SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Half-Strength Compound Sodium Lactate Intravenous Infusion, solution for infusion

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

1000 ml of solution contains:

Active substances:

Sodium chloride	3.0	g
Sodium lactate	1.61	g
(as 50 % m/m sodium lactate solution, 3.2 g)
Potassium chloride	0.2	g
Calcium chloride dihydrate	0.14	g
Electrolyte concentrations
Sodium	65.5	mmol/l
Potassium	2.7	mmol/l
Calcium	1.0	mmol/l
Chloride	55.5	mmol/l
Lactate	14.5	mmol/l
Theoretical osmolarity	139	mOsm/ l mmol/l
Titration acidity (to pH 7.4) pH	< 1 5.0    - 7.0

For excipients see 6.1.

3. PHARMACEUTICAL FORM

Solution for infusion.

A clear, colourless aqueous solution.

4.1 Therapeutic indications

Correction or maintenance of fluid and electrolyte balances, depending upon the clinical condition of the patient. The solution is particularly indicated in the treatment of hypertonic and isotonic dehydration, for fluid and electrolyte supplementation in acid base homeostasis and in mild acidosis.

4.2 Posology and method of administration

Adults, the Elderly and Children

The dosage depends on the age, weight, clinical and biological (acid-base balance) conditions of the patient, concomitant therapy and should be determined by the prescribing physician.

General guidelines

Up to 40 ml fluid/kg body weight per day.

Infusion and drop rate:

Up to 5 ml/kg body weight per hour.

The prescribing doctor may determine individual adaptation of the dose and infusion rate, especially for children.

Monitoring

Adequate urine flow must be ensured and careful monitoring of serum electrolytes and acid-base status is essential.

Method of administration

Intravenous infusion via a peripheral or central vein.

Duration of use

Half-Strength Compound Sodium Lactate Intravenous Infusion may be administered as long as there is an indication for electrolyte and fluid administration.

This container contains a significant volume of air. To avoid risk of air embolism, this product must not be administered by pressure infusion.

4.3 Contraindications

Half-Strength Compound Sodium Lactate Intravenous Infusion is contraindicated in patients with

-    hyperhydration

-    hypotonic dehydration

-    impairment of lactate utilisation with hyperlactataemia (see also section 4.4).

-    Severe liver insufficiency

- Severe renal failure with oliguria or anuria

4.4 Special Warnings and Precautions for Use

Lactate utilisation may be impaired in the presence of hypoxia or hepatic insufficiency. This may be the case in patients with metabolic acidosis associated with beriberi, circulatory insufficiency, shock, cardiac decompensation, extracorporal circulation, hypothermia, glycogen storage disease, liver diseases, respiratory alkalosis, antidiabetic therapy with biguanides (see also section 4.5), antiretroviral HIV-therapy or other disorders involving reduced perfusion of body tissues. Serum lactate should be monitored carefully and if lactate accumulates during infusion, administration of the solution must be stopped.

Solutions containing sodium chloride must be used with caution in patients who have an impaired ability to handle sodium and fluid such as cardiac disease especially with a history of congested states or pulmonary oedema, cardio-pulmonary disease, patients with renal insufficiency, cirrhosis of the liver, hypernatraemia or patients receiving salt-retaining steroids.

Calcium salts should be given cautiously to patients with impaired renal function, cardiac disease, or sarcoidosis.

Potassium and calcium supplements should be administered with caution in patients with cardiac disease particularly in digitalised patients. Rapid lowering of plasma potassium concentrations in digitalised patients can cause cardiac glycoside toxicity.

Special caution must be exercised to avoid metabolic alkalosis resulting from excess administration.

Clinical supervision should include ECGs, regular checks of fluid balance and serum electrolytes.

4.5 Interactions with Other Medicinal Products and Other Forms of Interaction

In patients on digoxin, hypokalaemia may result in digoxin toxicity. Administration of hypotonic potassium solutions must be very careful in these patients. Calcium enhances the effects of digitalis glycosides on the heart and may thus also precipitate digitalis intoxication; therefore, parenteral calcium therapy must be cautious in patients receiving cardiac glycosides. It should also be considered that thiazide diuretics may increase the renal reabsorption of calcium, thereby leading to hypercalcaemia .

Lactic acid may accumulate in patients on medication with biguanides mainly when there are further risk factors such as age of > 60 years, decreased cardiac, renal and hepatic function, diabetic ketoacidosis, surgery, respiratory failure, ethanol intoxication and fasting.

Antiretroviral HIV-therapy may also be associated with lactic acid accumulation.

Corticosteroids are associated with the retention of sodium and water.

With respect to lactate it is to mention that alkalinisation of the urine following bicarbonate or bicarbonate precursor administration leads to increased renal clearance of acid drugs.

4.6 Pregnancy and lactation

For „Half-Strength Compound Sodium Lactate“ no controlled clinical data on exposed pregnancies are available. However, in many years of clinical experience with solutions such as Half-Strength Compound Sodium Lactate Intravenous Infusion no adverse effects on the course of pregnancy and the foetus have been reported in the literature. All components of „Half-Strength Compound Sodium Lactate“ are naturally present in the body and their biochemical properties are well known.

Yet caution should be exercised when prescribing to pregnant women.

4.7 Effects on ability to drive and use machines

Not known.

4.8 Undesirable effects

When used accordingly no adverse drug reactions are to be expected.

In patients with cardiac, renal or metabolic impairment or when the infusion is carried out too rapidly or to excess, it is possible that hyperhydration, acid-base imbalances, and electrolyte disturbances can result. Hyperhydration is associated with increased skin tension, venous congestion, and oedema.

Adverse reactions may be associated with the technique of administration including febrile response, infection at the site of injection, local pain or reaction, vein irritation, venous thrombosis or phlebitis extending from the site of injection and extravasation.

Adverse reactions may be associated with the medications added to the solution; the nature of the additive will determine the likelihood of any other undesirable effects.

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 at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

Symptoms

If excretory mechanisms are impaired or the infusion is either carried out too rapidly or to excess, hyperhydration, acid-base imbalances, and electrolyte disorders can result. The possible symptoms are described in section 4.8.

Excessive administration of lactate may lead to metabolic alkalosis. This is especially the case when renal compensatory mechanisms are insufficient. Symptoms of metabolic alkalosis are shortness of breath and muscle weakness associated with potassium depletion. In hypocalcaemic patients muscle hypertonicity, twitching, and tetany may develop and in epileptic patients seizures may aggravate in this clinical instance. Intravenous administration of lactate has also been reported to induce feelings of anxiety, especially in patients with anxiety states.

Emergency treatment, antidotes

Immediate stop of the infusion, ECG monitoring, if necessary enhancement of urine flow and thus fluid excretion and correction of electrolyte levels. Haemodialysis or peritoneal dialysis may be required in patients with renal insufficiency.

When overdose is related to medications added to the solution infused the signs and symptoms of overinfusion will be related to the nature of the additive being used. In the event of accidental overinfusion, 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

Half-Strength Compound Sodium Lactate Intravenous Infusion is an infusion solution for parenteral supply of water and electrolytes.

ATC code: B05BB01, Solutions affecting the electrolyte balance -Electrolytes

It contains the electrolytes sodium, potassium, calcium, and chloride and lactate in water. The concentrations of sodium, potassium, calcium, and chloride are about half those physiologically present in the serum.

Sodium is the major cation of the extracellular fluid and is principally responsible for the control of water distribution, fluid and electrolyte balance, and osmotic pressure of body fluids. Together with chloride and bicarbonate, sodium plays also an important role in the regulation of acid-base balance.

Potassium is the major cation of intracellular fluid and is essential for maintenance of acid-base balance, isotonicity, and electrodynamic characteristics of the cell. It is also an important activator in many enzymatic reactions.

Calcium has structural and regulatory functions in the body. It is a structural component in the extracellular matrices forming bones and teeth, and is essential in the maintenance of intracellular structures. The regulatory function of calcium is important for the cells reaction to physiological stimuli such as a hormones or neurotransmitters.

Chloride, the major extracellular anion, closely follows the physiologic disposition of sodium, and changes in the acid-base balance of the body are reflected by changes in serum chloride concentration.

Lactate is a key substrate in intermediary metabolism. Inter alia, it is oxidised to bicarbonate, thus exerting a mild and protracted alkalinising effect.

Due to its lower than physiological electrolyte concentrations, Half-Strength Compound Sodium Lactate Intravenous Infusion is especially suitable for water and electrolyte supply to patients in stated of hyperhydration.

5.2 Pharmacokinetic properties

Since the ingredients of „Half-Strength Compound Sodium Lactate“ are infused intravenously their bioavailability is 100 %.

Sodium and chloride mainly distribute in the extracellular space.

Plasma sodium concentration is normally regulated at a concentration of 135 -145 mmol/l and chloride at 95-107 mmol/l.

Infused potassium is actively transported into the cells, where its concentration is up to 40 times that outside the cell. Plasma potassium concentrations generally range from 3.5-5 mmol/l.

Potassium, sodium, and chloride are mainly excreted in urine but small amounts are lost via the skin and also the intestinal tract. Especially surgery results in increased urinary excretion of potassium while water and sodium is retained.

Serum total calcium levels are closely regulated at about 2.5 mmol/l. 99% of the total body calcium is located in bones and teeth. Of the remaining calcium 6 to 8 g are stored inside the cells and about 1 g is found in an exchangeable calcium pool, i.e. blood, liver and other body fluids.

Lactate is physiologically present in the blood at concentrations between 0.471.92 mmol/l with rising levels during exercise and in shock. Metabolism of lactate involves conversion to pyruvate. Pyruvate can enter the tricarboxylic acid cycle or can enter the gluconeogenic pathway to be converted to glucose. Metabolisation to carbon dioxide and water binds hydrogen ions and results in the formation of bicarbonate. Lactate metabolism is impaired in states of hypoxia and in liver insufficiency.

5.3 Preclinical Safety Data

Preclinical safety data are not relevant since its constituents are physiological components of animal and human plasma.

6. PHARMACEUTICAL PARTICULARS

6.1    List of Excipients

Water for injections.

6.2    Incompatibilities

Drugs containing oxalate, phosphate, or carbonate/bicarbonate may cause precipitation upon mixing with Half-Strength Compound Sodium Lactate Intravenous Infusion.

No other medicament or substance should be added to the fluid unless known to be compatible.

As with all parenteral solutions, before adding medications, compatibility of these additives with the product in the container must be assessed

It is the responsibility of the physician to judge the incompatibility of an additive medication with the Half-Strength Compound Sodium Lactate Intravenous Infusion by checking for eventual colour change and/or eventual precipitate, insoluble complexes or crystals apparition.

The Instructions for Use of the medication to be added must be consulted.

Before adding a drug, verify it is soluble and stable in water at the pH of HalfStrength Compound Sodium Lactate Intravenous Infusion.

When a compatible medication is added to this formulation, the solution must be administered immediately.

6.3 Shelf Life

Shelf life of the medicinal product as packaged for sale

Unopened: 3 years.

Shelf life after first opening the container

Not applicable. Product should be administered immediately after connecting to the giving set.

In-use shelf-life (Additives)

Chemical and physical stability of any additive medication at the pH of the Half-Strength Compound Sodium Lactate Intravenous Infusion in the container should be established prior to use.

From a microbiological point of view, the diluted product should be used immediately and infusion completed within 24 hours of the addition of any additive. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8 °C, unless dilution has taken place in controlled and validated aseptic conditions.

6.4 Special Precautions for Storage

Unopened: This medicinal product does not require any special storage conditions

6.5 Nature and Contents of Container

Polyethylene bottles,

contents: 500 ml, 1000 ml in packs of 10.

Instructions for use and handling

Use only if the solution is clear, without visible particles and if the container is undamaged.

The solution should not be administered if the container or its closure show visible signs of damage.

For single use only. Discard unused contents. Do not reconnect partially used containers.

Administer immediately following the insertion of infusion set.

The solution should be administered with sterile equipment using an aseptic technique. The equipment should be primed with the solution in order to prevent air entering the system.

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 after preparation, unless preparation has taken place in controlled and validated aseptic conditions.

In case of an adverse reaction, infusion must be stopped immediately.

7 MARKETING AUTHORISATION HOLDER

B. Braun Melsungen AG Carl-Braun-StraBe 1 34212 Melsungen, Germany

8. MARKETING AUTHORISATION NUMBER

PL 03551/0084

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

23/01/2009

10    DATE OF REVISION OF THE TEXT

07/10/2014