Identification
NameNaloxegol
Accession NumberDB09049
TypeSmall Molecule
GroupsApproved
Description

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.

Structure
Thumb
Synonyms
(5α,6α)-17-Allyl-6-[(20-hydroxy-3,6,9,12,15,18-hexaoxaicos-1-yl)oxy]-4,5-epoxymorphinan-3,14-diol
External IDs AZ-13337019 / NKTR-118
Product Ingredients
IngredientUNIICASInChI KeyDetails
Naloxegol oxalate65I14TNM33 1354744-91-4MNYIRXLCPODKLG-VUTNLTPYSA-NDetails
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MovantikTablet, film coated25 mg/1OralAstra Zeneca Lp2015-03-06Not applicableUs
MovantikTablet25 mgOralKnight Therapeutics Inc.2015-08-27Not applicableCanada
MovantikTablet12.5 mgOralKnight Therapeutics Inc.2015-08-27Not applicableCanada
MovantikTablet, film coated25 mg/1OralLake Erie Medical Dba Quality Care Produts Llc2015-03-06Not applicableUs
MovantikTablet, film coated12.5 mg/1OralAstra Zeneca Lp2015-03-06Not applicableUs
MovantikTablet, film coated25 mg/1OralAvera Mc Kennan Hospital2016-03-22Not applicableUs
MoventigTablet, film coated12.5 mgOralAstra Zeneca Ab2014-12-08Not applicableEu
MoventigTablet, film coated25 mgOralAstra Zeneca Ab2014-12-08Not applicableEu
MoventigTablet, film coated25 mgOralAstra Zeneca Ab2014-12-08Not applicableEu
MoventigTablet, film coated12.5 mgOralAstra Zeneca Ab2014-12-08Not applicableEu
MoventigTablet, film coated25 mgOralAstra Zeneca Ab2014-12-08Not applicableEu
MoventigTablet, film coated12.5 mgOralAstra Zeneca Ab2014-12-08Not applicableEu
MoventigTablet, film coated25 mgOralAstra Zeneca Ab2014-12-08Not applicableEu
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNII44T7335BKE
CAS number854601-70-0
WeightAverage: 651.794
Monoisotopic: 651.361861531
Chemical FormulaC34H53NO11
InChI KeyXNKCCCKFOQNXKV-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[[email protected]]1CC[[email protected]@]2(O)[[email protected]]3CC4=CC=C(O)C5=C4[[email protected]@]2(CCN3CC=C)[[email protected]]1O5
Pharmacology
Indication

Indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain.

Structured Indications
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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Mu-type opioid receptorProteinyes
antagonist
HumanP35372 details
Related Articles
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%).

ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcetaminophenThe serum concentration of Naloxegol can be increased when it is combined with Acetaminophen.Approved
AfatinibThe serum concentration of Naloxegol can be increased when it is combined with Afatinib.Approved
AlbendazoleThe serum concentration of Naloxegol can be increased when it is combined with Albendazole.Approved, Vet Approved
AlectinibThe serum concentration of Naloxegol can be increased when it is combined with Alectinib.Approved
AlfentanilThe serum concentration of Naloxegol can be increased when it is combined with Alfentanil.Approved, Illicit
AlvimopanThe risk or severity of adverse effects can be increased when Alvimopan is combined with Naloxegol.Approved
AmantadineThe serum concentration of Naloxegol can be increased when it is combined with Amantadine.Approved
Aminohippuric acidThe serum concentration of Naloxegol can be increased when it is combined with Aminohippuric acid.Approved
AmiodaroneThe serum concentration of Naloxegol can be increased when it is combined with Amiodarone.Approved, Investigational
AmitriptylineThe serum concentration of Naloxegol can be increased when it is combined with Amitriptyline.Approved
AmlodipineThe serum concentration of Naloxegol can be increased when it is combined with Amlodipine.Approved
AmprenavirThe serum concentration of Naloxegol can be increased when it is combined with Amprenavir.Approved
AmsacrineThe serum concentration of Naloxegol can be increased when it is combined with Amsacrine.Approved
AprepitantThe serum concentration of Naloxegol can be increased when it is combined with Aprepitant.Approved, Investigational
AstemizoleThe serum concentration of Naloxegol can be increased when it is combined with Astemizole.Approved, Withdrawn
AtazanavirThe serum concentration of Naloxegol can be increased when it is combined with Atazanavir.Approved, Investigational
AtenololThe serum concentration of Naloxegol can be increased when it is combined with Atenolol.Approved
AtomoxetineThe serum concentration of Naloxegol can be increased when it is combined with Atomoxetine.Approved
AtorvastatinThe serum concentration of Naloxegol can be increased when it is combined with Atorvastatin.Approved
AzelastineThe serum concentration of Naloxegol can be increased when it is combined with Azelastine.Approved
AzithromycinThe serum concentration of Naloxegol can be increased when it is combined with Azithromycin.Approved
BenzocaineThe serum concentration of Naloxegol can be increased when it is combined with Benzocaine.Approved
BepridilThe serum concentration of Naloxegol can be increased when it is combined with Bepridil.Approved, Withdrawn
BexaroteneThe serum concentration of Naloxegol can be decreased when it is combined with Bexarotene.Approved, Investigational
BiperidenThe serum concentration of Naloxegol can be increased when it is combined with Biperiden.Approved
BoceprevirThe serum concentration of Naloxegol can be increased when it is combined with Boceprevir.Withdrawn
BortezomibThe serum concentration of Naloxegol can be increased when it is combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Naloxegol can be decreased when it is combined with Bosentan.Approved, Investigational
BosutinibThe serum concentration of Naloxegol can be increased when it is combined with Bosutinib.Approved
BromocriptineThe serum concentration of Naloxegol can be increased when it is combined with Bromocriptine.Approved, Investigational
BuprenorphineThe risk or severity of adverse effects can be increased when Buprenorphine is combined with Naloxegol.Approved, Illicit, Investigational, Vet Approved
BuspironeThe serum concentration of Naloxegol can be increased when it is combined with Buspirone.Approved, Investigational
ButorphanolThe risk or severity of adverse effects can be increased when Butorphanol is combined with Naloxegol.Approved, Illicit, Vet Approved
CabazitaxelThe serum concentration of Naloxegol can be increased when it is combined with Cabazitaxel.Approved
CaffeineThe serum concentration of Naloxegol can be increased when it is combined with Caffeine.Approved
CanagliflozinThe serum concentration of Naloxegol can be increased when it is combined with Canagliflozin.Approved
CandesartanThe serum concentration of Naloxegol can be increased when it is combined with Candesartan.Approved
CaptoprilThe serum concentration of Naloxegol can be increased when it is combined with Captopril.Approved
CarbamazepineThe serum concentration of Naloxegol can be decreased when it is combined with Carbamazepine.Approved, Investigational
CarvedilolThe serum concentration of Naloxegol can be increased when it is combined with Carvedilol.Approved, Investigational
CaspofunginThe serum concentration of Naloxegol can be increased when it is combined with Caspofungin.Approved
CeritinibThe serum concentration of Naloxegol can be increased when it is combined with Ceritinib.Approved
ChloroquineThe serum concentration of Naloxegol can be increased when it is combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe serum concentration of Naloxegol can be increased when it is combined with Chlorpromazine.Approved, Vet Approved
ChlorpropamideThe serum concentration of Naloxegol can be increased when it is combined with Chlorpropamide.Approved
ChlorprothixeneThe serum concentration of Naloxegol can be increased when it is combined with Chlorprothixene.Approved, Withdrawn
CholesterolThe serum concentration of Naloxegol can be increased when it is combined with Cholesterol.Experimental
CilazaprilThe serum concentration of Naloxegol can be increased when it is combined with Cilazapril.Approved
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Naloxegol.Approved
CimetidineThe serum concentration of Naloxegol can be increased when it is combined with Cimetidine.Approved
CiprofloxacinThe serum concentration of Naloxegol can be increased when it is combined with Ciprofloxacin.Approved, Investigational
CitalopramThe serum concentration of Naloxegol can be increased when it is combined with Citalopram.Approved
ClarithromycinThe serum concentration of Naloxegol can be increased when it is combined with Clarithromycin.Approved
ClemastineThe serum concentration of Naloxegol can be increased when it is combined with Clemastine.Approved
ClofazimineThe serum concentration of Naloxegol can be increased when it is combined with Clofazimine.Approved, Investigational
ClomipramineThe serum concentration of Naloxegol can be increased when it is combined with Clomipramine.Approved, Vet Approved
ClotrimazoleThe serum concentration of Naloxegol can be increased when it is combined with Clotrimazole.Approved, Vet Approved
CobicistatThe serum concentration of Naloxegol can be increased when it is combined with Cobicistat.Approved
ColchicineThe serum concentration of Naloxegol can be increased when it is combined with Colchicine.Approved
ColforsinThe serum concentration of Naloxegol can be increased when it is combined with Colforsin.Experimental
ConivaptanThe serum concentration of Naloxegol can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe serum concentration of Naloxegol can be increased when it is combined with Crizotinib.Approved
CyclophosphamideThe serum concentration of Naloxegol can be increased when it is combined with Cyclophosphamide.Approved, Investigational
CyclosporineThe serum concentration of Naloxegol can be increased when it is combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Naloxegol can be decreased when it is combined with Dabrafenib.Approved
DaclatasvirThe serum concentration of Naloxegol can be increased when it is combined with Daclatasvir.Approved
DactinomycinThe serum concentration of Naloxegol can be increased when it is combined with Dactinomycin.Approved
DarunavirThe serum concentration of Naloxegol can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Naloxegol can be increased when it is combined with Dasatinib.Approved, Investigational
DaunorubicinThe serum concentration of Naloxegol can be increased when it is combined with Daunorubicin.Approved
DeferasiroxThe serum concentration of Naloxegol can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe serum concentration of Naloxegol can be increased when it is combined with Delavirdine.Approved
DesipramineThe serum concentration of Naloxegol can be increased when it is combined with Desipramine.Approved
DesloratadineThe serum concentration of Naloxegol can be increased when it is combined with Desloratadine.Approved, Investigational
DexamethasoneThe serum concentration of Naloxegol can be increased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DextromethorphanThe serum concentration of Naloxegol can be increased when it is combined with Dextromethorphan.Approved
DextropropoxypheneThe risk or severity of adverse effects can be increased when Dextropropoxyphene is combined with Naloxegol.Approved, Illicit, Withdrawn
DezocineThe risk or severity of adverse effects can be increased when Dezocine is combined with Naloxegol.Approved
DiclofenacThe serum concentration of Naloxegol can be increased when it is combined with Diclofenac.Approved, Vet Approved
DigoxinThe serum concentration of Naloxegol can be increased when it is combined with Digoxin.Approved
DihydroergotamineThe serum concentration of Naloxegol can be increased when it is combined with Dihydroergotamine.Approved
DiltiazemThe serum concentration of Naloxegol can be increased when it is combined with Diltiazem.Approved
DiprenorphineThe risk or severity of adverse effects can be increased when Diprenorphine is combined with Naloxegol.Illicit, Vet Approved
DipyridamoleThe serum concentration of Naloxegol can be increased when it is combined with Dipyridamole.Approved
DoxazosinThe serum concentration of Naloxegol can be increased when it is combined with Doxazosin.Approved
DoxepinThe serum concentration of Naloxegol can be increased when it is combined with Doxepin.Approved
DoxorubicinThe serum concentration of Naloxegol can be increased when it is combined with Doxorubicin.Approved, Investigational
DoxycyclineThe serum concentration of Naloxegol can be increased when it is combined with Doxycycline.Approved, Investigational, Vet Approved
DronabinolThe serum concentration of Naloxegol can be increased when it is combined with Dronabinol.Approved, Illicit
DronedaroneThe serum concentration of Naloxegol can be increased when it is combined with Dronedarone.Approved
EfavirenzThe serum concentration of Naloxegol can be decreased when it is combined with Efavirenz.Approved, Investigational
ElbasvirThe serum concentration of Naloxegol can be increased when it is combined with Elbasvir.Approved
EluxadolineThe risk or severity of adverse effects can be increased when Eluxadoline is combined with Naloxegol.Approved
EnalaprilThe serum concentration of Naloxegol can be increased when it is combined with Enalapril.Approved, Vet Approved
EnzalutamideThe serum concentration of Naloxegol can be decreased when it is combined with Enzalutamide.Approved
ErgonovineThe serum concentration of Naloxegol can be increased when it is combined with Ergonovine.Approved
ErgotamineThe serum concentration of Naloxegol can be increased when it is combined with Ergotamine.Approved
ErythromycinThe serum concentration of Naloxegol can be increased when it is combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe serum concentration of Naloxegol can be decreased when it is combined with Eslicarbazepine acetate.Approved
EstramustineThe serum concentration of Naloxegol can be increased when it is combined with Estramustine.Approved
EtoposideThe serum concentration of Naloxegol can be increased when it is combined with Etoposide.Approved
EtravirineThe serum concentration of Naloxegol can be increased when it is combined with Etravirine.Approved
FelodipineThe serum concentration of Naloxegol can be increased when it is combined with Felodipine.Approved, Investigational
FentanylThe serum concentration of Naloxegol can be increased when it is combined with Fentanyl.Approved, Illicit, Investigational, Vet Approved
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Naloxegol.Approved
FexofenadineThe serum concentration of Naloxegol can be increased when it is combined with Fexofenadine.Approved
FidaxomicinThe serum concentration of Naloxegol can be increased when it is combined with Fidaxomicin.Approved
FluconazoleThe serum concentration of Naloxegol can be increased when it is combined with Fluconazole.Approved
FluoxetineThe serum concentration of Naloxegol can be increased when it is combined with Fluoxetine.Approved, Vet Approved
FlupentixolThe serum concentration of Naloxegol can be increased when it is combined with Flupentixol.Approved, Withdrawn
FluphenazineThe serum concentration of Naloxegol can be increased when it is combined with Fluphenazine.Approved
FlurazepamThe serum concentration of Naloxegol can be increased when it is combined with Flurazepam.Approved, Illicit
FluvoxamineThe serum concentration of Naloxegol can be increased when it is combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe serum concentration of Naloxegol can be increased when it is combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Naloxegol can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe serum concentration of Naloxegol can be decreased when it is combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Naloxegol can be increased when it is combined with Fusidic Acid.Approved
GefitinibThe serum concentration of Naloxegol can be increased when it is combined with Gefitinib.Approved, Investigational
GenisteinThe serum concentration of Naloxegol can be increased when it is combined with Genistein.Investigational
GlyburideThe serum concentration of Naloxegol can be increased when it is combined with Glyburide.Approved
Gramicidin DThe serum concentration of Naloxegol can be increased when it is combined with Gramicidin D.Approved
GrepafloxacinThe serum concentration of Naloxegol can be increased when it is combined with Grepafloxacin.Withdrawn
HaloperidolThe serum concentration of Naloxegol can be increased when it is combined with Haloperidol.Approved
HydrocortisoneThe serum concentration of Naloxegol can be increased when it is combined with Hydrocortisone.Approved, Vet Approved
IdelalisibThe serum concentration of Naloxegol can be increased when it is combined with Idelalisib.Approved
ImatinibThe serum concentration of Naloxegol can be increased when it is combined with Imatinib.Approved
ImipramineThe serum concentration of Naloxegol can be increased when it is combined with Imipramine.Approved
IndinavirThe serum concentration of Naloxegol can be increased when it is combined with Indinavir.Approved
IndomethacinThe serum concentration of Naloxegol can be increased when it is combined with Indomethacin.Approved, Investigational
IsavuconazoniumThe serum concentration of Naloxegol can be increased when it is combined with Isavuconazonium.Approved, Investigational
IsradipineThe serum concentration of Naloxegol can be increased when it is combined with Isradipine.Approved
ItraconazoleThe serum concentration of Naloxegol can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Naloxegol can be increased when it is combined with Ivacaftor.Approved
IvermectinThe serum concentration of Naloxegol can be increased when it is combined with Ivermectin.Approved, Vet Approved
KetamineThe serum concentration of Naloxegol can be increased when it is combined with Ketamine.Approved, Vet Approved
KetoconazoleThe serum concentration of Naloxegol can be increased when it is combined with Ketoconazole.Approved, Investigational
LansoprazoleThe serum concentration of Naloxegol can be increased when it is combined with Lansoprazole.Approved, Investigational
LapatinibThe serum concentration of Naloxegol can be increased when it is combined with Lapatinib.Approved, Investigational
LevallorphanThe risk or severity of adverse effects can be increased when Levallorphan is combined with Naloxegol.Approved
LevofloxacinThe serum concentration of Naloxegol can be increased when it is combined with Levofloxacin.Approved, Investigational
LidocaineThe serum concentration of Naloxegol can be increased when it is combined with Lidocaine.Approved, Vet Approved
LisinoprilThe serum concentration of Naloxegol can be increased when it is combined with Lisinopril.Approved, Investigational
LofexidineThe risk or severity of adverse effects can be increased when Lofexidine is combined with Naloxegol.Approved, Investigational
LomitapideThe serum concentration of Naloxegol can be increased when it is combined with Lomitapide.Approved
LoperamideThe serum concentration of Naloxegol can be increased when it is combined with Loperamide.Approved
LopinavirThe serum concentration of Naloxegol can be increased when it is combined with Lopinavir.Approved
LoratadineThe serum concentration of Naloxegol can be increased when it is combined with Loratadine.Approved
LosartanThe serum concentration of Naloxegol can be increased when it is combined with Losartan.Approved
LovastatinThe serum concentration of Naloxegol can be increased when it is combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Naloxegol can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Naloxegol can be decreased when it is combined with Lumacaftor.Approved
MaprotilineThe serum concentration of Naloxegol can be increased when it is combined with Maprotiline.Approved
MebendazoleThe serum concentration of Naloxegol can be increased when it is combined with Mebendazole.Approved, Vet Approved
MefloquineThe serum concentration of Naloxegol can be increased when it is combined with Mefloquine.Approved
Megestrol acetateThe serum concentration of Naloxegol can be increased when it is combined with Megestrol acetate.Approved, Vet Approved
MeprobamateThe serum concentration of Naloxegol can be increased when it is combined with Meprobamate.Approved, Illicit
MethadoneThe serum concentration of Naloxegol can be increased when it is combined with Methadone.Approved
MethylnaltrexoneThe risk or severity of adverse effects can be increased when Methylnaltrexone is combined with Naloxegol.Approved
MetoprololThe serum concentration of Metoprolol can be increased when it is combined with Naloxegol.Approved, Investigational
MibefradilThe serum concentration of Naloxegol can be increased when it is combined with Mibefradil.Withdrawn
MiconazoleThe serum concentration of Naloxegol can be increased when it is combined with Miconazole.Approved, Investigational, Vet Approved
MidazolamThe serum concentration of Naloxegol can be increased when it is combined with Midazolam.Approved, Illicit
MifepristoneThe serum concentration of Naloxegol can be increased when it is combined with Mifepristone.Approved, Investigational
MitomycinThe serum concentration of Naloxegol can be increased when it is combined with Mitomycin.Approved
MitotaneThe serum concentration of Naloxegol can be decreased when it is combined with Mitotane.Approved
MitoxantroneThe serum concentration of Naloxegol can be increased when it is combined with Mitoxantrone.Approved, Investigational
ModafinilThe serum concentration of Naloxegol can be decreased when it is combined with Modafinil.Approved, Investigational
MorphineThe serum concentration of Naloxegol can be increased when it is combined with Morphine.Approved, Investigational
NafcillinThe serum concentration of Naloxegol can be decreased when it is combined with Nafcillin.Approved
NalbuphineThe risk or severity of adverse effects can be increased when Nalbuphine is combined with Naloxegol.Approved
nalmefeneThe risk or severity of adverse effects can be increased when nalmefene is combined with Naloxegol.Investigational
NalorphineThe risk or severity of adverse effects can be increased when Nalorphine is combined with Naloxegol.Approved, Vet Approved
NaloxoneThe risk or severity of adverse effects can be increased when Naloxone is combined with Naloxegol.Approved, Vet Approved
NaltrexoneThe risk or severity of adverse effects can be increased when Naltrexone is combined with Naloxegol.Approved, Investigational, Vet Approved
NaringeninThe serum concentration of Naloxegol can be increased when it is combined with Naringenin.Experimental
NefazodoneThe serum concentration of Naloxegol can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Naloxegol can be increased when it is combined with Nelfinavir.Approved
NeostigmineThe serum concentration of Naloxegol can be increased when it is combined with Neostigmine.Approved, Vet Approved
NetupitantThe serum concentration of Naloxegol can be increased when it is combined with Netupitant.Approved
NevirapineThe serum concentration of Naloxegol can be increased when it is combined with Nevirapine.Approved
NicardipineThe serum concentration of Naloxegol can be increased when it is combined with Nicardipine.Approved
NifedipineThe serum concentration of Naloxegol can be increased when it is combined with Nifedipine.Approved
NilotinibThe serum concentration of Naloxegol can be increased when it is combined with Nilotinib.Approved, Investigational
NisoldipineThe serum concentration of Naloxegol can be increased when it is combined with Nisoldipine.Approved
NitrazepamThe serum concentration of Naloxegol can be increased when it is combined with Nitrazepam.Approved
NitrendipineThe serum concentration of Naloxegol can be increased when it is combined with Nitrendipine.Approved
OlaparibThe serum concentration of Naloxegol can be increased when it is combined with Olaparib.Approved
OmeprazoleThe serum concentration of Naloxegol can be increased when it is combined with Omeprazole.Approved, Investigational, Vet Approved
OsimertinibThe serum concentration of Naloxegol can be increased when it is combined with Osimertinib.Approved
OxymorphoneThe risk or severity of adverse effects can be increased when Oxymorphone is combined with Naloxegol.Approved, Investigational, Vet Approved
P-NitrophenolThe serum concentration of Naloxegol can be increased when it is combined with P-Nitrophenol.Experimental
PaclitaxelThe serum concentration of Naloxegol can be increased when it is combined with Paclitaxel.Approved, Vet Approved
PalbociclibThe serum concentration of Naloxegol can be increased when it is combined with Palbociclib.Approved
Palmitic AcidThe serum concentration of Naloxegol can be increased when it is combined with Palmitic Acid.Experimental
PantoprazoleThe serum concentration of Naloxegol can be increased when it is combined with Pantoprazole.Approved
ParoxetineThe serum concentration of Naloxegol can be increased when it is combined with Paroxetine.Approved, Investigational
PentazocineThe risk or severity of adverse effects can be increased when Pentazocine is combined with Naloxegol.Approved, Vet Approved
PentobarbitalThe serum concentration of Naloxegol can be decreased when it is combined with Pentobarbital.Approved, Vet Approved
PerindoprilThe serum concentration of Naloxegol can be increased when it is combined with Perindopril.Approved
PhenobarbitalThe serum concentration of Naloxegol can be decreased when it is combined with Phenobarbital.Approved
PhenytoinThe serum concentration of Naloxegol can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PimozideThe serum concentration of Naloxegol can be increased when it is combined with Pimozide.Approved
PonatinibThe serum concentration of Naloxegol can be increased when it is combined with Ponatinib.Approved
PosaconazoleThe serum concentration of Naloxegol can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinThe serum concentration of Naloxegol can be increased when it is combined with Pravastatin.Approved
PrazosinThe serum concentration of Naloxegol can be increased when it is combined with Prazosin.Approved
PrednisoneThe serum concentration of Naloxegol can be increased when it is combined with Prednisone.Approved, Vet Approved
PrimidoneThe serum concentration of Naloxegol can be decreased when it is combined with Primidone.Approved, Vet Approved
ProbenecidThe serum concentration of Naloxegol can be increased when it is combined with Probenecid.Approved
ProgesteroneThe serum concentration of Naloxegol can be increased when it is combined with Progesterone.Approved, Vet Approved
PromethazineThe serum concentration of Naloxegol can be increased when it is combined with Promethazine.Approved
PropafenoneThe serum concentration of Naloxegol can be increased when it is combined with Propafenone.Approved
PropranololThe serum concentration of Naloxegol can be increased when it is combined with Propranolol.Approved, Investigational
ProtriptylineThe serum concentration of Naloxegol can be increased when it is combined with Protriptyline.Approved
QuercetinThe serum concentration of Naloxegol can be increased when it is combined with Quercetin.Experimental
QuinacrineThe serum concentration of Naloxegol can be increased when it is combined with Quinacrine.Approved
QuinidineThe serum concentration of Naloxegol can be increased when it is combined with Quinidine.Approved
QuinineThe serum concentration of Naloxegol can be increased when it is combined with Quinine.Approved
RanitidineThe serum concentration of Naloxegol can be increased when it is combined with Ranitidine.Approved
RanolazineThe serum concentration of Naloxegol can be increased when it is combined with Ranolazine.Approved, Investigational
ReboxetineThe serum concentration of Naloxegol can be increased when it is combined with Reboxetine.Approved, Investigational
RegorafenibThe serum concentration of Naloxegol can be increased when it is combined with Regorafenib.Approved
ReserpineThe serum concentration of Naloxegol can be increased when it is combined with Reserpine.Approved
RifabutinThe serum concentration of Naloxegol can be decreased when it is combined with Rifabutin.Approved
RifampicinThe serum concentration of Naloxegol can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Naloxegol can be decreased when it is combined with Rifapentine.Approved
RilpivirineThe serum concentration of Naloxegol can be increased when it is combined with Rilpivirine.Approved
RitonavirThe serum concentration of Naloxegol can be increased when it is combined with Ritonavir.Approved, Investigational
RolapitantThe serum concentration of Naloxegol can be increased when it is combined with Rolapitant.Approved
SaquinavirThe serum concentration of Naloxegol can be increased when it is combined with Saquinavir.Approved, Investigational
ScopolamineThe serum concentration of Naloxegol can be increased when it is combined with Scopolamine.Approved
SelegilineThe serum concentration of Naloxegol can be increased when it is combined with Selegiline.Approved, Investigational, Vet Approved
SertralineThe serum concentration of Naloxegol can be increased when it is combined with Sertraline.Approved
SildenafilThe serum concentration of Naloxegol can be increased when it is combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Naloxegol can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Naloxegol can be increased when it is combined with Simeprevir.Approved
SimvastatinThe serum concentration of Naloxegol can be increased when it is combined with Simvastatin.Approved
SirolimusThe serum concentration of Naloxegol can be increased when it is combined with Sirolimus.Approved, Investigational
SorafenibThe serum concentration of Naloxegol can be increased when it is combined with Sorafenib.Approved, Investigational
SpironolactoneThe serum concentration of Naloxegol can be increased when it is combined with Spironolactone.Approved
St. John's WortThe serum concentration of Naloxegol can be decreased when it is combined with St. John's Wort.Nutraceutical
StaurosporineThe serum concentration of Naloxegol can be increased when it is combined with Staurosporine.Experimental
StiripentolThe serum concentration of Naloxegol can be increased when it is combined with Stiripentol.Approved
SulfinpyrazoneThe serum concentration of Naloxegol can be increased when it is combined with Sulfinpyrazone.Approved
SulfisoxazoleThe serum concentration of Naloxegol can be increased when it is combined with Sulfisoxazole.Approved, Vet Approved
SumatriptanThe serum concentration of Naloxegol can be increased when it is combined with Sumatriptan.Approved, Investigational
SunitinibThe serum concentration of Naloxegol can be increased when it is combined with Sunitinib.Approved, Investigational
TacrineThe serum concentration of Naloxegol can be increased when it is combined with Tacrine.Withdrawn
TacrolimusThe serum concentration of Naloxegol can be increased when it is combined with Tacrolimus.Approved, Investigational
TamoxifenThe serum concentration of Naloxegol can be increased when it is combined with Tamoxifen.Approved
Taurocholic AcidThe serum concentration of Naloxegol can be increased when it is combined with Taurocholic Acid.Experimental
TelaprevirThe serum concentration of Naloxegol can be increased when it is combined with Telaprevir.Withdrawn
TelithromycinThe serum concentration of Naloxegol can be increased when it is combined with Telithromycin.Approved
TelmisartanThe serum concentration of Naloxegol can be increased when it is combined with Telmisartan.Approved, Investigational
TemsirolimusThe serum concentration of Naloxegol can be increased when it is combined with Temsirolimus.Approved
TerazosinThe serum concentration of Naloxegol can be increased when it is combined with Terazosin.Approved
TerfenadineThe serum concentration of Naloxegol can be increased when it is combined with Terfenadine.Withdrawn
TestosteroneThe serum concentration of Naloxegol can be increased when it is combined with Testosterone.Approved, Investigational
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Naloxegol.Withdrawn
TicagrelorThe serum concentration of Naloxegol can be increased when it is combined with Ticagrelor.Approved
TiclopidineThe serum concentration of Naloxegol can be increased when it is combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Naloxegol can be decreased when it is combined with Tocilizumab.Approved
TolvaptanThe serum concentration of Naloxegol can be increased when it is combined with Tolvaptan.Approved
TrifluoperazineThe serum concentration of Naloxegol can be increased when it is combined with Trifluoperazine.Approved
TriflupromazineThe serum concentration of Naloxegol can be increased when it is combined with Triflupromazine.Approved, Vet Approved
TrimethoprimThe serum concentration of Naloxegol can be increased when it is combined with Trimethoprim.Approved, Vet Approved
TrimipramineThe serum concentration of Naloxegol can be increased when it is combined with Trimipramine.Approved
VenlafaxineThe serum concentration of Naloxegol can be increased when it is combined with Venlafaxine.Approved
VerapamilThe serum concentration of Naloxegol can be increased when it is combined with Verapamil.Approved
VinblastineThe serum concentration of Naloxegol can be increased when it is combined with Vinblastine.Approved
VincristineThe serum concentration of Naloxegol can be increased when it is combined with Vincristine.Approved, Investigational
VinorelbineThe serum concentration of Naloxegol can be increased when it is combined with Vinorelbine.Approved, Investigational
VoriconazoleThe serum concentration of Naloxegol can be increased when it is combined with Voriconazole.Approved, Investigational
ZimelidineThe serum concentration of Naloxegol can be increased when it is combined with Zimelidine.Withdrawn
ZiprasidoneThe serum concentration of Naloxegol can be increased when it is combined with Ziprasidone.Approved
Food Interactions
  • A high-fat meal increased the extent and rate of naloxegol absorption. The Cmax and AUC were increased by approximately 30% and 45%, respectively. In clinical trials, naloxegol was dosed on an empty stomach approximately 1 hour prior to the first meal in the morning.
References
Synthesis ReferenceNot Available
General References
  1. 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. [PubMed:25471070 ]
  2. 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. [PubMed:26312011 ]
  3. 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. [PubMed:26150678 ]
External Links
ATC CodesA06AH03 — Naloxegol
AHFS Codes
  • 56:92
PDB EntriesNot Available
FDA labelDownload (530 KB)
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceAmount of NKTR-118 in Blood / Variation in the Heart's Electrical Cycle1
1CompletedBasic ScienceBioavailability / Drug- Drug Interactions / Healthy Volunteers1
1CompletedBasic ScienceBioavailability / Healthy Volunteers1
1CompletedBasic ScienceDrug Induced Constipation2
1CompletedBasic ScienceHealthy Volunteers1
1CompletedBasic ScienceHepatic; Functional Disturbance1
1CompletedBasic ScienceOpioid Induced Constipation (OIC)1
1CompletedTreatmentConstipation Drug Induced / Healthy Volunteers1
1RecruitingTreatmentConstipation, Signs and Symptoms, Digestive1
2CompletedTreatmentOpioid Induced Constipation (OIC)1
2Not Yet RecruitingTreatmentGastroparesis / Opioids Use1
2RecruitingTreatmentEsophagus Disorder / Opioid-Induced Disorders1
2RecruitingTreatmentOccasional Constipation1
3CompletedTreatmentOpioid Induced Constipation (OIC)4
3Not Yet RecruitingSupportive CareStage IIIB Lung Adenocarcinoma / Stage IIIB Non-Small Cell Lung Cancer / Stage IV Lung Adenocarcinoma / Stage IV Non-Small Cell Lung Cancer1
3Not Yet RecruitingTreatmentCritical Illness / Occasional Constipation1
3TerminatedTreatmentOpioid Induced Constipation (OIC)1
4CompletedTreatmentOpioid Induced Constipation (OIC)1
4Not Yet RecruitingTreatmentPostoperative pain1
4RecruitingPreventionOccasional Constipation2
4RecruitingTreatmentCancers / Occasional Constipation / Pain1
Not AvailableRecruitingNot AvailableOpioid Induced Constipation (OIC)3
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral12.5 mg
TabletOral25 mg
Tablet, film coatedOral12.5 mg/1
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral12.5 mg
Tablet, film coatedOral25 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8067431 No2004-12-162024-12-16Us
US8617530 No2002-10-182022-10-18Us
US7056500 No2004-06-292024-06-29Us
US7662365 No2002-10-182022-10-18Us
US9012469 No2012-04-022032-04-02Us
US7786133 No2007-12-192027-12-19Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0566 mg/mLALOGPS
logP1.73ALOGPS
logP1.36ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)10.14ChemAxon
pKa (Strongest Basic)8.54ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area126.77 Å2ChemAxon
Rotatable Bond Count24ChemAxon
Refractivity171.68 m3·mol-1ChemAxon
Polarizability72.87 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET featuresNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassPhenanthrenes and derivatives
Sub ClassNot Available
Direct ParentPhenanthrenes and derivatives
Alternative ParentsTetralins / Coumarans / Aralkylamines / Alkyl aryl ethers / 1-hydroxy-2-unsubstituted benzenoids / Piperidines / Tertiary alcohols / Trialkylamines / Cyclic alcohols and derivatives / 1,2-aminoalcohols
SubstituentsPhenanthrene / Tetralin / Coumaran / 1-hydroxy-2-unsubstituted benzenoid / Alkyl aryl ether / Aralkylamine / Piperidine / Cyclic alcohol / Tertiary alcohol / 1,2-aminoalcohol
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptorstertiary alcohol, aromatic ether, phenols, organic heteropentacyclic compound, polyether (CHEBI:82975 )

Targets

Kind
Protein
Organism
Human
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. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociati...
Gene Name:
OPRM1
Uniprot ID:
P35372
Uniprot Name:
Mu-type opioid receptor
Molecular Weight:
44778.855 Da
References
  1. 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. [PubMed:25471070 ]

Enzymes

Kind
Protein
Organism
Human
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Uniprot Name:
Cytochrome P450 3A4
Molecular Weight:
57342.67 Da
References
  1. 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. [PubMed:25471070 ]
Kind
Protein
Organism
Human
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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Uniprot Name:
Cytochrome P450 2D6
Molecular Weight:
55768.94 Da
References
  1. 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. [PubMed:25471070 ]
Kind
Protein
Organism
Human
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 imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Uniprot Name:
Cytochrome P450 2C19
Molecular Weight:
55930.545 Da
References
  1. 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. [PubMed:25471070 ]
Drug created on May 04, 2015 17:26 / Updated on September 01, 2017 12:01