Velphoro

Velphoro (sucroferric oxyhydroxide) is a phosphate binder indicated for the control of serum phosphorus levels in patients with chronic kidney disease on dialysis.

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Hemochromatosis (a genetic disorder which causes too much iron in the blood), history of or
• Liver disease or
• Major surgery in your stomach or bowels or
• Peritonitis (inflammation of peritoneum) or
• Stomach problems—This medicine has not been studied in patients with these conditions, but should be monitored for more serious side effects.

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (chewable tablets):
  • For control of phosphorus levels in patients with chronic kidney disease on dialysis:
    • Adults—500 milligrams (mg) three times a day with food. Your doctor may adjust your dose as needed. However, the dose is usually not more than 3000 mg per day.
    • Children—Use and dose must be determined by your doctor.

Hyperphosphatemia

Reduction of serum phosphorus in patients with chronic kidney disease (CKD) who are undergoing dialysis.1 2 3 4

• Importance of adhering to instructions about diet.10

• Importance of taking sucroferric oxyhydroxide as directed with meals.1

• Importance of chewing sucroferric oxyhydroxide tablets and not swallowing them whole.1 Inform patients that the tablets may be crushed to aid with chewing and swallowing.1

• Importance of instructing patients about any concomitantly used drugs that should be taken at a different time of day than when sucroferric oxyhydroxide is taken.1

• Potential for sucroferric oxyhydroxide to cause discolored (dark) stools.1

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

• Store in the original container at room temperature.
• Keep lid tightly closed.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Clinical Trial Experience

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 patients on hemodialysis and 57 patients on peritoneal dialysis exposed for up to 55 weeks. Dosage regimens ranged from 250 mg to 3,000 mg per day.

As expected with oral preparations containing iron, discolored (dark colored) feces was a commonly occurring adverse drug reaction.

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 and diarrhea (6%).

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. Similar 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%).

Postmarketing Experiences

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 Disorder: rash

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies were performed in mice and rats.

In the 2-year carcinogenicity study in mice, animals were given Velphoro by diet at doses of 250, 500 or 1,000 mg/kg/day. Rare but not statistically significant neoplastic adenocarcinomas were seen in the colon of male mice at doses of 500 and 1,000 mg/kg/day. For a 60 kg person, the no-observed-adverse-effect level (NOAEL) of 250 mg/kg/day represents 5 times (on a body weight basis) the maximum recommended clinical dose of 3,000 mg/day. In addition, an increased incidence of epithelial hyperplasia was seen in the colon at all dosage levels (i.e., ≥5 times the maximum recommended clinical dose) and in the cecum at the highest dosage (equivalent to 20 times the maximum recommended clinical dose). The development of adenocarcinoma in the male mice was considered not a genotoxic effect, but the result of chronic local irritation from high amounts of intraluminal Velphoro in the GI tract.

In the 2-year rat carcinogenicity study, animals were given Velphoro by diet at doses of 40, 150 or 500 mg/kg/day. No statistically significantly increased incidences of tumors were found, but there were increased incidences in epithelial hyperplasia with or without submucosal inflammation in duodenum, cecum and colon at the dose of 500 mg/kg/day (10 times the maximum recommended clinical dose).

Velphoro was not mutagenic, clastogenic or DNA damaging in vitro in the Ames bacterial reverse mutation test, or in the Chinese-hamster fibroblast chromosomal aberration test, or in vivo in the rat Comet assay or peripheral blood micronucleus test.

In rats, mating performance and fertility were unaffected by Velphoro at oral doses up to 800 mg/kg/day (16 times the maximum recommended clinical dose).

Animal Toxicity and/or Pharmacology

In pregnant rats given up to 800 mg/kg/day Velphoro by oral gavage from Days 6 to 17 post-mating, no embryo-fetal development toxicity was observed. This dose corresponds to 16 times the maximum recommended clinical dose.

In pregnant rabbits given 50, 100 or 200 mg/kg/day Velphoro by oral gavage, from Days 6 to 19 post-mating, the number of fetuses with incomplete/unossified epiphyses and metacarpals/phalanges was increased at the highest dose (corresponding to 4 times the recommended maximum clinical dose). Litter parameters were not adversely affected.

In pregnant rats given Velphoro at 100, 280, or 800 mg/kg/day by oral gavage from Day 6 post-mating to lactation Day 20, offspring body weight gain was lower at age 5-13 weeks and neuromuscular function was delayed at the dose of 800 mg/kg/day. This dose represented 16 times the maximum recommended clinical dose.

Velphoro (sucroferric oxyhydroxide) is a phosphate binder that helps prevent hypocalcemia (low levels of calcium in the blood) caused by elevated phosphorus.

Velphoro is used to control phosphorus levels in people with chronic kidney disease who are on dialysis.

Velphoro may also be used for purposes not listed in this medication guide.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.