NALOXEGOL TAB,ORAL
Clinical Criteria Summary
Exclusion Criteria
- Age less than 18 years
- Known or suspected gastrointestinal obstruction or at risk of recurrent obstruction
- Concomitant use with strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole)
- Known serious or severe hypersensitivity to naloxegol or its excipients
- Presence of severe or frequent diarrhea
Inclusion Criteria
- Patient is taking opioids for chronic, non-cancer pain (including chronic pain related to prior cancer or its treatment), does not require frequent opioid dose escalation, and is documented to have opioid induced constipation (OIC)
- Documentation of attempts to reduce constipation by change to less constipating analgesics or reduction of opioid dose, OR medical justification why changes are unable to be made in current regimen
- Documentation that benefits of opioid therapy exceed risks for the patient and all VA/DOD Directives/guidelines for prescribing and monitoring long-term opioids are being followed
- Intolerance or inadequate response to 1-month trials of: one stimulant laxative (e.g., bisacodyl, sennosides) AND a MIRALAX equivalent (twice daily) or other osmotic laxative (e.g., sorbitol, lactulose, magnesium citrate, magnesium hydroxide, glycerin rectal suppositories), unless contraindication or risk factor(s) for serious adverse event(s) exists
Laxative Management Prior to Initiation
- Maintenance laxative therapy should be discontinued before starting naloxegol
- Laxatives may be resumed if OIC symptoms persist after taking naloxegol for 3 days
- Bulk forming laxatives are relatively contraindicated in OIC
- Stool softeners (e.g., docusate) are considered low benefit and low harm for OIC and may be used but are not required prior to use of naloxegol in OIC
Dosing & Administration
- Recommended dose: 25 mg once daily in the morning
- If patient is unable to tolerate 25 mg, consider 12.5 mg daily
- If creatinine clearance is < 60 ml/min, 12.5 mg once daily is recommended with option to titrate to 25 mg daily if tolerated at the 12.5-mg dose
- Instruct patient to take on an empty stomach one hour prior to first meal of the day or two hours after a meal
- Consumption of grapefruit or grapefruit juice should be avoided
Monitoring & Safety Considerations
- OIC defined as < 3 spontaneous bowel movements (SBMs) per week on average with at least 25% of SBMs associated with straining, hard/lumpy stools, or sensation of incomplete evacuation; SBMs defined as bowel movements without rescue laxatives taken within past 24 hours
- Clinical response defined as ≥ 3 SBMs per week and a change from baseline of ≥ 1 SBM per week for at least 9 of the 12 study weeks and 3 of the last 4 weeks
- Monitor for opioid withdrawal symptoms (e.g., hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, yawning); frequency of GI adverse reactions related to opioid withdrawal was higher in patients taking methadone
- Disruptions in blood-brain barrier may increase risk of opioid withdrawal or reduced analgesia
- Use with caution in patients at risk for gastrointestinal perforation (e.g., peptic ulcer disease, diverticular disease, infiltrative GI malignancy, peritoneal metastases, Crohn’s disease)
- Pregnancy Category C: May cross fetus's immature blood-brain barrier and precipitate opioid withdrawal; use only if potential benefit justifies potential risk to fetus
- Nursing Mothers: Potential for opioid withdrawal and other serious adverse reactions in nursing infants; discontinue nursing or using naloxegol considering risks and benefits to mother
Prescription Duration & Renewal Criteria
- Initial prescription supply: Up to 2 weeks
- Renewal requires patient experiences clinically important benefit (improved constipation and abdominal pain) after an adequate therapeutic trial and tolerates treatment
- Adequate therapeutic trial is defined as 1 week