SYMPROIC SIDE EFFECTS

SIDE EFFECTS

Serious and important adverse reactions described elsewhere in labeling include:

• Gastrointestinal perforation
• Opioid withdrawal

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

The data described below reflect exposure to SYMPROIC in 1163 patients in clinical trials, including 487 patients with exposures greater than six months and 203 patients with exposures of 12 months.

The following safety data are derived from three double-blind, placebo-controlled trials in patients with OIC and chronic non-cancer pain: two 12-week studies (Studies 1 and 2) and one 52-week study (Study 3).

In Studies 1 and 2, patients on laxatives were required to discontinue their use prior to study enrollment. All patients were restricted to bisacodyl rescue treatment during the study. In Study 3, approximately 60% of patients in both treatment groups were on a laxative regimen at baseline; patients were allowed to continue using their laxative regimen throughout the study duration. The safety profile of SYMPROIC relative to placebo was similar regardless of laxative use.

Tables 1 and 2 list common adverse reactions occurring in at least 2% of patients receiving SYMPROIC and at an incidence greater than placebo. Table 1 shows pooled 12-week data from Studies 1 and 2. Table 2 shows 12-week data from Study 3.

Table 1: Common Adverse Reactions* in Patients with OIC and Chronic Non-Cancer Pain (12-week data from Studies 1 and 2)

Table 2: Common Adverse Reactions* in Patients with OIC and Chronic Non-Cancer Pain (12-week data from Study 3)

Adverse reactions up to 12 months in Study 3 are similar to those listed in Tables 1 and 2 (diarrhea: 11% vs. 5%, abdominal pain: 8% vs. 3%, and nausea: 8% vs. 6% for SYMPROIC and placebo, respectively).

Opioid Withdrawal

In Studies 1, 2 and 3, adverse reactions consistent with opioid withdrawal were based on investigator assessment and adjudicated based upon the occurrence of at least 3 adverse reactions potentially related to opioid withdrawal with onset of a constellation of those symptoms occurring on the same day or within one day of each other.

Adverse reactions of possible opioid withdrawal could include non-gastrointestinal (GI) symptoms (e.g., hyperhidrosis, hot flush or flushing, chills, tremor, tachycardia, anxiety, agitation, yawning, rhinorrhea, increased lacrimation, sneezing, feeling cold, and pyrexia), GI symptoms (e.g., vomiting, diarrhea, or abdominal pain), or both GI and non-GI symptoms.

In pooled Studies 1 and 2, the incidence of adverse reactions of opioid withdrawal was 1% (8/542) for SYMPROIC and 1% (3/546) for placebo. In Study 3 (52-week data), the incidence was 3% (20/621) for SYMPROIC and 1% (9/619) for placebo. Most SYMPROIC treated subjects experienced nearly equal incidence of GI only or both GI and non-GI symptoms.

Less Common Adverse Reactions

Two patients developed symptoms of hypersensitivity following a single dose of SYMPROIC. One patient reported bronchospasm and another rash.