What is Naloxegol used for?

Naloxegol: A Peripherally Acting Mu-Opioid Receptor Antagonist for Opioid-Induced Constipation

Naloxegol is specifically approved for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain. 1, 2

Mechanism of Action and Properties

Naloxegol is a peripherally acting mu-opioid receptor antagonist (PAMORA) that works by:

• Blocking mu-opioid receptors in the gastrointestinal tract, thereby decreasing the constipating effects of opioids 2
• Maintaining central opioid analgesia due to limited blood-brain barrier penetration 2
• Acting as a PEGylated derivative of naloxone with enhanced peripheral selectivity 1

The medication is administered orally once daily at a recommended dose of 25 mg, with a lower starting dose of 12.5 mg for patients with renal impairment 2.

Clinical Efficacy

Naloxegol has demonstrated significant efficacy in treating OIC:

• In phase III clinical trials, 41.9% of patients receiving naloxegol 25 mg achieved response to therapy compared to 29.4% with placebo 1
• Treatment results in approximately one additional spontaneous bowel movement (SBM) per week compared to placebo 1
• The medication improves SBM response rate with a risk ratio of 1.43 (95% CI, 1.19 to 1.71) compared to placebo 1
• Efficacy is maintained over 12 weeks of treatment 1

Patient Selection and Assessment

Naloxegol is indicated for patients with:

• Confirmed OIC defined as <3 SBMs/week with accompanying symptoms (hard stools, straining, incomplete evacuation) 1
• Chronic non-cancer pain on stable opioid regimens 1, 2
• Inadequate response to first-line laxative therapy 1

The Bowel Function Index can be used to assess OIC severity and monitor response, with a score ≥30 indicating clinically significant constipation requiring therapy escalation 1, 3.

Administration Guidelines

• Take on an empty stomach, approximately 1 hour before the first meal of the day 2
• Available in 12.5 mg and 25 mg tablets 2
• Can be crushed and mixed with water for oral administration or via nasogastric tube if needed 2
• Avoid use with strong CYP3A4 inhibitors as they can significantly increase naloxegol exposure 2

Dosage Adjustments

• Standard dose: 25 mg once daily 1, 2
• Reduced dose (12.5 mg once daily) recommended for patients with:
  • Moderate to severe renal impairment 2
  • Concomitant use of moderate CYP3A4 inhibitors 2
• Avoid use in patients with severe hepatic impairment (Child-Pugh Class C) 2

Common Adverse Effects

The most common adverse events include:

• Abdominal pain, diarrhea, nausea, and flatulence 1
• These effects are typically mild to moderate and transient, occurring within 1-2 days after dosing 2, 4
• No evidence of significant opioid withdrawal or reversal of central analgesic effects at recommended doses 1, 4

Clinical Considerations and Caveats

• Naloxegol has not been approved for use in patients with OIC and cancer pain 1
• Food increases the bioavailability of naloxegol, which is why it should be taken on an empty stomach 2, 5
• Steady state is achieved within 2-3 days with minimal accumulation 5
• Patients with prior laxative failure may still benefit from naloxegol therapy 6
• The American Gastroenterological Association recommends naloxegol as a second-line treatment for OIC after laxative failure 1

Alternative PAMORAs

Other PAMORAs that may be considered include:

• Naldemedine: Approved for OIC in both cancer and non-cancer pain patients 1
• Methylnaltrexone: Available in both oral and subcutaneous forms 1

For patients with OIC, the American Gastroenterological Association strongly recommends naloxegol over no treatment when laxatives have failed 1.