Active ingredients: Electrolytes.
Lactated Ringer S.A.L.F. solution for infusion
Why is Lactated Ringer used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Electrolytes.
THERAPEUTIC INDICATIONS
Replacement therapy for loss of extracellular fluids and electrolytes, when it is necessary to correct mild and moderate acidotic states, but not severe. Treatment of mild or moderate but not severe haemorrhagic shock.
Contraindications When Lactated Ringer's should not be used
- Hypersensitivity to the active substances or to any of the excipients;
- severe kidney failure;
- hypercalcemia, hypercalciuria or severe kidney disease;
- hypernatremia
- hydrosaline plethora.
- hyperkalemia or in cases of potassium retention;
- ventricular fibrillation (calcium chloride can increase the risk of arrhythmias);
- kidney stones (can be exacerbated with the administration of calcium);
- sarcoidosis (the hypercalcemia typical of this condition may be potentiated);
- hypercoagulability;
- concomitant therapy with cardiac glycosides (see Interactions);
- metabolic and respiratory alkalosis.
- untreated Addison's disease;
- heat cramps;
- concomitant treatment with ceftriaxone in neonates (≤28 days of age), even when using separate infusion lines. See sections Interactions, Undesirable Effects and Dose, method and time of administration.
In conjunction with blood transfusions, the solution should not be administered via the same infusion catheter with whole blood due to the possible risk of clotting.
Precautions for use What you need to know before taking Ringer Lactate
Due to the presence of sodium, use with caution in patients with congestive heart failure, severe renal insufficiency and in clinical states in which there is edema with saline retention; in patients treated with cardiac inotropic drugs or with corticosteroid or corticotropic drugs. Sodium salts should be administered with caution to patients with hypertension, heart failure, peripheral or pulmonary edema, impaired renal function, pre-eclampsia, or other conditions associated with sodium retention (see Interactions).
For the presence of potassium, administration should be guided by serial electrocardiograms; potassium is not indicative of cellular potassium concentrations. High plasma potassium concentrations can cause death from cardiac depression, arrhythmias or arrest. To avoid potassium poisoning, the infusion should be performed at a controlled rate (see Dose, method and time of administration).
The medicinal product should be administered with caution in patients:
- with renal insufficiency (administration of solutions containing potassium ions in patients with impaired renal function may cause potassium retention);
- with heart failure, especially if digitized;
- with adrenal insufficiency;
- with liver failure;
- with familial periodic paralysis;
- with congenital myotonia;
- in the early post-operative stages.
Due to the presence of calcium, the medicine should be used with great caution in patients:
- with kidney pathologies
- with heart disease
- who have received a blood transfusion as calcium ion concentrations may differ from those expected.
Since calcium chloride is an acidifier, caution should be exercised if it is administered in conditions such as renal disease, cor pulmonale, respiratory acidosis or respiratory failure, where acidification may aggravate the clinical picture. In addition, caution should be used in conditions in which may experience an increased risk of hypercalcaemia, such as chronic renal failure, dehydration or electrolyte imbalance.
Since calcium salts may increase the risk of arrhythmias, care should be taken in prolonging the administration of calcium chloride in patients with heart disease.
Administration of calcium chloride can cause vasodilation resulting in lowering of blood pressure.
Calcium chloride solution is irritating and therefore should not be administered intramuscularly or subcutaneously or into perivascular tissue as tissue necrosis may occur.
Due to the presence of lactate, the medicine should be used with caution in patients with lactic acidosis and in case of alteration of the oxidative processes that prevent the use of lactate (shock, hypoxemia).
Monitoring of the electrocardiogram is essential during the infusion of the medicinal product and it is good practice to monitor the balance of fluids, electrolytes, plasma osmolarity and acid-base balance.
Plasma calcium concentrations and urine calcium concentrations should be monitored frequently to avoid hypercalciuria, as hypercalciuria can lead to hypercalcemia.
Interactions Which drugs or foods can modify the Lactated Ringer's effect
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
The use of drugs such as potassium-sparing diuretics may increase the risk of hyperkalaemia, particularly in the presence of renal dysfunction. Therefore, serum potassium levels should be closely monitored in such cases.
The use of drugs such as ACE inhibitors that cause decreased aldosterone levels can lead to potassium retention. Serum potassium levels should therefore be closely monitored.
Corticosteroids are associated with sodium and water retention, resulting in edema and hypertension: therefore, caution should be exercised in concomitant administration of sodium salts and corticosteroids (see Precautions for use).
Calcium Chloride Solution can interact with the following medicines:
- thiazide diuretics, as hypercalcemia may occur due to decreased renal excretion of calcium;
- cardioactive glycosides (digitalis), digoxin and digitoxin, since a concomitant use can increase the risk of arrhythmias considering that the inotropic effect and the toxic effects are synergistic;
- verapamil (and other calcium channel blockers), as concomitant use may decrease the antihypertensive effect of verapamil;
- medicines containing magnesium, as it may increase the risk of hypercalcaemia or hypermagnesemia, especially in patients with kidney problems;
- neuromuscular blockers: calcium salts can cancel the action of non-depolarising blockers; in some cases an increase and prolongation of the action 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 separate infusion lines are used (fatal risk of ceftriaxone-calcium salt precipitation in the bloodstream of the newborn, see Side Effects).
- In patients over 28 days of age (including adults) ceftriaxone should not be administered concomitantly with calcium-containing intravenous solutions including Lactated Ringer's S.A.L.F. solution for infusion through the same infusion line (e.g. through Y-connector).
- If the same line is used for sequential administration, the line should be flushed with a compatible liquid between infusions.
Warnings It is important to know that:
Use immediately after opening the container. The solution must be clear, colorless and free from visible particles. It is used for one uninterrupted administration and any residue cannot be used.
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
There are no data on possible adverse effects of the medicinal product when administered during pregnancy or breastfeeding or on reproductive capacity.
Therefore, the medicine should not be used during pregnancy and breastfeeding, unless absolutely necessary and only after evaluating the risk / benefit ratio.
Effects on ability to drive and use machines
The medicine does not affect the ability to drive or use machines.
Important information about some of the ingredients: none.
Dosage and method of use How to use Ringer Lactate: Dosage
The solution is isotonic with blood and should be administered with caution by intravenous infusion and at a controlled rate of infusion.
Shake well before administration.
The dose is dependent on the age, weight and clinical condition of the patient.
The medicinal product 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.
Children
In children, the safety and efficacy of the medicine have not been established.
Too rapid infusions 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 discontinued if the patient experiences pain or redness at the injection site as this may indicate drug extravasation.
It is recommended that the patient remain lying down for a short time after administration.
Incompatibility with lactated Ringer's S.A.L.F.
Due to the presence of calcium chloride it is incompatible with:
- magnesium sulfate - formation of a precipitate;
- medicines containing phosphate: formation of a precipitate of calcium phosphate;
- carbonate-containing medicines: formation of a precipitate of calcium carbonate;
- medicines containing tartrate: formation of a precipitate of calcium tartrate.
Incompatibilities of calcium chloride have been found with:
- aminophylline - for the formation of a precipitate;
- amphotericin B: for the development of numbness;
- cefamandolo: due to the presence of sodium carbonate in the preparation of cefamandolo;
- ceftriaxone sodium: for the formation of a precipitate, therefore the administration of calcium solution must not take place within 48 hours following the administration of ceftriaxone;
- cephalothin: due to physical incompatibility;
- cefradine: due to the presence of sodium carbonate in the preparation of cefradine;
- chlorphenamine: due to physical incompatibility;
- dobutamine - for the development of numbness;
- oily emulsion: due to the presence of flocculate;
- sodium heparin;
- indomethacin: for the formation of a precipitate;
- sodium nitrofurantoin;
- promethazine: for the formation of a precipitate:
- propofol - for the formation of precipitate;
- streptomycin: since calcium could inhibit the activity of streptomycin;
- tetracyclines: calcium salts can complex tetracyclines.
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 Contraindications, Interactions and Side Effects sections).
Use the solution immediately after opening the container. The container is for one uninterrupted administration 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 the intravenous infusion.
Overdose What to do if you have taken too much Ringer Lactate
Symptoms
High plasma potassium concentrations can cause death from cardiac depression, arrhythmias or arrest.
The administration of excessive doses of sodium chloride can lead, depending on the clinical condition of the patient, to hypernatremia and / or hypervolemia.
Hypernatremia and excessive sodium retention where there is a defective excretion of sodium in the kidney causes dehydration of the internal organs, especially the brain, and the accumulation of extracellular fluids with edema that can affect the cerebral, pulmonary and peripheral circulation with appearance of pulmonary and peripheral edema.
The accumulation of chlorine ions causes a reduction in the concentration of bicarbonate ions leading to acidosis.
When high doses of calcium chloride are administered, hypercalcaemia may occur especially in patients with kidney disease. The typical symptoms of hypercalcemia are: feeling of thirst, nausea, vomiting, constipation, polyuria, abdominal pain, muscle weakness, mental disorders and, in severe cases, cardiac arrhythmia and coma. We speak of hypercalcemia when plasma calcium concentrations exceed 2.6 mmol / l; therefore these concentrations must be constantly monitored.
Treatment
Immediately discontinue the infusion and institute corrective therapy to reduce plasma levels of excess ions and restore acid-base balance if necessary (see Precautions for use). The patient should be observed for evaluate the appearance of any signs and symptoms related to the drug administered, guaranteeing the patient the relative symptomatic and support measures as needed.
In case of high natremia, loop diuretics can be used. In case of hyperkalaemia, glucose (associated or not with insulin) or sodium bicarbonate can be administered by intravenous infusion. Immediate discontinuation of the infusion and any other calcium-containing drugs. In the event of severe overdose (plasma concentrations> 2.9 mmol / l), the following measures should be taken:
- rehydration by administering a 0.9% sodium colide solution;
- use of non-thiazide diuretics to promote calcium elimination;
- monitoring of plasma levels of potassium and calcium with immediate restoration of levels to normal values;
- monitoring of cardiac function, use of beta-blockers to reduce the risk of cardiac arrhythmia;
- possible use of hemodialysis.
Elevated plasma electrolyte levels may require the use of dialysis.
In case of accidental ingestion / intake of an overdose of Lactated Ringer's S.A.L.F. notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of Lactated Ringer's S.A.L.F., ask your doctor or pharmacist
Side Effects What are the side effects of Ringer's Lactate
Like all medicines, Lactated Ringer's can cause side effects, although not everybody gets them.
Below are the side effects of lactated Ringer's. Insufficient data are available to establish the frequency of the individual effects listed.
Gastrointestinal disorders
Gastrointestinal disturbances and irritation, thirst, reduced salivation, nausea, vomiting, diarrhea, abdominal pain, constipation, metallic taste, calcareous taste.
Nervous system disorders
Neuromuscular disorders, muscle stiffness, paraesthesia, flaccid paralysis, weakness, confusion, headache, dizziness, restlessness, irritability, convulsions, coma, death
Psychiatric disorders
Somnolence, confusional states, mental disorders.
Cardiac pathologies
Arrhythmias, tachycardia, bradycardia, conduction disturbances, disappearance of the P wave, widening of the QRS in the electrocardiographic trace, syncope, ventricular fibrillation, cardiac arrest.
Vascular pathologies
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's syndrome (milk-alkali syndrome).
Musculoskeletal and connective tissue disorders
Muscle weakness.
General disorders and administration site conditions
Febrile responses, infusion site infection, local pain or reaction, redness, rash, venous irritation, thrombosis or venous phlebitis extending from the infusion site, extravasation, tissue necrosis, abscess formation, skin calcification.
Precipitation of the calcium-ceftriaxone salt
Serious, and in some cases fatal, adverse reactions have been reported rarely in preterm infants and term infants (intravenously aged. The presence of calcium-ceftriaxone salt precipitation has been detected post mortem in the lungs and kidneys. L "The high risk of precipitation in neonates is a consequence of their low blood volume and the longer half-life of ceftriaxone compared to adults (see Contraindications and Interactions sections).
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 had other risk factors (e.g. . fluid restriction, bedridden patients). The risk of precipitate formation increases in immobilized or dehydrated patients.This event can be symptomatic or asymptomatic, can cause renal failure and anuria, and is reversible upon discontinuation of administration.
Precipitation of calcium ceftriaxone salt in the gallbladder has been observed, mainly in patients treated with doses above the recommended standard 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 with slow infusions (20-30 minutes). This effect is generally asymptomatic, but in rare cases the precipitations have been accompanied by clinical symptoms, such as pain, nausea and vomiting. In these cases symptomatic treatment is recommended. Precipitation is generally reversible upon discontinuation of administration.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Undesirable effects can also be reported 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.
Expiry and Retention
Expiry: see the expiry date printed on the package. The expiry date refers to the product in intact packaging, correctly stored.
Warning: do not use the medicine after the expiry date shown on the package.
Conservation conditions
Store in the original package and tightly closed container. Do not refrigerate or freeze.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment. Keep this medicine out of the reach and sight of children.
Composition and pharmaceutical form
COMPOSITION
1000 ml contain
Active ingredients: sodium chloride 6.0 g
potassium chloride 0.4 g
calcium chloride dihydrate 0.27 g
sodium lactate 5.46 g
Excipients: Water for injections.
mEq / liter: Na + 132
K + 5
Ca ++ 4
Cl- 112
Lactate 29
theoretical osmolarity: (mOsm / liter) 280
pH: 5.5-7.0
PHARMACEUTICAL FORM AND CONTENT
Solution for infusion, sterile and non-pyrogenic.
100ml glass bottle; 500ml glass bottle; 500ml PP bottle; 500ml PVC bag;
1000 ml PVC bag; 3000 ml PVC bag; 15 PVC free bags of 500 ml and 10 PVC free bags of 1000 ml.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
RINGER LATTATO S.A.L.F. SOLUTION FOR INFUSION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
1000 ml contain
Active principles: sodium chloride 6.0 g;
potassium chloride 0.4 g;
calcium chloride dihydrate 0.27 g;
sodium lactate 60% 5.46 g.
mEq / liter: Na + 132
K + 5
Ca ++ 4
Cl- 112
Lactate 29
theoretical osmolarity: (mOsm / liter) 280
pH: 5,5-7,0
03.0 PHARMACEUTICAL FORM
Solution for infusion, sterile and non-pyrogenic.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Replacement therapy for loss of extracellular fluids and electrolytes, when it is necessary to correct mild and moderate acidotic states, but not severe.
Treatment of mild or moderate but not severe haemorrhagic shock.
04.2 Posology and method of administration
The solution is isotonic with blood and should be administered with caution by intravenous infusion and at a controlled rate of infusion.
Shake well before administration.
The dose is dependent on the age, weight and clinical condition of the patient.
The medicinal product 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.
Children
In children, the safety and efficacy of the medicine have not been established.
Too rapid infusions 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 discontinued if the patient experiences pain or redness at the injection site as this may indicate drug extravasation.
It is recommended that the patient remain lying down for a short time after administration.
04.3 Contraindications
- Hypersensitivity to the active ingredients or to any of the excipients;
- severe renal insufficiency;
- hypercalcemia, hypercalciuria or severe kidney disease;
- hypernatremia;
- hydro-saline plethora;
- hyperkalemia or in cases of potassium retention;
- ventricular fibrillation (calcium chloride can increase the risk of arrhythmias);
- kidney stones (can be exacerbated by the administration of calcium);
- sarcoidosis (the hypercalcemia typical of this condition may be potentiated);
- hypercoagulability;
- concomitant therapy with cardiac glycosides (see section 4.5);
- metabolic and respiratory alkalosis;
- untreated Addison's disease;
- heat cramps.
In conjunction with blood transfusions, the solution should not be administered via the same infusion catheter with whole blood due to the possible risk of clotting.
04.4 Special warnings and appropriate precautions for use
Due to the presence of sodium, use with caution in patients with congestive heart failure, severe renal insufficiency and in clinical states in which there is edema with saline retention; in patients treated with cardiac inotropic drugs or with corticosteroid or corticotropic drugs.
Sodium salts should be administered with caution to patients with hypertension, heart failure, peripheral or pulmonary edema, impaired renal function, pre-eclampsia, or other conditions associated with sodium retention (see section 4.5).
For the presence of potassium, administration should be guided by serial electrocardiograms; potassium is not indicative of cellular potassium concentrations. High plasma potassium concentrations can cause death from cardiac depression, arrhythmias or arrest. To avoid potassium poisoning, the infusion should be performed at a controlled rate (see section 4.2).
The medicinal product should be administered with caution in patients:
- with renal insufficiency (the administration of solutions containing potassium ions in patients with decreased renal function, can cause potassium retention);
- with heart failure, especially if digitized;
- with adrenal insufficiency;
- with liver failure;
- with family periodic paralysis;
- with congenital myotonia;
- in the early post-operative stages.
Due to the presence of calcium, the medicine should be used with great caution in patients:
- with kidney diseases
- with heart disease
- who have received a blood transfusion as the calcium ion concentrations may differ from those expected.
Since calcium chloride is an acidifier, caution should be exercised if it is administered in conditions such as renal disease, cor pulmonale, respiratory acidosis or respiratory failure, in which acidification can aggravate the clinical picture.
In addition, caution should be exercised in conditions where an increased risk of hypercalcaemia, such as chronic renal failure, dehydration or electrolyte imbalance, may occur.
Since calcium salts may increase the risk of arrhythmias, care should be taken in prolonging the administration of calcium chloride in patients with heart disease.
Administration of calcium chloride can cause vasodilation resulting in lowering of blood pressure.
Calcium chloride solution is irritating and, therefore, should not be administered intramuscularly or subcutaneously or in peri-vascular tissue as tissue necrosis may occur.
Due to the presence of lactate, the medicine should be used with caution in patients with lactic acidosis and in case of alteration of the oxidative processes that prevent the use of lactate (shock, hypoxemia).
Monitoring of the electrocardiogram is essential during the infusion of the medicinal product and it is good practice to monitor the balance of fluids, electrolytes, plasma osmolarity and acid-base balance.
Plasma calcium concentrations and urine calcium concentrations should be monitored frequently to avoid hypercalciuria, as hypercalciuria can lead to hypercalcemia.
Use immediately after opening the container. The solution must be clear, colorless and free from visible particles. It is used for one uninterrupted administration and any residue cannot be used.
Important information about some of the ingredients: none.
04.5 Interactions with other medicinal products and other forms of interaction
The use of drugs such as potassium-sparing diuretics may increase the risk of hyperkalaemia, particularly in the presence of renal dysfunction. Therefore, serum potassium levels should be closely monitored in such cases.
The use of drugs such as ACE inhibitors that cause a decrease in aldosterone levels can lead to potassium retention.
Therefore it is necessary to closely monitor the serum potassium levels.
Corticosteroids are associated with sodium and water retention, resulting in edema and hypertension: therefore, caution should be used in concomitant administration of sodium salts and corticosteroids (see section 4.4).
Calcium Chloride Solution can interact with the following medicines:
- thiazide diuretics, as hypercalcemia may occur due to a lower renal excretion of calcium;
- cardioactive glycosides (digitalis), digoxin and digitoxin, since a concomitant use can increase the risk of arrhythmias considering that the inotropic effect and the toxic effects are synergistic;
- verapamil (and other calcium channel blockers), as concomitant use may decrease the antihypertensive effect of verapamil;
- medicines containing magnesium, as it may increase the risk of hypercalcaemia or hypermagnesemia, especially in patients with kidney problems;
- neuromuscular blockers: calcium salts can cancel the action of non-depolarising blockers; in some cases an increase and prolongation of the action of tubocurarine has also been observed.
04.6 Pregnancy and lactation
There are no data on possible adverse effects of the medicinal product when administered during pregnancy or breastfeeding or on reproductive capacity.
Therefore, the medicine should not be used during pregnancy and breastfeeding, unless absolutely necessary and only after evaluating the risk / benefit ratio.
04.7 Effects on ability to drive and use machines
The medicine does not affect the ability to drive and use machines.
04.8 Undesirable effects
Lactated Ringer's side effects are listed below, organized according to the MedDRA organ-system classification.
Insufficient data are available to establish the frequency of the individual effects listed.
Gastrointestinal disorders
Gastrointestinal disturbances and irritation, thirst, reduced salivation, nausea, vomiting, diarrhea, abdominal pain, constipation, metallic taste, calcareous taste.
Nervous system disorders
Neuromuscular disorders, muscle stiffness, paraesthesia, flaccid paralysis, weakness, confusion, headache, dizziness, restlessness, irritability, convulsions, coma, death
Psychiatric disorders
Somnolence, confusional states, mental disorders.
Cardiac pathologies
Arrhythmias, tachycardia, bradycardia, conduction disturbances, disappearance of the P wave, widening of the QRS in the electrocardiographic trace, syncope, ventricular fibrillation, cardiac arrest.
Vascular pathologies
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's syndrome (milk-alkali syndrome).
Musculoskeletal and connective tissue disorders
Muscle weakness.
General disorders and administration site conditions
Febrile responses, infusion site infection, local pain or reaction, redness, rash, venous irritation, thrombosis or venous phlebitis extending from the infusion site, extravasation, tissue necrosis, abscess formation, skin calcification.
04.9 Overdose
Symptoms
High plasma potassium concentrations can cause death from cardiac depression, arrhythmias or arrest.
The administration of excessive doses of sodium chloride can lead, depending on the clinical condition of the patient, to hypernatremia and / or hypervolemia. Hypernatremia and excessive sodium retention where there is a defective excretion of sodium in the kidney causes dehydration of the internal organs, especially the brain, and the accumulation of extracellular fluids with edema that can affect the cerebral, pulmonary and peripheral circulation with appearance of pulmonary and peripheral edema.
The accumulation of chlorine ions causes a reduction in the concentration of bicarbonate ions leading to acidosis.
When high doses of calcium chloride are administered, hypercalcaemia may occur especially in patients with kidney disease. The typical symptoms of hypercalcemia are: feeling of thirst, nausea, vomiting, constipation, polyuria, abdominal pain, muscle weakness, mental disorders and, in severe cases, cardiac arrhythmia and coma. We speak of hypercalcemia when plasma calcium concentrations exceed 2.6 mmol / l; therefore these concentrations must be constantly monitored.
Treatment
Immediately discontinue the infusion and institute corrective therapy to reduce plasma levels of excess ions and restore acid-base balance if necessary (see section 4.4).
The patient must be kept under observation to assess the appearance of any signs and symptoms related to the drug administered, guaranteeing the patient the relative symptomatic and support measures as needed.
In case of high natremia, loop diuretics can be used.
In case of hyperkalaemia, glucose (with or without insulin) or sodium bicarbonate can be administered by intravenous infusion.
In the event of a moderate overdose of calcium chloride, treatment involves an "immediate discontinuation of" the infusion and any other calcium-containing drugs. In the event of a severe overdose (plasma concentrations> 2.9 mmol / l), the following measures should be taken:
- rehydration by administering a 0.9% sodium colide solution;
- use of non-thiazide diuretics to favor the elimination of calcium;
- monitoring of plasma levels of potassium and calcium with immediate restoration of levels to normal values;
- monitoring of cardiac function, use of beta-blockers to reduce the risk of cardiac arrhythmia;
- possible use of hemodialysis.
Elevated plasma electrolyte levels may require the use of dialysis.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: electrolytes.
ATC code: B05BB01.
Lactated Ringer's provides electrolytes and water needed for patient rehydration.
Sodium is the main extracellular cation while chloride is its main anion. The sodium concentration is generally responsible for the volume of extracellular fluids.
Sodium is important in maintaining fluid osmolarity, transmembrane potential and acid-base balance.
Ions, such as sodium, circulate across the cell membrane using various transport mechanisms, including the sodium pump (Na-K-ATPase). Sodium plays an important role in cardiac neurotransmission and electrophysiology, and also in its renal metabolism.
Potassium is the main cation in intracellular fluids and plays a fundamental role in the electrolyte balance of fluids. The normal concentration of potassium in the intracellular fluid compartment is approximately 160 mEq / l. The standard range of plasma potassium is 3.5-5.0 mEq / L. The kidney is the organ that regulates the normal balance of potassium but does not cause its reabsorption as readily as for sodium. Daily potassium turnover in healthy adults averages 50-150 mEq and represents 1.5-5% of the body's total potassium content.
Calcium is an essential element for maintaining the functionality of the nervous, muscular and skeletal systems and the permeability of cell membranes and capillaries. Calcium is an important activator of various enzymatic reactions, essential in numerous physiological processes, such as nerve impulse transmission, cardiac contraction, skeletal muscle contraction, renal function, respiration and blood coagulation. Calcium, moreover. , plays a role in regulating (i) the release and storage of neurotransmitters and hormones, (ii) the binding with amino acids, (iii) the absorption of cyanocobalamine (vitamin B12) and (iv) the secretion of gastrin. The calcium contained in the bones is in constant exchange with that present in the plasma. Plasma calcium concentrations are strictly kept within their limits by endocrine control performed by parathyroid hormone, calcitonin and vitamin D. Under the influence of this control, when plasma calcium levels fall, calcium is released from the bones; when, instead, the plasma levels are too high, calcium is sequestered in the bones.
Chloride is predominantly an extracellular anion. Intracellular chloride is present in high concentrations in red blood cells and in the gastric mucosa. The reabsorption of chloride follows that of sodium.
Lactic acid, which is physiologically produced by the anaerobic lactacid metabolism, is slowly metabolized to bicarbonate as a function of cellular oxidative activity.
05.2 "Pharmacokinetic properties
After administration, the sodium is distributed in the fluids and tissues of the body.
The kidney maintains the sodium concentration in the extracellular fluids within a range of between 0.5% and 10% of the filtered amount. Sodium homeostasis is regulated by the renin-angiotensin-aldosterone system. Under volume depleted conditions, less sodium reaches the kidney and this stimulates the release of renin from the cells of the juxtaglomerular system. Renin converts l " angiotensinogen into angiotensin I, in turn transformed into angiotensin II by the converting enzyme (ACE). Angiotensin II causes an increase in the reabsorption of sodium, and therefore, by osmotic effect, of water in the proximal tubule. Angiotensin II also stimulates the release of aldosterone from the adrenal cortex; Aldosterone increases the direct reabsorption of sodium at the loop of Henle, distal tubule and collecting duct.
Sodium is eliminated to a small extent also with sweating and faeces in a quantity of about 7% of the introduced quantity.
Calcium is normally present in plasma in concentrations from 2.15 to 2.60 mmol / l.
About 99% of total calcium is contained in bones and teeth, mainly in the form of hydroxyapatite [Ca10 (PO4) 6 (OH) 2]; however, small traces of calcium carbonate and calcium phosphate are also present. The remaining 1% is contained in tissues other than bones and in liquids. About 50% of plasma calcium is present in the ionized form (physiologically active form), 45% is protein bound (mainly albumin) and 5% is complexed with phosphate, citrate and other anions. Following changes in serum albumin of 1g / dl, calcium concentrations can vary by about 0.02 mmol / l. Hyperproteinemia is associated with increases in total calcium concentrations, while hypoproteinemia with decreases in the same. Acidosis causes an increase in the concentration of calcium ions, while alkalosis a decrease.
Approximately 80% of calcium is excreted via the faeces; this is calcium not absorbed or secreted via bile and pancreatic juices into the intestinal lumen. The remaining 20% of calcium is excreted via the kidney with a renal clearance of 50 - 300 mg / day More than 95% of the calcium filtered through the renal glomeruli is reabsorbed in the ascending tract of the loop of Henle and in the distal and proximal tubules. Urinary calcium excretion is decreased by parathyroid hormone, thiazide diuretics and vitamin D, while it is increased by calcitonin, other diuretics and growth hormone.
In the case of chronic renal insufficiency, calcium excretion decreases due to the reduction of the filtration rate.
However, renal acidosis can cause increased renal excretion. Renal excretion is higher with a high-protein diet than with a low-protein diet.
The potassium ion, the chloride ion and the lactate ion follow the normal metabolic pathways of the organism.
05.3 Preclinical safety data
Preclinical data have little clinical relevance in light of the vast experience acquired with the use of the drug in humans.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Water for injections.
06.2 Incompatibility
Due to the presence of calcium chloride it is incompatible with:
- magnesium sulfate: formation of a precipitate;
- medicines containing phosphate: formation of a calcium phosphate precipitate;
- medicines containing carbonate: formation of a precipitate of calcium carbonate;
- medicines containing tartrate: formation of a precipitate of calcium tartrate.
Incompatibilities of calcium chloride have been found with:
- aminophylline: for the formation of precipitate;
- amphotericin B: for the development of numbness;
- cefamandolo: due to the presence of sodium carbonate in the preparation of cefamandolo;
- ceftriaxone sodium: for the formation of a precipitate, therefore the administration of calcium solution must not take place within 48 hours following the administration of ceftriaxone;
- cephalothin: due to physical incompatibility;
- cefradine: due to the presence of sodium carbonate in the preparation of cefradine;
- chlorphenamine: due to physical incompatibility;
- dobutamine: for the development of numbness;
- fat emulsion: due to the presence of flocculate;
- sodium heparin;
- indomethacin: for the formation of a precipitate;
- sodium nitrofurantoin;
- promethazine: for the formation of a precipitate:
- propofol: for the formation of precipitate;
- streptomycin: since calcium could inhibit the activity of streptomycin;
- tetracyclines: calcium salts can complex tetracyclines.
06.3 Period of validity
24 months.
Use the solution immediately after opening the container. The container is for one uninterrupted administration and any residue cannot be used.
06.4 Special precautions for storage
Store in the original package and tightly closed container. Do not refrigerate or freeze.
06.5 Nature of the immediate packaging and contents of the package
100ml glass bottle;
500ml glass bottle;
500ml PP bottle;
500ml PVC bag;
1000 ml PVC bag;
3000 ml PVC bag;
500 ml PVC free bag e
1000 ml PVC free bag.
06.6 Instructions for use and handling
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 the intravenous infusion.
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
S.A.L.F. S.p.A. Pharmacological Laboratory - Via Marconi, 2 - Cenate Sotto (BG)
08.0 MARKETING AUTHORIZATION NUMBER
A.I.C. 030723011 - 100 ml glass bottle.
A.I.C. 030723035 - 500 ml glass bottle.
A.I.C. 030723112 - 500 ml PP bottle.
A.I.C. 030723050 - 500 ml PVC bag.
A.I.C. 030723062 - 1000 ml PVC bag.
A.I.C. 030723074 - 3000 ml PVC bag.
A.I.C. 030723124 - 15 PVC free bags of 500 ml.
A.I.C. 030723136 - 10 PVC free bags of 1000 ml.
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
08 November 1993/05 May 2008
10.0 DATE OF REVISION OF THE TEXT
AIFA Determination February 20, 2013
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