Compound Sodium Lactate Intravenous Infusion Bp
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Compound Sodium Lactate Intravenous Infusion BP (Hartmann’ s Solution)
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
6.0 g/l 3.22 g/l 400 mg/l 270 mg/l
Sodium Chloride Ph. Eur. Sodium Lactate Ph. Eur. Potassium Chloride Ph. Eur. Calcium Chloride Ph. Eur.
This provides 131 mmol/l Na+, 5 mmol/l K+, 2 mmol/l Ca+, 111 mmol/l Cl and 29 mmol/l Lactate.
3 PHARMACEUTICAL FORM
Solution for infusion.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For prophylactic and replacement therapy requiring the use of Sodium Chloride and Lactate, with minimal amounts of Calcium and Potassium.
4.2 Posology and method of administration
Posology
Adults, the Elderly and Children:
Dosage, rate, and duration of administration are to be individualized and depend upon the indication for use, the patient’s age, weight, clinical condition, and concomitant treatment, and on the patient’s clinical and laboratory response to treatment.
Recommended dosage:
The amount of Compound Sodium Lactate solution needed to restore normal blood volume is 3 to 5 times the volume of lost blood.
The recommended dosage is:
for adults : 500 ml to 3Liters /24h
for infants, toddlers and children : 20 ml to 100 ml / kg / 24 h
Administration rate:
The infusion rate is usually 40 mL/kg/24h in adults.
Use in paediatric patients
The safety and efficacy of Compound Sodium Lactate solution in children has not been established by adequate and well-controlled trials; however, the use of electrolyte solutions in the paediatric population is referenced in the medical literature. Lactate-containing solutions should be administered with particular caution to neonates and infants less than 6 months of age.
Paediatric infusion rates is 5 ml/kg/h in average but the value varies with age:
• infants: 6-8 mL/kg/h,
• toddlers: 4-6 mL/kg/h
• children: 2-4 mL/kg/h.
In children with burns, the dose is on average 3.4 mL/kg/per cent burn at 24 h post-burn and
6.3 mL/kg/per cent burn at 48 h.
In severely head-injured children the dose is on average 2850 mL/m2.
Infusion rate and total volume can be higher in surgery or in case of need.
Note:
- infants and toddlers: aged from 28 days to 23 months (a toddler is an infant who can walk)
- children: age from 2 to 11 years
Use in geriatric patients
When selecting the type of infusion solution and the volume/rate of infusion for a geriatric patient,
consider that geriatric patients are generally more likely to have cardiac, renal, hepatic, and other diseases or concomitant drug therapy.
Method of administration:
The solution is for intravenous administration through a sterile and non-pyrogenic administration set using aseptic technique. The equipment should be primed with the solution in order to prevent air entering the system.
The solution should be inspected visually for particulate matter and discoloration prior to administration. Do not administer unless the solution is clear, free from visible particles and the seal is intact. Do not remove unit from overwrap until ready for use. The inner bag maintains the sterility of the solution. Administer immediately following the insertion of infusion set.
Do not connect flexible plastic containers in series in order to avoid air embolism due to possible residual air contained in the primary container. Pressurizing intravenous solutions contained in flexible plastic containers to increase flow rates can result in air embolism if the residual air in the container is
not fully evacuated prior to administration. Use of a vented intravenous administration set with the vent in the open position could result in air embolism. Vented intravenous administration sets with the vent in the open position should not be used with flexible plastic containers.
Additives may be introduced before infusion or during infusion through the injection site. When making additions to Compound Sodium Lactate solution, aseptic technique must be used. Mix the solution thoroughly when additives have been introduced. Do not store solutions containing additives.
For information on incompatibilities and preparation of the product with additives, please see sections 6.2 and 6.6.
4.3 Contraindications
As for other calcium-containing infusion solutions, concomitant administration of ceftriaxone and Compound Sodium Lactate solution is contraindicated in newborns (<28 days of age), even if separate infusion lines are used (risk of fatal ceftriaxone-calcium salt precipitation in the neonate’s bloodstream). For patients over 28 days of age please see section 4.4.
Compound Sodium Lactate solution is also contraindicated in patients with
• A known hypersensitivity to sodium lactate.
• Extracellular hyperhydration or hypervolemia
• Severe renal insufficiency (with oliguria/anuria)
• Uncompensated cardiac failure
• Hyperkalemia
• Hypercalcaemia
• Metabolic alkalosis
• Ascitic cirrhosis
• Severe metabolic acidosis
• Conditions associated with increased lactate levels (hyperlactatemia) including lactic acidosis, or impaired lactate utilization, such as severe hepatic insufficiency.
• Concomitant digitalis therapy (see section 4.5 Interactions with other medicinal products and other forms of interaction).
4.4 Special warnings and precautions for use Hypersensitivity reactions
The infusion must be stopped immediately if any signs or symptoms of a suspected hypersensitivity reaction develop. Appropriate therapeutic countermeasures must be instituted as clinically indicated.
Incompatibilities
Ceftriaxone
In patients older than 28 days (including adults), ceftriaxone must not be administered simultaneously with intravenous calcium-containing solutions, including Compound Sodium Lactate solution, through the same infusion line. If the same infusion line is used for sequential administration, the line must be thoroughly flushed between infusions with a compatible fluid. For patients under 28 days please see section 4.3.
Electrolyte balance
Hypernatraemia
Compound Sodium Lactate solution should only be administered to patients with hypernatraemia after careful consideration of the underlying cause and alternative intravenous fluids. Monitoring of plasma sodium and volume status during treatment is recommended.
Compound Sodium Lactate solution should be administered with particular caution in patients with conditions predisposing to hypernatraemia (such as adrenocortical insufficiency, diabetes insipidus or extensive tissue injury) and in patients with cardiac disease.
Hyperchloraemia
Compound Sodium Lactate solution should only be administered to patients with hyperchloraemia after careful consideration of the underlying cause and alternative intravenous fluids. Monitoring of plasma chloride and acid-base balance during treatment is recommended.
Compound Sodium Lactate solution should be administered with particular caution to patients with conditions predisposing to hyperchloraemia (such as renal failure and renal tubular acidosis, diabetes insipidus), and patients with urinary diversion or patients taking certain diuretics (carbonic anhydrase inhibitors eg acetazolamide) or steroids (androgens, estrogens corticosteroids) and in patients with severe dehydration.
Use in patients with potassium deficiency
Although Compound Sodium Lactate solution has a potassium concentration similar to the concentration in plasma, it is insufficient to produce a useful effect in case of severe potassium insufficiency and therefore it should not be used for this purpose.
Use in patients at risk for hyperkalaemia
Compound Sodium Lactate solution should be administered with particular caution to patients with conditions predisposing to hyperkalaemia (such as severe renal impairment or adrenocortical insufficiency, acute dehydration, or extensive tissue injury or burns) and in patients with cardiac disease. The plasma potassium level of the patient must be particularly closely monitored in patients at risk of hyperkalaemia.
Use in patients at risk for hypercalcaemia
Calcium chloride is an irritant, therefore care should be taken to prevent extravasation during intravenous injection and intramuscular injection must be avoided. Solutions containing calcium salts should be used with caution in patients with conditions predisposing to hypercalcaemia, such as patients with renal impairment and granulomatous diseases associated with increased calcitriol synthesis such as sarcoidosis, calcium renal calculi or a history of such calculi.
Fluid balance/renal function
Use in patients with renal impairment
Compound Sodium Lactate solution should be administered with particular caution to patients with renal impairment. In such patients administration of Compound Sodium Lactate solution may result in sodium and/or potassium retention.
Risk of Fluid and/or Solute Overload and Electrolyte Disturbances
Depending on the volume and rate of infusion, intravenous administration of Compound
Sodium Lactate solution can cause
• fluid and/or solute overload resulting in overhydration and, for example, congested
states, including pulmonary congestion and edema.
• clinically relevant electrolyte disturbances and acid-base imbalance.
Clinical evaluation and periodic laboratory determinations may be necessary to monitor changes in fluid balance, electrolyte concentrations and acid-base balance during prolonged parenteral therapy or whenever the condition of the patient or the rate of administration warrants such evaluation.
High volume infusion must be used under specific monitoring in patients with cardiac or pulmonary failure.
Use in patients with hypervolemia, overhydration or conditions causing sodium retention and edema
Compound Sodium Lactate solution should be administered with particular caution to hypervolemic or overhydrated patients.
Due to the sodium chloride content Compound Sodium Lactate solution should be administered with particular caution to patients with conditions that may cause sodium retention, fluid overload and edema, such as patients with primary hyperaldosteronism, secondary hyperaldosteronism (associated with, e.g., hypertension, congestive heart failure, renal artery stenosis, or nephrosclerosis), or preeclampsia. (see also Section 4.5)
Acid-base balance
Use in patients at risk for alkalosis
Compound Sodium Lactate solution should be administered with particular caution to patients at risk for alkalosis. Because lactate is metabolized to bicarbonate, administration may result in, or worsen, metabolic alkalosis. Seizure may be precipitated by the alkalosis induced by lactate but this is uncommon.
Other warnings
Administration of citrate anticoagulated/preserved blood
Due to the risk of coagulation precipitated by its calcium content, Compound Sodium Lactate solution must not be added to or administered simultaneously through the same tubing with citrate anticoagulated/preserved blood.
Use in patients with type 2 diabetes
Lactate is a substrate for gluconeogenesis. Therefore glucose levels should be carefully monitored in patients receiving Compound Sodium Lactate.
Administration
Adding other medication or using an incorrect administration technique might cause the appearance of fever reactions due to the possible introduction of pyrogens. In such case the infusion must be stopped immediately.
For information on incompatibilities and preparation of the product with additives, please see sections 6.2 and 6.6.
During long term parenteral treatment, a convenient nutritive supply must be given to the patient.
4.5 Interaction with other medicinal products and other forms of interaction
Ceftriaxone: See section 4.3 and 4.4 for more information
Interaction related to the presence of sodium:
Caution is advised when administering Compound Sodium Lactate solution to patients treated with drugs that may increase the risk of sodium and fluid retention (with oedema and hypertension), such as corticosteroids.
Interaction related to the presence of potassium:
Because of its potassium content, Compound Sodium Lactate solution should be administered with caution in patients treated with agents or products that can cause hyperkalemia or increase the risk of hyperkalemia, such as
- Potassium-sparing diuretics (amiloride, spironolactone, triamterene, alone or in association).
- Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor antagonists
- Tacrolimus, cyclosporin
Administration of potassium in patients treated with such medications can produce severe and potentially fatal hyperkalemia, particularly in patients with severe renal insufficiency.
Interaction related to the presence of calcium:
Administration of calcium may increase the effects of digitalis and lead to serious or fatal cardiac arrhythmia. Therefore, larger volumes or a faster infusion rates should be used with caution in patients treated with digitalis glycosides.
- Caution is advised when administering Compound Sodium Lactate solution to patients treated with thiazide diuretics or vitamin D, as these can increase the risk of hypercalcemia.
- Bisphosphonates, fluoride, some fluoroquinolones and tetracyclines which are less absorbed (lower availability) when administered with calcium.
Interaction related to the presence of lactate (which is metabolized into bicarbonate):
Caution is advised when administering Compound Sodium Lactate solution to patients treated with drugs for which renal elimination is pH dependent. Due to the alkalinizing action of lactate (formation of bicarbonate), Compound Sodium Lactate solution may interfere with the elimination of such drugs.
- Renal clearance of acidic drugs such as salicylates, barbiturates, and lithium may be increased because of the alkalinisation of urine by the bicarbonate resulting from lactate metabolism.
- Renal clearance of alkaline drugs, such as sympathomimetics (e.g. ephedrine, pseudoephedrine) and stimulants (e.g. dexamphetamine sulphate, phenfluramine hydrochloride) may be decreased.
4.6. Pregnancy and Lactation
The safety of this medicinal product for use in human pregnancy has not been established.
4.7 Effects on ability to drive and use machines
There is no information of the effects of Compound Sodium Lactate solution on the ability to operate an automobile or other heavy machinery.
4.8 Undesirable effects
The following adverse reactions (listed by MedDRA System Organ Class) have been reported spontaneously during the post-market experience.
|
Immune System Disorders |
Hypersensitivity/Infusion reactions including Anaphylactic/Anaphylactoid reaction, possibly manifested by one or more of the following symptoms: Angioedema, Chest pain, Chest discomfort, Decreased heart rate, Tachycardia, Blood pressure decreased, Respiratory distress, Bronchospasm, Dyspnea, Cough, Urticaria, Rash, Pruritus, Erythema, Flushing, Throat irritation, Paresthesias, Hypoesthesia oral, Dysgeusia, Nausea, Anxiety, Pyrexia, Headache |
|
Metabolism and Nutrition Disorders |
Hyperkalemia |
|
General Disorders and Administration Site Conditions |
Infusion Site Reactions manifested by one or more of the following symptoms: Phlebitis, Infusion site inflammation, Infusion site swelling, Infusion site rash, Infusion site pruritus, Infusion site erythema, Infusion site pain, Infusion site burning |
The following adverse reactions have been reported spontaneously during the use of other sodium-lactate containing solutions:
• Hypersensitivity: Laryngeal oedema (Quincke’s oedema), skin swelling, nasal congestion, sneezing
• Electrolyte disturbances
• Hypervolemia
• Panic Attack
• Other infusion site reactions: Infection at the site of injection, extravasation, infusion site anaesthesia (numbness).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme.
Website: www.mhra.gov.uk/yellowcard
4.9 Overdose
An excessive volume or too high a rate of administration of Compound Sodium Lactate solution may lead to fluid and sodium overload with a risk of oedema (peripheral and/or pulmonary), particularly when renal sodium excretion is impaired. In this case extra renal dialysis may be necessary.
Excessive administration of potassium may lead to the development of hyperkalemia, especially in patients with renal impairment. Symptoms include paresthesia of the extremities, muscle weakness, paralysis, cardiac arrhythmias, heart block, cardiac arrest, and mental confusion.
Excessive administration of calcium salts may lead to hypercalcemia. Symptoms of hypercalcemia may include anorexia, nausea, vomiting, constipation, abdominal pain, muscle weakness, mental disturbances, polydipsia, polyuria, nephrocalcinosis, renal calculi, and, in severe cases, cardiac arrhythmias and coma. Too rapid intravenous injection of calcium salts may also lead to many of the symptoms of hypercalcemia as well as to chalky taste, hot flushes, and peripheral vasodilatation. Mild asymptomatic hypercalcemia will usually resolve on stopping administration of calcium and other contributory drugs such as vitamin D. If hypercalcemia is severe, urgent treatment (such as loop diuretics, hemodialysis, calcitonin, bisphosphonates, trisodium edetate) is required.
Excessive administration of lactate may lead to metabolic alkalosis. Metabolic alkalosis may be accompanied by hypokalemia, Symptoms may include mood changes, tiredness, shortness of breath, muscle weakness, and irregular heartbeat. Muscle hypertonicity, twitching, and tetany may develop especially in hypocalcemic patients. Treatment of metabolic alkalosis due to bicarbonate overdose consists mainly of appropriate correction of fluid and electrolyte balance. Replacement of calcium, chloride, and potassium may be of particular importance.
When overdose is related to medications added to the solution infused, the signs and symptoms of over infusion will be related to the nature of the additive being used. In the event of accidental over infusion, treatment should be discontinued and the patient should be observed for the appropriate signs and symptoms related to the drug administered. The relevant symptomatic and supportive measures should be provided as necessary.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Potassium - Potassium is an essential body electrolyte. It is the principle cation of intracellular fluid and is involved in numerous enzymatic reactions and physiological processes including nerve conduction, muscle contraction and carbohydrate metabolism. Potassium balance is one of the most important electrolyte balances to maintain.
Sodium - Sodium is the principle cation in extracellular fluid and is the main osmotic component in the control of blood volume. Any disturbance in the sodium balance can disturb the synchronisation of neuromuscular function.
Chloride - Chloride is the most abundant anion in the extracellular fluid and functions to maintain the osmotic pressure of the blood and thus blood volume and arterial pressure, chloride concentration is regulated secondary to the regulation of sodium concentrate. With each sodium ion reabsorbed in the renal tubules, a chloride or bicarbonate ion is also reabsorbed. Thus a depletion of chloride ions will cause an increase in bicarbonate ions and a hypochloremic metabolic alkalosis will result.
Calcium - Calcium is the most abundant electrolyte in the human body. Only a very small fraction of the body’s total calcium content is present in the extracellular fluid. The small quantities of calcium present in plasma play a very important role in blood coagulation. Calcium is also necessary for normal neuromuscular and cardiac functioning.
Lactate - Lactate ions play a major role in the carbonic acid-base buffer system. The lactate is slowly converted into bicarbonate, which is the second most abundant extracellular anion. Bicarbonate is an essential part of the carbonic acid-base buffer system, which helps to regulate plasma pH, hydrogen ion concentration and acid-base balance.
5.2. Pharmacokinetic Properties
Potassium - Potassium salts other than phosphate, sulphate and tartrate are generally readily absorbed from the gastro-intestinal tract. Potassium is excreted mainly by the kidneys; it is secreted in the distal tubules which are also the site of sodium-potassium exchange. The capacity of the kidneys to conserve potassium is poor and urinary excretion of potassium continues even when there is severe depletion. Some potassium is excreted in the faeces and small amounts may also appear in saliva, sweat, bile and pancreatic juice.
Sodium - Sodium is absorbed readily from the gastrointestinal tract, mainly in the small intestine. Sodium is excreted primarily in the urine and urinary excretion usually mirrors sodium intake. In times of sodium deprivation, the kidneys conserve sodium well by producing urine with a low sodium concentration. Sodium may also be found in other bodily secretions, such as sweat and gastrointestinal juices.
Chloride - Chloride is absorbed readily from the gastrointestinal tract. Excretion from the body is chiefly via the urine, but chloride may also be lost via sweat and gastrointestinal secretions.
Calcium - The principal site of absorption of calcium is the small intestine. Approximately 80% of orally ingested calcium appear in the faeces. The remaining portion is absorbed and largely excreted in the urine. The amount of calcium excreted in the urine is less than that absorbed from the gastrointestinal tract since some of the absorbed calcium is resecreted into the lumen of the small intestine.
Lactate - The body’s main source of bicarbonate is internal metabolism. Lactate ions are slowly converted into bicarbonate, and so play a part in acid-base regulation. Once converted, the bicarbonate ions are regulated by the kidneys.
Preclinical Safety Data
5.3.
Not applicable.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium Hydroxide Ph. Eur. for pH adjustment Lactic Acid Ph. Eur. for pH adjustment Water for Injection Ph. Eur. to 1000ml
6.2 Incompatibilities
Ceftriaxone must not be mixed with calcium-containing solutions including Compound Sodium Lactate solution. See also sections 4.3 and 4.4.
As with all parenteral solutions additives may be incompatible. Compatibility of the additives with the Compound Sodium Lactate solution and Viaflo container must be assessed before addition. After addition of the additive, incompatibility may become visible by a possible colour change and/or the appearance of precipitates, insoluble complexes or crystals.
The Instructions for Use of the medication to be added and other relevant literature must be consulted.
Before adding a substance or medication, verify that it is soluble and/or stable in water and that the pH range of Compound Sodium Lactate solution is appropriate (pH 5.0 to 7.0).
When making additions to Compound Sodium Lacate solution, aseptic technique must be used. Mix the solution thoroughly when additives have been introduced. Do not store solutions containing additives.
As a guidance the following medications are incompatible with the Compound Sodium Lactate solution (non-exhaustive listing):
Aminocaproic acid Amphotericin B Metaraminol tartrate Cefamandole Ceftriaxone Cortisone acetate Diethylstilbestrol Etamivan Ethyl alcohol
Phosphate and carbonate solutions
Oxytetracycline Thiopental sodium Versenate disodium
Medications with partial incompatibility with Compound Sodium Lactate Solution:
Tetracycline stable for 12 hours Ampicillin sodium
- concentration of 2%-3% stable for 4 hours
- concentration >3% must be given within 1 hour
Minocycline stable for 12 hours Doxycycline stable for 6 hours
Additives known or determined to be incompatible should not be used.
6.3. Shelf Life
The shelf life is 24 months providing the unit has not been opened.
6.4. Special Precautions for Storage
Store below 25oC.
6.5. Nature and Contents of Container
The solution is supplied in a clear, collapsible, polyvinyl chloride (Viaflex®) infusion bag, overwrapped with high density polyethylene and polypropylene and containing 500 or l000ml of a clear, colourless, sterile, non-pyrogenic aqueous solution for parenteral administration to human beings.
6.6 Special precautions for disposal
After opening the container, the contents should be used immediately and should not be stored for a subsequent infusion.
Discard after single use.
Discard any unused portion.
Do not reconnect partially used bags.
Opening
• Remove the Viaflex container from the overpouch just before use.
• Check for minute leaks by squeezing inner bag firmly. If leaks are found, discard solution, as sterility may be impaired
Check the solution for clarity and absence of foreign matter. If solution is not clear or contains foreign matter, discard the solution.
Preparation for administration
Use sterile material for preparation and administration.
• Suspend container from eyelet support.
• Use an aseptic technique to prepare the administration set.
• Remove blue protector from outlet port and insert set connector well into port.
• Prime set and regulate administration as required.
• If administration set becomes blocked do not pump contents back into container but replace equipment.
• Discard any unused portion and equipment after use. Do not store or reconnect partly used containers.
Techniques for injection of additive medications
Warning: Some additives may be incompatible. Check additive compatibility with both the solution and container prior to use. When additive is used, verify isotonicity prior to parenteral administration. Thorough and careful aseptic mixing of any additive is mandatory. Solutions containing additives should be used immediately and not stored.
To add medication before administration
• Disinfect medication site.
• Using syringe with 20 gauge (0.90 mm) to 22 gauge (0.70 mm) needle, puncture resealable medication port and inject.
• Mix solution and medication thoroughly. For high-density medication such as potassium chloride, tap the ports gently while ports are upright and mix.
Caution: Do not store bags containing added medications.
To add medication during administration
• Close clamp on the set
• Disinfect medication site.
• Using syringe with 20 gauge (0.9 mm) to 22 gauge (0.70 mm) needle, puncture resealable medication port and inject.
• Remove container from IV pole and/or turn to an upright position.
• Evacuate both ports by tapping gently while the container is in an upright position.
• Mix solution and medication thoroughly.
• Return container to in use position, re-open the clamp and continue administration.
7 MARKETING AUTHORISATION HOLDER
Baxter Healthcare Ltd., Caxton Way,
Thetfolk,
Norfolk,
IP24 3SE,
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 00116/5048R
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
12/07/2001
10 DATE OF REVISION OF THE TEXT
13/05/2015