What is the recommended dosing for Naloxegol (generic name) in patients with opioid-induced constipation and impaired renal function?

Naloxegol Dosing in Patients with Opioid-Induced Constipation and Impaired Renal Function

For patients with opioid-induced constipation and impaired renal function (creatinine clearance <60 mL/min), the recommended starting dose of naloxegol is 12.5 mg once daily, which may be increased to 25 mg once daily if well tolerated but symptoms persist. 1

Dosing Guidelines for Naloxegol

Standard Dosing

• The standard recommended dose of naloxegol for opioid-induced constipation (OIC) is 25 mg once daily in the morning 2
• If not tolerated, the dose can be reduced to 12.5 mg once daily 1
• Naloxegol should be taken on an empty stomach at least 1 hour before the first meal of the day or 2 hours after a meal 1

Renal Impairment Dosing

• For patients with creatinine clearance (CLcr) <60 mL/min (moderate, severe, or end-stage renal impairment), start with 12.5 mg once daily 1
• If the 12.5 mg dose is well tolerated but OIC symptoms continue, the dose may be increased to 25 mg once daily 1
• Careful monitoring for adverse reactions is recommended when using the higher dose in renally impaired patients due to potential for markedly increased drug exposure 1

Efficacy and Safety Considerations

Efficacy

• Naloxegol has demonstrated efficacy in treating OIC with response rates significantly higher than placebo 2
• At 25 mg dosing, naloxegol showed a 41.9% response rate compared to 29.4% with placebo in non-cancer pain patients 2
• Naloxegol improves spontaneous bowel movement (SBM) frequency and reduces straining during defecation 2, 3

Safety in Renal Impairment

• Renal impairment increases naloxegol exposure, necessitating dose adjustment 1, 4
• The primary route of naloxegol elimination is hepatic metabolism, with renal excretion playing a minimal role 4
• Despite minimal renal excretion, patients with renal impairment may have higher systemic exposure to naloxegol 4

Administration Considerations

• Discontinue maintenance laxative therapy prior to initiating naloxegol 1
• Laxatives can be used as needed if suboptimal response occurs after three days of naloxegol treatment 1
• Avoid consumption of grapefruit or grapefruit juice during treatment with naloxegol 1
• For patients unable to swallow tablets, naloxegol can be crushed and mixed with water 1

Drug Interactions in Renal Impairment

• Avoid concomitant use with strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) as this is contraindicated 1
• If moderate CYP3A4 inhibitors (e.g., diltiazem, erythromycin, verapamil) must be used, reduce naloxegol dose to 12.5 mg once daily 1
• Strong CYP3A4 inducers may decrease naloxegol concentrations and reduce efficacy 1

Common 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, 5
• Gastrointestinal adverse effects typically occur early in treatment and are generally mild to moderate in severity 2, 5
• Adverse events leading to discontinuation occur in approximately 9.4% of patients on naloxegol compared to 4.2% on placebo 2

Clinical Pearls and Caveats

• Pain scores and mean daily opioid doses typically remain stable during naloxegol treatment, indicating no reduction in analgesic efficacy 2, 5
• Naloxegol is a substrate for P-glycoprotein transporter, which limits its ability to cross the blood-brain barrier 6
• Discontinue naloxegol if treatment with the opioid pain medication is also discontinued 1
• Patients receiving opioids for less than 4 weeks may be less responsive to naloxegol 1