PREPOPIK SIDE EFFECTS

SIDE EFFECTS

The following serious or otherwise important adverse reactions for bowel preparations are described elsewhere in the labeling:

• Serious Fluid and Electrolyte Abnormalities
• Cardiac Arrhythmias
• Seizures
• Use in Patients with Renal Impairment
• Colonic Mucosal Ulceration, Ischemic Colitis and Ulcerative Colitis
• Use in Patients with Significant Gastrointestinal Disease
• Aspiration
• Risk of Vomiting and Other Gastrointestinal Complications with Ingestion of Undissolved Powder

Clinical Trials 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 clinical trials of another drug and may not reflect the rates observed in practice.

In randomized, multicenter, controlled clinical trials, nausea, headache, and vomiting were the most common adverse reactions (>1%) following Prepopik administration. The patients were not blinded to the study drug. Since abdominal bloating, distension, pain/cramping, and watery diarrhea are known to occur in response to colon cleansing preparations, these effects were documented as adverse events in the clinical trials only if they required medical intervention (such as a change in study drug or led to study discontinuation, therapeutic or diagnostic procedures, met the criteria for a serious adverse event), or showed clinically significant worsening during the study that was not in the frame of the usual clinical course, as determined by the investigator.

Prepopik was compared for colon cleansing effectiveness with a preparation containing two liters (2L) of polyethylene glycol plus electrolytes solution (PEG + E) and two 5-mg bisacodyl tablets, all administered the day before the procedure. Table 1 displays the most common adverse reactions in Study 1 and Study 2 for the Prepopik Split-Dose and Day-Before dosing regimens, respectively, each as compared to the comparator preparation.

Table 1: Treatment-Emergent Adverse Reactions observed in at Least (>1%) of Patients using the Split-Dose Regimen and Day-Before Regimen **

Electrolyte Abnormalities

In general, Prepopik was associated with numerically higher rates of abnormal electrolyte shifts on the day of colonoscopy compared to the preparation containing 2L of PEG + E plus two x 5-mg bisacodyl tablets (Table 2). These shifts were transient in nature and numerically similar between treatment arms at the Day 30 visit.

Table 2: Shifts from Normal Baseline to Outside the Normal Range at Day 7 and Day 30

Pediatrics

In the pediatric patients aged 9 to 16 years who received Prepopik, the most common adverse reactions (> 5%) were nausea, vomiting, and abdominal pain. Electrolytes abnormalities were observed in pediatric patients similar to those seen in adults. Three patients had abnormally low glucose levels (40 to 47 mg/dL). Two patients received Prepopik and one received the comparator (PEG). The abnormal values occurred at the colonoscopy visit for one patient (Prepopik) and at the 5-day follow up visit for the other two patients (Prepopik and PEG). All three patients were asymptomatic.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of other oral formulations of sodium picosulfate, magnesium oxide and anhydrous citric acid similar to Prepopik. 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.

Hypersensitivity: rash, urticaria, purpura, and anaphylaxis

Gastrointestinal: abdominal pain, diarrhea, fecal incontinence, aphthoid ileal ulcers, ischemic colitis

Neurologic: generalized tonic-clonic seizures with and without hyponatremia in epileptic patients.