Patients with acute peptic ulcer, ulcerative colitis, Crohn’s disease or bowel obstruction were not included in FOSRENOL® clinical studies. Caution should be used in patients with these conditions.
Abdominal x-rays of patients taking lanthanum carbonate may have a radio-opaque appearance typical of an imaging agent.
There were no differences in the rates of fracture or mortality in patients treated with FOSRENOL® compared to alternative therapy for up to 3 years. The duration of treatment exposure and time of observation in the clinical program are too short to conclude that FOSRENOL® does not affect the risk of fracture or mortality beyond 3 years.
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.
Notify your physician that you are taking FOSRENOL® prior to an abdominal x-ray (see PRECAUTIONS, Diagnostic Tests).
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 and pharmacokinetics of FOSRENOL® are unaffected by co-administration 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 chloride at doses up to 0.1 mg/kg, a dose that produced plasma lanthanum concentrations >2000 times the peak human plasma concentration.
Lanthanum carbonate, at doses up to 2000 mg/kg/day (3.4 times the MRHD), did not affect fertility or mating performance of male or female rats.
Pregnancy Category C. No adequate and well-controlled studies have been conducted in pregnant women. The effect of FOSRENOL® on the absorption of vitamins and other nutrients has not been studied in pregnant women. FOSRENOL® is not recommended for use during pregnancy.
In pregnant rats, oral administration of lanthanum carbonate at doses as high as 2000 mg/kg/day (3.4 times the MRHD) resulted in no evidence of harm to the fetus. In pregnant rabbits, oral administration of lanthanum carbonate at 1500 mg/kg/day (5 times the MRHD) was associated with a reduction in maternal body weight gain and food consumption, increased post-implantation loss, reduced fetal weights, and delayed fetal ossification. Lanthanum carbonate administered to rats from implantation through lactation at 2000 mg/kg/day (3.4 times the MRHD) caused delayed eye opening, reduction in body weight gain, and delayed sexual development (preputial separation and vaginal opening) of the offspring.
Labor and Delivery
No lanthanum carbonate treatment-related effects on labor and delivery were seen in animal studies. The effects of lanthanum carbonate on labor and delivery in humans is unknown.
It is not known whether lanthanum carbonate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when FOSRENOL® is administered to a nursing woman.
Of the total number of patients in clinical studies of FOSRENOL®, 32% (538) were ≥ 65, while 9.3% (159) were ≥ 75. No overall differences in safety or effectiveness were observed between patients ≥ 65 years of age and younger patients.
While growth abnormalities were not identified in long-term animal studies, lanthanum was deposited into developing bone including growth plate. The consequences of such deposition in developing bone in pediatric patients are unknown. Therefore, the use of FOSRENOL® in this population is not recommended.