Pharmaceutical compound
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| 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 | |
| Pharmacokinetic data | |
| Protein binding | ~4.2% |
| Metabolism | Liver (CYP3A) |
| Elimination half-life | 6–11 h |
| Excretion | Feces (68%), urine (16%) |
| Identifiers | |
IUPAC name
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| CAS Number | |
| PubChem CID | |
| ChemSpider | |
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| CompTox Dashboard (EPA) | |
| Chemical and physical data | |
| Formula | C34H53NO11 |
| Molar mass | 651.794 g·mol |
| 3D model (JSmol) | |
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Naloxegol (INN; PEGylated naloxol; 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. It was approved in 2014 in adult patients with chronic, non-cancer pain. Doses of 25 mg were found safe and well tolerated for 52 weeks. When given concomitantly with opioid analgesics, naloxegol reduced constipation-related side effects, while maintaining comparable levels of analgesia.
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.
Medical use
Naloxegol is indicated for the treatment of opioid-induced constipation (OIC) in people with chronic non-cancer pain.
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.
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. The pegylation of the 6-α-hydroxyl side chain of naloxol prevents the drug from crossing the blood–brain barrier (BBB).
References
- "Prescription medicines: registration of new chemical entities in Australia, 2016". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
- "Health Canada New Drug Authorizations: 2015 Highlights". Health Canada. 4 May 2016. Retrieved 7 April 2024.
- "Moventig EPAR". European Medicines Agency (EMA). 8 December 2014. Retrieved 28 September 2024.
- 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. Retrieved 14 May 2012.
- "Nektar | R&D Pipeline | Products in Development | CNS/Pain | Oral Naloxegol (NKTR-118) and Oral NKTR-119". Archived from the original on 13 February 2012. Retrieved 14 May 2012.
- "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 10 May 2015.
- 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.
- ^ 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.
- ^ "Movantik prescribing information highlights" (PDF). Retrieved 14 August 2019.
- "Schedules of Controlled Substances: Removal of Naloxegol From Control". www.deadiversion.usdoj.gov. Archived from the original on 9 March 2016. Retrieved 27 February 2016.
- "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. PMID 25666542. S2CID 207488539.
- Technically, the molecule that is attached via the ether link is O-methyl-heptaethylene glycol , molecular weight 340.4, CAS number 4437-01-8. See "Compound Summary for CID 526555, Pubchem Compound 4437-01". PubChem Compound Database. Bethesda, MD: NCBI, U.S. NLM. 2016. Archived from the original on 5 February 2016. Retrieved 28 January 2016.
| Drugs for constipation (laxatives and cathartics) (A06) | |
|---|---|
| Stool softeners | |
| Stimulant laxatives | |
| Bulk-forming laxatives | |
| Lubricant laxatives | |
| Osmotic laxatives | |
| Enemas | |
| Opioid antagonists | |
| Others | |
