Velphoro

5 WARNINGS AND PRECAUTIONS Patients with peritonitis during peritoneal dialysis, significant gastric or hepatic disorders, history of recent major gastrointestinal surgery, or with a history of hemochromatosis or other diseases with iron accumulation have not been included in clinical studies with Velphoro. Monitor effect and iron homeostasis in such patients. ( 5.1 ) 5.1 Monitoring in Patients with Gastrointestinal Disorders or Iron Accumulation Disorders Each chewable tablet contains 500 mg iron (equivalent to 2,500 mg sucroferric oxyhydroxide) [see Clinical Pharmacology (12.3) ] . Patients with peritonitis during peritoneal dialysis, significant gastric or hepatic disorders, following major gastrointestinal (GI) surgery, or with a history of hemochromatosis or other diseases with iron accumulation have not been included in clinical studies with Velphoro. Monitor effect and iron homeostasis in such patients.

6 ADVERSE REACTIONS The most common adverse drug reactions to Velphoro chewable tablets in clinical trials were discolored feces (12%) and diarrhea (6%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Medical Care Renal Therapies Group, LLC at 1-800-323-5188 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience Adult Patients Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the 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. The safety data derived from Velphoro clinical trials reflect exposure to Velphoro in 2 active-controlled clinical studies involving a total of 778 adult patients on hemodialysis and 57 adult patients on peritoneal dialysis exposed for up to 55 weeks. Dosage regimens ranged from 250 mg to 3,000 mg per day. In a parallel design, dose-finding study of Velphoro with a treatment duration of 6 weeks in hemodialysis patients, adverse reactions for Velphoro (N=128) were similar to those reported for the active-control group (sevelamer hydrochloride) (N=26), with the exception of discolored feces (12%) which did not occur in the active-control group. Diarrhea was reported in 6% of patients treated with Velphoro. In a 55-week, open-label, active-controlled, parallel design, safety and efficacy study involving 968 hemodialysis patients and 86 peritoneal dialysis patients treated with either Velphoro (N=707 including 57 peritoneal dialysis patients) or the active-control (sevelamer carbonate) (N=348 including 29 peritoneal dialysis patients), adverse reactions occurring in more than 5% in the Velphoro group were diarrhea (24%), discolored feces (16%), and nausea (10%). The majority of diarrhea events in the Velphoro group were mild and transient, occurring soon after initiation of treatment, and resolving with continued treatment. Adverse reactions occurred at similar rates in hemodialysis and peritoneal dialysis patients. The most common adverse reactions (>1%) leading to withdrawal were diarrhea (4%), product taste abnormal (2%), and nausea (2%). Pediatric Patients In an open-label, randomized study, with a 10-week dose titration period and 24-week safety extension, 60 patients 6 to 18 years of age received at least one dose of Velphoro, including 30 patients (50%) exposed for at least 19 weeks [see Clinical Studies (14.3) ] . The safety profile of Velphoro in pediatric patients was similar to that observed in adult patients. Velphoro is not approved in pediatric patients 6 years to less than 9 years of age because of the lack of an appropriate dosage strength. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of Velphoro that are not included in other sections of labeling. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal Disorders: tooth discoloration Skin and Subcutaneous Tissue Disorders: rash