NALDEMEDINE 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 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John’s Wort)
- Concomitant use with other opioid antagonists
- Severe hepatic impairment (Child-Pugh class C)
- Hypersensitivity to naldemedine or product 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
- Documented 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
- All VA/DOD Directives/guidelines for prescribing and monitoring long-term opioids are being followed
Laxative Trial Requirements
- Intolerance or inadequate response to 1-month trials of:
- One stimulant laxative (e.g., bisacodyl, sennosides) AND
- MIRALAX equivalent (twice daily) or other osmotic laxative (e.g., sorbitol, lactulose, magnesium citrate, Mg hydroxide, glycerin rectal suppositories)
- Maintenance laxative therapy does not need to be discontinued before starting naldemedine
- Bulk forming laxatives are relatively contraindicated in OIC
- Stool softeners (e.g., docusate) are considered low benefit and low harm for OIC; may be used but are not required prior to use of naldemedine
Dosage and Administration
- Adults: 0.2 mg once daily with or without food
- Alteration of analgesic dosing regimen prior to initiating naldemedine is not required
- Patients receiving opioids for less than 4 weeks may be less responsive to naldemedine
Monitoring, Safety, and Special Populations
- OIC clinical trial definition: ≤3 spontaneous bowel movements (SBMs) per week during a 2-week run-in period with a total of ≤4 SBMs; ≥1 symptom (straining, lumpy/hard stools, sensation of incomplete evacuation, or anorectal obstruction/blockage) for ≥25% of bowel movements; ≥78% compliance with daily diary entries
- SBMs defined as bowel movements without rescue laxatives taken within the past 24 hours
- Response defined as ≥3 SBMs per week and an increase from baseline of ≥1 SBM per week for at least 9 of 12 study weeks and 3 of the last 4 weeks
- Monitor for opioid withdrawal symptoms (e.g., abdominal pain, diarrhea, nausea, vomiting, hyperhidrosis, pyrexia, anxiety); disruptions in the blood-brain barrier may increase risk
- GI perforation warning: Use with caution in patients at risk for gastrointestinal perforation (e.g., peptic ulcer disease, diverticular disease, infiltrative gastrointestinal malignancy, peritoneal metastases, Crohn’s disease)
- Drug interactions: Avoid concomitant use with strong CYP3A inducers and other opioid antagonists; monitor for naldemedine-related adverse reactions during concomitant use with moderate/strong CYP3A4 inhibitors (e.g., fluconazole, itraconazole) and P-gp inhibitors (e.g., cyclosporine)
- Pregnancy: No human data; potential for fetal opioid withdrawal; weigh risks vs benefits
- Nursing Mothers: No human data; weigh risks vs benefits; breastfeeding may be resumed 3 days after the final dose of naldemedine
Initial Prescription Supply
- Up to 2 weeks
Renewal Criteria
- 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
- Discontinue naldemedine if treatment with the opioid pain medication is discontinued