RINGER 50 ML Roztwór do infuzji

Treść ulotki

1. Ringer Acetato Diaco
   1. What is RINGER ACETATO DIACO and what is it 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 ACETATO DIACO
   6. Contents of the pack and other information

Ringer Acetato 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

Read this leaflet carefully before using this medicine as 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 pass it on to others, even if they have the same symptoms as you, as it could be harmful.
• If any side effects occur, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

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

RINGER ACETATO DIACO contains the active ingredients sodium chloride, potassium chloride, calcium chloride
dihydrate, sodium acetate and belongs to the category of rehydrating, electrolyte replenishing (salt) drugs,
alkalizing agents (which lower blood acidity).
RINGER ACETATO DIACO is used in the replacement therapy of extracellular fluid and
electrolyte losses (liquids and salts), when it is necessary to correct mild and moderate, but not severe, acidotic states.
See your doctor if you do not feel better or if you feel worse.

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

Pay particular attention if:

• you suffer from acute illnesses, pain, post-operative 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 drug that increases the effect of vasopressin (a hormone that regulates water retention in the body), as this could increase the risk of hospitalization;
• you have low levels of sodium in the blood (hyponatremia).

Do not use RINGER ACETATE 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 levels of calcium in the blood), hypercalciuria (high levels of calcium in the urine) or severe kidney disease;
• In case of hypernatremia (increased levels of sodium);
• In case of hydrosaline plethora (retention of water and salts);
• In case of hyperkalemia (increased levels of potassium) or in cases of 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 exacerbated by the administration of calcium);
• In case of sarcoidosis, a chronic inflammatory disease (hypercalcemia typical of this condition may be potentiated);
• In case of hypercoagulability (increased tendency of the blood to form clots);
• In case of concomitant therapy with cardiotonic glycosides, used in some heart diseases (see “Other medicines and RINGER ACETATE DIACO”);
• If you suffer from untreated Addison's disease (renal insufficiency);
• In case of heat cramps.
• Through the same infusion catheter with whole blood during blood transfusions. During blood transfusions, the solution should not be administered through the same infusion catheter with whole blood due to the possible risk of coagulation.
• In concomitance with ceftriaxone (an antibiotic) in newborns (≤28 days of age), even in case of use of separate infusion lines. See paragraphs “Other medicines and RINGER ACETATE DIACO”, “Possible side effects”.

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

• use with caution if you suffer from congestive heart failure, severe renal failure and in clinical conditions where edema exists with salt retention;
• use with caution if you are being treated with medicines with inotropic cardiac action (which increase heart contraction) or with corticosteroid or corticotropic medicines (cortisone and similar).
• use with caution if you suffer from high blood pressure, heart failure, peripheral or pulmonary edema, reduced kidney function, preeclampsia (pregnancy disease with high blood pressure and kidney problems) or other conditions associated with sodium retention (see paragraph “Other medicines and RINGER ACETATE DIACO”).

Due to the presence of potassium:

• administration must be guided through serial electrocardiograms; the concentration of potassium in the blood is not indicative of intracellular potassium concentrations. High concentrations of potassium in the blood can cause death due to loss of heart function (cardiac depression), heart rhythm problems (arrhythmias) or cardiac arrest. To avoid potassium intoxication, the infusion must be performed at a controlled rate (see “How to use Ringer Acetate Diaco”);
• use with caution if you suffer from renal insufficiency (administration of solutions containing potassium ions if you suffer from decreased renal function may cause potassium retention);
• use with caution if you suffer from heart failure, especially if on digitalis therapy;
• use with caution if you suffer from adrenal insufficiency;
• use with caution if you suffer from liver failure;
• use with caution if you suffer from familial periodic paralysis (muscle contraction disorder);
• use with caution if you suffer from congenital myotonia (muscle contraction disorder);
• use with caution in the early post-operative period.

For the presence of calcium:

• use with caution if you are affected by kidney diseases
• use with caution if you are affected by heart diseases
• use with caution if you have received a blood transfusion as the concentrations of calcium ions may be different from those expected.
• use with caution if you are administered in conditions such as kidney diseases, pulmonary heart, respiratory acidosis (increased blood acidity) or respiratory failure, as calcium chloride is an acidifier and acidification can worsen the clinical picture.
• use with caution in conditions where there is a risk of hypercalcemia (increased levels of calcium), such as chronic renal failure, dehydration or electrolyte imbalance.
• Pay attention if you suffer from heart diseases as calcium salts can increase the risk of arrhythmias (heart rhythm disturbances), therefore if you belong to this category of patients, you should be careful to prolong the administration of calcium chloride.
• A lowering of blood pressure may occur. The administration of calcium chloride can cause vasodilation with a consequent lowering of blood pressure.
• Tissue death may occur. Calcium chloride solution is irritating and therefore should not be administered intramuscularly or subcutaneously or into perivascular tissue as tissue death may occur.

During the infusion of the medicine, monitoring of the electrocardiogram is essential and it is good
practice to monitor fluid balance, electrolytes, plasma osmolarity and acid-base balance
(fluid, salt and blood acidity balance),
Frequent monitoring of plasma calcium concentrations and urine calcium concentrations is necessary to avoid hypercalciuria (increased levels of calcium in the urine), as hypercalciuria can turn into hypercalcemia (increased levels of calcium in the blood).
Due to the presence of acetate, the medicine must be used with caution in patients with metabolic and respiratory alkalosis (decreased blood acidity) and in those conditions where there is an increase in the level or
insufficient utilization of this ion, such as in mild or moderate liver failure.
Special attention must be paid in case of:

• acute illness, pain, post-operative stress, infections, burns, diseases of the central nervous system
• heart, liver or kidney diseases
• treatment with drugs that increase the effect of vasopressin (a hormone that regulates water retention in the body) because these can increase the risk of acquired hyponatremia (low sodium levels) in a hospital setting. (See also section "Othermedicines and Ringer Acetate Diaco”)

All patients must be carefully monitored. In cases where the normal regulation of water content
within the blood is affected due to increased secretion of vasopressin,
also called antidiuretic hormone, infusion of fluids with low sodium chloride concentration (hypotonic fluids) can determine a low level of sodium in the blood (hyponatremia). This can lead to headache, nausea, seizures, lethargy, vomiting, coma, brain swelling (cerebral edema) and death. Consequently, these symptoms (acute symptomatic hyponatremic encephalopathy) are considered a medical emergency. (see also the section "Possible side effects").
Children, women of childbearing potential and patients with brain diseases 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 for single and uninterrupted administration and any residue cannot be used.

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

Other medicines and RINGER ACETATE DIACO
Tell your doctor or pharmacist if you are taking, have recently taken or may take any
other medicines.
.

• The use of medicines such as potassium-sparing diureticsmay increase the risk of hyperkalemia (increased levels of potassium in the blood), especially in the presence of renal dysfunction. Therefore, potassium levels in the blood must be closely monitored in such cases.
• The use of medicines such as ACE inhibitors(used in the treatment of high blood pressure and some heart diseases) which cause a decrease in aldosterone levels, can lead to potassium retention. Therefore, potassium levels must be closely monitored.
• Corticosteroids (cortisone and similar)are associated with sodium and water retention, resulting in edema and high blood pressure; therefore, caution is needed when administering sodium salts and corticosteroids together (see paragraph “Warnings and precautions”).
• Medicines that stimulate the release of vasopressin: chlorpropamide, clofibrate, carbamazepine, vincristine, selective serotonin reuptake inhibitors, 3,4-methylenedioxymethamphetamine, ifosfamide, antipsychotics, narcotics.
• Medicines that potentiate the action of vasopressin: chlorpropamide, NSAIDs, cyclophosphamide.
• Vasopressin analogs: desmopressin, oxytocin, vasopressin, terlipressin.
• Other medicines that increase the risk of hyponatremia also include diuretics in general and antiepileptics such as oxcarbazepine.

Calcium chloride solution may interact with the following medicines:

• thiazide diuretics (used in the treatment of high blood pressure and some heart diseases), as hypercalcemia (high levels of calcium in the blood) may occur due to decreased renal elimination of calcium;
• cardiotonic glycosides (digitalis), digoxin and digitoxin (used in some heart diseases), as concomitant use may increase the risk of arrhythmias (heart rhythm disturbances);
• Verapamil (and other calcium channel blocking medicines), as concomitant use may decrease the antihypertensive (blood pressure lowering) effect of verapamil;
• medicines containing magnesium, as it may increase the risk of hypercalcemia (increased levels

of calcium) or hypermagnesemia (increased levels of magnesium), especially in patients with kidney disorders;

• neuromuscular blockers (used during surgical procedures to block muscle contraction): calcium salts can cancel the action of non-depolarizing blockers; in some cases, an increase and prolongation of the action of tubocurarine (neuromuscular blocker) has also been observed.

As with other solutions containing calcium, concomitant treatment with ceftriaxoneis
contraindicated in newborns (≤28 days of age), even in case of use of separate infusion lines (risk
of fatal precipitation of ceftriaxone-calcium aggregates in the newborn's bloodstream, see “Possible
side effects”).
In patients over 28 days of age (including adults), ceftriaxone should not be administered in
concomitance with intravenous solutions containing calcium, including RINGER ACETATE DIACO, through
the same infusion line (e.g. through a Y-connector).
If the same line is used for sequential administrations, the line must be flushed with a
compatible liquid between infusions.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning a pregnancy, or if you are breastfeeding, ask your doctor or pharmacist for advice before using this medicine.
Ringer acetate Diaco should be administered with particular caution in pregnant women during
labor, especially for serum sodium, if administered in association with oxytocin (a hormone that
can induce labor and control bleeding), due to the risk of hyponatremia (see paragraphs
“Warnings and precautions”, “Other medicines and Ringer Acetate Diaco”, “Side effects”).
This medicine should not be used during pregnancy and breastfeeding unless absolutely necessary
and only after assessing the risk/benefit ratio.

Driving and using machines
The medicine does not impair the ability to drive vehicles or use machines.

3. How to use RINGER ACETATE DIACO

Use this medicine following exactly the instructions of 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 infusion volume) depends on your age, weight and your
clinical conditions (e.g. burns, surgeries, head injuries, infections).
The medicine should only be administered 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 of body weight, up to a maximum of 40 ml of
solution/kg of body weight.

Use in children
In children, the safety and efficacy of the medicine have not been established.
Infusions that are too rapid can cause local pain and the infusion rate must be adjusted in
relation to tolerance.
Do not inject intramuscularly, subcutaneously, or into perivascular tissues.
Administration should be stopped if the patient experiences pain or redness at the injection site, as
this may indicate extravasation of the drug.
It is advisable that you remain lying down for a short period after administration.
Incompatibilities with RINGER ACETATE DIACO
Due to the presence of calcium chloridethe medicine is incompatible with:

• magnesium sulfate: formation of a precipitate;
• medicines containing phosphates: formation of a calcium phosphate precipitate;
• medicines containing carbonate: formation of a calcium carbonate precipitate;
• medicines containing tartrate: formation of a calcium tartrate precipitate.
• aminophylline (a bronchodilator): due to precipitate formation;
• amphotericin B (an antibiotic): for the development of numbness;
• cefamandole (an antibiotic): due to the presence of sodium carbonate in the preparation of cefamandole;
• ceftriaxone sodium: due to precipitate formation, therefore the administration of calcium solution should not occur within 48 hours of the administration of ceftriaxone; calcium saltscan form aggregates with many drugs and this can lead to the formation of precipitates.Physical incompatibility has been reported with ceftriaxone (see paragraphs “Do not take RingerAcetate Diaco”, “Other medicines and Ringer Acetate Diaco” and “Possible side effects”).
• cephalothin (an antibiotic): due to physical incompatibility;
• cefradine (an antibiotic): due to the presence of sodium carbonate in the preparation of cefradine;
• chlorphenamine (an antihistamine): due to physical incompatibility;
• dobutamine (used in some emergency cases, to promote cardiac contraction): for the development of numbness;
• fat emulsion: due to the presence of flocculate;
• sodium heparin (used to thin the blood);
• indometacin (an anti-inflammatory): due to precipitate formation;
• nitrofurantoin sodium (antibiotic);
• promethazine (an antihistamine): due to precipitate formation;
• propofol (anesthetic): due to precipitate formation;
• streptomycin (antibiotic): as calcium may inhibit the activity of streptomycin;
• tetracyclines (antibiotics): calcium salts can complex tetracyclines.

Use immediately after opening the container. The container is for single and uninterrupted
administration only and any residue cannot be used.

Shake well before administration.
Do not use the medicine if the solution is not clear, colorless or if it contains particles.
Take all usual precautions to maintain sterility before and during intravenous infusion.
Calcium salts can form complexes with many drugs and this can lead to the formation of
precipitates.
Physical incompatibility has been reported with ceftriaxone (see paragraphs “Do not use RINGER ACETATE
DIACO”, “Other medicines and RINGER ACETATE DIACO”, Possible side effects”).

If you use more RINGER ACETATE DIACO than you should

Symptoms
High plasma concentrations of potassiumcan cause death, due to cardiac depression, arrhythmias
(heartbeat disturbances) or arrest.
Administration of excessive doses of sodium chloride can lead, depending on your clinical condition,
to hypernatremia (increased levels of sodium in the blood) and/or hypervolemia (increased blood volume).
Hypernatremia and excessive sodium retention where there is a defective elimination of sodium at
kidney level determines dehydration of internal organs, particularly the brain, and the accumulation of
extracellular fluids with edema that can affect the cerebral, pulmonary and peripheral circulation with
the onset of pulmonary and peripheral edema.
The accumulation of chloride ions determines a reduction in the concentration of bicarbonate ions leading to acidosis
(increased blood acidity).
In case of administration of high doses of calcium chloride, hypercalcemia (increased
levels of calcium) may occur, especially in patients with kidney disease. The typical symptoms of hypercalcemia are:
thirst, nausea, vomiting, constipation, increased urine production, abdominal pain, muscle weakness,
mental disorders and, in severe cases, even cardiac arrhythmia (heartbeat disturbance) and coma. Hypercalcemia is spoken of when plasma calcium concentrations exceed 2.6 mmol/l; therefore, these concentrations must be constantly monitored.

Treatment
Immediately stop the infusion and institute corrective therapy to reduce plasma levels of
ions that are in excess and restore, if necessary, the acid-base balance (see paragraph
“Warnings and precautions”).
You will have to be kept under observation to assess the appearance of any signs and symptoms related to
the medicine administered, in order to guarantee you the relative symptomatic and supportive measures as
needed.
In case of high levels of sodium in the blood, loop diuretics can be used.
In case of hyperkalemia (high levels of potassium in the blood), glucose (with or without insulin) or sodium bicarbonate can be administered by intravenous infusion.
In case of modest overdose of calcium chloride, treatment involves immediate suspension
of the infusion and any other drug containing calcium. In case of severe overdose (plasma concentrations > 2.9 mmol/l), the following measures must be taken:

• rehydration by administering a 0.9% sodium chloride solution;
• use of non-thiazide diuretics to promote calcium elimination;
• monitoring of potassium and calcium levels in the blood with immediate restoration of levels to normal values;
• monitoring of cardiac function, use of beta-blockers to reduce the risk of cardiac arrhythmia (heartbeat disturbance);
• possible recourse to hemodialysis (blood purification method)

High values of salt levels in the blood may require dialysis.
In case of accidental ingestion/intake of an excessive dose of RINGER ACETATE DIACO, immediately warn
the doctor or go to the nearest hospital.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Below are listed the side effects of Ringer acetate. Sufficient data are not available to
establish the frequency of the individual effects listed.

• Gastrointestinal disturbances and irritation, thirst, reduced salivation, nausea, vomiting, diarrhea, abdominal pain, constipation, metallic taste, chalky taste.
• Neuromuscular disturbances, muscle rigidity, paresthesia (tingling), flaccid paralysis (muscle paralysis), weakness, mental confusion, headache, dizziness, restlessness, irritability, convulsions, coma, death.
• Drowsiness, confusion, mental disorders.
• Arrhythmia, tachycardia, bradycardia, conduction disturbances, disappearance of the P wave, QRS widening on the electrocardiogram, ventricular fibrillation (heart rhythm disturbances and electrocardiogram alterations), syncope (fainting), cardiac arrest.
• Low blood pressure, high blood pressure, peripheral edema, vasodilation, flushing.
• Hypernatremia or hyponatremia (increased or decreased levels of sodium in the blood), hypervolemia (increased blood volume), hyperchloremia (increased levels of chlorine in the blood)
• Headache, nausea, convulsions, lethargy and vomiting. This may be caused by a low level of sodium in the blood. When sodium levels in the blood become very low, water enters brain cells and causes them to swell. This results in increased pressure in the skull and causes hyponatremic encephalopathy.
• Difficulty breathing, respiratory arrest, pulmonary edema, pneumothorax (presence of air in the pleural cavity).
• Reduced lacrimation
• Renal failure, polyuria (increased urine production)
• Hypercalcemia (increased levels of calcium in the blood), Burnett's syndrome (milk-alkali syndrome, which occurs when excessive amounts of poorly acidic substances are taken),
• Muscle weakness
• Fever, infection at the infusion site, extravasation, tissue death, abscess formation (pus collections), skin calcification, pain or local reaction, redness, rash, vein irritation, thrombosis (circulation problems due to blood clot formation in the veins) or venous phlebitis (inflammation of the veins) extending from the infusion site

Additional side effects in children
Calcium-ceftriaxone salt precipitation
Rarely, serious, and in some cases fatal, side effects have been reported in premature infants and in term infants (age ≤ 28 days) who had been treated with ceftriaxone and calcium intravenously. Calcium-ceftriaxone salt aggregates were found at autopsy in the lungs and kidneys. The high risk of precipitation in neonates is a consequence of their low blood volume and the fact that ceftriaxone
remains in circulation longer than in adults (see paragraphs “Do not use RINGER ACETATE DIACO” and
“Other medicines and RINGER ACETATE 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 with total doses greater than 10 grams and who presented 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 (lack of urine production) and is reversible with discontinuation of
administration.
Calcium-ceftriaxone salt precipitation has been observed in the gallbladder, mainly in patients
treated with doses higher than the standard recommended dose. In children, prospective studies have shown
a variable incidence of precipitation with intravenous administration; in some studies
the incidence was greater than 30%. This incidence appears to be lower when infusions are administered
slowly (20-30 minutes). This effect is generally asymptomatic, but in rare cases precipitations have been
accompanied by clinical symptoms such as pain, nausea and vomiting. In these cases, symptomatic
treatment is recommended. Precipitation generally regresses with discontinuation of
administration.
In case of an adverse reaction, stop administration and keep the unused portion for
possible examinations.

Reporting of side effects
If you get any side effects, even if not listed in this leaflet, tell your
doctor, pharmacist or nurse. You can also report side effects directly through
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 sight and reach of children.
Do not use this medicine after the expiry date which is stated on the packaging.
The expiry date refers to the product in intact packaging, correctly 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 for single and uninterrupted
administration and any remaining solution cannot be used.
Do not use this medicine if the solution is not clear, colourless or if it contains particles.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What RINGER ACETATO DIACO contains

• The active ingredients 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 contents of the pack
Solution for infusion, sterile and apyrogenic.
Bottle of 50 ml
Bottle of 100 ml.
Bottle of 250 ml.
Bottle of 500 ml.
Bottle of 1000 ml

Marketing Authorisation 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)