Important Safety Information Full Prescribing Information
Symproic

For opioid-induced constipation 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

DOSING AND ADMINISTRATION

With Symproic, there are options

One 0.2 mg tablet, once daily

Any time of day

With or without laxatives

With or without food

  • Alteration of analgesic dosing regimen prior to initiating Symproic is not required
  • Patients receiving opioids for fewer than 4 weeks may be less responsive to Symproic
  • Discontinue Symproic if treatment with the opioid pain medication is also discontinued
  • Subjects with mild, moderate, and severe renal disease, and end-stage renal disease requiring hemodialysis had similar pharmacokinetics to subjects with normal renal function
    • No dose adjustments of Symproic are required in patients with renal impairment
  • No dose adjustments of Symproic are required in patients with mild or moderate hepatic impairment. Avoid use in patients with severe hepatic impairment

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 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.

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 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.

Adverse Reactions

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.

Indication

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.

Please see Full Prescribing Information and Medication Guide for Symproic.

References: 1. Argoff CE, Brennan MJ, Camilleri M, et al. Consensus recommendations on initiating prescription therapies for opioid-induced constipation. Pain Med. 2015;16(12):2324-2337. 2. Kalso E, Edwards JE, Moore RA, McQuay HJ. Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain. 2004;112(3):372-380. 3. Cook SF, Lanza L, Zhou X, et al. Gastrointestinal side effects in chronic opioid users: results from a population-based survey. Aliment Pharmacol Ther. 2008;27(12):1224-1232. 4. Brown RT, Zuelsdorff M, Fleming M. Adverse effects and cognitive function among primary care patients taking opioids for chronic nonmalignant pain. J Opioid Manag. 2006;2(3):137-146. 5. Tuteja AK, Biskupiak J, Stoddard GJ, Lipman AG. Opioid-induced bowel disorders and narcotic bowel syndrome in patients with chronic non-cancer pain. Neurogastroenterol Motil. 2010;22(4):424-e96. 6. Coyne KS, LoCasale RJ, Datto CJ, Sexton CC, Yeomans K, Tack J. Opioid-induced constipation in patients with chronic noncancer pain in the USA, Canada, Germany, and the UK: descriptive analysis of baseline patient-reported outcomes and retrospective chart review. Clinicoecon Outcomes Res. 2014;6:269-281. 7. Emmanuel A, Johnson M, McSkimming P, Dickerson S. Laxatives do not improve symptoms of opioid-induced constipation: results of a patient survey Pain Med. 2017;18(10):1932-1940. doi:10.1093/pm/pnw240 8. Camilleri M, Drossman DA, Becker G, Webster LR, Davies AN, Mawe GM. Emerging treatments in neurogastroenterology: a multidisciplinary working group consensus statement on opioid-induced constipation. Neurogastroenterol Motil. 2014;26(10):1386-1395. 9. Hale M, Wild J, Reddy J, Yamada T, Arjona Ferreira JC. Naldemedine versus placebo for opioid-induced constipation (COMPOSE-1 and COMPOSE-2): two multicentre, phase 3, double-blind, randomised, parallel-group trials. Lancet Gastroenterol Hepatol. 2017;2(8):555-564.