Naloxegol

Naloxegol
Names
Trade namesMovantik, Moventig
Other namesPEGylated naloxol;[1] NKTR-118
IUPAC name
  • (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
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • US: C (Risk not ruled out)
    Routes of
    use    		By mouth
    External links
    AHFS/Drugs.comMonograph
    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)
    SMILES
    • COCCOCCOCCOCCOCCOCCOCCO[C@H]1CC[C@]2([C@H]3Cc4ccc(c5c4[C@]2([C@H]1O5)CCN3CC=C)O)O
    InChI
    • 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. 1 2 3 4 5 6 7 8 "Naloxegol Monograph for Professionals". Drugs.com. Archived from the original on 21 January 2021. Retrieved 11 November 2021.
    3. 1 2 3 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. 1 2 "Movantik prescribing information highlights". AstraZeneca. Archived from the original on 2019-05-02. Retrieved 2019-08-14.
    9. 1 2 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.
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