Novefazol

Novefazol A is an ion-exchange resin that is recommended for the treatment of hyperkalaemia associated with anuria or severe oliguria. It is also used to treat hyperkalaemia in patients requiring dialysis and in patients on regular haemodialysis or on prolonged peritoneal dialysis.

Novefazol is indicated for the treatment of hyperkalemia.

Limitation Of Use

Novefazol should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.

Novefazol A is for oral or rectal administration only.

The dosage recommendations detailed in this section are a guide only; the precise requirements should be decided on the basis of regular serum electrolyte determinations.

Adults, including the elderly:

Oral

The usual dose is 15g three or four times a day. Each dose should be given as a suspension in a small amount of water or, for greater palatability, in syrup (but not fruit juices which contain potassium), in the ratio of 3 to 4ml per gram of resin.

Rectal

This route should be reserved for the patient who is vomiting or who has upper gastrointestinal tract problems, including paralytic ileus or it may be used simultaneously with the oral route for more rapid initial results. The resin may be given rectally as a suspension of 30g resin in 150ml of water or 10% dextrose, as a daily retention enema. In the initial stages administration by this route as well as orally may help to achieve a more rapid lowering of the serum potassium level.

The enema should if possible be retained for at least nine hours following which the colon should be irrigated to remove the resin. If both routes are used initially it is probably unnecessary to continue rectal administration once the oral resin has reached the rectum.

Children:

Oral

In smaller children and infants correspondingly smaller doses should be employed by using as a guide a rate of 1mEq of potassium per gram of resin as the basis for calculation. An appropriate initial dose is 1g/kg body weight daily in divided doses, in acute hyperkalaemia. Dosage may be reduced to 0.5g/kg of body weight daily in divided doses for maintenance therapy.

The resin is given orally, preferably with a drink (not a fruit squash because of the high potassium content) or a little jam or honey.

Rectal

When refused by mouth it should be given rectally, using a dose at least as great as that which would have been given orally, diluted in the same ratio as described for adults.

Following retention of the enema, the colon should be irrigated to ensure adequate removal of the resin.

Neonates:

Novefazol A should not be given by the oral route. With rectal administration, the minimum effective dosage within the range 0.5g/kg to 1g/kg should be employed diluted as for adults and with adequate irrigation to ensure recovery of the resin.

General Information

Administer Novefazol at least 3 hours before or 3 hours after other oral medications. Patients with gastroparesis may require a 6 hour separation

Recommended Dosage

The intensity and duration of therapy depend upon the severity and resistance of hyperkalemia.

Oral

The average total daily adult dose of Novefazol is 15 g to 60 g, administered as a 15-g dose (four level teaspoons), one to four times daily.

Rectal

The average adult dose is 30 g to 50 g every six hours.

Preparation And Administration

Prepare suspension fresh and use within 24 hours.

Do not heat Novefazol as it could alter the exchange properties of the resin.

One level teaspoon contains approximately 3.5 g of Novefazol and 15 mEq of sodium.

Oral Suspension

Suspend each dose in a small quantity of water or syrup, approximately 3 to 4 mL of liquid per gram of resin. Administer with patient in an upright position.

Enema

After an initial cleansing enema, insert a soft, large size (French 28) rubber tube into the rectum for a distance of about 20 cm, with the tip well into the sigmoid colon, and tape in place.

Administer as a warm (body temperature) emulsion in 100 mL of aqueous vehicle and flush with 50 to 100 ml of fluid. A somewhat thicker suspension may be used, but do not form a paste.

Agitate the emulsion gently during administration. The resin should be retained for as long as possible and follow by a cleansing enema with a nonsodium containing solution. Ensure an adequate volume of cleansing solution (up to 2 liters) is utilized.

- In patients with plasma potassium levels below 5mmol/litre.

- History of hypersensitivity to polystyrene sulfonate resins.

- Obstructive bowel disease.

- Novefazol A should not be administered orally to neonates and is contraindicated in neonates with reduced gut motility (post-operatively or drug-induced).

Novefazol is contraindicated in patients with the following conditions:

• Hypersensitivity to polystyrene sulfonate resins
• Obstructive bowel disease
• Neonates with reduced gut motility

Sorbitol: Gastrointestinal stenosis, intestinal ischemia and its complications (necrosis and perforation) may occur in patients treated with polystyrene sulfonate, especially in patients using sorbitol.8 Undesirable effects).

Hypokalaemia: 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 to 5mmol/litre.

Other electrolyte disturbances: Because the resin may bind calcium and magnesium ions, deficiencies of these electrolytes may occur. Accordingly, patients should be monitored for all applicable electrolyte disturbances.

Other risks: In the event of clinically significant constipation, treatment should be discontinued until normal bowel movement has resumed. Magnesium-containing laxatives should not be used.

The patient should be positioned carefully when ingesting the resin, in order to avoid aspiration, which may lead to bronchopulmonary complications.

Children and neonates: In neonates, sodium polystyrene sulfonate should not be given by the oral route. 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.

Patients at risk from an increase in sodium load: Care should be taken when administering to patients in whom an increase in sodium load may be detrimental (i.e. congestive heart failure, hypertension, renal damage or oedema). In such instances, adequate clinical and biochemical control is essential. The calcium form of the resin may have advantages in this situation.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Intestinal Necrosis

Cases of intestinal necrosis, some fatal, and other serious gastrointestinal adverse events (bleeding, ischemic colitis, perforation) have been reported in association with Novefazol use. The majority of these cases reported the concomitant use of sorbitol. Risk factors for gastrointestinal adverse events were present in many of the cases including prematurity, history of intestinal disease or surgery, hypovolemia, and renal insufficiency and failure. Concomitant administration of sorbitol is not recommended.

• Use only in patients who have normal bowel function. Avoid use in patients who have not had a bowel movement post-surgery.
• Avoid use in patients who are at risk for developing constipation or impaction (including those with history of impaction, chronic constipation, inflammatory bowel disease, ischemic colitis, vascular intestinal atherosclerosis, previous bowel resection, or bowel obstruction). Discontinue use in patients who develop constipation.

Electrolyte Disturbances

Monitor serum potassium during therapy because severe hypokalemia may occur.

Novefazol is not totally selective for potassium, and small amounts of other cations such as magnesium and calcium can also be lost during treatment. Monitor calcium and magnesium in patients receiving Novefazol.

Fluid Overload In Patients Sensitive To High Sodium Intake

Each 15 g dose of Novefazol contains 1500 mg (60 mEq) of sodium. Monitor patients who are sensitive to sodium intake (heart failure, hypertension, edema) for signs of fluid overload. Adjustment of other sources of sodium may be required.

Risk Of Aspiration

Cases of acute bronchitis or bronchopneumonia caused by inhalation of sodium polystyrene sulfonate particles have been reported. Patients with impaired gag reflex, altered level of consciousness, or patients prone to regurgitation may be at increased risk. Administer Novefazol with the patient in an upright position.

Binding To Other Orally Administered Medications

Novefazol may bind orally administered medications, which could decrease their gastrointestinal absorption and lead to reduced efficacy. Administer other oral medications at least 3 hours before or 3 hours after Novefazol. Patients with gastroparesis may require a 6 hour separation..

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Studies have not been performed.

Use In Specific Populations

Pregnancy

Risk Summary

Novefazol is not absorbed systemically following oral or rectal administration and maternal use is not expected to result in fetal risk.

Lactation

Risk Summary

Novefazol is not absorbed systemically by the mother, so breastfeeding is not expected to result in risk to the infant.

Pediatric Use

Studies of safety and efficacy have not been conducted in pediatric patients.

In pediatric patients, as in adults, Novefazol is expected to bind potassium at the practical exchange ratio of 1mEq potassium per 1 gram of resin.

In neonates, Novefazol should not be given by the oral route. In both children and neonates, excessive dosage or inadequate dilution could result in impaction of the resin. Premature infants or low birth weight infants may have an increased risk for gastrointestinal adverse effects with Novefazol. use.

- Metabolism and nutrition disorders

9 Overdose).

Cases of hypomagnesaemia have been reported.

- Gastrointestinal disorders

Gastric irritation, anorexia, nausea, vomiting, constipation and occasionally diarrhoea may occur.5 Interactions).

- Respiratory, thoracic and mediastinal disorders

Some cases of acute bronchitis and/or broncho-pneumonia associated with inhalation of particles of sodium polystyrene sulfonate have been described.

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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

The following adverse reactions are discussed elsewhere in the labeling:

• Intestinal Necrosis
• Electrolyte Disturbances
• Aspiration

The following adverse reactions have been identified during post-approval use of Novefazol. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or establish a causal relationship to drug exposure.

Gastrointestinal: anorexia, constipation, diarrhea, fecal impaction, gastrointestinal concretions (bezoars), ischemic colitis, nausea, ulcerations, vomiting, gastric irritation, intestinal obstruction (due to concentration of aluminium hydroxide)

Metabolic: systemic alkalosis

Biochemical disturbances from overdosage may give rise to clinical signs of symptoms of hypokalaemia, including irritability, confusion, delayed thought processes, muscle weakness, hyporeflexia and eventual paralysis. Apnoea may be a serious consequence of this progression. Electrocardiographic changes may be consistent with hypokalaemia; cardiac arrhythmia may occur. Hypocalcaemic tetany may occur. 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.

Overdosage may result in electrolyte disturbances including hypokalemia, hypocalcemia, and hypomagnesemia. Appropriate measures should be taken to correct serum electrolytes (potassium, calcium, magnesium), and the resin should be removed from the alimentary tract by appropriate use of laxatives or enemas.

Novefazol A is a cation exchange resin for the treatment of hyperkalaemia.

The effective lowering of serum potassium with Novefazol may take hours to days.

Ion exchange resins with a particle size ranging from 5 - 10 micrometres (as in Novefazol A) are not absorbed from the gastro-intestinal tract and are wholly excreted in the faeces.

The in vivo efficiency of sodium-potassium exchange resins is approximately 33 percent; hence, about one third of the resin's actual sodium content is delivered to the body.

Novefazol is not absorbed systemically.