What is the recommended treatment and dosage for Movantik (naloxegol) in managing opioid-induced constipation?

Movantik (Naloxegol) for Opioid-Induced Constipation

Movantik (naloxegol) is indicated at 25 mg once daily on an empty stomach for adults with opioid-induced constipation from chronic non-cancer pain, but only after traditional laxatives have failed to provide adequate relief. 1

FDA-Approved Indication and Patient Selection

• Naloxegol is FDA-approved specifically for opioid-induced constipation in adults 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. 1
• Patients receiving opioids for less than 4 weeks may be less responsive to naloxegol and should be counseled accordingly. 1
• Naloxegol should only be initiated after insufficient response to traditional laxatives—it is not a first-line agent. 2, 3

Dosing and Administration

Standard Dosing:

• The recommended dose is 25 mg once daily taken on an empty stomach at least 1 hour before the first meal or 2 hours after a meal. 1
• If patients cannot tolerate the 25 mg dose, reduce to 12.5 mg once daily. 1
• Discontinue all maintenance laxative therapy prior to starting naloxegol; laxatives can be used as needed if suboptimal response occurs after 3 days. 1

Renal Impairment:

• For patients with creatinine clearance <60 mL/min (moderate, severe, or end-stage renal impairment), start with 12.5 mg once daily. 1
• If well tolerated but symptoms persist, may increase to 25 mg once daily, recognizing the increased risk of adverse reactions with higher exposures in renal impairment. 1

Drug Interactions:

• Avoid concomitant use with moderate CYP3A4 inhibitors (diltiazem, erythromycin, verapamil); if unavoidable, reduce dose to 12.5 mg once daily. 1
• Contraindicated with strong CYP3A4 inhibitors (clarithromycin, ketoconazole) as these significantly increase naloxegol exposure and may precipitate opioid withdrawal. 1
• Avoid grapefruit or grapefruit juice during treatment. 1

Alternative Administration:

• For patients unable to swallow tablets whole, crush to powder, mix with 4 ounces (120 mL) water, and drink immediately; rinse glass with another 4 ounces and drink. 1
• Can be administered via nasogastric tube using specific flushing protocol outlined in the FDA label. 1

Mechanism and Clinical Efficacy

• Naloxegol is a PEGylated derivative of naloxone that antagonizes peripheral μ-opioid receptors in the gastrointestinal tract without crossing the blood-brain barrier, thereby preserving central analgesia. 3, 4
• The American Gastroenterological Association recommends naloxegol over no treatment for laxative-refractory opioid-induced constipation with strong recommendation based on moderate quality evidence. 2
• Clinical trials demonstrated bowel movement response in 42-49% of patients not responsive to laxatives, compared to placebo. 5, 6
• Meta-analysis showed peripherally acting μ-opioid receptor antagonists (including naloxegol) had a relative risk of failure to respond of 0.70 (95% CI, 0.64-0.75) with number needed to treat of 5. 5

Critical Safety Considerations and Contraindications

Absolute Contraindications:

• Known or suspected gastrointestinal obstruction or patients at risk of recurrent obstruction due to potential for gastrointestinal perforation. 1
• Concomitant use with strong CYP3A4 inhibitors. 1
• Known serious or severe hypersensitivity reaction to naloxegol or its excipients. 1

Opioid Withdrawal Risk:

• Clusters of symptoms consistent with opioid withdrawal (hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, yawning) have occurred with naloxegol. 1
• Patients receiving methadone had higher frequency of gastrointestinal adverse reactions potentially related to opioid withdrawal. 1
• Patients with disruptions to the blood-brain barrier are at increased risk for opioid withdrawal or reduced analgesia; monitor closely. 1

Common Adverse Events:

• Most frequent treatment-emergent adverse events include abdominal pain (17.8%), diarrhea (12.9%), nausea (9.4%), headache (9.0%), flatulence (6.9%), and upper abdominal pain (5.1%). 7
• Most gastrointestinal adverse events occur early, are mild to moderate in severity, and resolve during or after discontinuation. 7
• Pain scores and opioid doses remained stable in long-term studies with no attributable opioid withdrawal adverse events. 7

Clinical Algorithm for Implementation

1. Rule out mechanical obstruction or impaction before initiating naloxegol—this is mandatory. 3, 1
2. Assess for other causes of constipation (hypercalcemia, hypokalemia, hypothyroidism, diabetes). 3
3. Confirm inadequate response to traditional laxatives (stimulant laxatives with or without stool softeners). 2, 3
4. Initiate naloxegol 25 mg once daily (or 12.5 mg if renal impairment or intolerance). 1
5. Discontinue maintenance laxatives but allow as-needed use after 3 days if suboptimal response. 1
6. Monitor for opioid withdrawal symptoms and gastrointestinal adverse events, particularly in first few weeks. 1, 7
7. Discontinue naloxegol if opioid therapy is discontinued. 1

Common Pitfalls to Avoid

• Never initiate naloxegol without first ruling out bowel obstruction—this can lead to perforation. 3, 1
• Do not use as first-line therapy—traditional laxatives must be tried first per guidelines and FDA indication. 2, 3, 1
• Do not combine with strong CYP3A4 inhibitors—this is an absolute contraindication due to risk of precipitating opioid withdrawal. 1
• Do not assume all PAMORAs are interchangeable—naloxegol is specifically indicated for chronic non-cancer pain, while methylnaltrexone is for advanced illness/palliative care. 3
• Do not forget to adjust dose in renal impairment—start at 12.5 mg for CrCl <60 mL/min. 1