9.5.2.2 Phosphate-binding agents

Patients with chronic kidney disease (CKD) develop impaired excretion of dietary phosphate leading to hyperphosphataemia. Hyperphosphataemia can ultimately lead to a condition called mineral and bone disorder in chronic kidney disease (CKD-MBD). CKD-MBD is characterised by high bone turnover, increased musculoskeletal morbidity (including bone pain and muscle weakness) and exaggerated marrow fibrosis. Epidemiological data have demonstrated an association between elevated serum phosphorus, parathyroid hormone (PTH), and calcium caused by CKD and increased morbidity, mortality, hospitalisation, reduced quality of life and increased cost of care.

All available phosphate-binding agents reduce phosphorus levels compared to placebo. There is insufficient data to establish the comparative superiority of novel non-calcium binding agents over calcium-containing phosphate binders for patient-focused outcomes including all-cause mortality and CV endpoints.

Treatment guidance for hyperphosphataemia in CKD:

1. Patients with chronic kidney disease (CKD) stage 3-5 should be referred to the renal dieticians for assessment and dietary phosphate restriction
2. If serum phosphate above 1.78mmol/L consider a calcium based phosphate binder (see treatment options below)
   1. Many patients with serum calcium greater than 2.37mmol/L may receive a calcium-based phosphate binder but close monitoring is essential
3. For patients on dialysis with serum phosphate greater than 1.78mmol/L- consider calcium or non-calcium based phosphate binder (see treatment options below)

Aluminium

Aluminium hydroxide

• Capsules

Dose

• 4–20 capsules daily in divided doses with meals

Notes

1. Aluminium hydroxide may be used as a phosphate binder and has a considerably low acquisition cost than the other non-calcium based agents. Prescribers should be mindful of aluminium accumulation and monitor patients appropriately.

Calcium

Drugs used not listed here:

• Calcium carbonate, see section 9.5.1 Calcium and magnesium

Phosex

(Calcium acetate)

• Tablets 1g (£19.79 = 180 tablets)

Indications

• Hyperphosphataemia

Dose

• Initially 1 tablet 3 times daily with meals, adjusted according to serum-phosphate concentration (usual dose 4–6 tablets daily); maximum 12 tablets daily

Notes

1. Prescribe by brand (to aid identification where products contain multiple ingredients, or to prevent confusion where multiple brands contain similar ingredients)

Renacet

(Calcium acetate)

• Tablets 475mg, 950mg (£13.50 = 200 x 475mg tablets)

Indications

• Hyperphosphataemia

Dose

• 475–950mg, to be taken with breakfast and with snacks, 0.95–2.85g, to be taken with main meals and 0.95–1.9g, to be taken with supper, dose to be adjusted according to serum-phosphate concentration; maximum 6.65g per day.

Notes

1. Prescribe by brand (to aid identification where products contain multiple ingredients, or to prevent confusion where multiple brands contain similar ingredients)

Osvaren

(Calcium acetate with magnesium carbonate)

• Tablets (435mg + 235mg) (£24.00 = 180 tablets)

Indications

• Hyperphosphataemia

Dose

• Initially 1 tablet 3 times daily with meals, adjusted according to serum-phosphate concentration (usual dose 3–10 tablets daily); maximum 12 tablets daily

Notes

1. Prescribe by brand (to aid identification where products contain multiple ingredients, or to prevent confusion where multiple brands contain similar ingredients)
2. Osvaren may be used in patients at risk of hypercalcaemia

Lanthanum carbonate

• Chewable tablets 500mg, 750mg, 1g (£182.60 = 90 x 750mg tablets)
• Oral powder sachets 750mg, 1g (£182.60 = 90 x 750mg sachets)

Dose

• Usual dose range 1.5–3.0 g daily in divided doses with or immediately after meals

Notes

1. Although lanthanum is licensed for use in patients not on dialysis their routine use in this patient population is not recommended locally.

Sevelamer carbonate

• Tablets 800mg (£26.18 = 180 tablets)

Dose

• Usual dose approximately 6g daily in 3 divided doses

Notes

1. Although sevelamer carbonate is licensed for use in patients not on dialysis their routine use in this patient population is not recommended locally.

Sevelamer hydrochloride

• Renagel tablets 800mg (£167.04 = 180 tablets)

Dose

• Usual dose range 2.4g–12.0g daily in 3 divided doses

Sucroferric oxyhydroxide

• Chewable tablets 500mg

Indications

• Hyperphosphataemia in adult patients with chronic kidney disease on haemodialysis or peritoneal dialysis (NHS England commissioned)

Notes

1. Tablets must be chewed or crushed, not swallowed whole

9.5.2.3 Burosumab

Burosumab

• Solution for injection vials 10mg in 1ml, 20mg in 1ml, 30mg in 1ml

Notes

1. NICE HST8: Burosumab (Crysvita) is recommended for treating X-linked hypophosphataemia (XLH) with radiographic evidence of bone disease in children aged 1 year and over, and young people with growing bones (October 2018) (NHS England commissioned)