Methylnaltrexone is a selective antagonist of opioid binding at the mu-opioid receptor. As a quaternary amine, the ability of methylnaltrexone to cross the blood-brain barrier is restricted. This allows methylnaltrexone to function as a peripherally-acting mu-opioid receptor antagonist in tissues such as the gastrointestinal tract, thereby decreasing the constipating effects of opioids without impacting opioid-mediated analgesic effects on the central nervous system.

• 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, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation. • RELISTOR injection is indicated for the treatment of OIC in adults with advanced illness or pain caused by active cancer who require opioid dosage escalation for palliative care.

Administration Instructions • Be within close proximity to toilet facilities once administered. • Discontinue if treatment with opioid pain medication is also discontinued. • In adult patients with chronic non-cancer pain and OIC: o Patients receiving opioids for less than 4 weeks may be less responsive to RELISTOR. o Discontinue all maintenance laxative therapy before starting RELISTOR; may resume laxatives if there is a suboptimal response to RELISTOR after 3 days. o Re-evaluate the continued need for RELISTOR when opioid regimen is changed to avoid adverse reactions. • In patients with chronic non-cancer pain and OIC, take RELISTOR tablets with water on an empty stomach at least 30 minutes before the first meal of the day. See package insert for complete information.

The most common adverse reactions are: OIC in adult patients with chronic non-cancer pain. • RELISTOR tablets (≥ 2%): abdominal pain, diarrhea, headache, abdominal distention, vomiting, hyperhidrosis, anxiety, muscle spasms, rhinorrhea, and chills. • RELISTOR injection (≥ 1%): abdominal pain, nausea, diarrhea, hyperhidrosis, hot flush, tremor, and chills. OIC in adult patients with advanced illness . • RELISTOR injection (≥ 5%): abdominal pain, flatulence, nausea, dizziness, and diarrhea.

Patients with known or suspected mechanical gastrointestinal obstruction and at increased risk of recurrent obstruction.

• Gastrointestinal Perforation: Consider the overall risk benefit in patients with known or suspected lesions of the GI tract. Monitor for severe, persistent or worsening abdominal pain; discontinue if development of symptoms. • Severe or Persistent Diarrhea: Discontinue if severe or persistent diarrhea occurs during treatment. • Opioid Withdrawal: Consider the overall risk benefit in patients with disruptions to the blood-brain barrier. Monitor closely for symptoms of opioid withdrawal.