Symproic® (naldemedine) is indicated for the treatment of opioid‑induced constipation (OIC) in adult patients with chronic non‑cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation.
IMPORTANT SAFETY INFORMATION
• Patients with known or suspected gastrointestinal (GI) obstruction and patients at increased risk of recurrent obstruction, due to the potential for GI perforation.
• Patients with a history of a hypersensitivity reaction to Symproic. Reactions have included bronchospasm and rash.
WARNINGS AND PRECAUTIONS
Cases of GI perforation have been reported with use of another peripherally acting opioid antagonist in patients with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the GI tract. Monitor for the development of severe, persistent, or worsening abdominal pain; discontinue if this symptom develops.
Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, increased lacrimation, hot flush/flushing, pyrexia, sneezing, feeling cold, abdominal pain, diarrhea, nausea, and vomiting have occurred in patients treated with Symproic.
Patients having disruptions to the blood‑brain barrier may be at increased risk for opioid withdrawal or reduced analgesia. Take into account the overall risk‑benefit profile when using Symproic in such patients. Monitor for symptoms of opioid withdrawal in such patients.
Avoid use with strong CYP3A inducers (e.g., rifampin) because they may reduce the efficacy of Symproic.
Use with moderate (e.g., fluconazole) and strong (e.g., itraconazole) CYP3A inhibitors and P‑glycoprotein inhibitors (e.g., cyclosporine) may increase Symproic concentrations. Monitor for potential adverse reactions.
Avoid use of Symproic with another opioid antagonist due to potential for additive effect and increased risk of opioid withdrawal.
USE IN SPECIFIC POPULATIONS
Symproic crosses the placenta and may precipitate opioid withdrawal in a fetus due to the immature fetal blood‑brain barrier. Symproic should be used during pregnancy only if the potential benefit justifies the potential risk. Because of the potential for serious adverse reactions, including opioid withdrawal in breastfed infants, a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.
Avoid use in patients with severe hepatic impairment. No dose adjustment of Symproic is required in patients with mild or moderate hepatic impairment.
The most common adverse reactions with Symproic as compared to placebo in clinical trials were: abdominal pain (8% vs 2%), diarrhea (7% vs 2%), nausea (4% vs 2%), and gastroenteritis (2% vs 1%).
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.
To report suspected Adverse Reactions, contact Shionogi at 1‑800‑849‑9707 or FDA at 1‑800‑FDA‑1088 or www.fda.gov/medwatch.