4.1. Therapeutic indications

Velphoro is indicated for the control of serum phosphorus levels in adult chronic kidney disease (CKD) patients on haemodialysis (HD) or peritoneal dialysis (PD).

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.

Velphoro should be used within the context of a multiple therapeutic approach, which could include calcium supplement, 1,25-dihydroxy vitamin D3 or one of its analogues, or calcimimetics to control the development of renal bone disease.

4.2. Posology and method of administration

Posology

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

The recommended starting doses for paediatric patients in different age groups are described in Table 1.

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

Patient age (years)

Daily starting dose

Dose increases or decreases

Maximum recommended daily dose

≥2 to <6

500 mg

125 or 250 mg

1,250 mg

≥6 to <9

750 mg

125, 250 or 375 mg

2,500 mg

≥9 to <12

1,000 mg

250 or 500 mg

3,000 mg

Serum phosphorus levels must be monitored and the dose of sucroferric oxyhydroxide up or down titrated once per two weeks by adjusting the daily dose as indicated in Table 1 until an acceptable serum phosphorus level is reached, with regular monitoring afterwards.

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.

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

Additional formulation and strength available

Velphoro is also available as chewable tablets (500 mg iron) for use in adult and paediatric patients 6 years of age and older. 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. Velphoro oral powder was not studied in adults. For patients 2 to <6 years of age oral powder should be administered as chewable tablet formulation is not appropriate for this age group.

Paediatric population <2 years of age

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

Renal impairment

Velphoro is indicated for the control of serum phosphorus levels in adult CKD patients on HD or PD. There is no clinical data available in patients with earlier stages of renal impairment.

Hepatic impairment

Patients with severe hepatic impairment were excluded from participating in clinical studies with sucroferric oxyhydroxide. However, no evidence of hepatic impairment or significant alteration of hepatic enzymes were observed in the clinical studies with sucroferric oxyhydroxide. See further information in section 4.4.

Method of administration

Oral use.

In order to maximise the adsorption of dietary phosphate, the total daily dose (total number of sachets) should be divided across the main meals of the day, i.e. meals with the highest phosphate content. When total number of sachets cannot be equally divided by the number of main meals, rest of the dose should be taken with one or two main meals. The optimal way to give the total daily dose of Velphoro to individual patients should be decided based on their feeding regimens.

Before administration, Velphoro oral powder should be mixed with a small amount of soft food (such as apple sauce) or with non-carbonated beverage or water and taken with meals. Each sachet of oral powder requires minimum 5 mL of liquid for suspension, e.g. 2 sachets shall be suspended in minimum 10 mL. The amount of liquid could be increased if total daily fluid intake remains in line with dietary instructions for individual patient.

Patients should take Velphoro oral powder within 30 minutes after being suspended. Velphoro oral powder should not be heated (e.g. in a microwave) or added to heated food or liquids. The mixture should be stirred vigorously as the powder will not dissolve completely and remain in suspension with a red-brown colour. If necessary, the suspension should be resuspended right before administration.

The prescribed dose of Velphoro oral powder suspended in water as described above, may be administered via an enteral feeding tube >6 FR (French catheter scale). Follow the manufacturer's instructions for the feeding tube to administer the medicinal product. To ensure adequate dosing, after administration of the oral suspension, the enteral feeding tube must be flushed with water. See section 6.6 for further details.

4.3. Contraindications

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

• Haemochromatosis and any other iron accumulation disorders.

4.4. Special warnings and precautions for use

Peritonitis, gastric and hepatic disorders and gastrointestinal surgery

Patients with a recent history of peritonitis (within the last 3 months), significant gastric or hepatic disorders and patients with major gastrointestinal surgery have not been included in clinical studies with Velphoro. Velphoro treatment should only be used in these patients following careful assessment of benefit/risk.

Discoloured stool

Sucroferric oxyhydroxide can cause discoloured (black) stool. Discoloured (black) stool may visually mask gastrointestinal bleeding (see section 4.5).

Information about sucrose and starches (carbohydrates)

Velphoro contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicinal product.

It may be harmful to the teeth.

Velphoro contains potato starch and pregelatinised maize starch. Patients with diabetes should take notice that one sachet of Velphoro oral powder is equivalent to approximately 0.7 g of carbohydrates (equivalent to 0.056 bread units).

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

Velphoro is almost not absorbed from the gastrointestinal tract. Although the potential for interactions with medicinal products seems low, for concomitant treatment with medicinal products with a narrow therapeutic window, the clinical effect and adverse events should be monitored, on initiation or dose-adjustment of either Velphoro or the concomitant medicinal product, or the physician should consider measuring blood levels. When administering any medicinal product that is already known to interact with iron (like alendronate and doxycycline) or has the potential to interact with sucroferric oxyhydroxide based only on in vitro studies like levothyroxine, the medicinal product should be administered at least one hour before or two hours after Velphoro.

In vitro studies with the following active substances did not show any relevant interaction: acetylsalicylic acid, cephalexin, cinacalcet, ciprofloxacin, clopidogrel, enalapril, hydrochlorothiazide, metformin, metoprolol, nifedipine, pioglitazone and quinidine.

Interaction studies have only been performed in healthy volunteers. They have been conducted in healthy human male and female subjects with losartan, furosemide, digoxin, warfarin, and omeprazole. Concomitant administration of Velphoro did not affect the bioavailability of these medicinal products as measured by the area under the curve (AUC).

Data from clinical studies have shown that sucroferric oxyhydroxide does not affect the lipid lowering effects of HMG-CoA reductase inhibitors (e.g., atorvastatin and simvastatin). In addition, post-hoc analyses from clinical studies demonstrated no impact of Velphoro on iPTH lowering effect of oral Vitamin D analogues. Vitamin D and 1,25-dihydroxy Vitamin D levels remained unchanged.

Velphoro does not affect guaiac based (Haemoccult) or immunological based (iColo Rectal and Hexagon Obti) faecal occult blood tests.

4.6. Fertility, pregnancy and lactation

Pregnancy

There are no available clinical data from the use of sucroferric oxyhydroxide on exposed human pregnancies.

Reproductive and developmental toxicity studies in animals revealed no risk with respect to pregnancy, embryonic/foetal development, parturition or postnatal development (see section 5.3). Sucroferric oxyhydroxide should only be used by pregnant women if clearly needed following careful assessment of benefit/risk.

Breast-feeding

There are no available clinical data from the use of Velphoro in breast-feeding women. Since absorption of iron from this medicinal product is minimal (see section 5.2), excretion of iron from sucroferric oxyhydroxide in breast milk is unlikely. A decision on whether to continue breast-feeding or to continue therapy with sucroferric oxyhydroxide should be made taking into account the benefit of breast-feeding to the child and the benefit of Velphoro therapy to the mother.

Fertility

There are no data on the effect of Velphoro on fertility in humans. In animal studies, there were no adverse effects on mating performance, fertility, and litter parameters following treatment with sucroferric oxyhydroxide (see section 5.3).

4.7. Effects on ability to drive and use machines

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

4.8. Undesirable effects

Summary of the safety profile

The current safety profile of Velphoro is based on a total of 778 patients on haemodialysis and 57 patients on peritoneal dialysis, who received sucroferric oxyhydroxide treatment of up to 55 weeks.

In these clinical trials, approximately 43% of the patients experienced at least one adverse reaction during Velphoro treatment, and 0.36% of the adverse reactions were reported as serious. The majority of the adverse reactions reported from trials were gastrointestinal disorders, with the most frequently reported adverse reactions being diarrhoea and discoloured faeces (very common). The vast majority of these gastrointestinal disorders occurred early during treatment and abated with time with continued dosing. No dose-dependent trends were observed in the adverse reaction profile of Velphoro.

Tabulated list of adverse reactions

Adverse reactions reported from the use of Velphoro at doses from 250 mg iron/day to 3,000 mg iron/day in these patients (n=835) are listed in Table 2.

The reporting rate is classified as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100).

Table 2 Adverse reactions detected in clinical trials

System organ class

Very common

Common

Uncommon

Metabolism and nutrition disorders

Hypercalcaemia

Hypocalcaemia

Nervous system disorders

Headache

Respiratory, thoracic and mediastinal disorders

Dyspnoea

Gastrointestinal disorders

Diarrhoea*

Faeces discoloured

Nausea

Constipation

Vomiting

Dyspepsia

Abdominal pain

Flatulence

Tooth discolouration

Abdominal distension

Gastritis

Abdominal discomfort

Dysphagia

Gastro-oesophageal reflux disease (GORD)

Tongue discolouration

Skin and subcutaneous tissue disorders

Pruritus Rash

General disorders and administration site conditions

Product taste abnormal

Fatigue

Description of selected adverse reactions

*Diarrhoea

Diarrhoea occurred in 11.6% of patients in clinical trials. In the 55 weeks long term studies, the majority of these diarrhoea adverse reactions were transient, occurred early during treatment initiation and led to treatment discontinuation in 3.1% of the patients.

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%).

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

4.9. Overdose

Any instances of overdose of Velphoro (e.g. hypophosphataemia) should be treated by standard clinical practice.