VELTASSA Powder for oral suspension Ref.[8679] Active ingredients: Patiromer

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.

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.

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).

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

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.

^* 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 the national reporting system listed in Appendix V.

Not applicable.