In adult patients with chronic non‑cancer pain on opioid therapy who have failed non‑pharmacologic measures, what is Movantik (naloxegol) used for?

What is Movantik Used For?

Movantik (naloxegol) is used to treat opioid-induced constipation in adult patients with chronic non-cancer pain who have failed conventional laxative therapy. 1

FDA-Approved Indication

• Movantik is specifically indicated for opioid-induced constipation (OIC) 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
• It is NOT FDA-approved for use in patients with active cancer pain. 2

When to Use Movantik: Treatment Algorithm

First-line management:

• Start prophylactic stimulant laxatives when initiating opioid therapy, aiming for one non-forced bowel movement every 1-2 days. 2
• Traditional laxatives (stimulant laxatives with or without stool softeners) should be tried first. 3, 4

When to escalate to Movantik:

• Movantik is indicated only after inadequate response to conventional laxatives. 2, 3
• Discontinue maintenance laxative therapy before starting Movantik; laxatives may be resumed if OIC symptoms persist after 3 days of Movantik. 1

Critical pre-treatment assessment:

• Always rule out mechanical bowel obstruction or fecal impaction before initiating Movantik—this is a contraindication. 3, 1
• Assess for other causes of constipation: hypercalcemia, hypokalemia, hypothyroidism, and diabetes mellitus. 3

How Movantik Works

• Movantik is a pegylated derivative of naloxone that blocks peripheral μ-opioid receptors in the gut without crossing the blood-brain barrier. 2, 3
• It preserves central opioid analgesia while reversing constipation—no alteration in analgesic dosing is required when starting Movantik. 2, 1, 5
• The pegylation increases oral bioavailability and enhances peripheral selectivity, and it acts as a substrate for P-glycoprotein transporter, limiting CNS entry. 2

Efficacy Data

• 41.9% of patients on naloxegol 25 mg achieved response versus 29.4% on placebo, with response defined as ≥3 spontaneous bowel movements per week with an increase from baseline of ≥1 SBM/week for at least 9 of 12 weeks. 2
• Movantik improves spontaneous bowel movement frequency and reduces straining during defecation. 2, 4
• Patients receiving opioids for less than 4 weeks may be less responsive to Movantik. 1

Dosing

Standard dosing:

• 25 mg once daily in the morning on an empty stomach (at least 1 hour before or 2 hours after the first meal). 4, 1
• If not tolerated, reduce to 12.5 mg once daily. 1

Renal impairment (CrCl < 60 mL/min):

• Start at 12.5 mg once daily; may increase to 25 mg once daily if tolerated, with close monitoring for adverse reactions. 1

Hepatic impairment:

• Avoid in severe hepatic impairment. 1

Safety Profile and Common Pitfalls

Common adverse effects:

• Abdominal pain (17.8%), diarrhea (12.9%), nausea (9.4%), headache (9.0%), and flatulence (6.9%). 2, 4
• Adverse events leading to discontinuation occur in approximately 9.4% of patients versus 4.2% on placebo. 2, 4

Critical warnings:

• Monitor for severe abdominal pain and/or diarrhea—discontinue if severe symptoms develop; consider restarting at 12.5 mg once daily if appropriate. 1
• Risk of gastrointestinal perforation: Consider overall risk-benefit in patients with known or suspected GI tract lesions; monitor for severe, persistent, or worsening abdominal pain. 1
• Opioid withdrawal: Consider risk-benefit in patients with disruptions to the blood-brain barrier; monitor for withdrawal symptoms. 1

Drug interactions to avoid:

• Contraindicated with strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole). 1
• Avoid grapefruit or grapefruit juice. 1
• With moderate CYP3A4 inhibitors (e.g., diltiazem, erythromycin, verapamil), reduce dose to 12.5 mg once daily and monitor for adverse reactions. 1
• Concomitant use with strong CYP3A4 inducers (e.g., rifampin) is not recommended due to decreased naloxegol concentrations. 1
• Avoid concomitant use with other opioid antagonists due to potential additive effect and increased risk of opioid withdrawal. 1

When to discontinue:

• Discontinue Movantik if treatment with the opioid pain medication is also discontinued. 1

Comparative Context

• Among peripherally acting mu-opioid receptor antagonists (PAMORAs), subcutaneous methylnaltrexone shows the highest efficacy. 2
• Naldemedine has stronger evidence (high-quality) compared to naloxegol (moderate-quality evidence). 2
• However, the American Gastroenterological Association strongly recommends naloxegol over no treatment for laxative-refractory OIC. 2