naloxegol
{{Short description|Medication used in the treatment for Opioid-Induced Constipation}}
{{Use dmy dates|date=September 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Drugbox
| image = Naloxegol.svg
| image_class = skin-invert-image
| width =
| alt =
| tradename = Movantik, Moventig
| Drugs.com = {{Drugs.com|parent|movantik}}
| DailyMedID = Naloxegol
| pregnancy_AU =
| pregnancy_category =
| routes_of_administration = By mouth
| ATC_prefix = A06
| ATC_suffix = AH03
| ATC_supplemental =
| legal_AU = S4
| legal_CA = Rx-only
| legal_CA_comment = {{cite web | title=Health Canada New Drug Authorizations: 2015 Highlights | website=Health Canada | date=4 May 2016 | url=https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/health-canada-new-drug-authorizations-2015-highlights.html | access-date=7 April 2024}}
| legal_UK =
| legal_US = Rx only
| legal_US_comment =
| legal_EU = Rx only
| legal_status =
| CAS_number = 854601-70-0
| CAS_supplemental =
| PubChem = 56959087
| DrugBank =
| ChemSpiderID = 28651656
| ChEBI = 82975
| UNII = 44T7335BKE
| KEGG = D10479
| 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
| C= 34| H= 53 | N=1 | O= 11
| smiles = COCCOCCOCCOCCOCCOCCOCCO[C@H]1CC[C@]2([C@H]3Cc4ccc(c5c4[C@]2([C@H]1O5)CCN3CC=C)O)O
| StdInChI = 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
| StdInChIKey = XNKCCCKFOQNXKV-ZRSCBOBOSA-N
| synonyms = NKTR-118
| density =
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| specific_rotation =
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| bioavailability =
| protein_bound = ~4.2%
| elimination_half-life = 6–11 h
| excretion = Feces (68%), urine (16%)
}}
Naloxegol (INN; PEGylated naloxol;{{cite book | vauthors = Seifert R, Wieland T, Mannhold R, Kubinyi H, Folkers G | title = G Protein-Coupled Receptors as Drug Targets: Analysis of Activation and Constitutive Activity | url = https://books.google.com/books?id=pIrnOKH-7HcC&pg=PA227 | access-date = 14 May 2012 | date = 17 July 2006 | publisher = John Wiley & Sons | isbn = 978-3-527-60695-5 | page = 227}} 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.{{cite web | url = http://www.nektar.com/product_pipeline/cns_pain_oral_nktr-118and119.html | title = Nektar | R&D Pipeline | Products in Development | CNS/Pain | Oral Naloxegol (NKTR-118) and Oral NKTR-119 | access-date = 2012-05-14 | url-status = dead | archive-url = https://web.archive.org/web/20120213133752/http://www.nektar.com/product_pipeline/cns_pain_oral_nktr-118and119.html | archive-date = 2012-02-13 }} It was approved in 2014 in adult patients with chronic, non-cancer pain.{{Cite news|url =http://www.astrazeneca-us.com/media/press-releases/Article/20140916-fda-approves-movantik-naloxegol-tablets-cii|title =FDA approves MOVANTIK™ (naloxegol) Tablets C-II for the treatment of opioid-induced constipation in adult patients with chronic non-cancer pain|date =16 September 2014|archive-url =https://web.archive.org/web/20150510025921/http://www.astrazeneca-us.com/media/press-releases/Article/20140916-fda-approves-movantik-naloxegol-tablets-cii|archive-date =2015-05-10|url-status =live}} Doses of 25 mg were found safe and well tolerated for 52 weeks.{{cite journal | vauthors = Webster L, Chey WD, Tack J, Lappalainen J, Diva U, Sostek M | title = Randomised clinical trial: the long-term safety and tolerability of naloxegol in patients with pain and opioid-induced constipation | journal = Alimentary Pharmacology & Therapeutics | volume = 40 | issue = 7 | pages = 771–9 | date = October 2014 | pmid = 25112584 | doi = 10.1111/apt.12899 | s2cid = 34286557 | url = https://deepblue.lib.umich.edu/bitstream/2027.42/108643/1/apt12899.pdf | doi-access = free }} When given concomitantly with opioid analgesics, naloxegol reduced constipation-related side effects, while maintaining comparable levels of analgesia.{{cite journal | vauthors = Garnock-Jones KP | title = Naloxegol: a review of its use in patients with opioid-induced constipation | journal = Drugs | volume = 75 | issue = 4 | pages = 419–25 | date = March 2015 | pmid = 25666542 | doi = 10.1007/s40265-015-0357-2 | s2cid = 207488539 }}
The most common side effects are abdominal pain, diarrhea, nausea, flatulence, vomiting, and headache.
Naloxegol was previously a Schedule II drug in the United States because of its chemical similarity to opium alkaloids. It was officially decontrolled in January 2015. It was reclassified as a prescription drug after the FDA and DEA concluded that the impermeability of the blood–brain barrier to this compound made it non-habit-forming, and so without the potential for abuse.{{cite web|url=http://www.deadiversion.usdoj.gov/fed_regs/rules/2015/fr0123_3.htm|title=Schedules of Controlled Substances: Removal of Naloxegol From Control|website=www.deadiversion.usdoj.gov|access-date=2016-02-27|archive-url=https://web.archive.org/web/20160309173010/http://www.deadiversion.usdoj.gov/fed_regs/rules/2015/fr0123_3.htm|archive-date=2016-03-09|url-status=live}}
Medical use
Naloxegol is indicated for the treatment of opioid-induced constipation (OIC) in people with chronic non-cancer pain.{{Cite web|title=Movantik prescribing information highlights|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204760s000lbl.pdf|access-date=2019-08-14|website=}}{{Cite web |title=Naloxegol for Opioid-Induced Constipation in Patients with Noncancer Pain |url=https://homeworkmarket.us/uploads/20211/NaloxegolforOpioid-InducedConstipation1.pdf }}
Side effects
The most common side effects are abdominal pain, diarrhea, nausea, flatulence, vomiting, and headache.
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.{{cite journal | vauthors = Garnock-Jones KP | title = Naloxegol: a review of its use in patients with opioid-induced constipation | journal = Drugs | volume = 75 | issue = 4 | pages = 419–25 | date = March 2015 | pmid = 25666542 | doi = 10.1007/s40265-015-0357-2 | s2cid = 207488539 }}
If naloxegol is coadministered with other opioid antagonists, there is a potential for additive effect and increased risk of opioid withdrawal.
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.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 {{cite book|chapter-url=https://pubchem.ncbi.nlm.nih.gov/compound/4437-01-8#section=Top|title=PubChem Compound Database |publisher=NCBI, U.S. NLM|year=2016|location=Bethesda, MD |chapter=Compound Summary for CID 526555, Pubchem Compound 4437-01|access-date=28 January 2016|archive-url=https://web.archive.org/web/20160205030929/http://pubchem.ncbi.nlm.nih.gov/compound/4437-01-8#section=Top#section=Top|archive-date=2016-02-05|url-status=live}} The pegylation of the 6-α-hydroxyl side chain of naloxol prevents the drug from crossing the blood–brain barrier (BBB).
References
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{{Opioid receptor modulators}}
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Category:Drugs developed by AstraZeneca
Category:Mu-opioid receptor antagonists