Naloxegol

Naloxegol is a peripherally acting mu-opioid receptor antagonist indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain. Naloxegol is derived from naloxone, but with a polyethylene glycol (PEG) moiety attached. This PEGylation significantly limits naloxegol's ability to cross the blood-brain barrier, thereby minimizing interference with the analgesic effects of opioid medications within the central nervous system. Instead, it primarily targets opioid receptors in the gastrointestinal (GI) tract.

Mechanism of Action: Opioids commonly cause constipation by binding to mu-opioid receptors in the GI tract, slowing peristalsis and reducing intestinal secretions. Naloxegol works by competitively binding to these mu-opioid receptors in the GI tract, effectively blocking the constipating effects of opioids without significantly affecting the pain relief provided by opioids acting in the brain.

Administration: Naloxegol is administered orally, typically once daily.

Adverse Effects: Common side effects of naloxegol include abdominal pain, diarrhea, nausea, flatulence, and vomiting. More serious adverse effects, although less common, can include opioid withdrawal symptoms.

Contraindications and Precautions: Naloxegol is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction or at increased risk of recurrent obstruction. It should be used with caution in patients with certain pre-existing gastrointestinal conditions. The drug should be discontinued if severe or persistent abdominal pain or worsening gastrointestinal symptoms develop. Caution is also advised when co-administering with strong CYP3A4 inhibitors.

Pharmacokinetics: Naloxegol is absorbed after oral administration and undergoes metabolism primarily by CYP3A4.