IS OIC GETTING IN THE WAY?

Opioids bind to the mu-opioid receptors in the gut, which may lead to OIC1

About 40%-50% of patients receiving opioid therapy for chronic non-cancer pain report developing OIC2-5

In a longitudinal study of 493 adults with chronic non-cancer pain and OIC, 83% reported straining to pass bowel movements6

Laxatives do not address the underlying mechanism of OIC7

OIC is defined as a change in baseline bowel habits upon initiation of opioid therapy, including any of the following8:

  • Decreased frequency
  • Straining
  • Incomplete evacuation
  • Harder stool consistency
OIC=opioid-induced constipation; OTC=over the counter.

Not all constipation is the same

Watch the video below to learn how opioids interact with the body, which can cause a distinct form of constipation called OIC.

Transcript

Opioids are used to treat a wide variety of pain conditions including chronic and cancer related pain. These therapies have proven analgesic efficacy that are associated with a number of adverse eventssuch as nausea, vomiting, and constipation. Opioid receptors are highly expressed within the spinal cords. Dorsal Horn, which relays pain signals to the central nervous system and areas of the brain involved in pain transmission. Most opioids produce analgesia by binding to mu opioid receptors within the central nervous system, including the dorsal horn at the spinal cord. This reduces neuronalexcitability by impacting neurotransmission leading to an overall inhibitory effect on the neuron resulting in pain relief. However, opioid receptors are also widely distributed throughout the peripheral nervous system, including the gastrointestinal system. Constipation in opiate users is a common adverse event resulting from the activation of Mu opioid receptors on neurons in the myenteric and submucosal plexuses at the enteric nervous system or ENS within the GI tract.

This activation slows Gi motility and reduces secretions into the gut lumen. This can lead to a distinctform of constipation called opioid induced constipation. OIC. This consists in a change from baselinebowel habits characterized by any of the following, reduce bowel movement frequency, the development or worsening of straining to pass bowel movements, a sense of incomplete rectal evacuation or harder stool consistency. Various pharmacological approaches are used to treat opioidinduced constipation, including over the counter laxatives and prescription medications such as secretagogues and peripherally acting mu opioid receptor antagonist or PAMORAs. However, PAMORAs, are specifically targeted therapy that acts on the opioid receptor, reversing the constipating effects of opioid therapy.

INDICATION

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

Contraindications

  • 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 www.fda.gov/medwatch.