Naloxegol
 | |
| Clinical data | |
|---|---|
| Trade names | Movantik, Moventig |
| Other names | NKTR-118 |
| AHFS/Drugs.com | movantik |
| License data | |
| Routes of administration | By mouth |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokineticdata | |
| Protein binding | ~4.2% |
| Metabolism | Liver(CYP3A) |
| Eliminationhalf-life | 6–11 h |
| Excretion | Feces (68%), urine (16%) |
| Identifiers | |
| |
| CAS Number | |
| PubChemCID | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| CompTox Dashboard(EPA) | |
| Chemical and physical data | |
| Formula | C34H53NO11 |
| Molar mass | 651.794g·mol−1 |
| 3D model (JSmol) | |
| |
| |
Naloxegol(INN;PEGylated naloxol;[3]trade namesMovantikandMoventig) is aperipherally acting μ-opioid receptor antagonistdeveloped byAstraZeneca,licensed fromNektar Therapeutics,for the treatment ofopioid-inducedconstipation.[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 pureopioid antagonistNaloxegol has no potential for abuse.
Naloxegol was previously aSchedule IIdrug in the United States because of its chemical similarity to opium alkaloids. It was officially decontrolled on 23 January 2015. It was reclassified as aprescription drugafter theFDAandDEAconcluded that theimpermeabilityof theblood–brain barrierto this compound made it non-habit-forming, and so without the potential forabuse.[8]
Medical use[edit]
Naloxegol is indicated for the treatment ofopioid-induced constipation(OIC) in patients with chronic non-cancer pain.[9][10]It is recommended that any maintenancelaxativebe 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[edit]
The most common side effects for naloxegol include:[9]
Pharmacodynamic properties[edit]
Naloxegol inhibits opioid binding inμ-opioid receptorsin the gastrointestinal tract, thus decreasing the constipating effects (slowing of gastrointestinal motility and transit,hypertonicity,increased fluid reabsorption) associated withopioids.[11]
If naloxegol is coadministered with otheropioid antagonists,there is a potential for additive effect and increased risk ofopioid withdrawal.[9]
Mechanism of action[edit]
Chemically, naloxegol is apegylated(polyethylene glycol-modified)derivativeof α-naloxol.Specifically, the 6-α-hydroxyl group of α-naloxolis connected via anetherlinkage to the freehydroxyl groupof a monomethoxy-terminated n=7oligomerofPEG,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 amethyl group.[12]The pegylation of the 6-α-hydroxyl side chainofnaloxolprevents the drug from crossing theblood–brain barrier(BBB).[7]As such, it can be considered the antithesis of the peripherally-acting opiateloperamidewhich 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[edit]
- ^"Prescription medicines: registration of new chemical entities in Australia, 2016".Therapeutic Goods Administration (TGA).21 June 2022.Retrieved10 April2023.
- ^"Health Canada New Drug Authorizations: 2015 Highlights".Health Canada.4 May 2016.Retrieved7 April2024.
- ^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.ISBN978-3-527-60695-5.Retrieved14 May2012.
- ^"Nektar | R&D Pipeline | Products in Development | CNS/Pain | Oral Naloxegol (NKTR-118) and Oral NKTR-119".Archived fromthe originalon 2012-02-13.Retrieved2012-05-14.
- ^"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.Archivedfrom the original on 2015-05-10.
- ^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.PMID25112584.S2CID34286557.
- ^abGarnock-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.PMID25666542.S2CID207488539.
- ^"Schedules of Controlled Substances: Removal of Naloxegol From Control".www.deadiversion.usdoj.gov.Archivedfrom the original on 2016-03-09.Retrieved2016-02-27.
- ^abcd"Movantik prescribing information highlights"(PDF).Retrieved2019-08-14.
- ^"Naloxegol for Opioid-Induced Constipation in Patients with Noncancer Pain"(PDF).
- ^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.PMID25666542.S2CID207488539.
- ^Technically, the molecule that is attached via the ether link isO-methyl-heptaethylene glycol [that is, methoxyheptaethylene glycol, CH3OCH2CH2O(CH2CH2O)5CH2CH2OH], molecular weight 340.4,CAS number4437-01-8. See"Compound Summary for CID 526555, Pubchem Compound 4437-01".PubChem Compound Database.Bethesda, MD, USA:NCBI,U.S.NLM.2016.Archivedfrom the original on 2016-02-05.Retrieved28 January2016.