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Go with SYMPROIC® (naldemedine): Proven efficacy for OIC

SYMPROIC is indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic noncancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (eg, weekly) opioid dosage escalation.


SYMPROIC is the only PAMORA with both a strong recommendation and high quality of evidence from the American Gastroenterological Association.3


SYMPROIC is contraindicated for patients with known or suspected gastrointestinal obstruction or at increased risk of recurrent obstruction and for patients with a history of a hypersensitivity reaction to naldemedine.


SYMPROIC was studied in two 12-week clinical trials and a 52-week safety study.1,6 Learn more about each study below.

Go with SYMPROIC®: Proven efficacy for OIC

SYMPROIC is indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic noncancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation.


SYMPROIC is the only PAMORA with both a strong recommendation and high quality of evidence from the American Gastroenterological Association.3


SYMPROIC is contraindicated for patients with known or suspected gastrointestinal obstruction or at increased risk of recurrent obstruction and for patients with a history of a hypersensitivity reaction to naldemedine.


SYMPROIC was studied in two 12-week clinical trials and a 52-week safety study.1,6 Learn more about each study below.

Responder rate
More Frequent
More Complete
With Less Straining
Long-term

SYMPROIC clinical trials included over 1000 patients with OIC2

Two replicate, 12-week, randomized, double-blind, placebo-controlled trials2,6Chart showing randomization used in study
Patient demographics2,6Chart showing patient demographics of those included in study
Study population2,6
  • Eligible patients with OIC and chronic noncancer pain received a stable opioid morphine equivalent daily dose of at least 30 mg for 4 weeks or more before enrollment and self-reported OIC
  • OIC was confirmed through a 2-week run-in period and was defined as no more than 4 SBMs over 14 consecutive days and fewer than 3 SBMs in a given week, with at least 25% of the SBMs associated with one or more of the following conditions: (1) straining, (2) hard or lumpy stools, (3) having a sensation of incomplete evacuation, or (4) having a sensation of anorectal obstruction/blockage. SBM was defined as a BM without rescue laxative taken within the past 24 hours
  • Patients were not using laxatives or were willing to discontinue laxatives
  • Patients were excluded if they had no BMs over the 7 consecutive days before and during the 2-week screening period; patients who had never taken laxatives were excluded, as well as those with evidence of significant structural abnormalities of the gastrointestinal tract

    • BM=bowel movement; SBM=spontaneous bowel movement.

Proven efficacy in two 12-week, randomized, double-blind, placebo-controlled clinical trials

The efficacy of SYMPROIC was assessed in 2 studies using a responder analysis. A responder was defined as a patient who had at least 3 SBMs per week and a change from baseline of at least 1 SBM per week for at least 9 out of the 12 weeks and 3 out of the last 4 weeks in the 2 studies.

Responder rates were significantly higher with SYMPROIC than with placebo2,6Chart of Primary Endpoint for responder rate
Primary endpoint: Responder rate2,6Chart showing responder rate outcomes in two studies vs placebo

Patients taking SYMPROIC had SBMs more frequently, more completely, and with less straining compared to placebo2,6

More frequent SBMs with SYMPROIC

Secondary endpoint: Frequency of SBMs per week from baseline to the first week2Chart showing frequency of SBMs against baseline after 1 week on Symproic vs placebo

Statistically significant increase in frequency of SBMs per week from baseline to Week 1 vs placebo2

Statistically significant increase in frequency of SBMs per week from baseline to the last 2 weeks vs placebo2

SYMPROIC is contraindicated in patients with known or suspected gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation and patients with a history of a hypersensitivity reaction to naldemedine. Reactions have included bronchospasm and rash.
Secondary endpoint: Frequency of SBMs per week from baseline to the last 2 weeks2Chart showing frequency of SMBs against baseline after 2 weeks on Symproic vs placebo

More complete SBMs with SYMPROIC

Secondary endpoint: Frequency of CSBMs2Chart showing frequency of CSBMs in last two weeks of study

Statistically significant increase in frequency of complete SBMs (CSBMs) per week from baseline to the last 2 weeks vs placebo2

More SBMs with less straining with SYMPROIC

Statistically significant increase in frequency of SBMs with less straining per week from baseline to the last 2 weeks vs placebo2

Secondary endpoint: Frequency of SBMs with less straining2 Chart showing frequency of SBMs with less straining in the last two weeks of study

SYMPROIC is the only therapy with both a strong recommendation and high quality of evidence from the American Gastroenterological Association3*


*For laxative-refractory OIC.

Proven long-term efficacy with SYMPROIC®

Significant and sustained increase in bowel movements from baseline vs placebo over 52 weeks1Chart plotting significant and sustained increase in bowel movements from baseline vs placebo over 52 weeks

SYMPROIC (naldemedine) is the only PAMORA with a double-blind, placebo-controlled, long-term efficacy study3


Cases of gastrointestinal 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 gastrointestinal tract (e.g., peptic ulcer disease, Ogilvie’s syndrome, diverticular disease, infiltrative gastrointestinal tract malignancies, or peritoneal metastases). Take into account the overall risk-benefit profile when using SYMPROIC in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn’s disease). Monitor for the development of severe, persistent, or worsening abdominal pain; discontinue SYMPROIC in patients who develop this symptom.

SYMPROIC had low rates of abdominal pain across 3 studies1,2,6


Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Abdominal pain occurred in at least 8% of patients receiving SYMPROIC and at an incidence greater than placebo. Abdominal pain includes abdominal discomfort and pain in both the upper and lower abdomen.
SYMPROIC Tolerability
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.
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 Collegium Pharmaceutical, Inc. at 1-855-331-5615 or the FDA at 1-800-FDA-1088 or www.fda.gov/safety/medwatch.

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