Naloxegol
Laxatives
Laxatives
A PEG-linked naloxone that stays out of the brain. It blocks gut opioid receptors to treat opioid-induced constipation in chronic non-cancer pain.
Quick facts
- Group
- Laxatives
- Target
- Mu-opioid receptor in the gut (peripherally restricted antagonist)
- Used for
- Opioid-induced constipation
- Key effects
- Abdominal pain · Nausea · Headache
- Monitor
- Bowel movements and abdominal pain
- ATC
- A06AH03
No doses: the clinician sets them by the current guideline.
Mechanism of action
Naloxegol is naloxone joined to a polyethylene glycol (PEG) polymer. PEG makes it a substrate of the P-glycoprotein efflux pump, so very little crosses the blood-brain barrier. It blocks mu-opioid receptors in the gut, which reverses opioid-induced slowing of the bowel, while central pain relief is largely kept.
- PEG keeps naloxegol out of the brain (P-gp efflux)
- It blocks mu receptors in the gut wall
- Opioid constipation eases; analgesia stays
Indications
- Opioid-induced constipation in adults with chronic non-cancer pain
Adverse effects
Common
- Abdominal pain, diarrhoea, flatulence
- Nausea, vomiting
- Headache
- Sweating, chills, anxiety, irritability, yawning
Contraindications
- Known or suspected intestinal obstruction
- Caution with conditions that weaken the gut wall: ulcers, Crohn's disease, diverticulitis, bowel cancer, Ogilvie's syndrome
Key interactions
- Grapefruit and other CYP3A inhibitors
- Higher naloxegol levels; grapefruit is avoided
- St John's wort and other CYP3A inducers
- Lower naloxegol levels and less effect
- Other laxatives
- Usually stopped when naloxegol is started
What is monitored
- Bowel movements and abdominal pain
- Signs of opioid withdrawal or loss of pain control
Administration and safety
- Oral tablet, taken once a day before or well after the first meal; it can be crushed in water or given by nasogastric tube as instructed.
- Other laxatives are usually stopped when it is started.
- Stopped if the opioid is stopped.
Pregnancy and breastfeeding
Human data are limited; use in pregnancy is discussed with the prescriber and needs a clear benefit.
Nursing care
- Ask about bowel obstruction, ulcers, Crohn's disease, diverticulitis or bowel cancer before starting.
- Review the medication list for CYP3A inhibitors and inducers, and advise against grapefruit.
- Teach to stop and call for severe or worsening abdominal pain.
- Ask about sweating, chills or yawning (withdrawal-like symptoms) and pain control.
Pharmacokinetics
- Metabolism
- Mainly hepatic CYP3A
- Elimination
- Metabolites mostly in faeces, some in urine
Test yourself
Think of the answer, then tap the question to see it.
Why does naloxegol not block opioid analgesia in the brain?
Its PEG chain makes it a P-glycoprotein substrate, so little crosses the blood-brain barrier.
Which fruit is avoided and why?
Grapefruit, because it inhibits CYP3A and raises naloxegol levels.
Which condition is a contraindication?
Known or suspected intestinal obstruction.
Connections
← Back to the class: Laxatives
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Naloxegol: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.