Naloxegol Oxalate (1 brand name, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- MOVANTIK
Indications and Usage
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.
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, diarrhea, abdominal pain, anxiety, irritability, and yawning [see Drug Interactions (7.1)and Clinical Pharmacology (12.3) ]. Patients who have had a known serious or severe hypersensitivity reaction to MOVANTIK or any of its excipients [see Adverse Reactions (6.2)] .
Adverse Reactions
Serious and important adverse reactions described elsewhere in labeling include: Opioid withdrawal [see Warnings and Precautions (5.1)] Severe abdominal pain and/or diarrhea [see Warnings and Precautions (5.2)] Gastrointestinal perforation [see Warnings and Precautions (5.3)]
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.
Overdosage
In a clinical study of patients with OIC a daily dose of 50 mg (twice the recommended dosage), administered over 4 weeks, was associated with an increased incidence of GI adverse reactions, such as abdominal pain, diarrhea, and nausea. These adverse reactions frequently occurred within 1-2 days after dosing. No antidote is known for naloxegol. Dialysis was noted to be ineffective as a means of elimination in a clinical study in patients with renal failure. If a patient on opioid therapy receives an overdose of naloxegol, the patient should be monitored closely for potential evidence of opioid withdrawal symptoms such as chills, rhinorrhea, diaphoresis, or reversal of central analgesic effect. Base treatment on the degree of opioid withdrawal symptoms, including changes in blood pressure and heart rate, and on the need for analgesia.