Naloxegol
Medication used in the treatment for Opioid-Induced Constipation
From Wikipedia, the free encyclopedia
Naloxegol (INN; PEGylated naloxol;[4] 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.[5] It was approved in 2014 in adult patients with chronic, non-cancer pain.[6] Doses of 25 mg were found safe and well tolerated for 52 weeks.[7] When given concomitantly with opioid analgesics, naloxegol reduced constipation-related side effects, while maintaining comparable levels of analgesia.[8]
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| Trade names | Movantik, Moventig |
| Other names | NKTR-118 |
| AHFS/Drugs.com | movantik |
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| Routes of administration | By mouth |
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| Protein binding | ~4.2% |
| Metabolism | Liver (CYP3A) |
| Elimination half-life | 6–11 h |
| Excretion | Feces (68%), urine (16%) |
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| Formula | C34H53NO11 |
| Molar mass | 651.794 g·mol−1 |
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The most common side effects are abdominal pain, diarrhea, nausea, flatulence, vomiting, and headache.[9]
Naloxegol was previously a Schedule II drug in the United States because of its chemical similarity to noroxymorphone.[10] 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.[11]
Medical use
Naloxegol is indicated for the treatment of opioid-induced constipation (OIC) in people with chronic non-cancer pain.[9][12]
Side effects
The most common side effects are abdominal pain, diarrhea, nausea, flatulence, vomiting, and headache.[9]
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.[8]
If naloxegol is coadministered with other opioid antagonists, there is a potential for additive effect and increased risk of opioid withdrawal.[9]
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.[13] The pegylation of the 6-α-hydroxyl side chain of naloxol prevents the drug from crossing the blood–brain barrier (BBB).[8]
