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Overall tolerability comparable to placebo in clinical trials*

*Total treatment-emergent adverse event (TEAE) rates from Study 1 were 49% for SYMPROIC (n=271) and 45% for placebo (n=272). Total TEAE rates from Study 2 were 50% for SYMPROIC (n=271) and 48% for placebo (n=274).

Overall tolerability comparable to placebo in clinical trials*

*Total treatment-emergent adverse event (TEAE) rates from Study 1 were 49% for SYMPROIC (n=271) and 45% for placebo (n=272). Total TEAE rates from Study 2 were 50% for SYMPROIC (n=271) and 48% for placebo (n=274).

Low rate of GI adverse reactions, including abdominal pain

Postmarketing cases of GI perforation, including fatal cases, were reported when SYMPROIC was used in patients at risk of GI perforation (eg., GI cancer, past GI surgery, diverticulitis, chemotherapy/radiation).

12-week data from Studies 1 and 22,612-week data from 2 Studies showing improvements in abdominal pain, diarrhea, nausea and gastroenteritis
*Adverse reactions occurring in ≥2% of patients receiving SYMPROIC and at an incidence greater than placebo.
†Abdominal pain includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, and gastrointestinal pain.

Opioid withdrawal comparable to placebo2,6

  • 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

Clusters of 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.

Explore the SYMPROIC dosing and administration guidelines

SYMPROIC Dosing

What are the side effects of SYMPROIC®?

In SYMPROIC (naldemedine) clinical trials, patients experienced low rates of adverse reactions, including abdominal pain.1,2,6


Common side effects of SYMPROIC

  • Abdominal pain
  • Diarrhea
  • Nausea
  • Gastroenteritis
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.

What are the side effects of SYMPROIC®?

In SYMPROIC (naldemedine) clinical trials, patients experienced low rates of adverse reactions, including abdominal pain.1,2,6


Common side effects of SYMPROIC

  • Abdominal pain
  • Diarrhea
  • Nausea
  • Gastroenteritis
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.

Long-term tolerability over 52 weeks

12-week data from Study 31,2Data from study after 52 weeks showing sustained improvement
*Adverse reactions occurring in ≥2% of patients receiving SYMPROIC and at an incidence greater than placebo.
†Abdominal pain includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, and gastrointestinal pain.

Adverse reactions up to 12 months in Study 3 are similar to the 12-week data from all trials (diarrhea: 11% vs. 5%, abdominal pain: 8% vs. 3%, and nausea: 8% vs. 6% for SYMPROIC and placebo, respectively).

Cases of gastrointestinal (GI) perforation have been reported with use of another peripherally acting opioid antagonist, including SYMPROIC. Postmarketing cases of GI perforation, including fatal cases, were reported when SYMPROIC was used in patients at risk of GI perforation (eg., GI cancer, past GI surgery, diverticulitis, chemotherapy/radiation).

Low rates of opioid withdrawal1,2

  • In a long-term study (52-week data), the incidence of adverse reactions of opioid withdrawal was 3% (20/621) for SYMPROIC and 1% (9/619) for placebo
  • Clusters of 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

WARNINGS AND PRECAUTIONS

Opioid Withdrawal: 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.

SYMPROIC targets the underlying cause of OIC

SYMPROIC MOA
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.
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
Gastrointestinal Perforation

Cases of gastrointestinal (GI) perforation have been reported with use of another peripherally acting opioid antagonist, including SYMPROIC. Postmarketing cases of GI perforation, including fatal cases, were reported when SYMPROIC was used in patients at risk of GI perforation (eg., GI cancer, past GI surgery, diverticulitis, chemotherapy/radiation). SYMPROIC is contraindicated in patients with known or suspected gastrointestinal obstruction or in patients at risk of recurrent obstruction. 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.

Opioid Withdrawal

Clusters of 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%).

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.

Please see Full Prescribing Information and Medication Guide for SYMPROIC.

To report SUSPECTED ADVERSE REACTIONS, contact Collegium Pharmaceutical, Inc. at 855-331-5615 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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