SIDE EFFECTS
Serious and important adverse reactions described elsewhere in labeling include:
- Opioid withdrawal
- Severe abdominal pain and/or diarrhea
- Gastrointestinal perforation
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 MOVANTIK in 1497 patients in clinical trials, including 537 patients exposed for greater than six months, and 320 patients exposed for 12 months.
The safety data described in Table 1 are derived from two double-blind, placebo-controlled trials (Studies 1 and 2) in patients with OIC and non-cancer related pain. Study 3 (n=302) was a safety extension study that allowed patients from Study 1 to continue the same blinded treatment for an additional 12 weeks. Safety data for patients in Study 3 are similar to those listed in Table 1. Study 4 (n=844) was a Phase 3, 52-week, multi-center, open-label, randomized, parallel group, safety and tolerability study of naloxegol versus usual care treatment for OIC (as determined by the investigator and excluding peripheral opioid antagonists) in patients with non-cancer related pain. The population enrolled in Study 4 was similar to that of the other studies. Eligible patients were randomized in a 2:1 ratio to receive either naloxegol 25 mg once daily or usual care treatment for OIC. The most commonly used laxatives in the usual care group were rectal stimulants (e.g., bisacodyl), oral stimulants (e.g., senna), and oral osmotics (e.g., macrogol, magnesium). Safety data for patients in Study 4 are similar to those listed in Table 1.
Table 1 lists adverse reactions in pooled Studies 1 and 2 occurring in ≥ 3% of patients receiving MOVANTIK 12.5 mg or 25 mg and at an incidence greater than placebo.
Table 1. Adverse Reactions* in Patients with OIC and Non-Cancer Pain (Studies 1 and 2)
| Adverse Reaction | MOVANTIK 25 mg (n=446) |
MOVANTIK 12.5 mg (n=441) |
Placebo (n=444) |
| Abdominal Pain | 21% | 12% | 7% |
| Diarrhea | 9% | 6% | 5% |
| Nausea | 8% | 7% | 5% |
| Flatulence | 6% | 3% | 3% |
| Vomiting | 5% | 3% | 4% |
| Headache | 4% | 4% | 3% |
| Hyperhidrosis | 3% | <1% | <1% |
| *Adverse reactions occurring in ≥3% of patients receiving MOVANTIK 12.5 mg or 25 mg and at an incidence greater than placebo. | |||
Opioid Withdrawal
Possible opioid withdrawal, defined as at least three adverse reactions potentially related to opioid withdrawal that occurred on the same day and were not all related to the gastrointestinal system, occurred in less than 1% (1/444) of placebo subjects, 1% (5/441) receiving MOVANTIK 12.5 mg, and 3% (14/446) receiving MOVANTIK 25 mg in Studies 1 and 2 regardless of maintenance opioid treatment. Symptoms included but were not limited to hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Patients receiving methadone as therapy for their pain condition were observed in Studies 1 and 2 to have a higher frequency of gastrointestinal adverse reactions than patients receiving other opioids [39% (7/18) vs. 26% (110/423) in the 12.5 mg group; 75% (24/32) vs. 34% (142/414) in the 25 mg group].