RELISTOR Provided Rapid Relief for Adult Patients With Opioid-Induced Constipation (OIC)1-5

RELISTOR tablets: >25% of the time, adult patients with OIC and chronic non-cancer pain (CNCP) experienced an SBM within 4 hours of dosing1

tablets: <25% of the time, OIC patients with CNCP taking RELISTOR tablets experienced an SBM within 4 hours of dosing

*Defined as bowel movement without the use of any laxative in previous 24 hours.

During the 4-week double-blind period.

Three RELISTOR 150-mg tablets (450 mg total) once daily in the morning with water on an empty stomach at least 30 minutes before the first meal of the day.

 

  • In a 4-week randomized, double-blind, placebo-controlled study, the efficacy of RELISTOR tablets was evaluated in 401 adult patients (200 RELISTOR tablets, 201 placebo) with CNCP for which they were taking opioids2
  • All patients had OIC, defined as <3 SBMs per week, and at least one additional symptom of constipation2

IMPORTANT SAFETY INFORMATION

  • The most common adverse reactions (≥2%) were abdominal pain, diarrhea, headache, abdominal distention, vomiting, hyperhidrosis, anxiety, muscle spasms, rhinorrhea, and chills2

RELISTOR injection: a third of adult patients with OIC and CNCP experienced an SBM§ within 4 hours of their first dose2,3

: One-third of OIC patients with CNCP taking RELISTOR injection experienced an SBM within 4 hours of their first dose

§Defined as bowel movement without the use of any laxative in previous 24 hours.

 

  • In a 4-week double-blind, randomized, placebo-controlled study, the efficacy of RELISTOR injection for adult OIC was evaluated in 312 patients (150 RELISTOR injection, 162 placebo) with CNCP for which they were taking opiates2
  • All patients had OIC, defined as <3 SBMs per week and at least one additional symptom of constipation2

IMPORTANT SAFETY INFORMATION

  • The most common adverse reactions (≥1%) were abdominal pain, nausea, diarrhea, hyperhidrosis, hot flush, tremor, and chills2

RELISTOR injection can help provide rapid relief when laxatives aren’t sufficient in adult OIC patients with advanced illness on palliative care2,4,5

RELISTOR injection can help provide rapid relief when laxatives aren’t sufficient in OIC patient with advanced illness on palliative care

llRescue-free laxation within 4 hours of the first dose.

 

  • In a double-blind, randomized, placebo-controlled study, 154 adult patients (47 RELISTOR injection 0.15 mg/kg, 55 RELISTOR injection 0.3 mg/kg, 52 placebo) with advanced illness and OIC received a single dose of RELISTOR injection or placebo2
  • All patients had OIC, defined as either <3 bowel movements in the preceding week or no bowel movement within 2 days2
    • Patients maintained their regular laxative regimen for at least 3 days prior to study entry and throughout the study
    • Rescue laxatives were prohibited from 4 hours before to 4 hours after receiving an injection of study medication

IMPORTANT SAFETY INFORMATION

  • The most common adverse reactions (≥5%) were abdominal pain, flatulence, nausea, dizziness, and diarrhea2

 

RELISTOR injection can help provide rapid relief when laxatives aren’t sufficient in OIC patient with advanced illness on palliative care

Rescue-free laxation within 4 hours of the first dose.

 

  • In a 2-week double-blind, randomized, placebo-controlled trial followed by a subsequent open-label extension study of up to 4 months, the efficacy of RELISTOR injection was evaluated in 133 patients (62 RELISTOR injection, 71 placebo) with advanced illness and OIC2
  • All patients had OIC, defined as either <3 bowel movements in the preceding week or no bowel movement within 2 days2
    • Patients maintained their regular laxative regimen for at least 3 days prior to study entry and throughout the study
    • Rescue laxatives were prohibited from 4 hours before to 4 hours after receiving an injection of study medication

IMPORTANT SAFETY INFORMATION

  • The most common adverse reactions (≥5%) were abdominal pain, flatulence, nausea, dizziness, and diarrhea2
Approximately 50% of patients who responded experienced relief within 30 minutes.

#Had a response within 4 hours.

 

SBM=spontaneous bowel movement.

 

Indications

  • RELISTOR is an opioid antagonist. RELISTOR tablets and RELISTOR injection are indicated for the treatment of opioid-induced constipation (OIC) in adults with chronic non-cancer pain.
  • RELISTOR injection is also indicated for the treatment of OIC in adults with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. Limitations of Use: Use beyond four months has not been studied in the advanced illness population.

IMPORTANT SAFETY INFORMATION - RELISTOR tablets and RELISTOR injection

  • RELISTOR tablets and injection are contraindicated in patients with known or suspected gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation.
  • Cases of gastrointestinal perforation have been reported in adult patients with opioid-induced constipation and advanced illness 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 RELISTOR 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 RELISTOR in patients who develop this symptom.
  • If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with RELISTOR and consult their healthcare provider.
  • Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, and yawning have occurred in patients treated with RELISTOR. Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal and/or reduced analgesia and should be monitored for adequacy of analgesia and symptoms of opioid withdrawal.
  • Avoid concomitant use of RELISTOR with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.
  • The use of RELISTOR during pregnancy may precipitate opioid withdrawal in a fetus due to the immature fetal blood brain barrier and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Because of the potential for serious adverse reactions, including opioid withdrawal, in breastfed infants, advise women that breastfeeding is not recommended during treatment with RELISTOR. In nursing mothers, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
  • A dosage reduction of RELISTOR tablets and RELISTOR injection is recommended in patients with moderate and severe renal impairment (creatinine clearance less than 60 mL/minute as estimated by Cockcroft-Gault). No dosage adjustment of RELISTOR tablets or RELISTOR injection is needed in patients with mild renal impairment.
  • A dosage reduction of RELISTOR tablets is recommended in patients with moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment. No dosage adjustment of RELISTOR tablets is needed in patients with mild hepatic impairment (Child-Pugh Class A). No dosage adjustment of RELISTOR injection is needed for patients with mild or moderate hepatic impairment. In patients with severe hepatic impairment, monitor for methylnaltrexone-related adverse reactions.
  • In the clinical studies, the most common adverse reactions were:
    • OIC in adult patients with chronic non-cancer pain
      • RELISTOR tablets (≥2% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (14%), diarrhea (5%), headache (4%), abdominal distention (4%), vomiting (3%), hyperhidrosis (3%), anxiety (2%), muscle spasms (2%), rhinorrhea (2%), and chills (2%).
      • RELISTOR injection (≥1% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (21%), nausea (9%), diarrhea (6%), hyperhidrosis (6%), hot flush (3%), tremor (1%), and chills (1%).
    • OIC in adult patients with advanced illness
      • RELISTOR injection (≥5% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (29%), flatulence (13%), nausea (12%), dizziness (7%), and diarrhea (6%).

To report SUSPECTED ADVERSE REACTIONS, contact Salix at 1-800-508-0024 or FDA at 1-800-FDA-1088 or www.fda.gov/Safety/MedWatch/

Please click here for full Prescribing Information for RELISTOR tablets and RELISTOR injection.

REFERENCES:

  1. Data on file. Salix Pharmaceuticals.
  2. RELISTOR (methylnaltrexone bromide) Prescribing Information. Bridgewater, NJ: Salix Pharmaceuticals.
  3. Michna E, Blonsky ER, Schulman S, et al. Subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients with chronic nonmalignant pain: a randomized controlled study. J Pain. 2011;12(5):554-562.
  4. Slatkin N, Thomas J, Lipman AG, et al. Methylnaltrexone for treatment of opioid-induced constipation in advanced illness patients. J Support Oncol. 2009;7(1):39-46.
  5. Thomas J, Karver S, Cooney GA, et al. Methylnaltrexone for opioid-induced constipation in advanced illness. N Engl J Med. 2008;358(22):2332-2343.