This information is intended for use by health professionals

1. Name of the medicinal product

Potassium Chloride 0.15 % w/v and Glucose 10 % w/v Solution for Infusion BP

2. Qualitative and quantitative composition

Potassium Chloride: 1.5 g/l

Glucose (as monohydrate): 100.00 g/l

Each ml contains 100 mg glucose (as monohydrate) and 1.5 mg potassium chloride.

Approximately 1680 kJ/l (or 400 kcal/l)

mmol/l:

K+:

20

Cl-:20

mEq/l:

K+:

20

Cl-:20

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Solution for infusion.

Clear solution, free from visible particles.

Osmolarity 595 mOsm/l (approx)

pH: 3.5 to 6.5

4. Clinical particulars
4.1 Therapeutic indications

Potassium Chloride 0.15 % w/v and Glucose 10 % w/v Solution for Infusion is used in adults, the elderly, adolescents, children and infants (aged 28 days to 23 months) for:

• Prevention and treatment of potassium depletion and/or hypokalemia in cases where supply of water, potassium chloride and carbohydrates is required due to restriction of the intake of fluids and electrolytes by normal routes.

• Supply of carbohydrate and potassium during parenteral nutrition.

• Prevention and treatment of hypoglycaemia.

• Rehydration in case of water loss and dehydration states in patients with high carbohydrate need.

4.2 Posology and method of administration

The dosage and rate of administration of Potassium Chloride 0.15 % w/v and Glucose 10 % w/v Solution for Infusion depends on the age, weight, clinical and biological (acid-base balance) conditions of the patient, concomitant therapy and in particular the patient's hydration state.

The dose of potassium may be expressed in terms of mEq or mmol of potassium, mass of potassium or mass of potassium salt:

1g KCl = 525 mg of K+ or 13.4 mEq or 13.4 mmol of K+ and Cl- .

1 mmol K+ = 39.1 mg K+

General Posology

Adults and the elderly:

The recommended doses in Table 1 serve as a guideline for an average adult with a body weight of approximately 70 kg.

The infusion rate should not exceed the patient's glucose oxidation capacities in order to avoid hyperglycaemia. Therefore the maximum acute administration rate for adults and the elderly is 5 mg/kg/min (3 ml/kg/h).

Table 1

Guidance on the dose for administration to an adult (70 kg) (*)

Indication

Initial daily dose

Rate of administration

Recommended duration of treatment

Supply of carbohydrate alone, or as required, during parenteral nutrition.

From 500 ml to 3000 ml/24h

(from 7 to 40 ml/kg/24h)

The recommended maximum administration rate should not exceed the patient's rate of glucose oxidation, as this may cause hyperglycaemia: 5 mg/kg/min (3 ml/kg/h)

No limit on duration – dependent on the clinical condition of the patient.

Prevention and treatment of hypoglycaemia

Rehydration in case of water loss and dehydration states in patients with high carbohydrate need

Prevention of potassium depletion**

Typical dose - Up to 50 mmoles/24h**.

Similar doses may be adequate in mild potassium deficiency.

Patients with renal impairment should receive lower doses.

The maximal recommended dose of potassium is 2 to 3 mmol/kg/24h.

Treatment of potassium depletion**

The recommended dosage is 20 mmoles of potassium over 2 to 3 hours (7-10 mmol/h) under ECG control.**

Patients with renal impairment should receive lower doses.

The maximum recommended administration rate should not exceed 15-20 mmol/h.

*The largest volumes within recommended dose should be administered in 24 hours to avoid haemodilution.

** The dosage given under “General Posology” should not be exceeded.

Patients with renal impairment

Patients with renal impairment should receive lower doses.

Infants, toddlers, children and adolescents:

The recommended doses in Table 2 serve as a guideline for infants, toddlers, children and adolescents, as a function of body weight and age.

The infusion rate should not exceed the patient's glucose oxidation capacities in order to avoid hyperglycaemia. Therefore the maximum acute administration rate for infants, toddlers, children and adolescents is 10-18 mg/kg/min (6-11 ml/kg/h) depending on the age and the total body mass.

Table 2

Guidance on the dose for administration to infants, toddlers, children and adolescents (*)

Indication

Initial daily dose

Rate of administration

Recommended duration of treatment

Supply of carbohydrate alone, or as required, during parenteral nutrition.

0-10 kg body weight:

100 ml/kg/24h

10-20 kg body weight:

1000 ml + 50 ml/kg over 10 kg/24h

>20 kg body weight:

1500 ml + 20 ml/kg over 20 kg/24h

The maximum administration rate should not exceed the patient's rate of glucose oxidation, as this may cause hyperglycaemia:

Pre-term and term infant:

6-11 ml/kg/h

(10-18 mg/kg/min).

1-3 years:

5-8 ml/kg/h

(9-14 mg/kg/min).

4-6 years:

5-7 ml/kg/h

(8-11 mg/kg/min).

7-10 years:

4-7 ml/kg/h

(7-11 mg/kg/min).

>11 years:

4 ml/kg/h

(7-8.5 mg/kg/min).

No limit on duration – dependent on the clinical condition of the patient.

Prevention and treatment of hypoglycaemia

Rehydration in case of water loss and dehydration states in patients with high carbohydrate need

Prevention of potassium depletion**

Typical dose - Up to 50 mmoles/24h**.

Similar doses may be adequate in mild potassium deficiency.

Patients with renal impairment should receive lower doses.

The maximal recommended dose of potassium is 2 to 3 mmol/kg/24h.

Treatment of potassium depletion**

The recommended dosage is 20 mmoles of potassium over 2 to 3 hours (7-10 mmol/h) under ECG control.**

Patients with renal impairment should receive lower doses.

The maximum recommended administration rate should not exceed 15-20 mmol/h.

*The largest volumes within recommended dose should be administered in 24 hours to avoid haemodilution.

** The dosage given under “General Posology” should not be exceeded.

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.

Depending on the patient's clinical condition, a lower flow rate than recommended can be used in order to decrease the risk of undesirable osmotic diuresis.

When the solution is used for dilution or delivery of compatible therapeutic additives for administration intravenously, the directions for use of the additive therapeutic substances will dictate the appropriate volumes for each therapy.

Administration

Route of administration:

The solution is for administration by intravenous infusion using sterile and non-pyrogenic equipment. The solution contains potassium and should be administered via a large peripheral or central vein to diminish the risk of causing sclerosis. If infused through central vein, be sure the catheter is not in the atrium or ventricle to avoid localized hyperkalaemia.

The solution for infusion should be visually inspected before use.

Use only if the solution is clear, without visible particles and if the container is undamaged. Administer immediately following the insertion of infusion set.

When making additions, the final osmolarity of the mixture must be measured before administration. The mixture obtained must be administered through a central or peripheral venous line depending on its final osmolarity.

For information on incompatibilities and preparation of the product and additives, please see sections 6.2 and 6.6.

Rate of administration:

Solutions containing potassium should be administered slowly. As administered intravenously, potassium should not be given faster than 15 to 20 mmoles/h to avoid dangerous hyperkalaemia.

Monitoring:

Fluid balance, serum glucose, serum sodium and other electrolytes should be monitored before and during administration, especially in patients with increased non-osmotic vasopressin release (syndrome of inappropriate antidiuretic hormone secretion, SIADH) and in patients co-medicated with vasopressin agonist drugs due to the risk of hyponatraemia. Monitoring of serum sodium is particularly important for physiologically hypotonic fluids.

Potassium Chloride 0.15 % w/v and Glucose 10% w/v Solution may become extremely hypotonic after administration due to glucose metabolisation in the body (see sections 4.4, 4.5 and 4.8).

Adequate urine flow must be ensured.

Treatment should be carried out under regular and careful surveillance. Clinical and biological parameters, in particular fluid balance and the concentrations of glucose and electrolytes (especially potassium) in plasma must be monitored during administration. Higher dosage or high speed infusion must be performed under ECG control.

4.3 Contraindications

The solution is contraindicated in patients presenting with:

• Hyperchloremia and hyperkalemia that are not related to the concentration effect associated to a volume depletion,

• Uncompensated diabetes and diabetes insipidus,

• Hyperosmolar coma,

• Haemodilution and extracellular hyperhydration or hypervolaemia,

• Hyperglycaemia and hyperlactataemia,

• Severe renal insufficiency (with oliguria / anuria),

• Uncompensated cardiac failure,

• General oedema (including pulmonary and brain oedema) and ascitic cirrhosis,

• Other known glucose intolerances (such as metabolic stress situations),

• Addision's disease.

The contraindications related to any medicinal product that is added to the glucose solution should be considered.

4.4 Special warnings and precautions for use

Potassium Chloride 0.15 % w/v and Glucose 10 % w/v Solution for Infusion is a hypertonic solution with an approximate osmolarity of 595 mOsm/l.

High volume infusion must be used under specific monitoring in patients with cardiac, pulmonary or renal failure.

Administration should be carried out under regular and careful surveillance. Regular monitoring of clinical status, blood glucose level, plasma electrolyte concentrations, plasma creatinine levels, BUN level, acid-base balance and ECG is essential in patients receiving potassium therapy, particularly those with cardiac or renal impairment. Adequate urine flow must be ensured and fluid balance should be monitored.

Potassium salts should be administered with considerable care to patients with cardiac disease (myocardial infarction, cardiac arrhythmias, …) or conditions predisposing to hyperkalemia such as renal or adrenocortical insufficiency, acute dehydration, or extensive tissue destruction as occurs with severe burns.

Glucose intravenous infusions are usually isotonic solutions. In the body, however, glucose containing fluids can become extremely physiologically hypotonic due to rapid glucose metabolization (see section 4.2).

Depending on the tonicity of the solution, the volume and rate of infusion and depending on a patient's underlying clinical condition and capability to metabolize glucose, intravenous administration of glucose can cause electrolyte disturbances most importantly hypo- or hyperosmotic hyponatraemia.

Infusion of solutions containing glucose could be contraindicated in the first 24 hours following head trauma and blood glucose concentration should be closely monitored during intracranial hypertension episodes.

Administration of glucose containing solutions may lead to hyperglycemia. In this case, it is recommended not to use this solution after acute ischemic strokes as hyperglycemia has been implicated in increasing cerebral ischemic brain damage and impairing recovery.

If hyperglycemia occurs, rate of infusion should be adjusted or insulin administered.

In diabetic patients, the amount of infused glucose has to be taken into account and insulin requirements may be modified.

During long term treatment, a convenient nutritive treatment supply must be given to the patient.

As glucose tolerance may be impaired in patients with diabetes, renal failure or acute critical illness, clinical and biological parameters, in particular plasma-electrolytes including magnesaemia or phosphatemia and glycaemia should be particularly closely monitored. If hyperglycaemia occurs, the rate of infusion should be adjusted or insulin should be administered.

In case of prolonged administration or high glucose dose, care should be taken to avoid hypokalaemia by monitoring plasma potassium levels and administering a potassium supplement as appropriate.

The infusion of solutions containing glucose is contraindicated in the first 24 hours following head trauma and blood glucose concentration should be closely monitored during intracranial hypertension episodes.

Administration of glucose containing solutions may lead to hyperglycaemia. Therefore, it is recommended not to use glucose solution after acute ischaemic stroke as hyperglycaemia has been implicated in increasing cerebral ischaemic brain damage and impairing recovery.

Administration of solutions containing glucose may lead to decreased concentrations of potassium in the plasma. Therefore, potassium solutions containing glucose should not be used for the initial correction of hypokalaemia.

Glucose solution should not be administered through the same equipment as whole blood, as haemolysis and clumping can occur.

Hyponatraemia

Patients with non-osmotic vasopressin release (e.g. in acute illness, pain, post-operative stress, infections, burns, and CNS diseases), patients with heart-, liver- and kidney diseases and patients exposed to vasopressin agonists (see section 4.5) are at particular risk of acute hyponatraemia upon infusion of hypotonic fluids.

Acute hyponatraemia can lead to acute hyponatraemic encephalopathy (brain oedema) characterized by headache, nausea, seizures, lethargy and vomiting. Patients with brain oedema are at particular risk of severe, irreversible and life-threatening brain injury.

Children, women in the fertile age and patients with reduced cerebral compliance (e.g. meningitis, intracranial bleeding, and cerebral contusion) are at particular risk of the severe and life-threatening brain swelling caused by acute hyponatraemia

Do not use plastic containers connected in series. Such use could result in air embolism due to residual air being drawn from the primary container before the administration of the fluid from the secondary container is completed.

Special clinical monitoring is required at the beginning of any intravenous infusion.

4.5 Interaction with other medicinal products and other forms of interaction

Interaction related to the presence of glucose:

Concomitant administration of catecholamines and steroids decreases the glucose up-take.

Glucose should not be administered through the same infusion equipment as whole blood as haemolysis and clumping can occur.

Interaction related to the presence of potassium:

Solutions containing potassium should be used with caution, in patients receiving drugs that increase serum-potassium concentrations (e.g. potassium-sparing diuretics, ACE inhibitors, Angiotensin II receptors antagonists, ciclosporin, tacrolimus and drugs that contain potassium).

Drugs leading to an increased vasopressin effect

The below listed drugs increase the vasopressin effect, leading to reduced renal electrolyte free water excretion and increase the risk of hospital acquired hyponatraemia following inappropriately balanced treatment with i.v. fluids (see sections 4.2, 4.4 and 4.8).

• Drugs stimulating vasopressin release, e.g.: Chlorpropamide, clofibrate, carbamazepine, vincristine, selective serotonin reuptake inhibitors, 3.4-methylenedioxy-N-methamphetamine, ifosfamide, antipsychotics, narcotics

• Drugs potentiating vasopressin action, e.g.: Chlorpropamide, NSAIDs, cyclophosphamide

• Vasopressin analogues, e.g.: Desmopressin, oxytocin, terlipressin

Other medicinal products increasing the risk of hyponatraemia also include diuretics in general and antiepileptics such as oxcarbazepine.

4.6 Fertility, pregnancy and lactation

Hyperkalemic and hypokalemic serum levels lead to impaired cardiac function of the maternal and foetal hearts. Therefore, the maternal electrolyte levels are to be controlled regularly.

If used according to its intended purpose, Potassium Chloride 0.15 % w/v and Glucose 10 % w/v Solution for Infusion can be used safely during pregnancy and lactation as long as the maternal electrolyte and fluid balance are controlled and are within the physiologic ranges.

When a medicinal product is added, the nature of the drug and its use during pregnancy and lactation have to be considered separately.

Safety has not been established regarding fertility.

Potassium Chloride 0.15 % w/v and Glucose 10% w/v Solution should be administrated with special caution for pregnant women during labour particularly if administered in combination with oxytocin due to the risk of hyponatraemia (see section 4.4, 4.5 and 4.8).

4.7 Effects on ability to drive and use machines

Not relevant.

4.8 Undesirable effects

The following adverse reactions have been reported during administration of potassium chloride and glucose solutions for infusion. The adverse reactions are presented according to the Medical Dictionary for Regulatory Activities (MedDRA) system organ classification and are from post-marketing experience. Frequencies cannot be estimated from the available data.

Adverse reactions associated with the products:

System Organ Class

Adverse reactions (Preferred terms)

Immune system disorders

Allergic reaction

Metabolism and nutrition disorders

Hypervolaemia

Electrolyte imbalance (hypokalaemia, hypomagnesaemia and hypophosphataemia)

Hyperglycaemia

hospital acquired hyponatraemia***

Hemodilution

Nervous system disorders

hyponatraemic encephalopathy***

Cardiac disorders

Hidrosis (Sweating)

Investigations

Glycosuria

(***) Hospital acquired hyponatraemia may cause irreversible brain injury and death due to development of acute hyponatraemic encephalopathy (see sections 4.2 and 4.4).

Adverse reactions associated with the technique of administration:

System Organ Class

Adverse reactions (Preferred Terms)

Metabolism and nutrition disorders

Hypervolaemia

Vascular disorders

Vein injury (vein irritation)

Thrombophlebitis superficial (venous thrombosis)

General disorders and administration site conditions

Pyrexia (shivering, fever and febrile response)

Application site infection

Application site pain

Application site reaction

Injection site phlebitis

Injection site extravasation

In case of undesirable effect(s), the infusion must be discontinued.

4.9 Overdose

Prolonged administration of Potassium Chloride 0.15 % w/v and Glucose 10 % w/v Solution for Infusion may cause hyperglycaemia, hyperosmolarity, glycosuria, osmotic diuresis and dehydration. Rapid infusion may create a fluid inflation with haemodilution and hypervolaemia and, when the oxidation capacity of glucose is exceeded, it may cause hyperglycaemia. Decrease in serum potassium and inorganic phosphate may also occur.

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 and supportive measures should be provided as necessary.

Prolonged administration or rapid infusion of large volumes of iso-osmotic glucose solutions may cause edema or water intoxication.

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.

One of the important indicators of potassium toxicity are ECG changes including tall, peaked T-waves, depression of S-T segment, disapearance of the P-wave, prolongation of the Q-T interval, and widening and slurring of the QRS complex.

Treatment of hyperkalemia involves the administration of calcium, insulin or sodium bicarbonate, and exchange resins or dialysis.

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

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

Pharmacotherapeutic group (ATC code) : “electrolytes with carbohydrates” (B05BB02)

Potassium Chloride 0.15 % w/v and Glucose 10 % w/v Solution for Infusion is a hypertonic solution of electrolytes and glucose, with an approximate osmolarity of 595 mOsm/l.

The pharmacodynamic properties of this solution are those of its components (potassium, chloride and glucose).

Potassium is predominantly an intracellular cation, primarily found in muscle; only about 2% is present in the extracellular fluid. It is essential for numerous metabolic and physiological processes including nerve conduction, muscle contraction, and acid-base regulation.

Chloride is mainly an extracellular anion. Intracellular chloride is in high concentration in red blood cells and gastric mucosa.

Glucose is the principal source of energy in cellular metabolism. Glucose is given as a source of carbohydrate, alone or, as required, in parenteral nutrition. The Glucose 10% w/v solution provides a caloric intake of 400 kcal/l. Furthermore glucose solution for infusion allows hydric supplementation without ionic supplementation.

5.2 Pharmacokinetic properties

The pharmacokinetic properties of this solution are those of its components (potassium, chloride and glucose).

Intravenous administration of the solution provides an immediate supply of electrolytes and glucose to blood.

Factors influencing potassium transfer between intracellular and extracellular fluid such as acid-base disturbances can distort the relationship between plasma concentrations and total body stores. Potassium is excreted mainly by the kidneys; it is secreted in the distal tubules in exchange of sodium or hydrogen ions. The capacity of the kidneys to conserve potassium is poor and some urinary excretion of potassium continues even when there is severe depletion. Some potassium is excreted in the feces and small amounts may also be excreted in sweat.

The two main metabolic pathways of glucose are gluconeogenesis (energy storage) and glycogenolysis (energy release). Glucose metabolism is regulated by insulin. Glucose is metabolised via pyruvic or lactic acid to carbon dioxide and water with release of energy.

5.3 Preclinical safety data

Preclinical safety data of this solution for infusion in animals are not relevant since its constituents are physiological components of animal and human plasma.

Toxic effects are not to be expected if serum electrolytes are kept within physiological range.

The safety of potential additives should be considered separately.

6. Pharmaceutical particulars
6.1 List of excipients

Hydrochloric acid, concentrated

Water for Injections

6.2 Incompatibilities

As with all parenteral solutions incompatibility of the additive medications with the solution in Viaflo container must be assessed before addition.

In the absence of compatibility studies, this solution must not be mixed with other medicinal products.

It is the responsibility of the physician to judge the incompatibility of an additive medication with the Potassium Chloride 0.15 % w/v and Glucose 10 % w/v Solution for Infusion by checking for eventual color 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/or stable in water at the pH of the Potassium Chloride 0.15 % w/v and Glucose 10 % w/v Solution for Infusion ( pH: 3.5 to 6.5).

When a compatible medication is added to Potassium Chloride 0.15 % w/v and Glucose 10 % w/v Solution for Infusion, the solution must be administered immediately.

As a guidance, the following medications are incompatible with the Potassium Chloride 0.15 % w/v and Glucose 10 % w/v Solution for Infusion (non-exhaustive listing):

- Amphotericin B

- Dobutamine

- Ampicillin sodium

- Erythromycin lactobionate

- Mitomycin

Because of the presence of glucose, Potassium Chloride 0.15 % w/v and Glucose 10 % w/v Solution for Infusion should not be administered through the same infusion equipment as whole blood as haemolysis and clumping can occur.

Those additives known to be incompatible should not be used.

6.3 Shelf life

Unopened:

500 ml bag: 24 months

In-use shelf life (Additives):

Chemical and physical stability of any additive medication at the pH of the Potassium Chloride 0.15 % w/v and Glucose 10 % w/v Solution for Infusion in the Viaflo container should be established prior to use.

From a microbiological point of view, the diluted product must be used immediately. unless dilution has taken place under controlled and validated aseptic conditions. If not used immediately, in-use storage times and conditions are the responsibility of the user.

6.4 Special precautions for storage

No special precautions for storage.

For storage conditions after dilution of the medicinal product, see section 6.3.

6.5 Nature and contents of container

The bags known as Viaflo are composed of polyolefin/polyamide co-extruded plastic (PL 2442).

The bags are overwrapped with a protective plastic pouch composed of polyamide/polypropylene.

The bag size is 500 ml.

Outer carton contents:

20 bags or 24 bags of 500 ml.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Use only if the solution is clear, without visible particles and if the container is undamaged. Administer immediately following the insertion of infusion set.

Do not remove unit from overwrap until ready for use. The inner bag maintains the sterility of the medicinal product.

Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before the administration of the fluid from the secondary container is completed.

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.

Additives may be introduced before infusion or during infusion through the resealable medication port.

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.

Adding medication or using an incorrect administration technique might cause the appearance of fever reactions due to the possible introduction of pyrogens. In case of adverse reaction, infusion must be stopped immediately.

Discard after single use.

Discard any unused portion.

Do not reconnect partially used bags.

1. Opening

a. Remove the Viaflo container from the overpouch just before use.

b. Check for minute leaks by squeezing inner bag firmly. If leaks are found, discard solution, as sterility may be impaired.

c. Check the solution for limpidity and absence of foreign matters. If solution is not clear or contains foreign matters, discard the solution.

2. Preparation for administration

Use sterile material for preparation and administration.

a. Suspend container from eyelet support.

b. Remove plastic protector from outlet port at bottom of container:

- grip the small wing on the neck of the port with one hand,

- grip the large wing on the cap with the other hand and twist,

- the cap will pop off.

c. Use an aseptic method to set up the infusion

d. Attach administration set. Refer to complete directions accompanying set for connection, priming of the set and administration of the solution.

3. Techniques for injection of additive medications

Warning: Additives may be incompatible.

To add medication before administration

a. Disinfect medication site.

b. Using syringe with 19 to 22 gauge needle, puncture resealable medication port and inject.

c. 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

a. Close clamp on the set.

b. Disinfect medication site.

c. Using syringe with 19 to 22-gauge needle, puncture resealable medication port and inject.

d. Remove container from IV pole and/or turn to an upright position.

e. Evacuate both ports by tapping gently while the container is in an upright position.

f. Mix solution and medication thoroughly.

g. Return container to in use position, re-open the clamp and continue administration.

7. Marketing authorisation holder

Baxter Healthcare Ltd,

Caxton Way,

Thetford Norfolk IP24 3SE

United Kingdom

8. Marketing authorisation number(s)

PL 00116/0656

9. Date of first authorisation/renewal of the authorisation

02/07/2013

10. Date of revision of the text

March 2019