Drug Class Description
Drugs for treatment of hyperkalaemia and hyperphosphataemia

Generic Name
Lanthanum

Drug Description
Each chewable tablet contains lanthanum carbonate hydrate corresponding to 250 mg lanthanum. Each chewable tablet contains lanthanum carbonate hydrate corresponding to 500 mg lanthanum. Each chewable tablet contains lanthanum carbonate hydrate corresponding to 750 mg lanthanum. Each chewable tablet contains lanthanum carbonate hydrate corresponding to 1000 mg lanthanum

Presentation
Chewable tablet.250 mg: White, round, beveled-edge flat tablets embossed with 'S405/250' on one side.500 mg: White, round, beveled-edge flat tablets embossed with 'S405/500' on one side.750 mg: White, round, beveled-edge flat tablets embossed with 'S405/750' on one side.1000 mg: White, round, beveled-edge flat tablets embossed with 'S405/1000' on one side.

Indications
Fosrenol is indicated as a phosphate binding agent for use in the control of hyperphosphataemia in chronic renal failure patients on haemodialysis or continuous ambulatory peritoneal dialysis (CAPD).

Adult Dosage
Fosrenol is for oral administration.Tablets must be chewed and not swallowed whole.The experience with therapy beyond two years is limited. The risk /benefit from longer-term administration over two years should be carefully considered.Adults, including elderly ( > 65 years)Fosrenol should be taken with or immediately after food, with the daily dose divided between meals. Patients should adhere to recommended diets in order to control phosphate and fluid intake. Fosrenol is presented as a chewable tablet therefore avoiding the need to take additional fluid. Serum phosphate levels should be monitored and the dose of Fosrenol titrated every 2-3 weeks until an acceptable serum phosphate level is reached, with regular monitoring thereafter.Control of serum phosphate level has been demonstrated at doses starting from 750 mg per day. The maximum dose studied in clinical trials, in a limited number of patients, is 3750mg. Patients who respond to lanthanum therapy, usually achieve acceptable serum phosphate levels at doses of 1500 – 3000 mg lanthanum per day.Hepatic impairmentThe effect of hepatic impairment on Fosrenol pharmacokinetics has not been assessed. Due to its mechanism of action and the lack of liver metabolism doses in hepatic impairment should not be modified, but patients should be monitored carefully.

Child Dosage
The safety and efficacy of Fosrenol has not been established in patients below the age of 18 years.

Elderly Dosage
See Adult Dosage

Contra Indications
Hypersensitivity to lanthanum carbonate hydrate or to any of the excipients.Hypophosphataemia.

Special Precautions
Tissue deposition of lanthanum has been shown with Fosrenol in animal studies. In 105 bone biopsies from patients treated with Fosrenol, some for up to 4.5 years, rising levels of lanthanum were noted over time. No clinical data are available on deposition of lanthanum in other human tissues. Safety data exceeding 24 months are currently limited. The risk /benefit from longer-term administration should be carefully considered..Patients with acute peptic ulcer, ulcerative colitis, Crohn's disease or bowel obstruction were not included in clinical studies with Fosrenol. Fosrenol should be used in these patients following careful assessment of benefit and risk.Patients with renal insufficiency may develop hypocalcaemia. Fosrenol does not contain calcium. Serum calcium levels should therefore be monitored at regular time intervals for this patient population and appropriate supplements given.No pharmacokinetic data are available in patients with hepatic impairment. Lanthanum is not metabolised by liver enzymes but it is most likely excreted in the bile. Conditions resulting in a marked reduction of bile flow may be associated with incrementally slower elimination of lanthanum, which may result in higher plasma levels and increased tissue deposition of lanthanum. Caution should, therefore, be exercised in these patients, and monitoring of liver function may be required.Safety and efficacy of Fosrenol have not been established in paediatric patients; use in children is not recommended.Fosrenol should be discontinued if hypophosphataemia develops.Abdominal x-rays of patients taking lanthanum carbonate may have a radio-opaque appearance typical of an imaging agent.

Interactions
Lanthanum carbonate hydrate may increase gastric pH. It is recommended that compounds, which are known to interact with antacids, should not be taken within 2 hours of dosing with Fosrenol (e.g. chloroquine, hydroxychloroquine and ketoconazole).In healthy subjects, the absorption and pharmacokinetics of lanthanum were not affected by co-administration of citrate.Serum levels of fat-soluble vitamins A, D, E and K, were not affected by Fosrenol administration in clinical studies.Human volunteer studies have shown that co-administration of Fosrenol with digoxin, warfarin or metoprolol does not produce clinically-relevant changes in the pharmacokinetic profiles of these drugs.In simulated gastric juice, lanthanum carbonate hydrate did not form insoluble complexes with warfarin, digoxin, frusemide, phenytoin, metoprolol or enalapril, suggesting a low potential to affect the absorption of these drugs.However, interactions with drugs such as tetracycline, doxycycline and the floxacins are theoretically possible and if these compounds are to be co-administered, it is recommended that they not be taken within 2 hours of dosing with Fosrenol.Lanthanum carbonate hydrate is not a substrate for cytochrome P450 and does not significantly inhibit the activities of the major human cytochrome P450 isoenzymes, CYP1A2, CYP2D6, CYP3A4, CYP2C9 or CYP2C19 in vitro.

Adverse Reactions
The safety of Fosrenol for use in patients with end-stage renal failure (ESRF) on maintenance haemodialysis and peritoneal dialysis has been examined in three short-term, placebo-controlled, double-blind studies, three long-term, comparatorcontrolled studies, and three long-term open-label studies. These studies have provided a total safety database of 1754 patients treated with lanthanum carbonate hydrate with 495 patients with more than 1 year of treatment and 130 patients with more than 2 years of treatment and represents a mean exposure of 272.1 days (median 184.0 days, range 1-1123 days).Approximately 24% of all ESRF patients who participated in these clinical studies, reported a drug related adverse reaction, as determined by the investigator. No individual ADR was reported at a frequency greater than 10%. The most commonly reported adverse drug reactions, with the expection of hypocalcaemia, are gastrointestinal in nature; these are minimized by taking Fosrenol with food and generally abated with time with continued dosing.Organ SystemCommon Reactions (>1/100, <1/10) Uncommon Reactions (>1/1,000 to <1/100) Infections and InfestationsGastroenteritis, laryngitisBlood and lymphatic system disordersEosinophiliaEndocrine disordersHyperparathyroidismMetabolism and nutrition disordersHypocalcaemiaHypercalcaemia, hyperglycaemia, hyperphosphataemia, hypophosphataemia, anorexia, appetite increasedNervous system disordersDizziness, headache, taste alterationEar and Labyrinth disordersVertigoGastrointestinal disordersAbdominal pain, constipation, diarrhoea, dyspepsia, flatulence, nausea, vomitingEructation, indigestion, irritable bowel syndrome, dry mouth, oesophagitis, stomatitis, loose stools, tooth disorder, gastro-intestinal disorder NOS*Skin and subcutaneous tissue disordersAlopecia, itching, pruritus, erythematous rash, sweating increasedMusculoskeletal and connective tissue disordersArthralgia, myalgia, osteoporosisGeneral disordersAsthenia, chest pain, fatigue, malaise, peripheral oedema, pain, thirst.InvestigationsBlood aluminium increased, increase in GGT, increases in hepatic transaminases, alkaline phosphatase increased, weight decrease.* Not otherwise specifiedAlthough there have been a number of additional isolated reactions reported, none of these reactions are considered unexpected in this patient population.Transient QT changes have been observed but these were not associated with an increase of cardiac adverse events.

Manufacturer
Shire Pharmaceuticals Limited

Drug Availability
(POM)

Updated
11 August 2009