SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Sorbisterit, powder for oral/rectal suspension

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

1 g powder contains:

759 - 949 mg calcium polystyrene sulphonate, corresponding to 1.8 mmol calcium. Excipients with known effect: 50.74 mg - 240.74 mg sucrose 20 g powder contain:

15.18 - 18.98 g calcium polystyrene sulphonate, corresponding to 36 mmol calcium Excipients with known effect: 1.01 - 4.81 g sucrose

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Powder for oral/rectal suspension Cream to light brown fine powder

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Treatment of hyperkalaemia, in patients with acute and chronic renal insufficiency, including patients undergoing dialysis treatment.

4.2    Posology and method of administration

To be administered orally or as a retention enema.

The dosing recommendations are to be looked upon as guidelines. The exact need should be decided depending on regular clinical and biochemical controls.

The length of treatment needed with Sorbisterit cation exchange resin depends on the results of the daily measurement of the serum potassium. If serum potassium falls to 5 mmol/l, therapy should be suspended. When the serum potassium rises above 5 mmol/l, therapy should be recommenced.

Oral route:

In adults, including the elderly:

20 grams powder 1 to 3 times daily (1 measuring spoon), stirred into about 150 ml liquid.

Paediatric population:

0.5 to 1.0 g/kg body weight per day stirred into about 150 ml liquid. This preparation must be used in at least three divided doses over a period of 24 hours.

Calcium polystyrene sulphonate should not be given orally to neonates.

Sorbisterit must be taken after an interval of at least 3 hours after antacids and laxatives such as magnesium hydroxide, aluminium hydroxide or calcium carbonate. (see section 4.4).

Sorbisterit must be taken with food.

For suitable liquids for dilution of Sorbisterit before oral administration, see section 6.6.

Rectal route (Retention enema):

In adults, including the elderly:

After a cleansing enema, 40 g (2 measuring spoons) is suspended in 150 ml 5% glucose solution, administered 1 to 3 times daily. In the initial stages administration by the rectal route as well as orally may help to achieve a rapid lowering of the serum potassium level.

Duration of retention: 6 hours

Paediatric population:

When it cannot be given orally, a dose may be administered rectally 0.5 to 1.0 g/kg body weight per day suspended in 150 ml 5% glucose solution, administered in at least three divided doses over a period of 24 hours. Following the retention of the enema, the colon should be irrigated to ensure proper removal of the resin.

However, special care is required when administering rectally to children and neonates, since excessive dosage or inadequate dilution could result in impaction of the resin. The risk of gastrointestinal haemorrhage or necrosis of the colon means that special attention should be paid when being given to premature infants or neonates with a low bodyweight (see section 4.4).

4.3 Contraindications

The use of Sorbisterit is contraindicated in patients with:

-    plasma potassium levels below 5 mmol/l

-    conditions associated with hypercalcaemia (e.g. hyperthyroidism, multiple myeloma,

sarcoidosis and metastatic carcinoma)

-    hypersensitivity to the active substance or to any of the excipients listed in section 6.1

-    obstructive bowel disease

-    reduced motility of the gut

-    concomitant administration of sorbitol (see section 4.5)

-    risk of colonic necrosis

Neonates:

Sorbisterit should not be administered orally to neonates and is also contraindicated by any route in neonates with reduced gut motility (e.g. postoperatively or drug-induced).

4.4 Special warnings and precautions for use

Sorbisterit cation exchange resin is not sufficiently effective in cases of hyperkalaemia with potassium levels exceeding 6.5 mmol/l and/or changes in the ECG. In this situation, taking emergency measures (administration of sodium bicarbonate, glucose insulin drip) or dialysis must be considered.

The possibility of severe potassium depletion should be considered and adequate clinical and biochemical control is essential during treatment, especially in patients on digitalis. Administration of the resin should be stopped when the serum potassium falls below 5 mmol/l.

As a result of the intake of calcium, there is a chance of excessive elevation of the serum calcium, particularly in cases where the patient is receiving a calcium-rich diet or using other preparations that contain calcium, such as phosphate binders or vitamin D analogues. It is therefore advisable to monitor the serum calcium concentrations constantly.

The objectives of therapy with Sorbisterit cation exchange resin must be supported by other measures such as restriction of the potassium intake, monitoring of acidosis and the use of high-calorie foodstuffs.

Since Sorbisterit is like other polystyrene sulphonate resins in that it is not wholly selective for potassium, hypomagnesaemia may arise. The serum magnesium level must therefore be monitored during treatment with Sorbisterit.

Treatment with Sorbisterit must be stopped if clinically significant constipation occurs.

20 g Sorbisterit contain 4.81 g sucrose, corresponding to about 0.41 carbohydrate exchanges (CE). This should be considered in patients with diabetes mellitus.

Sorbisterit must be taken after an interval of at least 3 hours after antacids and laxatives such as magnesium hydroxide, aluminium hydroxide or calcium carbonate since concomitant administration may cause metabolic alkalosis (see section 4.5). Sorbitol must not be used as a laxative with Sorbisterit, neither orally nor rectally, because of the risk of colonic necrosis (see section 4.3).

Oral administration must be done with care to avoid aspiration. Sorbisterit must be administered to the patient in a sitting position if possible.

Patients with rare hereditary disorders such as fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase deficiency must not take this medicine.

Paediatric population

In neonates, calcium polystyrene sulphonate should not be given by the oral route (see section 4.3). In children and neonates, particular care is needed with rectal administration as excessive dosage or inadequate dilution could result in impaction of the resin. Due to the risk of digestive haemorrhage or colonic necrosis, particular care should be observed in premature infants or low birth weight infants.

4.5 Interaction with other medicinal products and other forms of interaction

Concomitant use contraindicated

Sorbitol (oral or rectal): Concomitant use of sorbitol with calcium polystyrene sulphonate may cause colonic necrosis. Therefore, concomitant administration of sorbitol with calcium polystyrene sulphonate is contraindicated (see section 4.3).

To be used with caution

-    Cation-donating agents: may reduce the potassium binding effectiveness of calcium polystyrene sulphonate.

-    Non-absorbable cation-donating antacids and laxatives: There have been reports of systemic alkalosis following concurrent administration of cation-exchange resins and non-absorbable cation-donating antacids and laxatives such as magnesium hydroxide, aluminium hydroxide and calcium carbonate. A certain interval must be observed with respect to these medications when taking Sorbisterit (see section 4.2 and 4.4).

-    Aluminium hydroxide: Intestinal obstruction due to concretions of aluminium hydroxide has been reported when aluminium hydroxide has been combined with the resin (sodium form).

-    Digitalis-like drugs: The toxic effects of digitalis on the heart, especially various ventricular arrhythmias and A-V nodal dissociation, are likely to be exaggerated if hypokalaemia and/or hypercalcaemia are allowed to develop (see section 4.4).

-    Lithium: Possible decrease of lithium absorption.

-    Levothyroxine: Possible decrease of levothyroxine absorption.

-    Tetracyclines: Possible decrease of tetracycline absorption due to calcium ions released from the resin into the gastrointestinal tract.

-    Thiazide diuretics or loop diuretics: Concomitant use of thiazide diuretics and loop diuretics can increase the risk of hypokalaemia.

-    Anticholinergics: Increased risk of gastrointestinal side effects from Sorbisterit due to reduced motility of the stomach.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no or limited amount of data from the use of calcium polystyrene sulphonate in pregnant women. Animal studies are insufficient with respect to reproduction toxicity (see section 5.3). The potential risk for humans is unknown. Sorbisterit should not be used during pregnancy unless the clinical condition of the woman requires treatment with calcium polystyrene sulphonate.

Breastfeeding

There is insufficient information on the excretion of calcium polystyrene sulphonate/metabolites in human milk.Sorbisterit should not be used during breastfeeding unless strictly necessary.

Fertility

No data is available.

4.7 Effects on ability to drive and use machines

Sorbisterit has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

The frequencies of side effects are categorised as follows:

Very Common:(> 1/10)

Common:(> 1/100,< 1/10)

Uncommon:(> 1/1000,< 1/100)

Rare:(> 1/10000,< 1/1000)

Very rare :(< 1/10000)

Not known (cannot be estimated from the available data)

Metabolism and nutrition disorders:

Common:    hypercalcaemia, hypokalaemia, hypomagnesaemia

Respiratory, thoracic and mediastinal disorders:

Very rare:    acute bronchitis and/or bronchopneumonia associated with the inhalation of

calcium polystyrene sulphonate

Gastrointestinal disorders:

Common:    nausea, vomiting

Uncommon:    constipation, diarrhoea, intestinal obstruction, gastric ulcers, colonic necrosis

leading to perforations, anorexia

Rare:    in severe cases occlusive ileus due to intestinal clumping of the resin, faecal

impaction following rectal administration in children, gastrointestinal concretions following oral administration in new-borns.

In premature infants and neonates with low birth weights, haematochezia has been observed after administering enemas containing polystyrene sulphonate resins.

In case of oral administration, patients may have difficulties swallowing the rather large amount of dissolved powder. The extent of this problem is a function of the individual disposition, the disease, the administration and the duration of the treatment.

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:

GB

Yellow Card Scheme,

Website: www.mhra.gov.uk/yellowcard.

MT

ADR Reporting The Medicines Authority Post-Licensing Directorate 203 Level 3, Rue, D'Argens GZR-1368 Gzira

Website: www.medicinesauthority.gov.mt e-mail: postlicensing.medicinesauthority@gov.mt.

4.9 Overdose

Biochemical disturbances from overdosage may give rise to clinical signs of symptoms of hypokalaemia, including ECG abnormalities, impaired heart function, irritability, confusion, delayed thought processes, muscle weakness, hyporeflexia and eventual paralysis. Electrocardiographic changes may be consistent with hypokalaemia or hypercalcaemia; cardiac arrhythmia may occur.

Further symptoms of overdose may be constipation and occlusive ileus, and sodium and water retention. Appropriate measures should be taken to correct serum electrolytes and the resin should be removed from the alimentary tract by appropriate use of laxatives or enemas.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Drugs for treatment of hyperkalaemia and hyperphosphataemia, ATC code: V03AE01

Mechanism of action

Sorbisterit is a cation exchange resin which releases calcium in the intestines and binds potassium. This reduces the absorption and metabolic availability of potassium.

5.2 Pharmacokinetic properties

Absorption /distribution / elimination:

The calcium bound in the resin is exchanged for the potassium present in the intestines. According to various publications, 1 g of the exchange resin can bind 0.7 mmol potassium in vivo.

Polystyrene resins are insoluble and non-absorbable. They pass through the intestinal tract and are almost completely excreted with the faeces. The bound potassium is subsequently excreted from the body together with the exchange resin in the faeces. Calcium released from the resin is partly absorbed. The electrolyte is subject to physiological pathways of absorption, distribution and elimination.

The capacity of Sorbisterit for potassium exchange depends to a considerable extent on pH because other cations such as ammonium and magnesium as well as lipids and proteins also have a high affinity for the exchange resin as they pass through the intestines.

5.3    Preclinical safety data

Preclinical studies on Sorbisterit are not available.

Single dose toxicity studies with oral, intraperitoneal or subcutaneous administration of calcium polystyrene sulphonate did not reveal a risk of acute toxicity. No further preclinical studies with calcium polystyrene sulphonate are available.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Sucrose

Anhydrous citric acid

6.2    Incompatibilities

Not applicable

6.3    Shelf life

3 years

3 months after first opening.

6.4    Special precautions for    storage

Keep the container tightly closed in order to protect from moisture.

6.5    Nature and contents    of    container

Polyethylene multidose container.

Pack size: 1 container with 500 g powder

A 20 g measuring spoon consisting of polystyrene accompanies the product.

6.6 Special precautions for disposal and other handling

Suitable liquids for dissolving Sorbisterit before oral administration are water, tea and soft drinks. Sorbisterit must not be taken with fruit juices that contain a high level of potassium.

Suitable liquids for dissolving Sorbisterit before rectal administration are 5% glucose solutions.

7    MARKETING AUTHORISATION HOLDER

Fresenius Medical Care Nephrologica Deutschland GmbH 61346 Bad Homburg,Germany

8    MARKETING AUTHORISATION NUMBER(S)

PL 29386/0001

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

20/03/2012

10    DATE OF REVISION OF THE TEXT

20/03/2012