What are the contraindications, lab monitoring requirements, and common side effects of Movantik (naloxegol) in adult patients with opioid-induced constipation?

Movantik (Naloxegol) Clinical Overview

Contraindications

Movantik is absolutely contraindicated in three specific situations that you must screen for before prescribing. 1

• Known or suspected gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to potential for gastrointestinal perforation 1
• Concomitant use with strong CYP3A4 inhibitors (clarithromycin, ketoconazole, itraconazole) because these significantly increase naloxegol exposure and may precipitate opioid withdrawal symptoms including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning 1
• Known serious or severe hypersensitivity reaction to naloxegol or any excipients 1

Additional High-Risk Situations Requiring Caution

• Patients with disruptions to the blood-brain barrier should be carefully evaluated for overall risk-benefit, as naloxegol may precipitate opioid withdrawal in these patients 1
• Patients with known or suspected GI tract lesions require careful risk-benefit assessment due to perforation risk; monitor for severe, persistent, or worsening abdominal pain 1
• Avoid in severe hepatic impairment 1

Laboratory Monitoring Requirements

No routine laboratory monitoring is required for Movantik. 1

• The FDA label does not specify any laboratory tests for monitoring during naloxegol therapy 1
• Renal function assessment is recommended before initiating therapy to determine appropriate dosing (reduce to 12.5 mg daily if CrCl <60 mL/min) 1
• Naloxegol is primarily eliminated via hepatic metabolism with minimal renal excretion, so renal monitoring during therapy is not necessary 2

Clinical Monitoring (Not Laboratory)

• Monitor for severe abdominal pain and/or diarrhea after initiating treatment; discontinue if severe symptoms develop 1
• Monitor for symptoms of opioid withdrawal (particularly in patients with blood-brain barrier disruption) 1
• Monitor pain scores to ensure opioid analgesia is maintained 3, 4

Most Common Side Effects

The most common adverse effects are gastrointestinal and occur early in treatment, typically resolving during or after discontinuation. 1, 4

Frequency of Common Adverse Events (≥3%)

• Abdominal pain: 17.8% (vs. 3.3% with usual care) 5, 1, 4
• Diarrhea: 12.9% (vs. 5.9% with usual care) 5, 1, 4
• Nausea: 9.4% (vs. 4.1% with usual care) 5, 1, 4
• Headache: 9.0% (vs. 4.8% with usual care) 5, 1, 4
• Flatulence: 6.9% (vs. 1.1% with usual care) 5, 1, 4
• Vomiting (≥3%) 1

Discontinuation Rates

• Adverse events leading to discontinuation: 9.4% with naloxegol vs. 4.2% with placebo 6, 5
• Most common reasons for discontinuation: diarrhea (11 patients) and abdominal pain (9 patients) in long-term studies 4

Important Safety Characteristics

• Most gastrointestinal adverse events are mild to moderate in severity and occur early in treatment 4
• Pain scores and opioid doses remain stable, indicating naloxegol does not interfere with central analgesia 3, 4
• No attributable opioid withdrawal adverse events were observed in long-term safety studies 4

Other Critical Considerations

Dosing and Administration

• Standard dose: 25 mg once daily in the morning on an empty stomach (at least 1 hour before or 2 hours after first meal) 5, 7, 1
• Reduce to 12.5 mg once daily if 25 mg not tolerated or if CrCl <60 mL/min 1
• Discontinue maintenance laxatives before starting naloxegol; may resume after 3 days if OIC symptoms persist 1
• Avoid grapefruit and grapefruit juice (CYP3A4 interaction) 1
• Discontinue naloxegol if opioid therapy is discontinued 1

Drug Interactions Requiring Dose Adjustment

• Moderate CYP3A4 inhibitors (diltiazem, erythromycin, verapamil): Reduce naloxegol to 12.5 mg daily and monitor for adverse reactions; avoid concomitant use if possible 1
• Strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin): Concomitant use not recommended as they decrease naloxegol concentrations 1
• Other opioid antagonists: Avoid concomitant use due to potential additive effects and increased opioid withdrawal risk 1

Patient Selection and Timing

• Indicated only for laxative-refractory OIC in adults with chronic non-cancer pain 7, 1
• Patients on opioids <4 weeks may be less responsive to naloxegol 1
• Not FDA-approved for active cancer pain requiring frequent opioid dose escalation 7, 1

Special Populations

• Pregnancy: May precipitate opioid withdrawal in pregnant women and the fetus 1
• Lactation: Breastfeeding not recommended 1
• Renal impairment (CrCl <60 mL/min): Start at 12.5 mg daily; may increase to 25 mg if tolerated with close monitoring 1

Unique Metabolic Consideration

• Naloxone may be detected in urine after naloxegol consumption, which could mislead clinicians interpreting urine drug screens 8
• Naloxegol is metabolized to naloxol and naloxone, both detectable in urine within 1 hour of administration 8

Efficacy Context

• Response rate: 41.9% vs. 29.4% with placebo (response defined as ≥3 spontaneous bowel movements per week with ≥1 increase from baseline for ≥9 of 12 weeks) 5, 7, 3
• Naloxegol has moderate-quality evidence compared to naldemedine (high-quality) and methylnaltrexone (highest efficacy among PAMORAs) 7, 9