Identification
- Summary
Naldemedine is an opioid antagonist used to to treat opioid-induced constipation.
- Brand Names
- Symproic
- Generic Name
- Naldemedine
- DrugBank Accession Number
- DB11691
- Background
Naldemedine is an opioid receptor antagonist Label. It is a modified form of Naltrexone to which a side chain has been added to increase molecular weight and polar surface area resulting in restricted transport across the blood brain barrier. Naldemedine was approved in 2017 in both the US and Japan for the treatment of Opioid-induced Constipation.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Naldemedine (DB11691)
- Weight
- Average: 570.646
Monoisotopic: 570.247834831 - Chemical Formula
- C32H34N4O6
- Synonyms
- Naldemedine
- External IDs
- S-297995
Pharmacology
- Indication
For the treatment of opioid-induced constipation Label.
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Naldemedine is an opioid receptor antagonist with restricted movement across the blood brain barrier Label. This allows it to antagonize the periperal effects of opioid drugs such as constipation without interfering with the effects on the central nervous system.
- Mechanism of action
Naldemedine binds to and antagonizes mu-, delta-, and kappa-opioid receptors Label. The binding of opioid agonists to peripheral mu-opioid receptors slows the transit of feces through the intestine resulting in constipation. By antagonizing mu-opioid receptors, naldemedine inhibits this effect.
Target Actions Organism AMu-type opioid receptor antagonistHumans ADelta-type opioid receptor antagonistHumans AKappa-type opioid receptor antagonistHumans - Absorption
Tmax is 0.75 h Label. Administration with a high-fat meal reduces Cmax by 35% and increases Tmax to 2.5 h.
- Volume of distribution
The apparent volume of disribution during the terminal phase is 155 L Label
- Protein binding
Naldemedine is 93-94% bound to human plasma proteins Label.
- Metabolism
Naldemedine is mainly metabolized to nor-naldemedine by CYP3A Label. Some metabolism to naldemedine-3-glucuronide occurs via UGT1A3. Both metabolites are acitive but less potent than naldemedine. The relative exposures of these metabolites are 9-13% and <3% for nor-naldemedine and naldemedine-3-glucuronide respectively. Naldemedine is also cleaved in the intestine to form benzamidine and naldemedine carboxylic acid.
- Route of elimination
57% of naldemedine is excreted in the urine with 16-18% as the parent compound and 35% is excreted in the feces Label.
- Half-life
The terminal elimination half life is 11 h Label.
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
The most common adverse effects of naldemedine are abdominal pain (11%), diarrhea (7%), nausea (6%), vomiting (3%), and gastroenteritis (3%) Label.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- 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 softwareAbacavir Abacavir may decrease the excretion rate of Naldemedine which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Naldemedine which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Naldemedine which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Naldemedine which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Naldemedine which could result in a lower serum level and potentially a reduction in efficacy. Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Naldemedine which could result in a higher serum level. Aclidinium Aclidinium may decrease the excretion rate of Naldemedine which could result in a higher serum level. Acrivastine Acrivastine may decrease the excretion rate of Naldemedine which could result in a higher serum level. Acyclovir Acyclovir may decrease the excretion rate of Naldemedine which could result in a higher serum level. Adefovir dipivoxil Adefovir dipivoxil may decrease the excretion rate of Naldemedine which could result in a higher serum level. 
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- Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of naldemedine.
- Take with or without food.
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 Naldemedine tosylate V1N8F1RVVO 1345728-04-2 WCYDLROFMZJJLE-RTMHEQJQSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Rizmoic Tablet, film coated 200 mcg Oral Shionogi B.V. 2020-12-16 Not applicable EU 
Rizmoic Tablet, film coated 200 mcg Oral Shionogi B.V. 2020-12-16 Not applicable EU Rizmoic Tablet, film coated 200 mcg Oral Shionogi B.V. 2020-12-16 Not applicable EU Rizmoic Tablet, film coated 200 mcg Oral Shionogi B.V. 2020-12-16 Not applicable EU Rizmoic Tablet, film coated 200 mcg Oral Shionogi B.V. 2020-12-16 Not applicable EU Rizmoic Tablet, film coated 200 mcg Oral Shionogi B.V. 2020-12-21 Not applicable EU Symproic Tablet 0.2 mg/1 Oral BioDelivery Sciences International Inc 2019-06-14 Not applicable US 
Symproic Tablet .2 mg/1 Oral Purdue Pharma LP 2017-03-23 2020-12-31 US Symproic Tablet 0.2 mg/1 Oral SHIONOGI INC. 2018-07-05 2020-12-31 US
Categories
- ATC Codes
- A06AH05 — Naldemedine
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as morphinans. These are polycyclic compounds with a four-ring skeleton with three condensed six-member rings forming a partially hydrogenated phenanthrene moiety, one of which is aromatic while the two others are alicyclic.
- Kingdom
- Organic compounds
- Super Class
- Alkaloids and derivatives
- Class
- Morphinans
- Sub Class
- Not Available
- Direct Parent
- Morphinans
- Alternative Parents
- Phenanthrenes and derivatives / Phenyloxadiazoles / Tetralins / Coumarans / 1-hydroxy-2-unsubstituted benzenoids / Alkyl aryl ethers / Aralkylamines / Piperidines / Benzene and substituted derivatives / Vinylogous acids show 13 more
- Substituents
- 1,2,4-oxadiazole / 1,2-aminoalcohol / 1-hydroxy-2-unsubstituted benzenoid / Alcohol / Alkyl aryl ether / Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle show 31 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 03KSI6WLXH
- CAS number
- 916072-89-4
- InChI Key
- AXQACEQYCPKDMV-RZAWKFBISA-N
- InChI
- InChI=1S/C32H34N4O6/c1-30(2,29-33-27(35-42-29)18-6-4-3-5-7-18)34-28(39)20-15-32(40)22-14-19-10-11-21(37)25-23(19)31(32,26(41-25)24(20)38)12-13-36(22)16-17-8-9-17/h3-7,10-11,17,22,26,37-38,40H,8-9,12-16H2,1-2H3,(H,34,39)/t22-,26+,31+,32-/m1/s1
- IUPAC Name
- (1S,5R,13R,17S)-4-(cyclopropylmethyl)-10,14,17-trihydroxy-N-[2-(3-phenyl-1,2,4-oxadiazol-5-yl)propan-2-yl]-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7,9,11(18),14-tetraene-15-carboxamide
- SMILES
- [H][C@@]12OC3=C4C(C[C@@]5([H])N(CC6CC6)CC[C@@]14[C@@]5(O)CC(C(=O)NC(C)(C)C1=NC(=NO1)C1=CC=CC=C1)=C2O)=CC=C3O
References
- General References
- FDA Approved Drug Products: Symproic (naldemidine tosylate) tablets for oral use [Link]
- External Links
- PubChem Compound
- 54732242
- PubChem Substance
- 347828056
- ChemSpider
- 28530803
- BindingDB
- 50503604
- 1876597
- ChEMBL
- CHEMBL2105755
- Wikipedia
- Naldemedine
- FDA label
- Download (209 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Treatment Opioid Induced Constipation (OIC) 3 2 Completed Treatment Opioid Induced Bowel Dysfunction 1 2 Completed Treatment Opioid Induced Constipation (OIC) 1 2 Terminated Treatment Postoperative Gastrointestinal Dysfunction 1 2, 3 Recruiting Prevention Acute Pancreatitis 1 1, 2 Recruiting Supportive Care Opioid Induced Constipation (OIC) 1 Not Available Recruiting Not Available Opioid Induced Constipation (OIC) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral 200 MCG Tablet Oral .2 mg/1 Tablet Oral 0.2 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9108975 No 2015-08-18 2031-11-11 US USRE46365 No 2017-04-11 2028-01-11 US USRE46375 No 2017-04-25 2026-10-05 US US10952968 No 2021-03-23 2033-05-13 US
Properties
- State
- Not Available
- Experimental Properties
Property Value Source water solubility Slightly soluble FDA Label - Predicted Properties
Property Value Source Water Solubility 0.227 mg/mL ALOGPS logP 3.14 ALOGPS logP 2.43 Chemaxon logS -3.4 ALOGPS pKa (Strongest Acidic) 9.86 Chemaxon pKa (Strongest Basic) 9.05 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 8 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 141.18 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 165.78 m3·mol-1 Chemaxon Polarizability 61.34 Å3 Chemaxon Number of Rings 8 Chemaxon Bioavailability 1 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
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Opioid receptor activity
- Specific Function
- G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine n...
- Gene Name
- OPRD1
- Uniprot ID
- P41143
- Uniprot Name
- Delta-type opioid receptor
- Molecular Weight
- 40368.235 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Opioid receptor activity
- Specific Function
- G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synt...
- Gene Name
- OPRK1
- Uniprot ID
- P41145
- Uniprot Name
- Kappa-type opioid receptor
- Molecular Weight
- 42644.665 Da
Enzymes
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- No
- 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...
Components:
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Retinoic acid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
- Gene Name
- UGT1A3
- Uniprot ID
- P35503
- Uniprot Name
- UDP-glucuronosyltransferase 1-3
- Molecular Weight
- 60337.835 Da
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Efflux transmembrane transporter activity
- Specific Function
- Drug efflux transporter present in a number of stem cells that acts as a regulator of cellular differentiation. Able to mediate efflux from cells of the rhodamine dye and of the therapeutic drug do...
- Gene Name
- ABCB5
- Uniprot ID
- Q2M3G0
- Uniprot Name
- ATP-binding cassette sub-family B member 5
- Molecular Weight
- 138639.48 Da
Drug created at October 20, 2016 20:40 / Updated at August 13, 2021 04:44