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®
(naldemedine). 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.
Symproic 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.
Full Prescribing Information and
Medication Guide for Symproic.
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