Information for the Patient:
FOSRENOL tablets should be taken with or immediately after meals. Tablets should be chewed completely before swallowing. Intact tablets should not be swallowed.
FOSRENOL is not metabolized.
Studies in healthy subjects have shown that FOSRENOL does not adversely affect the pharmacokinetics of warfarin, digoxin or metoprolol. The absorption of FOSRENOL is unaffected by coadministration with citrate-containing compounds (see CLINICAL PHARMACOLOGY: In Vitro/In Vivo Drug Interactions).
An in vitro study showed no evidence that FOSRENOL forms insoluble complexes with warfarin, digoxin, furosemide, phenytoin, metoprolol and enalapril in simulated gastric fluid. However, it is recommended that compounds known to interact with antacids should not be taken within 2 hours of dosing with FOSRENOL.
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Oral administration of lanthanum carbonate to rats for up to 104 weeks, at doses up to 1500 mg of the salt per kg/day [2.5 times the maximum recommended daily human dose (MRHD) of 5725 mg, on a mg/m2 basis, assuming a 60-kg patient] revealed no evidence of carcinogenic potential. In the mouse, oral administration of lanthanum carbonate for up to 99 weeks, at a dose of 1500 mg/kg/day (1.3 times the MRHD) was associated with an increased incidence of glandular stomach adenomas in male mice.
Lanthanum carbonate tested negative for mutagenic activity in an in vitro Ames assay using
Salmonella typhimurium and Escherichia coli strains and in vitro HGPRT gene mutation and chromosomal aberration assays in Chinese hamster ovary cells. Lanthanum carbonate also tested negative in an oral mouse micronucleus assay at doses up to 2000 mg/kg (1.7 times the MRHD), and in micronucleus and unscheduled DNA synthesis assays in rats given IV lanthanum chlori