NALOXEGOL OXALATE

12.1 Mechanism of Action 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.

Contraindications

• • 4 CONTRAINDICATIONS 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 [see Warnings and Precautions (5.3) ] . 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