled rate (see Dosage, route 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 post-operative period.
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 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 disorders, pulmonary heart disease, respiratory acidosis, or respiratory insufficiency, where acidification may worsen the clinical picture. Furthermore, 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 leading to a drop in blood pressure. Calcium chloride solution is irritating and therefore must not be administered intramuscularly, subcutaneously, or into peri-vascular tissues, as tissue necrosis may occur. During infusion of the medicinal product, continuous electrocardiographic monitoring is essential, and it is good practice to monitor fluid balance, electrolytes, plasma osmolarity, and acid-base balance. Plasma calcium concentrations and urinary calcium excretion 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 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 administering sodium salts concomitantly with corticosteroids (see Precautions for use).
Calcium chloride solution may interact with the following medicinal products:

thiazide diuretics, as hypocalcemia may occur due to reduced renal excretion of calcium;
cardiac glycosides (digitalis), digoxin and digitoxin, as concomitant use may increase the risk of arrhythmias, given the synergistic inotropic and toxic effects;
verapamil (and other calcium channel blockers), as concomitant use may reduce the antihypertensive effect of verapamil;
magnesium-containing medicinal products, as the risk of hypercalcemia or hypermagnesemia may increase, 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 administration with ceftriaxone is contraindicated in neonates (≤ 28 days of age), even when using separate infusion lines (risk of fatal precipitation of calcium-ceftriaxone 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 Galenica Senese infusion solution, through the same infusion line (e.g., via Y-connector).
When using the same line 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 and any residual solution must not be used.
Pregnancy and breastfeeding
Consult your doctor or pharmacist before taking any medicinal product.
No data are available on potential adverse effects of the medicinal product when administered during pregnancy or breastfeeding or on reproductive capacity.
Therefore, the medicinal product should not be used during pregnancy or breastfeeding unless clearly 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, ROUTE AND DURATION OF ADMINISTRATION
The solution is isotonic with blood and must be administered with caution by intravenous infusion at a controlled infusion rate.
Shake well before administration.
The 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.
Adults
The daily dose is approximately 20–30 ml of solution/kg body weight, up to a maximum of 40 ml of solution/kg body weight.
Children
In children, the safety and efficacy of the medicinal product have not been established.
Infusions that are too rapid may cause local pain, and the 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 of the drug.
It is advisable for the patient to remain lying down for a short period after administration.
Calcium salts may form complexes with many drugs, potentially leading to precipitate formation.
Physical incompatibility has been reported with ceftriaxone (see sections Contraindications, Interactions, and Undesirable effects).
Incompatibility with Ringer Galenica Senese
If used to dilute medicinal products, consult a pharmacist, if available, before adding any additives; 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 reported with:
aminophylline: due to precipitate formation;
amphotericin B: due to development of cloudiness;
cefamandole: due to presence of sodium carbonate in cefamandole formulation;
ceftriaxone sodium: due to precipitate formation; therefore, calcium-containing solution 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 cloudiness;
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.

Use the solution 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 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 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, where renal sodium excretion is impaired, cause dehydration of internal organs, especially the brain, and accumulation of extracellular fluid with edema affecting the cerebral, pulmonary, and peripheral circulation, leading to pulmonary and peripheral edema.
Accumulation of chloride ions reduces bicarbonate ion concentration, leading to acidosis.
In case of excessive administration of calcium chloride, hypercalcemia may occur, particularly 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 Precautions for use).
The patient should be closely observed for the onset 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 medicinal products. In case of severe overdose (plasma concentrations >2.9 mmol/l), the following measures should be taken:

rehydration via administration of 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 arrhythmias;
hemodialysis if necessary.
Elevated plasma electrolyte levels may require dialysis.

In case of accidental ingestion/absorption of an excessive dose of Ringer Galenica Senese, contact a doctor immediately or go to the nearest hospital.
If you have any doubts about the use of Ringer Galenica Senese, consult your doctor or pharmacist.
UNDESIRABLE EFFECTS
UNDESIRABLE EFFECTS
Like all medicinal products, Ringer may cause undesirable effects, although not everyone experiences them.
The undesirable effects of Ringer are listed below. 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, paresthesias, 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 the P wave, widening of the QRS complex on the electrocardiogram, 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.
Eye disorders
Reduced lacrimation.
Renal and urinary disorders
Renal failure, polyuria.
Metabolism and nutrition disorders
Hypercalcemia, Burnett syndrome (milk-alkali syndrome).
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
Serious, and in some cases fatal, adverse reactions have rarely been reported in preterm and full-term neonates (age < 28 days) who were 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).
Cases of renal precipitation have been reported, primarily 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, primarily in patients treated with doses above 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.
Reporting of undesirable effects
If you experience any undesirable effect, including those not listed in this leaflet, contact your doctor or pharmacist. Undesirable effects can also be reported directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili. Reporting undesirable effects contributes to providing more information on the safety of this medicinal product.
EXPIRY DATE AND STORAGE
Expiry date: see the date on the packaging.
The expiry date refers to the product in intact packaging, correctly stored.
Caution: do not use the medicinal product after the expiry date stated on the packaging.
Storage conditions
Vials: no special storage precautions required. Store in the original packaging and in a tightly closed container. Do not refrigerate or freeze.
Bags: store at a temperature not exceeding 30°C. 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 medicinal products no longer in use. This will help protect the environment.
Keep the medicinal product out of the reach and sight of children.
COMPOSITION
1000 ml contains
Active substances: sodium chloride 8.6 g
potassium chloride 0.3 g
calcium chloride dihydrate 0.3 g
Excipients: water for injections q.s. to 1000 ml.
mEq/liter: Na 147
K 4
Ca 4
Cl 155
theoretical osmolarity: (mOsm/liter) 308
pH: 5.0–7.0
PHARMACEUTICAL FORM AND CONTENT
Infusion solution, sterile and pyrogen-free.
Glass vial of 50 ml, 100 ml, 250 ml, 500 ml, and 1000 ml.
Plastic bag of 50 ml, 100 ml, 250 ml, 500 ml, and 1000 ml.
MARKETING AUTHORIZATION HOLDER
Industria Farmaceutica Galenica Senese S.r.l.
MANUFACTURER
Industria Farmaceutica Galenica Senese S.r.l.