Naloxegol
Identification
- Summary
Naloxegol is a peripherally-selective opioid antagonist used to treat opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain.
- Brand Names
- Movantik, Moventig
- Generic Name
- Naloxegol
- DrugBank Accession Number
- DB09049
- Background
Naloxegol, for "PEGylated naloxol" is a peripherally-selective opioid antagonist developed by AstraZeneca. It was approved by the FDA in September 2014 and is indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non‑cancer pain. The advantage of naloxegol over the opioid antagonist naloxone is that its PEGylated structure allows for high selectivity for peripheral opioid receptors and lack of entry into the central nervous system through the blood-brain barrier.
- Type
- Small Molecule
- Groups
- Approved
- Structure
- Weight
- Average: 651.794
Monoisotopic: 651.361861531 - Chemical Formula
- C34H53NO11
- Synonyms
- (5α,6α)-17-Allyl-6-[(20-hydroxy-3,6,9,12,15,18-hexaoxaicos-1-yl)oxy]-4,5-epoxymorphinan-3,14-diol
- Naloxegol
- External IDs
- AZ-13337019
- NKTR-118
Pharmacology
- Indication
Indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Opioid-induced constipation •••••••••••• ••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Use of opioids induces slowing of gastrointestinal motility and transit. Patients do not develop tolerance to these effects, unlike many other opioid side effects. Naloxegol antagonizes mu, delta, and kappa opioid receptors, having the highest affinity for mu. Antagonism of gastrointestinal mu-opioid receptors by naloxegol inhibits opioid-induced delay of gastrointestinal transit time.
- Mechanism of action
Naloxegol is an antagonist of opioid binding at the mu-opioid receptor. When administered at the recommended dose levels, naloxegol functions as a peripherally-acting mu-opioid receptor antagonist in tissues such as the gastrointestinal tract, thereby decreasing the constipating effects of opioids. Naloxegol has shown more than 6000 fold selectivity for the peripheral mu receptors, and its PEGylated form restricts its action only to the periphery, not affecting the pain-relieving mechanism of opioids in the central nervous system.
Target Actions Organism AMu-type opioid receptor antagonistHumans - Absorption
Following oral administration, naloxegol is absorbed with peak concentrations (Cmax) achieved in less than 2 hours.
- Volume of distribution
968 to 2140 L.
- Protein binding
~4.2%
- Metabolism
Naloxegol is metabolized primarily by the CYP P450 3A4 enzyme system and undergoes enterohepatic recycling. In a mass balance study in humans, a total of 6 metabolites were identified in plasma, urine and feces. These metabolites were formed via N-dealkylation, O-demethylation, oxidation and partial loss of the PEG chain. Human metabolism data suggests absence of major metabolites. The activity of the metabolites at the opioid receptor has not been determined.
- Route of elimination
Feces: 68% after oral administration. Urine: 16% after oral administration.
- Half-life
6-11 hours.
- Clearance
Feces (68%), urine (16%).
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of adverse effects can be increased when Naloxegol is combined with 1,2-Benzodiazepine. Abametapir The serum concentration of Naloxegol can be increased when it is combined with Abametapir. Abrocitinib The serum concentration of Naloxegol can be increased when it is combined with Abrocitinib. Acetazolamide The therapeutic efficacy of Acetazolamide can be decreased when used in combination with Naloxegol. Acetophenazine The risk or severity of hypotension and CNS depression can be increased when Acetophenazine is combined with Naloxegol. - Food Interactions
- Take on an empty stomach. High-fat food increases drug absorption. Take naloxegol at least 1 hour prior to the first meal of the day or 2 hours after the meal.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Naloxegol oxalate 65I14TNM33 1354744-91-4 MNYIRXLCPODKLG-VUTNLTPYSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Movantik Tablet, film coated 25 mg/1 Oral AstraZeneca Pharmaceuticals LP 2015-03-06 2022-12-31 US Movantik Tablet, film coated 25 mg/1 Oral Valinor Pharma, LLC 2023-03-28 Not applicable US Movantik Tablet 25 mg Oral Knight Therapeutics Inc. 2015-08-27 Not applicable Canada Movantik Tablet, film coated 25 mg/1 Oral Avera McKennan Hospital 2016-03-22 2017-05-24 US Movantik Tablet, film coated 12.5 mg/1 Oral AstraZeneca Pharmaceuticals LP 2015-03-06 2022-12-31 US
Categories
- ATC Codes
- A06AH03 — Naloxegol
- Drug Categories
- Alcohols
- Alimentary Tract and Metabolism
- Alkaloids
- Central Nervous System Agents
- Compounds used in a research, industrial, or household setting
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors (weak)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Drugs for Constipation
- Ethylene Glycols
- Glycols
- Heterocyclic Compounds, Fused-Ring
- Macromolecular Substances
- Miscellaneous GI Drugs
- Opiate Alkaloids
- Opioid Antagonists
- Opioids
- Peripheral Nervous System Agents
- Peripheral Opioid Receptor Antagonists
- Phenanthrenes
- Polymers
- Sensory System Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenanthrenes and derivatives. These are polycyclic compounds containing a phenanthrene moiety, which is a tricyclic aromatic compound with three non-linearly fused benzene.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Phenanthrenes and derivatives
- Sub Class
- Not Available
- Direct Parent
- Phenanthrenes and derivatives
- Alternative Parents
- Tetralins / Coumarans / Aralkylamines / Alkyl aryl ethers / 1-hydroxy-2-unsubstituted benzenoids / Piperidines / Tertiary alcohols / Trialkylamines / Cyclic alcohols and derivatives / 1,2-aminoalcohols show 5 more
- Substituents
- 1,2-aminoalcohol / 1-hydroxy-2-unsubstituted benzenoid / Alcohol / Alkyl aryl ether / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Coumaran / Cyclic alcohol show 16 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- tertiary alcohol, aromatic ether, phenols, organic heteropentacyclic compound, polyether (CHEBI:82975)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 44T7335BKE
- CAS number
- 854601-70-0
- InChI Key
- XNKCCCKFOQNXKV-ZRSCBOBOSA-N
- 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
- IUPAC Name
- (1S,5R,13R,14S,17S)-14-(2,5,8,11,14,17,20-heptaoxadocosan-22-yloxy)-4-(prop-2-en-1-yl)-12-oxa-4-azapentacyclo[9.6.1.0¹,¹³.0⁵,¹⁷.0⁷,¹⁸]octadeca-7,9,11(18)-triene-10,17-diol
- SMILES
- COCCOCCOCCOCCOCCOCCOCCO[C@H]1CC[C@@]2(O)[C@H]3CC4=CC=C(O)C5=C4[C@@]2(CCN3CC=C)[C@H]1O5
References
- General References
- Leonard J, Baker DE: Naloxegol: treatment for opioid-induced constipation in chronic non-cancer pain. Ann Pharmacother. 2015 Mar;49(3):360-5. doi: 10.1177/1060028014560191. Epub 2014 Dec 3. [Article]
- Anantharamu T, Sharma S, Gupta AK, Dahiya N, Singh Brashier DB, Sharma AK: Naloxegol: First oral peripherally acting mu opioid receptor antagonists for opioid-induced constipation. J Pharmacol Pharmacother. 2015 Jul-Sep;6(3):188-92. doi: 10.4103/0976-500X.162015. [Article]
- Jones R, Prommer E, Backstedt D: Naloxegol: A Novel Therapy in the Management of Opioid-Induced Constipation. Am J Hosp Palliat Care. 2015 Jul 6. pii: 1049909115593937. [Article]
- External Links
- KEGG Drug
- D10479
- PubChem Compound
- 56959087
- PubChem Substance
- 310264993
- ChemSpider
- 28651656
- 1551777
- ChEBI
- 82975
- ChEMBL
- CHEMBL2219418
- ZINC
- ZINC000095564694
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Naloxegol
- FDA label
- Download (530 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Drug Induced Constipation 1 4 Completed Treatment Opioid Induced Constipation (OIC) 2 4 Completed Treatment Postoperative pain 1 4 Terminated Prevention Constipation 2 4 Terminated Treatment Cancer / Constipation / Pain 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 12.5 mg Tablet Oral 25 mg Tablet, film coated Oral 12.5 mg/1 Tablet, film coated Oral 25 mg/1 Tablet, film coated Oral 12.5 MG Tablet, film coated Oral 25 MG - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8067431 No 2011-11-29 2024-12-16 US US8617530 No 2013-12-31 2022-10-18 US US7056500 No 2006-06-06 2024-06-29 US US7662365 No 2010-02-16 2022-10-18 US US9012469 No 2015-04-21 2032-04-02 US US7786133 No 2010-08-31 2027-12-19 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0566 mg/mL ALOGPS logP 1.73 ALOGPS logP 1.36 Chemaxon logS -4.1 ALOGPS pKa (Strongest Acidic) 10.14 Chemaxon pKa (Strongest Basic) 8.54 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 12 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 126.77 Å2 Chemaxon Rotatable Bond Count 24 Chemaxon Refractivity 171.68 m3·mol-1 Chemaxon Polarizability 72.87 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 261.7913511 predictedDarkChem Lite v0.1.0 [M-H]- 241.60416 predictedDeepCCS 1.0 (2019) [M+H]+ 261.3220511 predictedDarkChem Lite v0.1.0 [M+H]+ 243.42905 predictedDeepCCS 1.0 (2019) [M+Na]+ 261.5560511 predictedDarkChem Lite v0.1.0 [M+Na]+ 249.03487 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Voltage-gated calcium channel activity
- Specific Function
- Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone...
- Gene Name
- OPRM1
- Uniprot ID
- P35372
- Uniprot Name
- Mu-type opioid receptor
- Molecular Weight
- 44778.855 Da
References
- Leonard J, Baker DE: Naloxegol: treatment for opioid-induced constipation in chronic non-cancer pain. Ann Pharmacother. 2015 Mar;49(3):360-5. doi: 10.1177/1060028014560191. Epub 2014 Dec 3. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Leonard J, Baker DE: Naloxegol: treatment for opioid-induced constipation in chronic non-cancer pain. Ann Pharmacother. 2015 Mar;49(3):360-5. doi: 10.1177/1060028014560191. Epub 2014 Dec 3. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Leonard J, Baker DE: Naloxegol: treatment for opioid-induced constipation in chronic non-cancer pain. Ann Pharmacother. 2015 Mar;49(3):360-5. doi: 10.1177/1060028014560191. Epub 2014 Dec 3. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
Drug created at May 04, 2015 23:26 / Updated at February 20, 2024 23:55