Naloxegol

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Naloxegol
Clinical data
Trade namesMovantik, Moventig
Other namesNKTR-118
AHFS/Drugs.commovantik
License data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding~4.2%
MetabolismLiver (CYP3A)
Elimination half-life6–11 h
ExcretionFeces (68%), urine (16%)
Identifiers
  • (5α,6α)-4,5-epoxy-6-(3,6,9,12,15,18,21-heptaoxadocos-1-yloxy)-17-(2-propen-1-yl)morphinan-3,14-diol
JSmol)
  • COCCOCCOCCOCCOCCOCCOCCO[C@H]1CC[C@]2([C@H]3Cc4ccc(c5c4[C@]2([C@H]1O5)CCN3CC=C)O)O
  • InChI=1S/C34H53NO11/c1-3-9-35-10-8-33-30-26-4-5-27(36)31(30)46-32(33)28(6-7-34(33,37)29(35)25-26)45-24-23-44-22-21-43-20-19-42-18-17-41-16-15-40-14-13-39-12-11-38-2/h3-5,28-29,32,36-37H,1,6-25H2,2H3/t28-,29+,32-,33-,34+/m0/s1
  • Key:XNKCCCKFOQNXKV-ZRSCBOBOSA-N

Naloxegol (

INN; PEGylated naloxol;[3] trade names Movantik and Moventig) is a peripherally acting μ-opioid receptor antagonist developed by AstraZeneca, licensed from Nektar Therapeutics, for the treatment of opioid-induced constipation.[4] It was approved in 2014 in adult patients with chronic, non-cancer pain.[5] Doses of 25 mg were found safe and well tolerated for 52 weeks.[6] When given concomitantly with opioid analgesics, naloxegol reduced constipation-related side effects, while maintaining comparable levels of analgesia.[7]

The most common side effects are abdominal pain, diarrhea, nausea, flatulence, vomiting and headache. Patients often describe the above side effects to be similar to an instant withdrawal state brought on quickly rather than the 24 hours it may take to occur naturally. As a pure opioid antagonist Naloxegol has no potential for abuse.

Naloxegol was previously a

abuse.[8]

Medical use

Naloxegol is indicated for the treatment of

opioid-induced constipation (OIC) in patients with chronic non-cancer pain.[9][10] It is recommended that any maintenance laxative be discontinued before starting naloxegol or be held for at least 3 days. Naloxegol should be taken on an empty stomach at least two hours after the last meal.[9]

Side effects

The most common side effects for naloxegol include:[9]

Pharmacodynamic properties

Naloxegol inhibits opioid binding in μ-opioid receptors in the gastrointestinal tract, thus decreasing the constipating effects (slowing of gastrointestinal motility and transit, hypertonicity, increased fluid reabsorption) associated with opioids.[11]

If naloxegol is coadministered with other opioid antagonists, there is a potential for additive effect and increased risk of opioid withdrawal.[9]

Mechanism of action

Chemically, naloxegol is a

hydroxyl side chain of naloxol prevents the drug from crossing the blood–brain barrier (BBB).[7] As such, it can be considered the antithesis of the peripherally-acting opiate loperamide
which is utilized as an opiate-targeting anti-diarrheal agent that does not cause traditional opiate side-effects due to its inability to accumulate in the central nervous system in normal subjects.

References

  1. ^ "Prescription medicines: registration of new chemical entities in Australia, 2016". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
  2. ^ "Health Canada New Drug Authorizations: 2015 Highlights". Health Canada. 4 May 2016. Retrieved 7 April 2024.
  3. ISBN 978-3-527-60695-5
    . Retrieved 14 May 2012.
  4. ^ "Nektar | R&D Pipeline | Products in Development | CNS/Pain | Oral Naloxegol (NKTR-118) and Oral NKTR-119". Archived from the original on 2012-02-13. Retrieved 2012-05-14.
  5. ^ "FDA approves MOVANTIK™ (naloxegol) Tablets C-II for the treatment of opioid-induced constipation in adult patients with chronic non-cancer pain". 16 September 2014. Archived from the original on 2015-05-10.
  6. S2CID 34286557
    .
  7. ^
    S2CID 207488539
    .
  8. ^ "Schedules of Controlled Substances: Removal of Naloxegol From Control". www.deadiversion.usdoj.gov. Archived from the original on 2016-03-09. Retrieved 2016-02-27.
  9. ^ a b c d "Movantik prescribing information highlights" (PDF). Retrieved 2019-08-14.
  10. ^ "Naloxegol for Opioid-Induced Constipation in Patients with Noncancer Pain" (PDF).
  11. S2CID 207488539
    .
  12. NLM. 2016. Archived
    from the original on 2016-02-05. Retrieved 28 January 2016.
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