SYMPROIC® (naldemedine)

  • An opioid antagonist with binding affinities for mu-, delta-, and kappa-opioid receptors9
  • Designed to have reduced ability to cross the blood–brain barrier, thereby limiting its potential to interfere with centrally mediated opioid analgesia9

Only OIC therapy with a strong recommendation and high quality of evidence from the American Gastroenterological Association.10

PAMORA=peripherally acting mu-opioid receptor antagonist.

SYMPROIC® mechanism of action

Watch the video below to learn how SYMPROIC® may decrease the constipating effects of opioids.

Symproic (naidemedine) Mechanism of Action Video Thumbnail


This video is a visual representation of the SYMPROIC® (naldemedine) Mechanism of Action.

This video is not intended to represent the efficacy or safety shown in clinical trials.

Naldemedine, the active ingredient in SYMPROIC is a peripherally acting mu-opioid receptor antagonist, or PAMORA, that is approved 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.

Naldemedine is derived from naltrexone, which has been modified to include an added side chain, which increases the molecular weight and polar surface area, to reduce its ability to cross the blood-brain barrier. Naldemedine is also a substrate of the P-glycoprotein (PgP) efflux transporter. Becauseit has a reduced ability to cross the blood-brain barrier central nervous system penetration of nalmededine is expected to be negligible at the recommended dose levels, limiting the potential to interference with centrally mediated opioid analgesics. Naldemedine is designed to inhibit the peripheral effects of opioid medications by blocking their actions at opioid receptors such as those myenteric and submucosal plexuses of the enteric nervous system (ENS) within the GI tract.

Naldemedine binds to the mu-opioid receptors located on motor neurons and secretomotor neurons within the ENS. It antagonizes the mu-opoioid receptor mediated changes in neurotransmitter release. Thereby blocking the inhibitory effect of opioids on GI motility and secretions. This leads to the decrease in the constipating effects of opioids.


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 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.

Drug Interactions

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.

Adverse Reactions

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.

Please see Full Prescribing Information and Medication Guide for SYMPROIC®.

To report suspected Adverse Reactions, contact BioDelivery Sciences International, Inc. at 1-800-469-0261 or FDA at 1‑800‑FDA‑1088 or