4.1. Therapeutic indications

Veltassa is indicated for the treatment of hyperkalaemia in adults and adolescents aged 12 to 17 years.

4.2. Posology and method of administration

The onset of action of Veltassa occurs 4 – 7 hours after administration. It should not replace emergency treatment for life threatening hyperkalaemia (see section 4.4).

Posology

Veltassa is administered once daily. The recommended starting dose of Veltassa varies with age. Multiple sachets may be used to achieve the desired dose.

The daily dose may be adjusted in intervals of one week or longer, based on the serum potassium level and the desired target range. Serum potassium should be monitored when clinically indicated (see section 4.4). The duration of treatment should be individualized by the treating physician based on the need of serum potassium management. If serum potassium falls below the desired range, the dose should be reduced or discontinued.

Administration of Veltassa should be separated by 3 hours from other oral medicinal products (see section 4.5).

Adults

The recommended starting dose is 8.4 g patiromer once daily. The daily dose may be increased or decreased by 8.4 g, as necessary, to reach the desired target range, up to a maximum dose of 25.2 g daily.

Adolescents aged 12 to 17 years

The recommended starting dose is 4 g patiromer once daily. Adjust the daily dose of patiromer based on the serum potassium level and the desired target range, up to a maximum dose of 25.2 g daily. It is recommended to switch to 8.4 g patiromer sachets if doses above 7 g are needed.

Missed doses

If a dose is missed, the missed dose should be taken as soon as possible on the same day. The missed dose should not be taken with the next dose.

Special populations

Elderly

No special dose and administration guidelines are recommended for this population.

Patients on dialysis

There is limited data on the use of patiromer in patients on dialysis. No special dose and administration guidelines were applied to these patients in clinical trials. No paediatric patients receiving dialysis have been treated with patiromer.

Patients with end-stage renal disease (ESRD)

Patiromer has been studied only in a limited number of patients with estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m².

Paediatric population

The safety and efficacy of patiromer in children aged under 12 years have not yet been established. The data in adolescents aged 12 to 17 years are limited to 6 months exposure. Therefore, treatment beyond 6 months should be done with caution in adolescents aged 12 to 17 years (see section 4.4).

Method of administration

Oral use.

Veltassa should be mixed with water and stirred to a suspension of uniform consistency. The recommended total volumes for preparation of the suspension are dose dependent:

• 1 g patiromer: 10 mL

• 2 g patiromer: 20 mL

• 3 g patiromer: 30 mL

• 4 g patiromer: 40 mL

• >4 g patiromer: 80 mL

The suspension should be prepared according to the following steps:

• The first half of the recommended volume for the required dose should be poured into a glass and the complete dose of patiromer should be added, then stirred.

• The second half of the recommended volume should be added and the suspension stirred again thoroughly.

The powder will not dissolve. More water may be added to the mixture as needed for desired consistency. However, larger volumes might lead to an accelerated sedimentation of the powder.

The mixture should be taken within 1 hour of initial suspension. If powder remains in the glass after drinking, more water should be added and the suspension stirred and taken immediately. This may be repeated as needed to ensure the entire dose is administered.

According to personal preferences, following liquids or soft foods can be used instead of water to prepare the mixture by following the same steps as described above: apple juice, cranberry juice, pineapple juice, orange juice, grape juice, pear juice, apricot nectar, peach nectar, yoghurt, milk, thickener (for example: cornstarch), apple sauce, vanilla and chocolate pudding.

The potassium content of liquids or soft foods used to prepare the mixture should be considered as part of the dietary recommendations on potassium intake for each individual patient.

In general, cranberry juice intake should be limited to moderate amounts (for example less than 400 mL per day) due to its potential interaction with other medicinal products.

This medicine can be taken with or without meals. It should not be heated (e.g. microwaved) or added to heated foods or liquids. It should not be taken in its dry form.

Administration by nasogastric (NG) or percutaneous endoscopic gastrostomy (PEG) tube:

For doses up to 8.4 g patiromer, the suspension should be prepared as described above in the section relating to the oral administration. For doses above 8.4 g and up to 16.8 g patiromer a total volume of 160 mL should be used and for doses above 16.8 g and up to 25.2 g patiromer a total volume of 240 mL. These volumes ensure that the suspension readily flows through the tubes.

Compatibility has been shown with tubes made from polyurethane, silicone, and polyvinyl chloride. The recommended diameter of the tubes is 2.17 mm (6.5 Fr) or larger. After administration the tube should be flushed with water. For instructions on disposal, see section 6.6.

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4. Special warnings and precautions for use

Low magnesium

In clinical trials, serum magnesium values <1.4 mg/dL (0.58 mmol/L) occurred in 7.1% of adult patients treated with patiromer with 0.3% of patients developing a serum magnesium level <1.0 mg/dL (0.4 mmol/L). Mean decreases in serum magnesium were 0.137 mg/dL (0.0564 mmol/L) or less. In a clinical trial involving paediatric patients, mean decrease in serum magnesium at Week 26 was 0.35 mg/dL (0.1440 mmol/L). No patients reached serum magnesium <1.4 mg/dL (0.58 mmol/L) during the paediatric clinical trial.

Serum magnesium should be monitored for at least 1 month after initiating treatment and as clinically indicated during treatment, and magnesium supplementation considered in patients who develop low serum magnesium levels (see section 4.8).

Gastrointestinal disorders

Patients with a history of bowel obstruction or major gastrointestinal surgery, severe gastrointestinal disorders, or swallowing disorders were not included in the clinical trials. Gastrointestinal ischaemia, necrosis and/or intestinal perforation have been reported with other potassium binders. The benefits and risks of administering patiromer should be carefully evaluated in adult and paediatric patients with current or history of severe gastrointestinal disorders, before and during the treatment.

Discontinuing patiromer

When discontinuing patiromer, serum potassium levels may rise leading to recurrent hyperkalaemia, especially if renin-angiotensin-aldosterone system (RAAS) inhibitor treatment is continued. Patients should be instructed not to discontinue therapy without consulting their physicians. Increases in serum potassium may occur as early as 2 days after the last patiromer dose. There is limited information on serum potassium levels in paediatric patients on patiromer discontinuation.

Serum potassium levels

Serum potassium should be monitored as per standard practice when clinically indicated, including after changes are made to medicinal products that affect the serum potassium concentration (e.g. RAAS inhibitors or diuretics) and after the patiromer dose is titrated or discontinued.

Limitations of the clinical data

Severe hyperkalaemia

There is limited experience in patients with serum potassium concentrations greater than 6.5 mmol/L. In the paediatric population, experience is limited to patients with maximum serum potassium concentrations of 6.2 mmol/L. Veltassa should not be used as an emergency treatment for life-threatening hyperkalaemia because of its delayed onset of action (see section 4.2).

Long term exposure

There are limited clinical trial data in adults with an exposure of one year and longer. Clinical trials in paediatric patients have not included exposure longer than 6 months. Therefore, treatment beyond 6 months should be done with caution in adolescents aged 12 to 17 years.

Information about sorbitol

Veltassa contains sorbitol as part of the counterion complex. The sorbitol content is approximately 4 g (10.4 kcal) per 8.4 g of patiromer and approximately 0.5 g (1.2 kcal) per 1 g of patiromer.

Patients with hereditary fructose intolerance (HFI) should not take this medicinal product.

Information about calcium

Veltassa contains calcium as part of the counterion complex. Calcium is partially released some of which may be absorbed (see section 5.1). The benefits and risks of administering this medicinal product should be carefully evaluated in adult and paediatric patients at risk of hypercalcaemia. Serum calcium should be monitored for at least 1 month after initiating treatment and as clinically indicated during treatment.

4.5. Interaction with other medicinal products and other forms of interaction

Effect of patiromer on other medicinal products

Patiromer has the potential to bind some oral co administered medicinal products, which could decrease their gastrointestinal absorption. Increased bioavailability of co administrated medicinal products was not observed in the conducted drug-drug interaction studies. As patiromer is not absorbed or metabolised by the body, there are limited effects on the function of other medicinal products.

As precautionary measure, and based on the data summarised below, administration of patiromer should therefore be separated by at least 3 hours from other oral medicinal products.

In vivo studies

Concomitant administration of patiromer did not affect the bioavailability as measured by the area under the curve (AUC) of amlodipine, cinacalcet, clopidogrel, furosemide, lithium, metoprolol, trimethoprim, verapamil and warfarin. For these medicinal products no separation is needed.

Concomitant administration of patiromer showed reduced bioavailability of ciprofloxacin, levothyroxine and metformin. However, there was no interaction when patiromer and these medicinal products were taken 3 hours apart.

Interaction studies have only been performed in adults.

In vitro studies

In vitro studies have shown no potential interaction of patiromer with the following active substances: allopurinol, amoxicillin, apixaban, acetylsalicylic acid, atorvastatin, azilsartan, benazepril, bumetanide, canagliflozin, candesartan, captopril, cephalexin, dapagliflozin, digoxin, empagliflozin, enalapril, eplerenone, finerenone, fosinopril, glipizide, irbesartan, lisinopril, losartan, olmesartan, perindopril, phenytoin, quinapril, ramipril, riboflavin, rivaroxaban, sacubitril, sevelamer, spironolactone tacrolimus, torasemide, trandolapril, and valsartan.

In vitro studies have shown potential interaction of patiromer with bisoprolol, carvedilol, mycophenolate mofetil, nebivolol, quinidine, and telmisartan.

4.6. Fertility, pregnancy and lactation

Pregnancy

There are no data from the use of patiromer in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

As a precautionary measure, it is preferable to avoid the use of patiromer during pregnancy.

Breast-feeding

No effects on the breastfed newborn/infant are anticipated since the systemic exposure of the breast feeding woman to patiromer is negligible. A decision must be made whether to discontinue breast feeding or to discontinue/abstain from patiromer therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Fertility

There are no data on the effect of patiromer on fertility in humans. Animal studies showed no effects on reproductive function or fertility (see section 5.3).

4.7. Effects on ability to drive and use machines

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

4.8. Undesirable effects

Summary of the safety profile

The majority of the adverse reactions (ARs) reported from trials in adult patients were hypomagnesaemia (1.8%) and gastrointestinal disorders, with the most frequently reported ARs being constipation (3.7%), diarrhoea (3%), abdominal pain (1.4%), nausea (1.3%) and flatulence (1%). Gastrointestinal disorder reactions were generally mild to moderate in nature, did not appear to be dose related, generally resolved spontaneously or with treatment, and none were reported as serious. Hypomagnesaemia was mild to moderate, with 0.3% of patients developing a serum magnesium level <1 mg/dL (0.4 mmol/L) (see section 4.4).

Tabulated list of adverse reactions

Adverse reactions reported in clinical trials are listed below by system organ class (SOC) and by frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10) and uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000), not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

MedDRA system organ class

Common

Uncommon

Frequency not known

Immune System Disorders

Hypersensitivity(1,2)

Metabolism and nutrition disorders

Hypomagnesaemia

Gastrointestinal disorders

Constipation(3)*

Diarrhoea(4)*

Abdominal pain(5)

Nausea

Flatulence*

Vomiting

*Adverse reactions reported also in the paediatric clinical trials

1 ARs reported in the post-marketing setting.

2 Hypersensitivity reactions included rash, urticaria, swelling in the oral cavity and lips and were mild to moderate severity.

3 Constipation is an aggregate term combining the preferred terms constipation and faeces hard.

4 Diarrhoea is an aggregate term for diarrhoea and frequent bowel movements.

5 Abdominal pain is an aggregate term combining the preferred terms of abdominal discomfort, abdominal pain, abdominal pain upper and abdominal pain lower.

Paediatric population

The safety of patiromer for the treatment of hyperkalaemia has been studied in a single trial of 23 paediatric patients aged 6 to 17 years of age. The adverse reaction profile observed in paediatric patients was broadly consistent with the safety profile in adults. The safety of patiromer has not been studied in patients less than 6 years of age.

Adverse reactions were reported for 4 subjects overall; 3 in age group 12 to <18 years and 1 in age group 6 to <12 years. In 2 of these subjects, the adverse reactions belonged to the SOC gastrointestinal disorders, i.e., diarrhoea, constipation, frequent bowel movements, and flatulence. The remaining adverse drug reactions were blood calcium increased and hypokalaemia. These were all non-serious adverse reactions and mild to moderate in severity.

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

Website: https://yellowcard.mhra.gov.uk/ or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Since excessive doses of patiromer may result in hypokalaemia, serum potassium levels should be monitored. Patiromer is excreted after approximately 24 to 48 hours, based on average gastrointestinal transit time. If it is determined that medical intervention is required, appropriate measures to restore serum potassium may be considered.

Paediatric population

Doses in excess of 25.2 g patiromer per day for adolescents aged 12 to 17 years and in excess of 12 g for children 6 to less than 12 years old have not been tested. Since excessive doses of patiromer may result in hypokalaemia, serum potassium levels should be monitored. If it is determined that medical intervention is required, appropriate measures to restore serum potassium may be considered.