Naloxegol

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Naloxegol
Naloxegol.svg
Names
Trade namesMovantik, Moventig
Other namesPEGylated naloxol;[1] NKTR-118
  • (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
Clinical data
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
use
By mouth
External links
AHFS/Drugs.comMonograph
US NLMNaloxegol
Legal
License data
Legal status
Pharmacokinetics
Protein binding~4.2%
MetabolismLiver (CYP3A)
Elimination half-life6–11 h
ExcretionFeces (68%), urine (16%)
Chemical and physical data
FormulaC34H53NO11
Molar mass651.794 g·mol−1
3D model (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, sold under the brand names Movantik and Moventig, is a medication used for opioid-induced constipation in people with long term non-cancer pain.[2] It may be used when laxatives are not effective.[3] It is taken by mouth.[2] It generally dose not affect pain management.[3]

Common side effects include abdominal pain, diarrhea, nausea, and headache.[2] Other side effects may include opioid withdrawal and gastrointestinal perforation.[2] Use in pregnancy has not shown harm; however such use has not been well studied.[4] Chemically it is naloxone attached to polyethylene glycol (PEF).[2] It is a peripherally acting μ-opioid receptor antagonist, which prevents opioids from binding to receptors in the gut.[2]

Naloxegol was approved for medical use in the United States and Europe in 2014.[2][5] In the United States it costs about 360 USD per month as of 2021.[6] This amount in the United Kingdom costs the NHS about £55.[3] As of 2015 it is no longer a controlled substance in the United States.[7]

Medical use

Naloxegol is indicated for the treatment of opioid-induced constipation (OIC) in patients with chronic non-cancer pain. 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.[8]

When given concomitantly with opioid analgesics, naloxegol reduced constipation-related side effects, while maintaining comparable levels of analgesia.[9]

Dosage

It is generally taken at a dose of 25 mg per day.[2] This was found safe and well tolerated for 52 weeks.[10]

Mechanism of action

Chemically, naloxegol is a pegylated (polyethylene glycol-modified) derivative of α-naloxol. Specifically, the 6-α-hydroxyl group of α-naloxol is connected via an ether linkage to the free hydroxyl group of a monomethoxy-terminated n=7 oligomer of PEG, shown extending at the lower left of the molecule image at right. The "n=7" defines the number of two-carbon ethylenes, and so the chain length, of the attached PEG chain, and the "monomethoxy" indicates that the terminal hydroxyl group of the PEG is "capped" with a methyl group.[11] The pegylation of the 6-α-hydroxyl side chain of naloxol prevents the drug from crossing the blood-brain barrier (BBB).[9] 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.

Pharmacodynamics

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.[12]

If naloxegol is coadministered with other opioid antagonists, there is a potential for additive effect and increased risk of opioid withdrawal.[8]

References

  1. Seifert R, Wieland T, Mannhold R, Kubinyi H, Folkers G (17 July 2006). G Protein-Coupled Receptors as Drug Targets: Analysis of Activation and Constitutive Activity. John Wiley & Sons. p. 227. ISBN 978-3-527-60695-5. Archived from the original on 28 June 2014. Retrieved 14 May 2012.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 "Naloxegol Monograph for Professionals". Drugs.com. Archived from the original on 21 January 2021. Retrieved 11 November 2021.
  3. 3.0 3.1 3.2 BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 71. ISBN 978-0857114105.
  4. "Naloxegol (Movantik) Use During Pregnancy". Drugs.com. Archived from the original on 27 January 2021. Retrieved 11 November 2021.
  5. "Moventig". Archived from the original on 27 February 2021. Retrieved 11 November 2021.
  6. "Naloxegol Prices, Coupons & Savings Tips - GoodRx". GoodRx. Archived from the original on 31 October 2016. Retrieved 11 November 2021.
  7. "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.
  8. 8.0 8.1 "Movantik prescribing information highlights". AstraZeneca. Archived from the original on 2019-05-02. Retrieved 2019-08-14.
  9. 9.0 9.1 Garnock-Jones KP (March 2015). "Naloxegol: a review of its use in patients with opioid-induced constipation". Drugs. 75 (4): 419–25. doi:10.1007/s40265-015-0357-2. PMID 25666542. S2CID 207488539.
  10. Webster L, Chey WD, Tack J, Lappalainen J, Diva U, Sostek M (October 2014). "Randomised clinical trial: the long-term safety and tolerability of naloxegol in patients with pain and opioid-induced constipation" (PDF). Alimentary Pharmacology & Therapeutics. 40 (7): 771–9. doi:10.1111/apt.12899. PMID 25112584. S2CID 34286557. Archived from the original on 2021-10-28. Retrieved 2021-10-24.
  11. Technically, the molecule that is attached via the ether link is O-methyl-heptaethylene glycol [that is, methoxyheptaethylene glycol, CH3OCH2CH2O(CH2CH2O)5CH2CH2OH], molecular weight 340.4, CAS number 4437-01-8. See Pubchem Staff (2016). "Compound Summary for CID 526555, Pubchem Compound 4437-01". PubChem Compound Database. Bethesda, MD, USA: NCBI, U.S. NLM. Archived from the original on 2016-02-05. Retrieved 28 January 2016.
  12. Garnock-Jones KP (March 2015). "Naloxegol: a review of its use in patients with opioid-induced constipation". Drugs. 75 (4): 419–25. doi:10.1007/s40265-015-0357-2. PMID 25666542. S2CID 207488539.

External links

Identifiers: