Naloxegol

MOVANTIK ® 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. MOVANTIK is an opioid antagonist 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.

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.

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. Recommended dosage: 25 mg once daily, if not tolerated, reduce to 12.5 mg once daily.

MOVANTIK is contraindicated in: Patients with known or suspected gastrointestinal obstruction and patients at risk of recurrent obstruction, due to the potential for gastrointestinal perforation. Patients concomitantly using strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) because these medications can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Patients who have had a 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.

Serious and important adverse reactions described elsewhere in labeling include: Opioid withdrawal Severe abdominal pain and/or diarrhea Gastrointestinal perforation The most common adverse reactions in clinical trials (≥3%) are: abdominal pain, diarrhea, nausea, flatulence, vomiting, and headache.

Moderate CYP3A4 inhibitors (e.g., diltiazem, erythromycin, verapamil): Increased naloxegol concentrations, avoid concomitant use, if unavoidable, reduce dosage to 12.5 mg once daily and monitor for adverse reactions. Strong CYP3A4 inducers (e.g., rifampin): Decreased concentrations of naloxegol, concomitant use is not recommended. Other opioid antagonists: Potential for additive effect and increased risk of opioid withdrawal, avoid concomitant use.

Storage Store MOVANTIK at 20-25°C (68-77°F). Excursions permitted to 15-30°C (59-86°F).