What is the recommended treatment and dosage for opioid-induced constipation using Methylnaltrexone?

Methylnaltrexone for Opioid-Induced Constipation Treatment

Methylnaltrexone is recommended at a dose of 12 mg subcutaneously once daily for chronic non-cancer pain patients with opioid-induced constipation (OIC), or 450 mg orally once daily in the morning on an empty stomach. 1, 2

Formulations and Dosing

For Chronic Non-Cancer Pain OIC:

• Oral tablets: 450 mg taken once daily in the morning on an empty stomach (at least 30 minutes before first meal) 2
• Subcutaneous injection: 12 mg administered once daily 2, 3

For Advanced Illness/Cancer Pain OIC:

• Subcutaneous injection only: Weight-based dosing administered every other day as needed 2
  • 38 kg to <62 kg: 8 mg (0.4 mL)
  • 62 kg to 114 kg: 12 mg (0.6 mL)
  • <38 kg or >114 kg: 0.15 mg/kg

Efficacy and Mechanism of Action

Methylnaltrexone is a peripherally-acting mu-opioid receptor antagonist (PAMORA) that blocks opioid effects on the gastrointestinal tract without affecting centrally-mediated analgesia 1, 4. It works by:

• Antagonizing peripheral mu-opioid receptors in the GI tract
• Not crossing the blood-brain barrier, thus preserving pain control
• Producing bowel movements rapidly, often within 4 hours of administration 1

Clinical studies demonstrate:

• 54.6% of patients achieve response (≥3 rescue-free bowel movements/week) compared to 38.3% with placebo 1
• Laxation response (bowel movement within 4 hours) occurs in 27.7% of patients versus 8.8% with placebo 1
• Median time to laxation among responders is approximately 45 minutes 5

Patient Selection and Clinical Use

Methylnaltrexone should be used for:

1. Patients with OIC who have inadequate response to conventional laxatives 1, 6
2. Both chronic non-cancer pain patients and those with advanced illness 1, 2

Key considerations:

• Ensure patient has access to toilet facilities after administration 2
• Discontinue maintenance laxatives before starting methylnaltrexone 2
• Laxatives can be reintroduced if suboptimal response after 3 days 2
• Re-evaluate need when opioid regimen changes 2

Dosage Adjustments for Special Populations

Renal Impairment (CrCl <60 mL/min):

• Oral: Reduce to 150 mg once daily 2
• Subcutaneous: Reduce to 6 mg once daily for chronic non-cancer pain 2
• For advanced illness: Reduce dose by 50% (see weight-based chart in prescribing information) 2

Hepatic Impairment:

• Oral: Reduce to 150 mg once daily for moderate/severe impairment 2
• Subcutaneous: Consider dose reduction for severe hepatic impairment 2

Adverse Effects and Monitoring

Common adverse effects include:

• Abdominal pain
• Diarrhea
• Nausea
• Hyperhidrosis 3

Important monitoring considerations:

• Adverse events leading to discontinuation occur in approximately 4.9% of patients 1
• No significant changes in pain scores or evidence of opioid withdrawal have been observed 4
• No reduction in analgesic efficacy occurs with methylnaltrexone use 4

Clinical Pearls and Pitfalls

• Timing matters: Methylnaltrexone works rapidly, with most responders experiencing a bowel movement within 45 minutes to 4 hours 1, 5
• Non-responders: Approximately 50% of patients may not respond to methylnaltrexone regardless of dose increases 7
• Avoid dose escalation in non-responders as it increases toxicity without improving efficacy 7
• Contraindications: Do not use in patients with known or suspected mechanical gastrointestinal obstruction 2
• Discontinuation: Stop methylnaltrexone if opioid pain medication is discontinued 2
• Duration of treatment: Efficacy has been demonstrated for up to 3 months of treatment 5

Methylnaltrexone provides a targeted approach to OIC management by addressing the peripheral mechanism of opioid-induced constipation while preserving central analgesic effects, making it particularly valuable for patients who have failed conventional laxative therapy.