What is the recommended treatment and dosage for opioid-induced constipation with MOVANTIK (naloxegol) in adult patients with chronic non-cancer pain?

MOVANTIK (Naloxegol) for Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain

The recommended treatment for opioid-induced constipation (OIC) with MOVANTIK (naloxegol) is 25 mg once daily in the morning on an empty stomach, at least 1 hour before the first meal of the day or 2 hours after a meal. 1

Indication and Patient Population

• MOVANTIK is indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent opioid dosage escalation 1
• Patients receiving opioids for less than 4 weeks may be less responsive to MOVANTIK 1

Dosing Recommendations

• Standard recommended dose is 25 mg once daily in the morning 2, 1
• If patients cannot tolerate the 25 mg dose, reduce to 12.5 mg once daily 1
• For patients with renal impairment (creatinine clearance <60 mL/min), start with 12.5 mg once daily; may increase to 25 mg if well tolerated but OIC symptoms continue 1
• When used with moderate CYP3A4 inhibitors (e.g., diltiazem, erythromycin, verapamil), reduce dose to 12.5 mg once daily 1

Administration Instructions

• Take on an empty stomach at least 1 hour prior to the first meal of the day or 2 hours after a meal 1
• Discontinue all maintenance laxative therapy prior to initiation of MOVANTIK 1
• Laxative(s) can be used as needed if there is a suboptimal response to MOVANTIK after three days 1
• Avoid consumption of grapefruit or grapefruit juice during treatment 1
• For patients unable to swallow the tablet whole, it can be crushed to a powder, mixed with 4 ounces (120 mL) of water, and drunk immediately 1

Efficacy

• Naloxegol has demonstrated significantly higher response rates compared to placebo (41.9% vs. 29.4%) in treating OIC in non-cancer pain patients 2, 3
• Response is defined as ≥3 spontaneous bowel movements (SBMs) per week and an increase from baseline of ≥1 SBM for ≥9 of 12 weeks and ≥3 of the final 4 weeks 3
• Naloxegol 25 mg improves SBM frequency and reduces straining during defecation 2, 3
• Patients with inadequate response to laxatives before enrollment showed even higher response rates with naloxegol 25 mg (48.7% vs. 28.8% in one study and 46.8% vs. 31.4% in another) 3

Safety and Adverse Effects

• Most common adverse effects include abdominal pain (17.8%), diarrhea (12.9%), nausea (9.4%), headache (9.0%), and flatulence (6.9%) 2, 4
• Most gastrointestinal adverse events occur early in treatment, are mild to moderate in severity, and resolve during or after discontinuation 4
• Adverse events leading to discontinuation occur in approximately 9.4% of patients on naloxegol 2, 4
• Pain scores and mean daily opioid doses typically remain stable during treatment, indicating naloxegol doesn't interfere with pain control 4, 5

Contraindications and Precautions

• Contraindicated in patients with known or suspected gastrointestinal obstruction and patients at risk of recurrent obstruction 1
• Discontinue MOVANTIK if treatment with the opioid pain medication is also discontinued 1
• PAMORAs should not be used in patients with known or suspected mechanical bowel obstruction 6

Clinical Algorithm for OIC Management

1. First-line approach: Start with prophylactic stimulant laxatives (e.g., senna) with or without stool softeners when initiating opioid therapy 6
2. Titrate laxative dose with goal of one non-forced bowel movement every 1-2 days 6
3. If constipation persists, rule out bowel obstruction and other causes, add osmotic laxatives 6
4. For refractory OIC (inadequate response to laxatives), initiate MOVANTIK at 25 mg once daily 7, 6, 1
5. If 25 mg is not tolerated, reduce to 12.5 mg once daily 1
6. Monitor for adverse effects, particularly gastrointestinal symptoms 2, 4

Pitfalls to Avoid

• Don't rely on fiber supplements like psyllium, which are ineffective and may worsen constipation 6
• Don't use docusate alone as it has not shown benefit 6
• Don't delay initiating MOVANTIK when standard laxatives fail 6
• Don't use MOVANTIK in patients with mechanical bowel obstruction 6, 1
• Don't forget to maintain adequate fluid intake alongside therapy 6
• Don't continue maintenance laxative therapy when starting MOVANTIK; instead, discontinue and use laxatives as needed if response is suboptimal after three days 1