Lanthanum carbonate hydrate

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Fosrenol (Orphan)
500 mg, 750 mg and 1000 mg chewable tablets
Approved indication: hyperphosphataemia in chronic renal failure
Australian Medicines Handbook section 7.7

Patients being treated with continuous ambulatory peritoneal dialysis or haemodialysis for chronic renal failure are at risk of hyperphosphataemia. High phosporus concentrations are associated with increased mortality. To try and control hyperphosphataemia patients may be given binding agents such as calcium carbonate. These bind to phosphate in the gut to reduce its absorption.

Lanthanum is a rare earth element which can bind phosphate. The tablets of lanthanum carbonate hydrate dissociate in the acid environment of the upper gastrointestinal tract to release lanthanum ions. These ions bind with dietary phosphate to form lanthanum phosphate. As this compound is insoluble phosphate absorption is reduced. The dose is adjusted every 2-3 weeks until the serum phosphate concentration is controlled. Most patients will require a total daily dose of 1500-3000 mg. The tablets are chewed three times a day with meals.

A six-week double-blind study compared lanthanum to placebo in 145 patients with end-stage renal disease and a serum phosphorus of at least 1.8 mmol/L. There was a dose-related reduction in serum phosphorus within two weeks of starting therapy.¹

Another placebo-controlled trial enrolled 163 patients having haemodialysis. After a washout period and a dose-titration period, 94 patients were entered into a double-blind phase. This maintenance phase lasted for four weeks. At the end of this phase the serum phosphorus concentration in patients given placebo was similar to the concentration at the end of the washout period. The patients who continued lanthanum during the maintenance phase retained control of their phosphorus concentrations. At the end of the study their mean concentration was 1.92 mmol/L compared with 2.53 mmol/L in the placebo group.²

Comparative studies with other phosphate binders are limited. One study compared the effects of lanthanum carbonate and calcium carbonate on the development of renal osteodystrophy in 98 patients.³ After one year 15% of the patients given lanthanum had normal bone histology compared with only 3% of the patients given calcium carbonate. Both binders controlled the phosphorus concentration.

Lanthanum is less likely to cause hypercalcaemia than calcium-based binders, but it may have more gastrointestinal adverse effects such as diarrhoea, nausea and vomiting. Although only a little lanthanum is absorbed it is distributed into bone. Lanthanum is only slowly released (half-life greater than 26 weeks) and its long-term effects are unknown. Patients should not take lanthanum for more than two years.

Although lanthanum probably has advantages over calcium-based binders, so may sevelamer hydrochloride, another recently approved phosphate binder. There appear to be no published comparative trials of lanthanum and sevelamer. These drugs are more expensive than calcium carbonate and it is uncertain if their benefits outweigh their higher price.

manufacturer provided some dataa

The Transparency Score () is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.

Notes on references

At the time the comment was prepared, information about this drug was available on the website of the Food and Drug Administration in the USA (www.fda.gov).

At the time the comment was prepared, a scientific discussion about this drug was available on the website of the European Agency for the Evaluation of Medicinal Products (www.emea.eu.int).