Naloxegol is an antagonist of opioid binding at the mu-opioid receptor. When administered at the recommended dose levels, naloxegol functions as a peripherally-acting mu-opioid receptor antagonist in tissues such as the gastrointestinal tract, thereby decreasing the constipating effects of opioids. Naloxegol is a PEGylated derivative of naloxone, and is a substrate for the P-glycoprotein transporter (P-gp). Also, the presence of the PEG moiety in naloxegol reduces its passive permeability as compared with naloxone. Due to the reduced permeability and increased efflux of naloxegol across the blood-brain barrier, related to P-gp substrate properties, the CNS penetration of naloxegol is expected to be negligible at the recommended dose levels limiting the potential for interference with centrally mediated opioid analgesia.

MOVANTIK is an opioid antagonist indicated for the treatment of opioidinduced 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.

Administration: • Discontinue maintenance laxative therapy before starting MOVANTIK; may resume laxatives if patients have OIC symptoms after taking MOVANTIK for 3 days. • Alteration in analgesic dosing regimen prior to starting MOVANTIK is not required. • Patients receiving opioids for less than 4 weeks may be less responsive to MOVANTIK. • Take on an empty stomach at least 1 hour prior to the first meal of the day or 2 hours after the meal. • For patients who are unable to swallow the MOVANTIK tablet whole, the tablet can be crushed and given orally or administered via nasogastric tube, see full prescribing information. • Avoid consumption of grapefruit or grapefruit juice. • Discontinue if treatment with the opioid pain medication is also discontinued. See package insert for complete information.

The most common adverse reactions in clinical trials (≥ 3%) are: abdominal pain, diarrhea, nausea, flatulence, vomiting, and headache.

• Patients with known or suspected gastrointestinal obstruction and at increased risk of recurrent obstruction. • Concomitant use with strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole). • Known serious or severe hypersensitivity reaction to MOVANTIK or any of its excipients

• Opioid withdrawal: Consider the overall risk benefit in patients with disruptions to the blood-brain barrier. Monitor for symptoms of opioid withdrawal. • Severe abdominal pain and/or diarrhea: Monitor for the development of symptoms after initiating treatment with MOVANTIK and discontinue if severe symptoms develop. Consider restarting MOVANTIK at 12.5 mg once daily if appropriate. • 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.