Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
WARNINGS AND PRECAUTIONS (Revisions)
- Serious cases of gastrointestinal obstruction, ileus, subileus, gastrointestinal perforation and fecal impaction have been reported in patients taking association with lanthanum, some requiring surgery or hospitalization. Risk factors for gastrointestinal obstruction and gastrointestinal perforation identified from post-marketing reports in patients taking FOSRENOL Chewable Tablets include altered gastrointestinal anatomy (e.g., diverticular disease, peritonitis, history of gastrointestinal surgery, gastrointestinal colon cancer, gastrointestinal ulceration), hypomotility disorders (e.g., constipation, ileus, subileus, diabetic gastroparesis) and concomitant medications (e.g., calcium channel blockers). Some cases were reported in patients with no history of gastrointestinal disease.
- Advise patients who are prescribed FOSRENOL Chewable Tablets to chew the tablet completely to reduce the risk of serious adverse gastrointestinal events such as those described above.
The following adverse reactions are discussed in greater detail in other sections of the labeling:
- Gastrointestinal Adverse Effects
- intestinal perforation, intestinal obstruction, ileus, subileus
7 DRUG INTERACTIONS
- .... There are no empirical data on avoiding drug interactions between FOSRENOL and most concomitant oral drugs. For oral medications where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, consider separation of the timing of the administration of the two drugs. The duration of separation depends upon the absorption characteristics of the medication concomitantly administered, such as the time to reach peak systemic levels and whether the drug is an immediate release or an extended release product. Consider monitoring clinical responses or blood levels of concomitant medications that have a narrow therapeutic range.
- The most common adverse reactions for Fosrenol were gastrointestinal events, such as...abdominal pain
- In pooled active comparator controlled clinical trials, hypocalcemia was noted with an incidence of approximately 5% in both lanthanum and active comparator groups. A nonclinical study and a phase 1 study have shown reduced absorption of calcium in the intestine with lanthanum carbonate treatment.
- Bowel obstruction, ileus, and fecal impaction
5 WARNINGS AND PRECAUTIONS
5.1 Gastrointestinal Adverse Effects
- There have been reports of serious cases of gastrointestinal obstruction, ileus, and fecal impaction reported in association with lanthanum, some requiring surgery or hospitalization. Risk factors for gastrointestinal obstruction...
5.2 Diagnostic Tests
- Fosrenal has radio-opaque properties and therefore may give the appearance typical of an imaging agent during abdominal X-ray procedures.
6 ADVERSE REACTIONS
- Overall, the safety profile of Fosrenol has been studied in over 5200 subjects in completed clinical trials. The most common adverse reactions for Fosrenol were gastrointestinal events, such as nausea and vomiting and they generally abated over time with continued dosing.
6.1 Clinical Trials Experience
- ...added: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- ...Table 1 changed - please see PI for changes
- ...The safety of Fosrenol was studied in two long-term clinical trials, which included 1215 patients treated with Fosrenal and 944 with alternative therapy...
6.2 Postmarketing Experience
- The following adverse reactions have been identified during post-approval use of Fosrenol: constipation, dyspepsia, allergic skin reactions, hypophosphatemia, and tooth injury
7 DRUG INTERACTIONS
- Lanthanum in Fosrenol has the potential to bind to drugs with anionic (e.g., carboxyl, carbonyl and hydroxyl) groups......or three hours after Fosrenol. Monitor blood levels of the concomitant drugs that have a narrow therapeutic range
7.1 Drugs Binding to Antacids
- ...There is a potential for Fosrenol to interact with compounds which bind to cationicantacids (i.e. aluminum-, magnesium-, or calcium-based). Therefore, do not take such compounds within 2 hours...
7.2 Quinolone Antibiotics
- ...Co-administration of Fosrenol with quinolone antibiotics may...
- ...The bioavailability of levothyroxine was decreased by...
8 USE IN SPECIFIC POPULATIONS
- ...Studies in pregnant rabbits showed that...
8.4 Pediatric Use
- ...The safety and efficacy of Fosrenol in pediatric patients have not been established. While growth abnormalities...