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
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 the potential for additive effect and increased risk of opioid withdrawal.
Use in Specific Populations
Naldemedine 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® compared to placebo in two pooled 12-week studies were: abdominal pain (8% vs 2%), diarrhea (7% vs 2%), nausea (4% vs 2%), and gastroenteritis (2% vs 1%).
The incidence of adverse reactions of opioid withdrawal in two pooled 12-week studies was 1% (8/542) for SYMPROIC® and 1% (3/546) for placebo. In a 52-week study, the incidence was 3% (20/621) for SYMPROIC® and 1% (9/619) for placebo.
To report suspected Adverse Reactions, contact BioDelivery Sciences International, Inc. at 1-800-469-0261 or FDA at 1‑800‑FDA‑1088 or www.fda.gov/medwatch.