Ringer acetate Diaco

Package leaflet: information for the patient

RINGER ACETATE DIACO

6.0 g/l + 0.3 g/l + 0.22 g/l + 4.00 g/l solution for infusion
sodium chloride, potassium chloride, calcium chloride dihydrate, sodium acetate
Please read this leaflet carefully before using this medicine because 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 others, even if their symptoms are the same as yours, as it could be harmful.
• If any adverse reaction occurs, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

1. What RINGER ACETATE DIACO is and what it is used for
2. What you need to know before using RINGER ACETATE DIACO
3. How to use RINGER ACETATE DIACO
4. Possible side effects
5. How to store RINGER ACETATE DIACO
6. Contents of the pack and other information

1. What RINGER ACETATO DIACO is and what it is used for

RINGER ACETATO DIACO contains the active substances sodium chloride, potassium chloride, calcium chloride dihydrate, and sodium acetate. It belongs to the category of rehydration and electrolyte replacement medicines (replacement of salts and fluids), as well as alkalizing agents (which reduce blood acidity).
RINGER ACETATO DIACO is used in replacement therapy for losses of extracellular fluids and electrolytes (fluids and salts), when mild to moderate, but not severe, acidotic conditions need to be corrected.
If you do not feel better or feel worse, talk to your doctor.

2. What you need to know before using RINGER ACETATO DIACO

Take special care if:

• you suffer from acute illnesses, pain, postoperative stress, infections, burns, or diseases of the central nervous system;
• you have any type of heart, liver, or kidney disease;
• you have been treated with a medicine that increases the effect of vasopressin (a hormone regulating water retention in the body), as this may increase the risk of hospital-acquired hyponatremia;
• you have low levels of sodium in the blood (hyponatremia).

Do not use RINGER ACETATO DIACO

• If you are allergic to sodium chloride, potassium chloride, calcium chloride dihydrate, sodium acetate, or any of the other ingredients of this medicine (listed in section 6).
• In case of severe renal failure;
• In case of hypercalcemia (increased calcium levels in the blood), hypercalciuria (elevated calcium levels in urine), or severe kidney disorders;
• In case of hypernatremia (increased sodium levels);
• In case of hypervolemia (water and salt retention);
• In case of hyperkalemia (increased potassium levels) or conditions involving potassium retention;
• In case of ventricular fibrillation, a serious heart rhythm disorder (calcium chloride may increase the risk of arrhythmias);
• In case of severe liver failure;
• In case of kidney stones (may be worsened by calcium administration);
• In case of sarcoidosis, a chronic inflammatory disease (this condition may lead to exacerbated hypercalcemia);
• In case of hypercoagulability (increased tendency of blood to form clots);
• During concomitant therapy with cardioactive glycosides, used in certain heart conditions (see "Other medicines and RINGER ACETATO DIACO");
• If you have untreated Addison's disease (adrenal insufficiency);
• In case of heat cramps.
• Through the same infusion catheter used for whole blood during blood transfusions. During blood transfusions, this solution must not be administered through the same infusion line as whole blood due to the possible risk of coagulation.
• Concurrently with ceftriaxone (an antibiotic) in neonates (≤28 days of age), even when using separate infusion lines. See sections "Other medicines and RINGER ACETATO DIACO" and "Possible side effects".

Warnings and precautions
Talk to your doctor or pharmacist before using RINGER ACETATO DIACO.
Due to the presence of sodium:

• use with caution if you have congestive heart failure, severe renal failure, or clinical conditions associated with edema and salt retention;
• use with caution if you are being treated with cardiac inotropic agents (medicines that increase heart contraction) or corticosteroid or corticotropin medicines (cortisone and similar);
• use with caution if you have high blood pressure, heart failure, peripheral or pulmonary edema, reduced kidney function, preeclampsia (a pregnancy-related condition with high blood pressure and kidney problems), or other conditions associated with sodium retention (see section "Other medicines and RINGER ACETATO DIACO").

Due to the presence of potassium:

• administration should be guided by serial electrocardiograms; blood potassium concentration does not reliably reflect intracellular potassium levels. High blood potassium levels can cause cardiac depression leading to death, cardiac arrhythmias, or cardiac arrest. To avoid potassium intoxication, the infusion must be administered at a controlled rate (see "How to use RINGER ACETATO DIACO");
• use with caution if you have renal failure (administration of potassium-containing solutions in patients with impaired kidney function may cause potassium retention);
• use with caution if you have heart failure, especially if you are receiving digitalis therapy;
• use with caution if you have adrenal insufficiency;
• use with caution if you have liver failure;
• use with caution if you have familial periodic paralysis (a muscle contraction disorder);
• use with caution if you have congenital myotonia (a muscle contraction disorder);
• use with caution in the early postoperative period.

Due to the presence of calcium:

• use with caution if you have kidney disorders;
• use with caution if you have heart disorders;
• use with caution if you have recently received a blood transfusion, as calcium ion concentrations may differ from expected values;
• use with caution in conditions such as kidney disorders, cor pulmonale, respiratory acidosis (increased blood acidity), or respiratory failure, as calcium chloride is acidifying and may worsen the clinical condition;
• use with caution in conditions where there is an increased risk of hypercalcemia (elevated calcium levels), such as chronic renal failure, dehydration, or electrolyte imbalance;
• be cautious if you have heart disorders, as calcium salts may increase the risk of arrhythmias (heart rhythm disturbances); therefore, if you belong to this patient group, prolonged administration of calcium chloride should be carefully monitored;
• hypotension may occur. Administration of calcium chloride may cause vasodilation, resulting in low blood pressure;
• tissue necrosis may occur. Calcium chloride solution is irritating and must not be administered intramuscularly, subcutaneously, or into peri-vascular tissue, as this may lead to tissue necrosis.

During infusion of this medicine, continuous electrocardiogram monitoring is essential. It is good practice to monitor fluid balance, electrolytes, plasma osmolarity, and acid-base balance (fluid, electrolyte, and blood acidity balance).
Plasma calcium levels and urinary calcium excretion should be monitored frequently to avoid hypercalciuria (increased calcium in urine), which may progress to hypercalcemia (increased calcium in blood).

Due to the presence of acetate, this medicine should be used with caution in patients with metabolic or respiratory alkalosis (reduced blood acidity) and in conditions involving increased levels or inadequate utilization of acetate, such as mild to moderate liver failure.

Special attention should be paid in case of:

• acute illness, pain, postoperative stress, infections, burns, diseases of the central nervous system;
• heart, liver, or kidney diseases;
• treatment with medicines that increase the effect of vasopressin (a hormone regulating water retention in the body), as these may increase the risk of hospital-acquired hyponatremia (low sodium levels in blood). (See also section "Other medicines and RINGER ACETATO DIACO")

All patients must be closely monitored. In cases where normal regulation of blood water content is impaired due to increased secretion of vasopressin (also known as antidiuretic hormone), infusion of fluids with low sodium chloride concentration (hypotonic fluids) may lead to low sodium levels in the blood (hyponatremia). This may result in headache, nausea, seizures, lethargy, vomiting, coma, brain swelling (cerebral edema), and death. Therefore, these symptoms (acute symptomatic hyponatremic encephalopathy) are considered a medical emergency. (See also section "Possible side effects.")
Children, women of childbearing age, and patients with brain disorders such as meningitis, cerebral hemorrhage, cerebral contusion, and cerebral edema are particularly at risk of life-threatening cerebral edema caused by acute hyponatremia.

Use immediately after opening the container.
The solution must be clear, colorless, and free of visible particles.
It is intended for single, uninterrupted use; any remaining solution must not be reused.

Children and adolescents
The safety and efficacy of this medicine in children have not been established.
Children are particularly at risk of life-threatening cerebral edema caused by acute hyponatremia.
Concomitant therapy must be determined by a physician experienced in pediatric intravenous therapy, especially considering the potential risk of hyponatremia.

Other medicines and RINGER ACETATO DIACO
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

• The use of medicines such as potassium-sparing diuretics may increase the risk of hyperkalemia (increased potassium levels in blood), especially in the presence of renal dysfunction. Therefore, in such cases, blood potassium levels must be closely monitored.
• The use of medicines such as ACE inhibitors (used to treat high blood pressure and certain heart conditions), which reduce aldosterone levels, may lead to potassium retention. Therefore, blood potassium levels must be closely monitored.
• Corticosteroids (cortisone and similar) are associated with sodium and water retention, leading to edema and high blood pressure; therefore, caution is required when administering sodium salts concomitantly with corticosteroids (see section "Warnings and precautions").
• Medicines that stimulate vasopressin release: chlorpropamide, clofibrate, carbamazepine, vincristine, selective serotonin reuptake inhibitors, 3,4-methylenedioxy-N-methamphetamine, ifosfamide, antipsychotics, narcotics.
• Medicines that potentiate vasopressin action: chlorpropamide, NSAIDs, cyclophosphamide.
• Vasopressin analogs: desmopressin, oxytocin, vasopressin, terlipressin.
• Other medicines that increase the risk of hyponatremia include diuretics in general and antiepileptic medicines such as oxcarbazepine.

Calcium chloride solution may interact with the following medicines:

• Thiazide diuretics (used to treat high blood pressure and certain heart conditions), as hypercalcemia (elevated blood calcium levels) may occur due to reduced renal calcium excretion;
• Cardiac glycosides (digitalis), digoxin and digitoxin (used in certain heart conditions), as concomitant use may increase the risk of arrhythmias (heart rhythm disturbances);
• Verapamil (and other calcium channel blockers), as concomitant use may reduce the antihypertensive effect of verapamil;
• Magnesium-containing medicines, as this may increase the risk of hypercalcemia (elevated calcium levels) or hypermagnesemia (elevated magnesium levels), especially in patients with renal disorders;
• Neuromuscular blocking agents (used during surgery to block muscle contraction): calcium salts may antagonize the effect of non-depolarizing blockers; in some cases, an increased and prolonged effect of tubocurarine (a neuromuscular blocker) 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 complexes in the neonatal bloodstream; see "Possible side effects").
In patients older than 28 days (including adults), ceftriaxone must not be administered concurrently with intravenous calcium-containing solutions, including RINGER ACETATO 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.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before using this medicine.
RINGER ACETATO DIACO must be administered with particular caution in pregnant women during labor, especially regarding serum sodium levels, when administered concomitantly with oxytocin (a hormone used to induce labor and control bleeding), due to the risk of hyponatremia (see sections "Warnings and precautions", "Other medicines and RINGER ACETATO DIACO", "Side effects").
This medicine should not be used during pregnancy or breastfeeding unless absolutely necessary and only after careful assessment of the risk-benefit ratio.

Driving and using machines
This medicine does not affect the ability to drive or operate machinery.

3. How to use RINGER ACETATO DIACO

Use this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

The solution is isotonic (has a salt concentration equivalent to blood) and must be administered by intravenous infusion with caution and at a controlled infusion rate.

Shake well before administration.

The dose (frequency and volume of infusion) depends on your age, body weight, and clinical condition (e.g., burns, surgical procedures, head injuries, infections).

This medicine must be administered only if renal function is intact and at a rate not exceeding 10 mEq of potassium per hour.

Adults
The daily dose is approximately 20–30 mL of solution per kg of body weight, up to a maximum of 40 mL of solution per kg of body weight.

Use in children
In children, the safety and efficacy of this medicine have not been established.

Too rapid infusions 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 stopped if the patient experiences pain or redness at the injection site, as this may indicate extravasation of the drug.

It is advisable to remain lying down for a short period after administration.

Incompatibilities with RINGER ACETATO DIACO
Due to the presence of calcium chloride, this medicine is incompatible with:

• magnesium sulfate: formation of a precipitate;
• medicines containing phosphates: formation of calcium phosphate precipitate;
• medicines containing carbonates: formation of calcium carbonate precipitate;
• medicines containing tartrates: formation of calcium tartrate precipitate;
• aminophylline (a bronchodilator): due to precipitate formation;
• amphotericin B (an antibiotic): due to development of numbness;
• cefamandole (an antibiotic): due to the presence of sodium carbonate in the cefamandole formulation;
• ceftriaxone sodium: due to precipitate formation; therefore, calcium-containing solutions must not be administered within 48 hours after ceftriaxone administration; calcium salts may form complexes with many drugs, leading to precipitate formation. Physical incompatibility has been reported with ceftriaxone (see sections “Do not take RINGER ACETATO DIACO”, “Other medicines and RINGER ACETATO DIACO”, and “Possible side effects”).
• cephaltin (an antibiotic): due to physical incompatibility;
• cefradine (an antibiotic): due to the presence of sodium carbonate in the cefradine formulation;
• chlorpheniramine (an antihistamine): due to physical incompatibility;
• dobutamine (used in certain emergency situations to enhance cardiac contraction): due to development of numbness;
• fat emulsion: due to flocculation;
• sodium heparin (used to thin the blood);
• indomethacin (an anti-inflammatory): due to precipitate formation;
• sodium nitrofurantoin (an antibiotic);
• promethazine (an antihistamine): due to precipitate formation;
• propofol (an anesthetic): due to precipitate formation;
• streptomycin (an antibiotic): because calcium may inhibit the activity of streptomycin;
• tetracyclines (antibiotics): calcium salts may complex with tetracyclines.

Use immediately after opening the container. The container is intended for single, uninterrupted administration and any remaining solution must not be reused.

Shake well before administration.

Do not use the medicine if the solution is not clear and colorless or if it contains particles.

Take all usual precautions to maintain sterility before and during intravenous infusion.

Calcium salts may form complexes with many drugs, potentially leading to precipitate formation.

Physical incompatibility has been reported with ceftriaxone (see sections “Do not take RINGER ACETATO DIACO”, “Other medicines and RINGER ACETATO DIACO”, “Possible side effects”).

If you use more RINGER ACETATO DIACO than you should

Symptoms
High plasma concentrations of potassium may cause death due to cardiac depression, arrhythmias (abnormal heart rhythms), or cardiac arrest.

Excessive administration of sodium chloride may lead, depending on your clinical condition, to hypernatremia (increased sodium levels in the blood) and/or hypervolemia (increased blood volume). Hypernatremia and excessive sodium retention, particularly when renal sodium excretion is impaired, may result in dehydration of internal organs, especially the brain, and accumulation of extracellular fluid causing edema affecting the cerebral, pulmonary, and peripheral circulation, potentially leading to pulmonary and peripheral edema.

Accumulation of chloride ions reduces bicarbonate ion concentration, leading to acidosis (increased blood acidity).

In case of excessive administration of calcium chloride, hypercalcemia (increased calcium levels) may occur, especially in patients with renal disease. Typical symptoms of hypercalcemia include: sensation of thirst, nausea, vomiting, constipation, increased urine production, abdominal pain, muscle weakness, mental disturbances, and in severe cases, cardiac arrhythmia and coma. Hypercalcemia is defined as plasma calcium concentrations exceeding 2.6 mmol/L; therefore, such levels must be continuously monitored.

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 “Warnings and precautions”).

You should be closely monitored for the appearance of any signs or symptoms related to the administered medicine, so that appropriate symptomatic and supportive measures can be promptly provided as needed.

In case of high sodium levels in the blood, loop diuretics may be used.

In case of hyperkalemia (high potassium levels in the blood), intravenous glucose (with or without insulin) or sodium bicarbonate may be administered.

In case of mild overdose of calcium chloride, treatment includes immediate discontinuation of the infusion and of any other calcium-containing medication. In case of severe overdose (plasma concentrations > 2.9 mmol/L), the following measures should be taken:

• rehydration using 0.9% sodium chloride solution;
• use of non-thiazide diuretics to enhance calcium excretion;
• monitoring of blood potassium and calcium levels with immediate correction to normal values;
• monitoring of cardiac function, and use of beta-blockers to reduce the risk of cardiac arrhythmia;
• possible recourse to hemodialysis (a blood purification method).

Elevated blood levels of salts may require dialysis.

In case of accidental ingestion/overdose of RINGER ACETATO DIACO, contact your doctor immediately or go to the nearest hospital.

If you have any questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
The following are side effects associated with Ringer acetate. There are insufficient data available to
establish the frequency of individual listed side effects.

• Gastrointestinal disturbances and irritation, thirst, reduced salivation, nausea, vomiting, diarrhoea, abdominal pain, constipation, metallic taste, chalky taste.
• Neuromuscular disorders, muscle rigidity, paresthesia (tingling), flaccid paralysis (muscle paralysis), weakness, mental confusion, headache, dizziness, restlessness, irritability, seizures, coma, death.
• Drowsiness, confusional states, mental disturbances.
• Arrhythmia, tachycardia, bradycardia, conduction disorders, disappearance of the P wave, widening of the QRS complex on the electrocardiogram, ventricular fibrillation (abnormal heart rhythms and electrocardiogram changes), syncope (fainting), cardiac arrest.
• Low blood pressure, high blood pressure, peripheral oedema, vasodilation, hot flushes.
• Hypernatraemia or hyponatraemia (increased or decreased sodium levels in the blood), hypervolaemia (increased blood volume), hyperchloraemia (increased chloride levels in the blood).
• Headache, nausea, seizures, lethargy, and vomiting. This may be caused by low sodium levels in the blood. When blood sodium levels become very low, water enters brain cells causing them to swell. This leads to increased intracranial pressure and results in hyponatraemic encephalopathy.
• Breathing difficulties, respiratory arrest, pulmonary oedema, pneumothorax (presence of air in the pleural cavity).
• Reduced tear production.
• Renal failure, polyuria (increased urine production).
• Hypercalcaemia (increased calcium levels in the blood), Burnett's syndrome (milk-alkali syndrome, occurring when excessive amounts of poorly acidic substances are ingested).
• Muscle weakness.
• Fever, infusion site infection, extravasation, tissue necrosis, abscess formation (collections of pus), cutaneous calcification, pain or local reaction, redness, rash, venous irritation, thrombosis (circulatory problems due to blood clot formation in veins) or phlebitis (vein inflammation) extending from the infusion site.

Additional side effects in children
Calcium-ceftriaxone salt precipitation
Serious, and in some cases fatal, adverse reactions have been rarely reported in preterm and full-term neonates (age ≤ 28 days) treated with intravenous ceftriaxone and calcium. Autopsy findings revealed calcium-ceftriaxone salt aggregates in the lungs and kidneys. The high risk of precipitation in neonates is due to their low blood volume and prolonged ceftriaxone circulation time compared to adults (see sections “Do not use RINGER ACETATO DIACO” and “Other medicines and RINGER ACETATO DIACO”).
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 lead to renal failure and anuria (lack of urine production), and is reversible upon discontinuation of treatment.
Calcium-ceftriaxone salt precipitation in the gallbladder has been observed, primarily in patients treated with doses exceeding the standard recommended dose. In children, prospective studies have shown a variable incidence of precipitation with intravenous administration; in some studies, the incidence exceeded 30%. This incidence appears lower when infusions are administered slowly (over 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 usually resolves after discontinuation of administration.
In case of an adverse reaction, discontinue administration and retain the unused portion for possible testing.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse.
You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store RINGER ACETATO DIACO

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging.
The expiry date refers to the product stored in its original, undamaged packaging and properly stored.
Store in the original packaging and in a tightly closed container.
Do not refrigerate or freeze.
Use immediately after opening the container. The container is intended for single and uninterrupted administration; any remaining solution must not be used.
Do not use this medicine if the solution is not clear and colourless or if it contains particles.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What RINGER ACETATO DIACO contains

• The active substances are: Sodium chloride, Potassium chloride, Calcium chloride dihydrate, Sodium acetate. 1000 ml of solution contain 6 g of sodium chloride, 0.3 g of potassium chloride, 0.22 g of calcium chloride dihydrate, 4.00 g of sodium acetate.
• The other component is water for injections. mmol/litre: Na 132, K 4, Ca 3, Cl 110, Acetate as HCO 29. Theoretical osmolarity (mOsm/litre): 277. pH: 6.0 - 7.0

Description of the appearance of RINGER ACETATO DIACO and package contents
Infusion solution, sterile and pyrogen-free.
50 ml vial
100 ml vial
250 ml vial
500 ml vial
1000 ml vial

Marketing Authorization Holder and Manufacturer
Diaco Biofarmaceutici S.r.l.
Via Flavia n.124 - 34147 - Trieste (Italy)

Manufacturer
DIACO BIOFARMACEUTICI S.r.l.
Via Flavia n.124 - 34147 - Trieste (Italy)