Velphoro 500 mg chewable tablets

4.1       Therapeutic indications

Velphoro is indicated for the control of serum phosphorus levels in paediatric patients 2 years of age and older with CKD stages 4-5 (defined by a glomerular filtration rate <30 mL/min/1.73 m²) or with CKD on dialysis.

4.2       Posology and method of administration

Posology

Starting dose for adults and adolescents (≥12 years of age)

The recommended starting dose of Velphoro is 1,500 mg iron (3 tablets) per day, divided across the meals of the day.  Velphoro is for oral administration only and must be taken with meals. Patients receiving Velphoro should adhere to their prescribed diets.

Titration and maintenance for adults and adolescents (≥12 years of age)

Serum phosphorus levels must be monitored and the dose of sucroferric oxyhydroxideVelphoro up or down titrated in increments of 500 mg iron (1 tablet) per day every 2 – 4 weeks until an acceptable serum phosphorus level is reached, with regular monitoring afterwards.

In clinical practice, treatment will be based on the need to control serum phosphorus levels, though patients who respond to Velphoro therapy usually achieve optimal serum phosphorus levels at doses of 1,500 – 2,000 mg iron per day (3 to 4 tablets).

If one or more doses are missed, the normal dose of the medicinal product should be resumed with the next meal.

Maximum tolerated daily dose for adults and adolescents (≥12 years of age)

The maximum recommended dose is 3,000 mg iron (6 tablets) per day.

Starting dose, titration and maintenance for paediatric patients (2 to <12 years of age)

Velphoro is also available as 125 mg oral powder in sachet for use in paediatric patients 2 to <12 years of age. The choice of the formulation depends on patient’s age, preference, characteristics and compliance. When transitioning between formulations, the same recommended dose should be used. Recommended starting doses and dose titrations of Velphoro for paediatric patients 2 to <12 years of age are shown in the Table 1.

Table 1       Recommended starting doses and dose titrations for paediatric patients 2 to <12 years of age

For patients 2 to <6 years of age oral powder should be administered, as the chewable tablet formulation is not appropriate for this age group.

For patients 6 to <12 years of age Velphoro chewable tablets may be prescribed instead of or in combination with Velphoro oral powder in case the daily dose is 1,000 mg iron (2 chewable tablets) or more.

Serum phosphorus levels must be monitored and the dose of sucroferric oxyhydroxide up or down titrated in increments per day every 2 – 4 weeks until an acceptable serum phosphorus level is reached, with regular monitoring afterwards.

Paediatric population <2 years of age

The safety and efficacy of Velphoro in children and adolescents below the age of 18 2 years has not been established. No data are available.

4.8       Undesirable effects

Paediatric population

In general, the safety profile of Velphoro in paediatric (2 to <18 years of age) and adult patients was comparable. The adverse reactions most frequently reported were gastrointestinal disorders including diarrhoea (very common, 16.7%), vomiting (common, 6.1%), gastritis (common, 3.0%) and discoloured faeces (common, 3.0%).

5.1 Pharmacodynamic Properties

An open label clinical study investigated the efficacy and safety of Velphoro in paediatric patients 2 years of age and older with CKD, and hyperphosphatemia (CKD stages 4-5 (defined by a glomerular filtration rate <30 mL/min/l .73 m²) or with CKD on dialysis). Eighty-five subjects were  randomised to Velphoro  (N=66) or active control calcium acetate arm (N=19) for a 10-week dose titration (Stage 1), followed by a 24-week safety extension (Stage 2). Most patients were ≥12 years of age (66%). Eighty percent of patients were CKD patients on dialysis (67% on haemodialysis and 13% on peritoneal dialysis) and 20% were CKD patients not on dialysis.

The limited difference in reduction in mean serum phosphorus level from baseline to the end of Stage 1 in the Velphoro group (N=65) was not statistically significant with -0.120 (0.081) mmol/L (95% CI: -0.282, 0.043) based on the mixed model calculations with actual data showing a mean of 2.08 mmol/L at baseline and 1.91 mmol/L at the end of Stage 1 (reduction by 0.17 mmol/L). The effect was maintained during Stage 2, although some fluctuations in mean effect over time were noticed (0.099 (0.198) mmol/L (95% CI: -0.306, 0.504)).

The percentage of subjects with serum phosphorus levels within normal ranges increased from 37% at baseline to 61% at the end of Stage 1, and was 58% at the end of Stage 2, showing the sustainable phosphorus lowering effect of sucroferric oxyhydroxide. Among subjects whose serum phosphorus was above age-related normal ranges at baseline (N=40), serum phosphorus levels showed statistically significant decrease from baseline to the end of Stage 1, with the LS mean (SE) change -0.87 (0.30) mg/dL (95% CI: -1.47, -0.27; p=0.006).

The safety profile of Velphoro in paediatric patients was generally comparable to that previously observed in adult patients.

The European Medicines Agency has deferred the obligation to submit the results of studies with Velphoro in one or more subsets of the paediatric population in the treatment of hyperphosphataemia (see section 4.2 for information on paediatric use).