Enteral Naloxone for Opioid-Induced Constipation

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At a recent pharmacy committee meeting, we discussed the potential use of enteral naloxone for ICU patients with opioid-induced constipation.

Background:

  • Opioids bind to mu receptors within the gastrointestinal tract. Activation of the bowel opioid receptors slow gastric transit time, decreases gastric secretions, and reduces intestinal muscle tone leading to enhanced fluid absorption and subsequently dry and hard stools.
  • Naloxone (Narcan®) solution for oral/enteral use
    • Mechanism of action:
      • Pure opioid antagonist that competes and displaces opioid at opioid receptor sites
    • FDA-approved indication: Antidote; opioid antagonist
    • Mechanism of action:
      • As an antidote – pure opioid antagonist that competes and displaces opioids at opioid receptor sites
      • As an oral agent – Enteral administration of naloxone blocks opioid action at the intestinal receptor level but has low systemic bioavailability (if dosed properly) due to marked hepatic first-pass metabolism. As a result, oral naloxone only binds strong enough for a pharmacologic response at opioid receptors in the gastrointestinal tract without reducing the central effect of the opioid and precipitating systemic withdrawal.

Potential alternatives:

  • Methylnaltrexone (Relistor®) SQ 12mg/0.6mL (much more expensive)
  • Rectal treatments: Bisacodyl (Dulcolax®), Enema
  • Oral constipation medications:
    • Polyethylene glycol (Miralax®)
    • Bisacodyl (Dulcolax®)
    • Senna (Senokot®)

Administration:

  • Dose recommendations: 10 – 20 mcg/kg dose PO q8h (max dose: 400mcg) for 5 – 7 days, then re-evaluate therapy
  • Oral/enteral dose should be not administered intravenously to prevent systemic effect and withdrawal in patients

My take: Enteral naloxone (IV solution) may be helpful for opioid-induced constipation but caution is needed to assure it is administered enterally and at proper dose.

Some of the research studies:

  1. Tofil N, Benner K, Faro S, Winkler M. The Use of Enteral Naloxone to Treat Opioid-Induced Constipation in a Pediatric Intensive Care Unit. Pediatr Crit Care Med. 2006;7(3):254-272.
  2. Akkawi R, Eksborg S, Andersson A, et al. Effect of Oral Naloxone Hydrochloride on Gastrointestinal Transit in Premature Infants Treated with Morphine. Acta Paediatrica.2008;98:442-447
  3. Liu M, Wittbrodt E. Low-Dose Oral Naloxone Reverses Opioid-Induced Constipation and Analgesia. J Pain Symptom Manage. 2002;23(1):48-53
  4. Friedman J, Dello Buono F. Opioid antagonist in the Treatment of Opioid-Induced Constipation and Pruritus. Ann Pharmcother. 2001;35:85-91
  5. Meissner W, Schmidt U, Hartmann M, et al. Oral Naloxone Reverses Opioid-Associated Constipation. Pain. 2000;84:105-109

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