Lanthanum Carbonate Report (Adopted by the CCG Until Review and Further Notice)

New Medicine Lanthanum Carbonate Report (Adopted by the CCG until review and further notice)

Document Status Post Suffolk D&TC

Traffic Light Decision RED until shared care document produced then AMBER Prescriber’s Rating 3.Offers an advantage Date of Last Revision 10th May 2007

Approved Name Lanthanum Carbonate Trade Name Fosrenol™ Manufacturer Shire Legal Status POM Indication As a phosphate binding agent for use in the control of hyperphosphataemia in chronic renal failure patients on haemodialysis or continuous ambulatory peritoneal dialysis Dosage As required but normally 1,500mg to 3,000mg per day Cost 90 tablets of 500mg £114.13 90 tablets of 750mg £152.17 90 tablets of 1000mg £161.33 Possible Number of Suffolk Within Suffolk PCT 1,015 Patients Within Waveney area 223 Number Needed to Treat Not calculated Treatment Alternatives Aluminium hydroxide Calcium acetate Sevelamer Restricted diet Future Alternatives None known Possible Future Indications None known Prices MIMS April 2007

©David Evans Suffolk PCT Not to be used for promotional purposes Page 1 of 8 May be freely copied by NHS agencies

Evidence Reviewed

Paper, Review, Abstract etc. Level of evidence Gibson V London New Drugs Group APC/DTC Briefing III Document updated in March 2007 Lanthanum Carbonate (Fosrenol) www.nelm.nhs.uk Guérin AP, London GM, Marchais SJ, Metivier F Arterial I stiffening and vascular calcifications in end-stage renal disease Nephrol Dial Transplant 2000;15:1014-1021 D’Haese PC, Spasovski GB, Sikole A et al A multicenter study I on the effects of lanthanum carbonate (Fosrenol™) and calcium carbonate on renal bone disease in dialysis patients. Kidney International 2003;85:S73-S78. Finn WF on behalf of Study Group Lanthanum carbonate I versus standard therapy for the treatment of hyperphosphatemia: safety and efficacy in chronic maintenance hemodialysis patients. Clinical Nephrology (3)2006;65:191-202 Hutchison AJ, Maes B, Vanwalleghem J et al Long term I efficacy and tolerability of lanthanum carbonate results from a three year study. Nephron Clinical Practice 2006;102:c61-c71 Hutchison AJ, Maes B, Vanwalleghem J et al Efficacy, I tolerability and safety of lanthanum carbonate in hyperphosphatemia: A 6 month randomised, comparative trial versus calcium carbonate. Nephron Clinical Practice 2005;100:c8-c19. Joy MS, Finn WF, on behalf of Study Group Randomised, I double blind, placebo-controlled, dose-titration, phase III study assessing the efficacy and tolerability of lanthanum carbonate: A new phosphate binder for the treatment of hyperphosphatemia. American Journal of Kidney Diseases 2003;42:96-107. Chiang S.-S, Chen J.-B, Yang W.-C Lanthanum carbonate I (Fosrenol™) efficacy and tolerability in the treatment of hyperphosphatemic patients with end-stage renal disease Clinical Nephrology (6)2005;63:461-470 Freemont AJ, Hoyland JA, Denton J on behalf of Study Group I The effects of lanthanum carbonate and calcium carbonate on bone abnormalities in patients with end-stage renal disease Clinical Nephrology (6)2005;64:428-437 Level of evidence adapted from “Quick and Clean” : authorative health technology assessment for local health care contracting Andrew Stevens, Duncan Collin-Jones & John Gabbay Health Trends Vol 27 No 2 1995

©David Evans Suffolk PCT Not to be used for promotional purposes Page 2 of 8 May be freely copied by NHS agencies

Reviewer’s Comments

Raised serum phosphorous is a predictable accompaniment of end-stage renal disease in the absence of restriction of phosphate intake or the use of phosphate binders. The consequences include the development and progression of secondary hyperparathyroidism and a tendency to metastatic calcification. Both of these conditions may contribute to the mortality and morbidity seen in such patients.

Epidemiological studies have identified aortic stiffness as an independent predictor of cardio-vascular mortality in end-stage renal disease. Guérin et al observed that arterial and aortic stiffness is significantly influenced by the presence and extent of arterial calcification. Arterial calcification density increases with age, duration of haemodialysis, the fibrinogen level and the prescribed dose of calcium based phosphate binders.

Lanthanum carbonate is a non-calcium based phosphate binding agent licensed for the control of hyperphosphataemia in chronic renal failure patients on haemodialysis or continuous ambulatory peritoneal dialysis.

The product is derived from elemental lanthanum, a rare earth element which occurs naturally in tap water and is similar to aluminium.

Lanthanum carbonate dissociates in the acid environment of the upper gastrointestinal tract to release lanthanum ions. These ions bind with dietary phosphate to form lanthanum phosphate, which is highly insoluble and is thus excreted via the GI tract. It should be noted that lanthanum ions will be absorbed into the body during this process

Hyperphosphataemia affects the majority of patients with chronic renal failure and is associated with increased morbidity and mortality among end stage renal disease and dialysis patients.

Lanthanum carbonate appears to be comparable in efficacy to calcium carbonate.

There are a lack of comparative data with sevelamer and other phosphate binders including calcium acetate. In addition there are no comparative data with calcimimetics and vitamin D analogues.

Lanthanum has been associated with fewer calcium related side effects than standard therapy but does not appear to be better tolerated than calcium carbonate.

Data from short term studies suggest that low levels of lanthanum accumulate in bone and other tissues. There is currently no evidence of risk. In a paper Freemont et al suggest that there is no evidence of aluminium-like toxicity and there also appears to be a beneficial effect on bone-cell function and activity

©David Evans Suffolk PCT Not to be used for promotional purposes Page 3 of 8 May be freely copied by NHS agencies

compared with calcium carbonate. However some concern still remains over possible tissue and bone accumulation and the possible associated toxicity of lanthanum over the longer term.

Lanthanum carbonate may be a suitable alternative in patients who cannot tolerate calcium based phosphate binders and in patients with pre-existing hypercalcaemia.

Review

The enclosed London New Drugs Group APC/DTC Briefing Document updated in March 2007 gives full details of the trials carried out to study this preparation (with thanks to Victoria Gibson for permission to use the paper).

Adverse Effects etc.

For full information please refer to the Summary of Product Characteristics.

Economic Information

The use of calcium based phosphate binders has increased in recent years with an equivalent decrease in aluminium based binders given the associated serious toxicity with aluminium. Recent findings suggest that the long term use of calcium based products may lead to additional morbidity and mortality due to the increased risk of metastatic calcification. The true costs of treating the side effects associated with the use of calcium based products versus the use of lanthanum based products have yet to be clearly identified.

No trials comparing Lanthanum carbonate with sevelamer have been carried out.

The London New Drugs Group report suggests that there are 5,554 patients per million population with chronic kidney disease. It also suggests that 1,833 patients per million population were receiving treatment for end stage renal failure in 2002.

Using these figure is can be estimated that there are about 1,015 patients within the Suffolk PCT area and 223 patients within the Waveney area who are receiving treatment for end stage renal failure.

©David Evans Suffolk PCT Not to be used for promotional purposes Page 4 of 8 May be freely copied by NHS agencies

Charts to be used in the decision making process in Suffolk

Quality of Evidence categories Cost utility categories Per life year gained I Strong evidence from at least 1 RCT A Less than £3,000 II-1 Evidence from a well designed CT without randomisation B £3,000 to £20,000 II-2 Evidence from well designed cohort or case controlled study C > £20,000 II-3 Evidence from multiple time series or dramatic results D Negative life years III Opinions of respected clinicians or expert committees IV Evidence inadequate

Recommendations informed by cost utility and quality of evidence Key to Table at Right Quality of A B C D evidence ++ Strongly recommended I ++ (high) ++ - X + Recommended II ++ + - X - Beneficial but high cost III + - - X X Not recommended IV 0 0 0 0 (low) 0 Not proven

Adapted from

“Quick and Clean” : authorative health technology assessment for local health care contracting Andrew Stevens, Duncan Collin-Jones & John Gabbay Health Trends Vol 27 No 2 1995

To Decide If A Medication Is To Be Used In Suffolk

Criterion Tends to 2 Medium 4 Tends to poor good Quality of evidence in the papers reviewed IV III II-2 II-1 I Magnitude of effect inferred from the trials reviewed Low xxxx Medium xxxx High Known Side Effect Profile High xxxx Medium xxxx Low Known Interactions High xxxx Medium xxxx Low Concern re Possible Side Effects Not Yet Uncovered High xxxx Medium xxxx Low Balance of Benefit To Harm (side effects toxicity interactions etc) Poor xxxx Medium xxxx Good NNT High xxxx Medium xxxx Low Comparison Of Effectiveness With Other Medicines In Use For Poor xxxx Medium xxxx Good The Same Condition Severity of Condition to be Treated Trivial xxxx Medium xxxx Severe Cost Utility Score D C B ?A A Recommendations informed by cost utility and quality of 0 X - + ++ evidence

Prescriber’s Rating Definitions Bravo! -The drug is a major therapeutic advance in an area where previously no treatment was available. A real advance - The product is an important therapeutic innovation but has certain limitations. Offers an advantage - The product has some value but does not fundamentally change present therapeutic practice. Possibly Helpful - The product has minimal additional value, and should not change prescribing habits except in rare circumstances. Judgement reserved - The Committee postpones its judgement until better data and a more thorough evaluation of the drug are available. Nothing New - The product may be a new substance but is superfluous because it does not add to the clinical possibilities offered by previous products available. In most cases these are “me-too” products. Not acceptable - Product without evident benefit over others but with potential or real disadvantages.

With acknowledgement to Prescrire

To Decide Where A Medication Is To Be Used In Suffolk

Criterion Red Amber Green D Green Skills of the Experience Of The Condition Specific Specific Specific General prescriber Diagnosis Specific Specific Specific General Monitoring Progress Of Treatment Difficult Specific General General

Therapy Patient Selection Difficult Specific Specific Easy Initiation Of Treatment Difficult Difficult Easy Easy Dose Titration Difficult Specific Easy Easy Monitoring Of Side Effects Complex Easy Easy Easy Method Of Administration Complex Normal Normal Normal Discontinuation Of Treatment Complex Complex Easy Easy

M:\Drug & Therapeutics\Suffolk\