Identification
- Summary
Etonogestrel is a long-acting synthetic derived progestin contraceptive used in various devices such as contraceptive rings and intradermal implants.
- Brand Names
- Eluryng, Enilloring, Implanon, Nexplanon, Nuvaring
- Generic Name
- Etonogestrel
- DrugBank Accession Number
- DB00294
- Background
Etonogestrel molecule is a 3-ketodesogestrel or 19-nortestosterone which is a synthetic biologically active metabolite of progestin desogestrel.2 The first product including etonogestrel was developed by the Merck subsidiary Organon and FDA approved in 2001.6
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Etonogestrel (DB00294)
- Weight
- Average: 324.4565
Monoisotopic: 324.20893014 - Chemical Formula
- C22H28O2
- Synonyms
- 3-Ketodesogestrel
- 3-Oxodesogestrel
- Etonogestrel
- étonogestrel
- Etonogestrelum
- External IDs
- ORG 3236
- ORG-3236
Pharmacology
- Indication
Etonogestrel is administered in subdermal implants as long-acting reversible contraception. It is known to be effective in postpartum insertion including breastfeeding women.1
Etonogestrel is part of the long-acting contraceptive implants that prevent pregnancy. The implant's effect can remain for 5 years.8
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Therapies
- 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
Etonogestrel attains its therapeutic effect inhibiting fertility by impairing the release of the luteinizing hormone which is one of the most important reproductive hormones for ovulation. As well, etonogestrel is known to increase the viscosity of the cervical mucus hindering the passage of the spermatozoa and altering the lining in the uterus to prevent the implantation of the fertilized eggs in the endometrium.7
In clinical trials, etonogestrel was implanted and reported to avoid 100% of pregnancies over a three year period. When the implant was removed, normal periods were reinstalled within 90 days in 91% of the individuals. Fertility was established quickly with 20 reported pregnancies within 3 months of implant removal.7
The implants of etonogestrel release 40 mcg of etonogestrel daily and they usually provide a continuous contraception effect for 3 years. When the implant is administered, the failure rate is reported to be 0.1%. Some non-contraceptive effects are improved dysmenorrhea.4 All data of etonogestrel comes from patients between 80-130% of the body mass.
- Mechanism of action
Etonogestrel binds with high affinity to the progesterone and estrogen receptors in the target organs.7 From the target organs, they include the female reproductive tract, mammary gland, hypothalamus, and pituitary. Once bound, this drug changes the synthesis of different proteins which in order decreases the level of gonadotropin-releasing hormone and the luteinizing hormone.9
Target Actions Organism AProgesterone receptor agonistHumans - Absorption
Vaginal administration of etonogestrel is known to be significantly absorbed through the vaginal epithelium but it does not increase the levels of etonogestrel in the urine. On the other hand, oral administration is absorbed in the GI tract and it goes through the first-pass metabolism.2
When etonogestrel is administered subdermally it is absorbed rapidly into the bloodstream and it presents a bioavailability of 82%.5 It is reported that the implant releases around 60 mcg per day in the first 3 months and then decreases steady reaching a concentration of 30 mcg at the end of year 2.3
- Volume of distribution
The apparent volume of distribution of etonogestrel is of around 201 L.3
- Protein binding
Etonogestrel is highly bound to plasma proteins being mainly albumin followed by sex-hormone binding globulin.7 The protein bound form of the etonogestrel represents around 96-99% of the administered dose.5
- Metabolism
Etonogestrel is highly metabolized in the liver by the action of the cytochrome isoenzyme 3A4 mainly by the presence of hydroxylation, sulfate conjugation and glucuronide conjugation reactions.7
Hover over products below to view reaction partners
- Route of elimination
The elimination of etonogestrel and its metabolites is mainly done renally.7
- Half-life
The elimination half-life of etonogestrel is reported to be of 25 hours which indicates a reversible contraceptive effect.7
- Clearance
The clearance rate of etonogestrel is reported to be of 7.5 L/h.3
- Adverse Effects
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The reported LD50 of oral etonogestrel in the rat is reported to be higher than 2000 mg/kg.MSDS Overdosage can only happen when more than one implant is inserted. In cases of overdose, removal of the implant is recommended.Label
There aren't reports relating etonogestrel with carcinogenesis, mutagenesis or impaired fertility.Label
- 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 softwareAbacavir Etonogestrel may decrease the excretion rate of Abacavir which could result in a higher serum level. Abametapir The serum concentration of Etonogestrel can be increased when it is combined with Abametapir. Abciximab The therapeutic efficacy of Abciximab can be decreased when used in combination with Etonogestrel. Acarbose The therapeutic efficacy of Acarbose can be decreased when used in combination with Etonogestrel. Aceclofenac Aceclofenac may decrease the excretion rate of Etonogestrel which could result in a higher serum level. - Food Interactions
- Administer vitamin supplements.
- Avoid alcohol.
- Limit caffeine intake.
- Take at the same time every day.
- Take with 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.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Implanon Implant 68 mg/1 Subcutaneous Organon 2011-09-06 Not applicable US 
Nexplanon Implant 68 mg Subcutaneous Organon Canada Inc. 2020-08-17 Not applicable Canada 
Nexplanon Implant 68 mg/1 Subcutaneous Organon Pharmaceuticals USA 2011-05-09 2011-05-09 US Nexplanon Implant 68 mg/1 Subcutaneous Organon LLC 2021-06-01 Not applicable US Nexplanon Implant 68 mg/1 Subcutaneous Organon USA Inc. 2013-09-27 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image EluRyng Etonogestrel (0.120 mg/1d) + Ethinylestradiol (0.015 mg/1d) Ring Vaginal Amneal Pharmaceuticals LLC 2019-12-16 Not applicable US EnilloRing Etonogestrel (0.12 mg/1d) + Ethinylestradiol (0.015 mg/1d) Ring Vaginal Xiromed, Llc 2023-08-15 Not applicable US Etonogestrel and Ethinyl Estradiol Etonogestrel (0.120 mg/1d) + Ethinylestradiol (0.015 mg/1d) Insert, extended release Vaginal Teva Pharmaceuticals USA, Inc. 2021-01-19 Not applicable US Etonogestrel and Ethinyl Estradiol Vaginal Etonogestrel (0.12 mg/1d) + Ethinylestradiol (0.015 mg/1d) Ring Vaginal AvKARE 2023-09-21 Not applicable US Etonogestrel and Ethinyl Estradiol Vaginal Ring Etonogestrel (0.12 mg/1d) + Ethinylestradiol (0.015 mg/1d) Ring Vaginal NorthStar Rx LLC 2023-11-01 Not applicable US
Categories
- ATC Codes
- G03AC08 — Etonogestrel
- Drug Categories
- Adrenal Cortex Hormones
- Combination Contraceptives (with Estrogen and derivatives)
- Contraceptive Agents, Female
- Contraceptive Agents, Hormonal
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Fused-Ring Compounds
- Genito Urinary System and Sex Hormones
- Hormonal Contraceptives for Systemic Use
- Hyperglycemia-Associated Agents
- Intravaginal Contraceptives
- Norpregnanes
- Norpregnenes
- Norsteroids
- Progesterone Congeners
- Progestins
- Reproductive Control Agents
- Sex Hormones and Modulators of the Genital System
- Steroids
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as estrogens and derivatives. These are steroids with a structure containing a 3-hydroxylated estrane.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Steroids and steroid derivatives
- Sub Class
- Estrane steroids
- Direct Parent
- Estrogens and derivatives
- Alternative Parents
- 3-oxo delta-4-steroids / 17-hydroxysteroids / Delta-4-steroids / Cyclohexenones / Ynones / Tertiary alcohols / Cyclic alcohols and derivatives / Acetylides / Organic oxides / Hydrocarbon derivatives
- Substituents
- 17-hydroxysteroid / 3-oxo-delta-4-steroid / 3-oxosteroid / Acetylide / Alcohol / Aliphatic homopolycyclic compound / Carbonyl group / Cyclic alcohol / Cyclic ketone / Cyclohexenone
- Molecular Framework
- Aliphatic homopolycyclic compounds
- External Descriptors
- terminal acetylenic compound, 3-oxo steroid, 3-oxo Delta(4)-steroid, 17beta-hydroxy steroid (CHEBI:50777)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 304GTH6RNH
- CAS number
- 54048-10-1
- InChI Key
- GCKFUYQCUCGESZ-BPIQYHPVSA-N
- InChI
- InChI=1S/C22H28O2/c1-4-21-13-14(3)20-17-9-7-16(23)12-15(17)6-8-18(20)19(21)10-11-22(21,24)5-2/h2,12,17-20,24H,3-4,6-11,13H2,1H3/t17-,18-,19-,20+,21-,22-/m0/s1
- IUPAC Name
- (1R,3aS,3bS,9aR,9bS,11aS)-11a-ethyl-1-ethynyl-1-hydroxy-10-methylidene-1H,2H,3H,3aH,3bH,4H,5H,7H,8H,9H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthren-7-one
- SMILES
- [H][C@@]12CC[C@@](O)(C#C)[C@@]1(CC)CC(=C)[C@]1([H])[C@@]3([H])CCC(=O)C=C3CC[C@@]21[H]
References
- Synthesis Reference
- US20130123523
- General References
- Gariepy AM, Duffy JY, Xu X: Cost-Effectiveness of Immediate Compared With Delayed Postpartum Etonogestrel Implant Insertion. Obstet Gynecol. 2015 Jul;126(1):47-55. doi: 10.1097/AOG.0000000000000907. [Article]
- Roumen FJ: Review of the combined contraceptive vaginal ring, NuvaRing. Ther Clin Risk Manag. 2008 Apr;4(2):441-51. [Article]
- Wenzl R, van Beek A, Schnabel P, Huber J: Pharmacokinetics of etonogestrel released from the contraceptive implant Implanon. Contraception. 1998 Nov;58(5):283-8. [Article]
- Feisullin K. and Westhoff C. (2010). Principles of gender-specific medicine (2nd ed.). Academic press.
- Zaragoza Dorwald F. (2012). Lead optimization for medicinal chemists. Wiley-VCH.
- FDA approvals [Link]
- PMC [Link]
- NIH [Link]
- NIH [Link]
- External Links
- Human Metabolome Database
- HMDB0014439
- PubChem Compound
- 6917715
- PubChem Substance
- 46505321
- ChemSpider
- 5292944
- BindingDB
- 50423516
- 14584
- ChEBI
- 50777
- ChEMBL
- CHEMBL1531
- ZINC
- ZINC000011680067
- Therapeutic Targets Database
- DAP000855
- PharmGKB
- PA164771231
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Etonogestrel
- FDA label
- Download (1010 KB)
- MSDS
- Download (197 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 Active Not Recruiting Treatment Contraception 1 4 Active Not Recruiting Treatment Contraception / Drug Drug Interaction (DDI) / Human Immunodeficiency Virus (HIV) Infections 1 4 Completed Basic Science Contraception 2 4 Completed Basic Science Contraceptive; Complications, Intrauterine / Mucosal Inflammation 1 4 Completed Prevention Adolescence / Contraception / Postpartum state 1
Pharmacoeconomics
- Manufacturers
- Organon usa inc
- Packagers
- Diversified Healthcare Services Inc.
- NV Organon
- Organon Pharmaceuticals
- Dosage Forms
Form Route Strength Ring Vaginal Implant Subcutaneous 68 mg/1 Intrauterine device Intrauterine 68 mg Implant Subcutaneous 68.000 mg Implant Subcutaneous Implant Subcutaneous 68 mg Drug delivery system Vaginal Insert, extended release Vaginal Implant Subcutaneous 68 mg/implant - Prices
Unit description Cost Unit Implanon 68 mg implant 714.34USD each DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5150718 No 1992-09-29 2009-09-29 US US5989581 No 1999-11-23 2018-04-08 US US8722037 No 2014-05-13 2027-09-28 US US8888745 No 2014-11-18 2026-08-28 US US9757552 No 2017-09-12 2030-07-28 US US10821277 No 2020-11-03 2027-05-31 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 196-200ºC 'MSDS' boiling point (°C) 473.1ºC at 760 mmHg 'MSDS' water solubility Insoluble 'MSDS' logP 3.32 Zaragoza F. Lead optimization for medicinal chemists. 2012. Wiley pKa 10.4 Toral M. et al. J. Chil. Chem. 2013 - Predicted Properties
Property Value Source Water Solubility 0.00737 mg/mL ALOGPS logP 3.19 ALOGPS logP 3.6 Chemaxon logS -4.6 ALOGPS pKa (Strongest Acidic) 17.99 Chemaxon pKa (Strongest Basic) -1.5 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 37.3 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 96.35 m3·mol-1 Chemaxon Polarizability 37.83 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9437 Caco-2 permeable + 0.8167 P-glycoprotein substrate Substrate 0.6699 P-glycoprotein inhibitor I Inhibitor 0.6143 P-glycoprotein inhibitor II Non-inhibitor 0.8387 Renal organic cation transporter Non-inhibitor 0.7587 CYP450 2C9 substrate Non-substrate 0.8195 CYP450 2D6 substrate Non-substrate 0.9147 CYP450 3A4 substrate Substrate 0.7187 CYP450 1A2 substrate Non-inhibitor 0.8898 CYP450 2C9 inhibitor Non-inhibitor 0.8939 CYP450 2D6 inhibitor Non-inhibitor 0.9224 CYP450 2C19 inhibitor Inhibitor 0.8755 CYP450 3A4 inhibitor Non-inhibitor 0.7496 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5624 Ames test Non AMES toxic 0.9091 Carcinogenicity Non-carcinogens 0.9281 Biodegradation Not ready biodegradable 0.9864 Rat acute toxicity 2.1164 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8206 hERG inhibition (predictor II) Non-inhibitor 0.7741
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0002-0490000000-f19630a72a1129f10bf7 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0009000000-b5bebb33a5062d590f8f Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00di-0009000000-5841901b417f7378de6d Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-00os-0941000000-588588d658d42915d16d Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-00di-0009000000-4f0c71ed95015fc0fd5a Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-05te-0093000000-3078eb96b70401061db5 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0fvj-0900000000-a755734b0aa2fab59c28 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 190.0432595 predictedDarkChem Lite v0.1.0 [M-H]- 189.8947595 predictedDarkChem Lite v0.1.0 [M-H]- 178.43277 predictedDeepCCS 1.0 (2019) [M+H]+ 190.1252595 predictedDarkChem Lite v0.1.0 [M+H]+ 190.0743595 predictedDarkChem Lite v0.1.0 [M+H]+ 180.34915 predictedDeepCCS 1.0 (2019) [M+Na]+ 190.2997595 predictedDarkChem Lite v0.1.0 [M+Na]+ 186.83308 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Zinc ion binding
- Specific Function
- The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor ...
- Gene Name
- PGR
- Uniprot ID
- P06401
- Uniprot Name
- Progesterone receptor
- Molecular Weight
- 98979.96 Da
References
- Macpherson AM, Archer DF, Leslie S, Charnock-Jones DS, Makkink WK, Smith SK: The effect of etonogestrel on VEGF, oestrogen and progesterone receptor immunoreactivity and endothelial cell number in human endometrium. Hum Reprod. 1999 Dec;14(12):3080-7. [Article]
- Charnock-Jones DS, Macpherson AM, Archer DF, Leslie S, Makkink WK, Sharkey AM, Smith SK: The effect of progestins on vascular endothelial growth factor, oestrogen receptor and progesterone receptor immunoreactivity and endothelial cell density in human endometrium. Hum Reprod. 2000 Aug;15 Suppl 3:85-95. [Article]
- Sitruk-Ware R: Pharmacological profile of progestins. Maturitas. 2004 Apr 15;47(4):277-83. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Enzymes
- Kind
- Protein
- 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...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- PMC [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
- Zaragoza Dorwald F. (2012). Lead optimization for medicinal chemists. Wiley-VCH.
- PMC [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Androgen binding
- Specific Function
- Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone...
- Gene Name
- SHBG
- Uniprot ID
- P04278
- Uniprot Name
- Sex hormone-binding globulin
- Molecular Weight
- 43778.755 Da
References
- Zaragoza Dorwald F. (2012). Lead optimization for medicinal chemists. Wiley-VCH.
- PMC [Link]
Drug created at June 13, 2005 13:24 / Updated at November 03, 2023 23:39