2. QUALITATIVE AND QUANTITATIVE COMPOSITION

1000 ml Sterofundin ISO solution for infusion contain:

1000 ml Sterofundin ISO solution contain 0.2 g Sodium hydroxide (0.115 g Sodium).

For the full list of excipients, see section 6.1

3.    PHARMACEUTICAL FORM Solution for infusion.

A clear, colourless aqueous solution

pH:    5.1 - 5.9

Theoretical osmolarity:    309 mosm/l.

4.    CLINICAL PARTICULARS

4.1 Therapeutic indications

Replacement of extracellular fluid losses in the case of isotonic dehydration, where acidosis is present or imminent.

4.2. Posology and method of administration Posology

Adults, the elderly, adolescents and children:

The dosage depends on the age, weight, clinical and biological conditions of the patient and concomitant therapy.

Recommended dosage:

The recommended dosage is:

•    for adults, the elderly and adolescents : 500 ml to 3 litres /24h, corresponding to 1 to 6 mmol sodium / kg / 24 h and 0.03 to 0.17 mmol potassium / kg / 24 h.

•    for toddlers, infants and children : 20 ml to 100 ml / kg / 24 h, corresponding to 3 to 14 mmol sodium / kg / 24 h and 0.08 to 0.40 mmol potassium / kg / 24 h.

Administration rate:

The maximum infusion rate depends on the needs of the patient in fluid replacement and electrolytes, his weight, clinical condition, and biological status.

In paediatric patients the infusion rate is 5 ml/kg/h on average but the value varies with age: 6-8 ml/kg/h for infants, 4-6 ml/kg/h for toddlers, and 2-4 ml/kg/h for children.

Note:

•    infants and toddlers: age ranges from about 28 days to 23 months (a toddler is an infant who can walk)

•    children: age ranges from about 2 years to 11 years.

Paediatric population

The safety and efficacy of Sterofundin in newborn infants (below the age of 28 days) has not been established.

Method of administration

For intravenous use as infusion only.

Sterofundin ISO can be infused into peripheral veins (see section 3 for pH and theoretical osmolarity).

If administration is by rapid infusion under pressure, all air must be withdrawn from the plastic container and infusion set prior to infusion, as otherwise there is a risk of producing air embolism during infusion.

Fluid balance, plasma electrolyte concentrations and pH must be monitored during administration.

Sterofundin ISO may be administered as long as there is an indication for fluid replacement.

4.3 Contraindications

Sterofundin ISO must not be administered in the following situations:

-    Hypervolaemia

-    Severe congestive cardiac failure

-    Renal failure with oliguria or anuria

-    Severe general oedema

-    Hyperkalaemia

-    Hypercalcaemia

-    Metabolic alkalosis

4.4    Special warning and precautions for use

High volume infusion must be used under specific monitoring in patients with mild to moderate cardiac or pulmonary failure (for more severe conditions: see Section 4.3).

Solutions containing sodium chloride should be administered with caution to patients with

-    mild to moderate cardiac insufficiency, peripheral or pulmonary oedema or extracellular hyperhydration (for more severe conditions: see Section - 4.3),

-    hypernatraemia, hyperchloraemia, hypertonic dehydration, hypertension, impaired renal function, present or imminent eclampsia, aldosteronism or other conditions or treatment (e. g. corticoids/steroids) associated with sodium retention (see also Section 4.5).

Solutions containing potassium salts should be administered with caution to patients with cardiac disease, or conditions predisposing to hyperkalaemia such as renal or adrenocortical insufficiency, acute dehydration, or extensive tissue destruction as occurs with severe burns.

Because of the presence of calcium:

-    Care should be taken to prevent extravasation during intravenous infusion

-    The solution should be given cautiously to patients with impaired renal function or diseases associated with elevated vitamin D concentrations such as sarcoidosis.

-    In case of concomitant blood transfusion, the solution must not be administered via the same infusion set

Solutions containing metabolizable anions should be administered cautiously to patients with respiratory impairment.

Monitoring of the serum electrolytes, fluid balance, and pH is necessary. During long-term parenteral treatment, a convenient nutritive supply must be given to the patient.

This medicinal product contains 145 mmol sodium per 1000 ml. To be taken into consideration by patients on a controlled sodium diet.

4.5    Interaction with other medicinal products and other forms of interaction

Sodium, potassium, calcium, and magnesium are present in Sterofundin ISO in the same concentrations as in plasma. Hence, the administration of Sterofundin ISO in accordance with the recommended indications and contraindications does not increase the plasma concentrations of said electrolytes. In case there is a rise of any electrolyte's concentration due to other reasons the following interactions should be considered.

Related to sodium:

Corticoids/steroids and carbenoxolone may be associated with the retention of sodium and water (with oedema and hypertension).

Related to potassium:

-    Suxamethonium,

-    Potassium-sparing diuretics (amiloride, spironolactone, triamterene, alone or in association),

-    Tacrolimus, cyclosporine

may increase the concentration of potassium in the plasma and lead to potentially fatal hyperkalaemia notably in case of renal failure increasing the hyperkalaemic effect.

Related to calcium:

Digitalis glycosides (digitalis cardiotonics) may undergo enhancement of their effects during hypercalcaemia and lead to serious or fatal cardiac arrhythmia.

Vitamin D may induce hypercalcaemia.

4.6    Fertility, pregnancy and lactation

There are no data from the use of Sterofundin ISO in pregnant and lac-tating women. In the intended indication no risks have to be expected, when volume, electrolyte and acid/base levels are carefully monitored (see section 5.3).

Sterofundin ISO should be used with caution in toxaemia of pregnancy.

4.7    Effects on ability to drive and use machines

Sterofundin ISO has no influence on the ability to drive and use machines.

4.8    Undesirable effects

Signs of overdose may occur, see section 4.9.

Definition of frequency terms used in this section:

Rare: > 1/10,000 to < 1/1,000

Not known: Frequency cannot be estimated from the available data Immune system disorders

Frequency not known: Hypersensitivity reactions characterized by urticaria have been occasionally described after the intravenous administration of magnesium salts.

Gastrointestinal disorders

Although oral magnesium salts stimulate peristalsis, paralytic ileus has been rarely reported after intravenous infusion of magnesium sulphate.

BIBRAUN

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Package leaflet: Information for the user

B. Braun Melsungen AG ■ 34209 Melsungen, Germany

Sterofundin ISO

solution for infusion

What is in this leaflet

1.    What Sterofundin ISO is and what it is used for

2.    What you need to know before you receive Sterofundin ISO

3.    How to use Sterofundin ISO

4.    Possible side effects

5.    How to store Sterofundin ISO

6.    Contents of the pack and other information

1. What Sterofundin ISO is and what it is used for

Sterofundin ISO is a solution for infusion into a vein.

This solution replaces fluid that has been lost from the circulation. It can be used in conditions where your blood may become or has become slightly acidic.

2. What you need to know before you receive Sterofundin ISO

You will not be given Sterofundin ISO

if you have

-    too much fluid in the circulation,

-    severe heart disease with shortness of breath and swelling of the feet or the legs,

-    severe kidney disease and you are unable or almost unable to pass urine,

-    swelling of your body tissues due to fluid accumulation,

-    high levels of potassium or calcium in your blood,

-    or if your blood is too alkaline.

Warnings and precautions

Talk to your doctor or pharmacist before using Sterofundin ISO.

Special care will be taken with Sterofundin ISO Solution for infusion, if you have

-    any disease that makes it necessary to reduce your salt intake, such as mild or moderately impaired heart function, tissue swelling or fluid accumulation in the lungs

-    sarcoidosis (a chronic immune system disorder involving the lymph nodes and the connective tissue)

-    mildly or moderately increased blood pressure

-    acute water deficit e.g. following extensive tissue destruction as occurs with severe burns or due to impaired function of the adrenal glands

-    high levels of sodium or chloride in your blood

-    eclampsia (a complication occurring during pregnancy)

-    mild or moderate impairment of your kidney function

-    breathing problems

-    any disease or if you receive any medicine that may lead to reduced excretion of sodium.

If any of the above mentioned applies to you, your doctor will decide very carefully whether this solution is suitable for you.

Your body fluid level and the salt concentrations in your blood will be controlled while you receive Sterofundin ISO to make sure that they are normal.

Other medicines and Sterofundin ISO

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

It is particularly important that your doctor knows if you take, use or receive:

•    Drugs that make your body retain sodium and water such as

-    steroid hormones or

-    carbenoxolone

If these are used together with Sterofundin ISO your body water level and your blood sodium level may increase, leading to swelling and increased blood pressure.

•    Drugs with an influence on your blood potassium level such as

-    suxamethonium

-    some diuretics (water tablets) that lower your potassium excretion, e.g. amiloride, spironolactone, triamterene

-    tacrolimus, ciclosporin (drugs used e.g. to suppress the rejection of transplanted organs)

If these are used together with Sterofundin ISO your blood potassium level could rise, which may lead to adverse effects on your heart function. This is more likely to happen if you suffer from impaired kidney function.

•    Digitalis preparations (i.e. digoxin), which are used to treat heart weakness

The effect of these will become stronger when the blood calcium level rises and adverse effects such as irregular heartbeat may occur. Therefore your doctor will need to re-adjust your digoxin dose.

•    Vitamin D; this may lead to an increased blood calcium level.

Your doctor will know about the adverse effects that may be brought about by the combination of Sterofundin ISO and the aforementioned drugs. He will take care that the infusion you receive is dosed correctly. Some drugs do not mix with Sterofundin ISO. Doctors only add drugs to Sterofundin ISO if they are sure they are safe to mix.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Your doctor will decide whether this solution is suitable for you when you are pregnant.

This medicine will be used with caution in so-called toxaemia of pregnancy, a special complication that may occur during pregnancy.

Driving and using machines

Sterofundin ISO has no influence on the ability to drive or use machines. Sterofundin ISO contains sodium

If you are on a controlled sodium diet, please note that this medicinal product contains 145 mmol sodium per 1000 ml.

3. How to use Sterofundin ISO

Route of administration

This medicine is given into a vein by a drip.

Dosage

Your doctor will determine the amount of solution you need.

In adults, elderly patients and adolescents this may be 500 millilitres - 3 litres per day. The daily dose for babies and children may be between 20

-    100 millilitres per kg body weight per day.

Rate of administration

Your doctor will also determine how fast the solution will be infused, depending on your body weight and your condition.

Duration of treatment

Your doctor will determine how long you will receive this solution.

While you receive the infusion, your fluid and salt levels and your blood acid-base balance will be controlled.

If you receive more Sterofundin ISO than you should

As your dose is controlled by a doctor or nurse, it is unlikely that you will be given too much of this solution.

However, if accidentally you did receive too much or the solution has run in too fast, you might get symptoms such as

-    increase of skin tension

-    congestion in veins and swelling

-    accumulation of fluid in the lungs

-    shortness of breath

-    abnormalities in the water and salt composition of body fluids. Excessively high blood levels of one the individual components of Stero-fundin ISO may be associated with specific symptoms which your doctor will pay attention to.

In cases of overdose the infusion is stopped instantly and appropriate corrective therapy is started.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Some side effects may be caused by the administration technique. These may include feverish reactions, infection at the site of injection, local pain or reaction, vein irritation, blood clots in veins or inflammation of veins extending from the site of injection.

Allergic reactions to infused magnesium salts, presenting as rash, have been reported occasionally. The frequency of these reactions cannot be estimated from the available data.

Bowel paralysis has rarely been reported after infusion of magnesium sulphate. This may affect up to 1 in 1,000 people.

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. You can also report side effects directly via the Yellow Card Scheme at:

www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Sterofundin ISO

Keep this medicine out of the sight and reach of children.

Glass bottles and Polyethylene plastic bottles: Do not refrigerate or freeze. Plastic bags: Do not store above 25°C. Do not refrigerate or freeze.

The medicinal product will not be used if there are particles in the solution or the solution is cloudy or discoloured. The product will not be used if the container is leaking or otherwise damaged. This product is for single-use only, partially used containers will not be reconnected.

Do not use this medicine after the expiry date which is stated on the label or the carton after EXP.

6. Contents of the pack and other information

What Sterofundin ISO contains

• The active substances in Sterofundin ISO solution for infusion are:

Per 1000 ml this medicine contains:

Water for injections, Sodium Hydroxide (for pH adjustment)

What Sterofundin ISO looks like and contents of the pack

Sterofundin ISO is a solution for infusion (for administration by a vein drip). It is a clear colourless solution.

It comes in

•    Plastic bottles containing 250 ml, 500 ml, 1000ml, available in packs of 10 x 250 ml, 10 x 500 ml, 10 x 1000ml

•    Plastic bags containing 250 ml, 500 ml, 1000ml, available in packs of 20 x 250 ml, 20 x 500 ml, 10 x 1000ml

•    Glass bottles containing 250 ml, 500 ml, 1000ml, available in packs of 10 x 250 ml, 10 x 500 ml, 6 x 1000ml

Marketing Authorisation Holder and Manufacturer

B. Braun Melsungen AG

Carl-Braun-StraBe 1    Postal address:

34212 Melsungen    34209 Melsungen

Tel.: +49-5661-71-0 Fax: +49-5661-71-4567

BBRAUN

Schwarz 210x980 mm 85/12607589/1014 Latus: 1206 GroRbritannien Font size 9

85/12607589/1014

General disorders and administration site conditions 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 to 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

Overuse or too fast administration may lead to water and sodium overload with a risk of oedema, particularly when there is a defective renal sodium excretion. In this case extra renal dialysis may be necessary.

Excessive administration of potassium may lead to the development of hyperkalaemia, especially in patients with renal impairment. Symptoms include paresthesia of the extremities, muscle weakness, paralysis, cardiac arrhythmias, heart block, cardiac arrest, and mental confusion. Treatment of hyperkalaemia involves the administration of calcium, insulin (with glucose) sodium bicarbonate, exchange resins or dialysis.

Excessive parenteral administration of magnesium salts leads to the development of hypermagnesaemia, important signs of which are loss of deep tendon reflexes and respiratory depression, both due to neuromuscular blockade. Other symptoms of hypermagnesaemia may include nausea, vomiting, flushing of the skin, thirst, hypotension due to peripheral vasodilatation, drowsiness, confusion, muscle weakness, bradycardia, coma, and cardiac arrest.

Excessive administration of chloride salts may cause a loss of bicarbonate with an acidifying effect.

Excessive administration of compounds, such as acetate and malate, which are metabolised to form the bicarbonate anion may lead to metabolic alkalosis, especially in patients with impaired renal function. Symptoms may include mood changes, tiredness, shortness of breath, muscle weakness, and irregular heartbeat. Patients with additional hypocalcaemia may develop muscle hypertonicity, twitching, and tetany. Treatment of metabolic alkalosis associated with an increase in bicarbonate consists mainly of appropriate correction of fluid and electrolyte balance. Excessive administration of calcium salts may lead to hypercalcaemia. Symptoms of hypercalcaemia 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 hypercalcaemia as well as to a chalky taste, hot flushes, and peripheral vasodilation. Mild asymptomatic hypercalcaemia will usually resolve on stopping administration of calcium and other contributory drugs such as vitamin D. If hypercalcaemia is severe, urgent treatment (such as loop diuretics, haemodialysis, calcitonin, bisphosphonates, trisodium edetate) is required.

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

Pharmacotherapeutic group: Solutions affecting the electrolyte balance,

electrolytes

ATC code: B05BB01

This medicinal product is an isotonic electrolyte solution with electrolyte concentrations adapted to plasma electrolyte concentrations. It is used to correct extracellular fluid losses (i.e. losses of water and electrolytes in proportional amounts). The supply of the solution is aimed to restore as well as maintain normal osmotic conditions in the extracellular and intracellular space.

The anion pattern represents a balanced combination of chloride, acetate, and malate which counteracts metabolic acidosis.

5.2    Pharmacokinetic properties Absorption

Since the ingredients of Sterofundin ISO are infused intravenously their bioavailability is 100 %.

Distribution and Elimination

Sodium and chloride mainly distribute in the extracellular space, whereas the preferential distribution of potassium, magnesium and calcium is intracellular. The kidneys are the main route of excretion for sodium, potassium, magnesium, and chloride but small amounts are lost via the skin and intestinal tract. Calcium is excreted in approximately equal amounts in urine and endogenous intestinal secretion.

During the infusion of acetate and malate, their plasma levels rise and appear to reach a steady state. Following termination of the infusion, the acetate and malate concentrations rapidly diminish. Acetate and malate excretion in urine rises during the infusion. However, their metabolism by body tissues is so rapid that only a small fraction appears in urine.

5.3 Preclinical safety data

No preclinical studies have been conducted with Sterofundin ISO. There are no data of relevance to the prescriber additional to those already included elsewhere in the SPC.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients Water for injections,

sodium hydroxide (for pH adjustment)

6.2    Incompatibilities

Admixture of the medicinal product with medications containing carbonates, phosphates, sulphates or tartrates may lead to precipitation.

6.3    Shelf life

Shelf life of the medicinal product as packaged for sale: in glass bottles and polyethylene plastic bottles: 3 years in plastic bags: 2 years Shelf life after first opening of the container:

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8 °C unless reconstitution / dilution (etc) has taken place in controlled and validated aseptic conditions.

6.4    Special precautions for storage

Glass bottles and Polyethylene plastic bottles: Do not refrigerate or freeze. Plastic bags: Do not store above 25°C. Do not refrigerate or freeze.

6.5    Nature and contents of container

The solution for infusion is packed in type II glass bottles with butyl rubber stoppers, in polyethylene plastic bottles or in plastic bags with outer protective bags. The primary bag consists of a three layer plastic laminate with a polypropylene inner layer and a polyamide outer layer.

Glass bottle: 1 x / 10 x 250 ml 1 x / 10 x 500 ml 1 x / 6 x 1,000 ml

Polyethylene plastic bottle: 1 x / 10 x 250 ml

1 x / 10 x 500 ml

1 x / 10 x 1,000 ml

Plastic bag: 1 x / 20 x 250 ml

1 x / 20 x 500 ml

1 x / 10 x 1,000 ml

Not all package sizes may be marketed.

6.6    Special precautions for disposal and other handling

Only for intravenous use.

Single use only.

Do not reconnect partially used containers.

Unused solution should be discarded.

Do not use if container or closure is damaged. Only clear solutions practically free from particles should be used.

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.

If using plastic bags, surrounding bag must only be removed immediately before use.

For further information please refer to section 4.2.

7    MARKETING AUTHORISATION HOLDER

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

Phone: +49 5661 710 Fax: +49 5661 71 4567

8    MARKETING AUTHORISATION NUMBER(S)

PL 03551/0100

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 15^th July 2005 Date of latest renewal: 18^th January 2010

10    DATE OF REVISION OF THE TEXT

October 2014

BBRAUN

B. Braun Melsungen AG

34209 Melsungen, Germany

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The following information is intended for healthcare professionals only: Symptoms associated with excessive overdose of the individual components of the solution

•    Symptoms of hyperkalaemia

paraesthesia in extremities, muscle weakness, paralysis, cardiac arrythmia, asystole, mental confusion.

•    Symptoms of hypermagnesaemia:

loss of tendon reflexes and dyspnoea, nausea, vomiting, flushing of the skin, thirst, drop of blood pressure, drowsiness, confusion, muscle weakness, bradycardia, coma, cardiac arrest.

•    Symptoms of hyperchloraemia: loss of bicarbonate, acidosis.

•    Symptoms of hypercalcaemia:

anorexia, nausea, vomiting, constipation, abdominal pain, muscle weakness, mental disturbances, polydipsia, polyuria, nephrocalcinosis, and, in severe cases, cardiac arrhythmia and coma. Too rapid injection of calcium salts my lead to chalky taste and hot flushes.

• Symptoms of excessive overdose of acetate and malate:

Metabolic alkalosis, which may lead to mood changes, tiredness, dyspnoea, muscle weakness, and cardiac arrythmia, in the presence of low calcium levels also twitching and cramps.

Handling

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.

If using plastic bags, surrounding bag must only be removed immediately before use.

If administration is by rapid infusion under pressure, all air must be withdrawn from the plastic container and infusion set prior to infusion, as otherwise there is a risk of producing air embolism during infusion.

Fluid balance, plasma electrolyte concentrations and pH must be monitored during administration. Sterofundin ISO may be administered as long as there is an indication for fluid replacement.

B. Braun Melsungen AG

34209 Melsungen Germany

Schwarz 210x980 mm 85/12607589/1014 Latus: 1206 GroBbritannien Font size 9

-