etonogestrel Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
steroids, progestogens	1110	54048-10-1

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: etonogestrel implanon 3-Oxodesogestrel	metabolite of DESOGESTREL; structure given in first source; Implanon: implant containing etonogestrel (3-keto-desogestrel) Molecular weight: 324.46 Formula: C22H28O2 CLOGP: 3.35 LIPINSKI: 0 HAC: 2 HDO: 1 TPSA: 37.30 ALOGS: -4.64 ROTB: 1 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

etonogestrel
implanon
3-Oxodesogestrel

metabolite of DESOGESTREL; structure given in first source; Implanon: implant containing etonogestrel (3-keto-desogestrel)

Molecular weight: 324.46
Formula: C22H28O2
CLOGP: 3.35
LIPINSKI: 0
HAC: 2
HDO: 1
TPSA: 37.30
ALOGS: -4.64
ROTB: 1

Status: OFP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
68	mcg	s.c. implant

ADMET properties:

Property	Value	Reference
BA (Bioavailability)	76 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	0.51 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	0.10 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.01 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution)	2.87 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	2 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.02 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	25 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Oct. 3, 2001	FDA

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Incorrect product administration duration	6268.17	49.57	1098	8651	1397	2346939
Complication associated with device	6106.76	49.57	1108	8641	1961	2346375
No adverse event	4530.36	49.57	1048	8701	8480	2339856
Device difficult to use	3540.96	49.57	617	9132	708	2347628
Unintended pregnancy	3163.57	49.57	629	9120	2122	2346214
Metrorrhagia	3139.40	49.57	604	9145	1625	2346711
Inappropriate schedule of product administration	2925.34	49.57	777	8972	11427	2336909
Pulmonary embolism	2921.07	49.57	844	8905	17239	2331097
Device expulsion	2810.65	49.57	578	9171	2402	2345934
Device breakage	2735.26	49.57	513	9236	1134	2347202
Pregnancy with implant contraceptive	2306.16	49.57	374	9375	143	2348193
Menstruation irregular	2287.41	49.57	441	9308	1190	2347146
Device deployment issue	2108.69	49.57	363	9386	354	2347982
Menorrhagia	1971.13	49.57	447	9302	3159	2345177
Product quality issue	1904.68	49.57	542	9207	10287	2338049
Device dislocation	1869.86	49.57	422	9327	2906	2345430
Deep vein thrombosis	1735.89	49.57	525	9224	12407	2335929
Amenorrhoea	1628.13	49.57	351	9398	1888	2346448
Complication of device removal	1148.51	49.57	201	9548	232	2348104
Implant site pain	1082.96	49.57	192	9557	253	2348083
Medical device removal	1061.08	49.57	191	9558	291	2348045
Weight increased	978.57	49.57	394	9355	21943	2326393
Abortion spontaneous	894.43	49.57	322	9427	13123	2335213
Vaginal haemorrhage	884.54	49.57	252	9497	4728	2343608
Pregnancy with contraceptive device	783.41	49.57	165	9584	769	2347567
Device kink	579.88	49.57	104	9645	152	2348184
Complication of device insertion	567.17	49.57	111	9638	325	2348011
Abortion induced	552.14	49.57	161	9588	3275	2345061
Dysmenorrhoea	537.12	49.57	116	9633	621	2347715
Maternal exposure before pregnancy	492.01	49.57	111	9638	749	2347587
Menstruation delayed	482.37	49.57	95	9654	290	2348046
Migraine	478.97	49.57	192	9557	10461	2337875
Headache	472.05	49.57	378	9371	79801	2268535
General anaesthesia	465.52	49.57	75	9674	23	2348313
Vaginal discharge	423.43	49.57	100	9649	845	2347491
Abnormal withdrawal bleeding	398.56	49.57	63	9686	10	2348326
Medical device discomfort	394.46	49.57	81	9668	323	2348013
Pain in extremity	383.92	49.57	260	9489	42280	2306056
Mood swings	374.05	49.57	118	9631	3151	2345185
Depression	371.68	49.57	219	9530	27913	2320423
Product storage error	359.85	49.57	125	9624	4535	2343801
Menstrual disorder	354.11	49.57	87	9662	882	2347454
Haemorrhage	345.84	49.57	154	9595	10885	2337451
Surgery	342.52	49.57	126	9623	5409	2342927
Implant site pruritus	335.82	49.57	59	9690	70	2348266
Exposure during pregnancy	329.52	49.57	195	9554	25024	2323312
Vulvovaginal discomfort	314.19	49.57	71	9678	482	2347854
Adverse event	312.96	49.57	129	9620	7530	2340806
Thrombosis	310.40	49.57	135	9614	9009	2339327
Intentional medical device removal by patient	302.90	49.57	51	9698	36	2348300
Hypomenorrhoea	286.60	49.57	53	9696	101	2348235
Implant site scar	275.89	49.57	46	9703	28	2348308
Medical device site discomfort	269.72	49.57	44	9705	18	2348318
Hypercoagulation	268.62	49.57	58	9691	309	2348027
Implant site fibrosis	266.97	49.57	43	9706	13	2348323
Ovarian cyst	266.89	49.57	81	9668	1892	2346444
Ectopic pregnancy	265.69	49.57	66	9683	702	2347634
Acne	263.77	49.57	90	9659	3086	2345250
Muscle spasms	258.85	49.57	158	9591	21408	2326928
Anxiety	256.16	49.57	176	9573	29183	2319153
Hypoaesthesia	252.63	49.57	152	9597	20063	2328273
Expired product administered	241.11	49.57	68	9681	1216	2347120
Pregnancy on contraceptive	231.30	49.57	50	9699	268	2348068
Menstruation normal	225.50	49.57	37	9712	17	2348319
Pulmonary infarction	219.26	49.57	52	9697	447	2347889
Polymenorrhoea	215.29	49.57	46	9703	231	2348105
Chest pain	213.64	49.57	155	9594	27982	2320354
Nausea	201.34	49.57	281	9468	111908	2236428
Abdominal pain	200.84	49.57	162	9587	34212	2314124
Back pain	199.50	49.57	156	9593	31503	2316833
Vena cava filter insertion	198.56	49.57	34	9715	30	2348306
Implant site infection	196.39	49.57	43	9706	247	2348089
Cervical dysplasia	195.27	49.57	51	9698	672	2347664
Implant site erythema	193.60	49.57	37	9712	91	2348245
Menometrorrhagia	193.03	49.57	41	9708	199	2348137
Coagulopathy	186.42	49.57	68	9681	2841	2345495
Chlamydial infection	183.45	49.57	35	9714	85	2348251
Product shape issue	178.67	49.57	31	9718	32	2348304
Withdrawal bleed	175.99	49.57	30	9719	25	2348311
Vulvovaginal mycotic infection	172.20	49.57	48	9701	820	2347516
Discomfort	164.65	49.57	73	9676	5086	2343250
Cerebral venous sinus thrombosis	158.35	49.57	38	9711	345	2347991
Abortion	157.70	49.57	45	9704	840	2347496
Breast pain	154.68	49.57	49	9700	1322	2347014
Product administration error	152.78	49.57	64	9685	3879	2344457
Fungal infection	152.24	49.57	68	9681	4821	2343515
Pelvic pain	149.23	49.57	52	9697	1897	2346439
Smear cervix abnormal	149.13	49.57	35	9714	286	2348050
Implant site swelling	146.79	49.57	29	9720	90	2348246
Breast tenderness	146.59	49.57	39	9710	554	2347782
Implant site bruising	142.91	49.57	26	9723	43	2348293
Product use issue	140.30	49.57	87	9662	12082	2336254
Oligomenorrhoea	138.08	49.57	31	9718	203	2348133
Incorrect route of product administration	137.27	49.57	65	9684	5271	2343065
Cerebrovascular accident	136.90	49.57	104	9645	20082	2328254
Maternal exposure during pregnancy	136.25	49.57	92	9657	14771	2333565
Infertility female	132.81	49.57	29	9720	164	2348172
Mood altered	128.36	49.57	51	9698	2695	2345641
Product use in unapproved indication	126.39	49.57	79	9670	11121	2337215
Poor quality product administered	124.84	49.57	37	9712	793	2347543
Cerebral venous thrombosis	118.77	49.57	31	9718	407	2347929
Vaginal infection	117.53	49.57	36	9713	866	2347470
Device failure	115.82	49.57	42	9707	1723	2346613
Implant site reaction	115.55	49.57	23	9726	75	2348261
Product colour issue	115.10	49.57	27	9722	220	2348116
Female sterilisation	111.29	49.57	23	9726	95	2348241
Pain	110.50	49.57	155	9594	61702	2286634
Uterine leiomyoma	106.01	49.57	38	9711	1507	2346829
Urinary tract infection	105.06	49.57	106	9643	29836	2318500
Vulvovaginal pain	102.66	49.57	28	9721	439	2347897
Weight decreased	102.40	49.57	102	9647	28269	2320067
Thrombectomy	102.24	49.57	20	9729	58	2348278
Thrombophlebitis superficial	102.23	49.57	31	9718	720	2347616
Product dose omission	95.13	49.57	113	9636	38144	2310192
Anticoagulation drug level below therapeutic	93.82	49.57	20	9729	99	2348237
Off label use	92.83	49.57	157	9592	73441	2274895
Papilloma viral infection	92.52	49.57	24	9725	307	2348029
Product prescribing error	91.57	49.57	41	9708	2919	2345417
Polycystic ovaries	91.43	49.57	22	9727	202	2348134
Libido decreased	90.12	49.57	26	9723	505	2347831
Gastrooesophageal reflux disease	87.38	49.57	58	9691	9037	2339299
Embolism venous	87.01	49.57	23	9726	318	2348018
Dizziness	85.96	49.57	134	9615	58531	2289805
Overdose	85.88	49.57	79	9670	19828	2328508
Abdominal pain lower	85.58	49.57	39	9710	2894	2345442
Pulmonary mass	83.87	49.57	34	9715	1892	2346444
Scar	80.60	49.57	33	9716	1884	2346452
Device embolisation	79.19	49.57	13	9736	6	2348330
Swelling	78.64	49.57	69	9680	16281	2332055
Hypertension	78.40	49.57	87	9662	27274	2321062
Vulvovaginal burning sensation	77.51	49.57	22	9727	402	2347934
Dyspareunia	77.36	49.57	22	9727	405	2347931
Implant site irritation	75.23	49.57	14	9735	28	2348308
Cholecystectomy	75.18	49.57	30	9719	1602	2346734
Accidental underdose	75.05	49.57	19	9730	219	2348117
Coital bleeding	74.11	49.57	16	9733	85	2348251
Emotional disorder	73.28	49.57	32	9717	2145	2346191
Dysfunctional uterine bleeding	73.24	49.57	18	9731	182	2348154
Tonsillectomy	72.40	49.57	19	9730	255	2348081
Implant site inflammation	72.25	49.57	14	9735	38	2348298
Vulvovaginal swelling	71.98	49.57	17	9732	143	2348193
Alopecia	71.88	49.57	75	9674	21926	2326410
Iron deficiency anaemia	71.13	49.57	31	9718	2068	2346268
Syncope	70.89	49.57	66	9683	16809	2331527
Obesity	69.94	49.57	28	9721	1508	2346828
Paraesthesia	69.85	49.57	74	9675	22014	2326322
Rhinitis allergic	68.81	49.57	23	9726	737	2347599
Uterine dilation and curettage	68.08	49.57	18	9731	249	2348087
Pregnancy	67.56	49.57	47	9702	7902	2340434
Asthma	67.32	49.57	54	9695	11260	2337076
Device physical property issue	66.52	49.57	17	9732	204	2348132
Bacterial vaginosis	66.39	49.57	16	9733	148	2348188
Infertility	66.29	49.57	16	9733	149	2348187
Caesarean section	65.00	49.57	36	9713	4045	2344291
Uterine haemorrhage	64.47	49.57	22	9727	752	2347584
Superior sagittal sinus thrombosis	64.22	49.57	16	9733	172	2348164
Fatigue	64.13	49.57	146	9603	84727	2263609
Bipolar disorder	63.40	49.57	25	9724	1293	2347043
Endometriosis	62.10	49.57	21	9728	698	2347638
Muscle strain	60.32	49.57	23	9726	1086	2347250
Antiphospholipid antibodies positive	58.94	49.57	14	9735	121	2348215
Breast cancer female	58.68	49.57	24	9725	1366	2346970
Drug interaction	57.85	49.57	77	9672	29086	2319250
Bacterial vulvovaginitis	57.29	49.57	14	9735	138	2348198
Vulvovaginal candidiasis	57.09	49.57	17	9732	370	2347966
Implant site cellulitis	56.39	49.57	10	9739	13	2348323
Post thrombotic syndrome	55.84	49.57	13	9736	102	2348234
Implant site paraesthesia	55.65	49.57	9	9740	3	2348333
Hormone level abnormal	54.53	49.57	17	9732	434	2347902
Seizure	53.83	49.57	68	9681	24398	2323938
Implant site necrosis	53.64	49.57	9	9740	6	2348330
Leukocytosis	52.75	49.57	30	9719	3546	2344790
Road traffic accident	52.65	49.57	32	9717	4276	2344060
Thrombophlebitis	52.59	49.57	19	9730	770	2347566
Pleuritic pain	52.26	49.57	18	9731	633	2347703
Limb discomfort	51.61	49.57	29	9720	3350	2344986
Vitamin D deficiency	50.13	49.57	22	9727	1492	2346844
Venous stent insertion	49.80	49.57	9	9740	14	2348322
Contusion	49.77	49.57	48	9701	12762	2335574
Endometrial ablation	49.67	49.57	11	9738	67	2348269

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event

Pharmacologic Action:

Source	Code	Description
ATC	G03AC08	GENITO URINARY SYSTEM AND SEX HORMONES SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM HORMONAL CONTRACEPTIVES FOR SYSTEMIC USE Progestogens
FDA Chemical/Ingredient	N0000011301	Progesterone Congeners
FDA EPC	N0000175602	Progestin
CHEBI has role	CHEBI:49323	contraceptive drug
CHEBI has role	CHEBI:49324	female contraceptive drug
MeSH PA	D003270	Contraceptive Agents
MeSH PA	D003271	Contraceptive Agents, Female
MeSH PA	D000080066	Contraceptive Agents, Hormonal
MeSH PA	D012102	Reproductive Control Agents

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Contraception	indication	13197004
Heart valve disorder	contraindication	368009	DOID:4079
Hypercholesterolemia	contraindication	13644009
Toxic shock syndrome	contraindication	18504008	DOID:14115
Myocardial infarction	contraindication	22298006	DOID:5844
Diplopia	contraindication	24982008
Retinal hemorrhage	contraindication	28998008
Depressive disorder	contraindication	35489007
Migraine	contraindication	37796009	DOID:6364
Hypertensive disorder	contraindication	38341003	DOID:10763
Disorder of gallbladder	contraindication	39621005	DOID:0060262
Body fluid retention	contraindication	43498006
Thrombosis of retinal vein	contraindication	46085004
Chronic heart failure	contraindication	48447003
Dementia	contraindication	52448006
Systemic lupus erythematosus	contraindication	55464009	DOID:9074
Hyperlipidemia	contraindication	55822004	DOID:1168
Cerebrovascular disease	contraindication	62914000	DOID:6713
Thrombophlebitis	contraindication	64156001	DOID:3875
Intermenstrual bleeding - irregular	contraindication	64996003
Diabetes mellitus	contraindication	73211009	DOID:9351
Kidney disease	contraindication	90708001	DOID:557
Malignant neoplasm of liver	contraindication	93870000	DOID:3571
Deep venous thrombosis	contraindication	128053003
Seizure disorder	contraindication	128613002
Bed-ridden	contraindication	160685001
Asthma	contraindication	195967001	DOID:2841
Cerebrovascular accident	contraindication	230690007
Pulmonary thromboembolism	contraindication	233935004
Disease of liver	contraindication	235856003	DOID:409
Cholestasis of pregnancy	contraindication	235888006
Metabolic syndrome X	contraindication	237602007	DOID:14221
Endometrial carcinoma	contraindication	254878006	DOID:2871
Pregnancy, function	contraindication	289908002
Hypertriglyceridemia	contraindication	302870006
Functional visual loss	contraindication	313165001
Non-Q wave myocardial infarction	contraindication	314207007
Malignant tumor of ovary	contraindication	363443007	DOID:2394
Thromboembolic disorder	contraindication	371039008
Disorder of coronary artery	contraindication	414024009
Obesity	contraindication	414916001	DOID:9970
Estrogen receptor positive tumor	contraindication	416053008
Porphyria	contraindication	418470004
Optic disc edema	contraindication	423341008	DOID:146
Hypertensive urgency	contraindication	443482000
Carcinoma of female breast	contraindication	447782002
Smokes tobacco daily	contraindication	449868002
Worsening Headache Disorder	contraindication
Major Surgery with Prolonged Post-Operative Immobilization	contraindication
Diabetes with Vascular Disease Complication	contraindication
Benign Hepatic Cell Adenoma	contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	13.93	acidic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
68MG/IMPLANT	IMPLANON	ORGANON USA INC	N021529	July 17, 2006	DISCN	IMPLANT	IMPLANTATION	9757552	July 28, 2030	PREVENTION OF PREGNANCY
68MG/IMPLANT	NEXPLANON	ORGANON USA INC	N021529	May 31, 2011	RX	IMPLANT	IMPLANTATION	9757552	July 28, 2030	PREVENTION OF PREGNANCY

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Progesterone receptor	Nuclear hormone receptor	P06401	PRGR_HUMAN	AGONIST			WOMBAT-PK	CHEMBL
Estrogen receptor	Nuclear hormone receptor	P03372	ESR1_HUMAN				WOMBAT-PK
Sex hormone-binding globulin	Secreted	P04278	SHBG_HUMAN		Kd	8.23	CHEMBL

External reference:

ID	Source
4021294	VUID
N0000179018	NUI
C0047683	UMLSCUI
D04104	KEGG_DRUG
304GTH6RNH	UNII
6832	INN_ID
326451000	SNOMEDCT_US
396050000	SNOMEDCT_US
14584	RXNORM
d04772	MMSL
16189	MMSL
4021294	VANDF
007906	NDDF
CHEMBL1531	ChEMBL_ID
DB00294	DRUGBANK_ID
CHEBI:50777	CHEBI
6917715	PUBCHEM_CID
CHEMBL1697750	ChEMBL_ID
7590	IUPHAR_LIGAND_ID
C044815	MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
IMPLANON	HUMAN PRESCRIPTION DRUG LABEL	1	0052-0272	IMPLANT	68 mg	SUBCUTANEOUS	NDA	18 sections
NuvaRing	HUMAN PRESCRIPTION DRUG LABEL	2	0052-0273	INSERT, EXTENDED RELEASE	0.12 mg	VAGINAL	NDA	20 sections
Nexplanon	HUMAN PRESCRIPTION DRUG LABEL	1	0052-4330	IMPLANT	68 mg	SUBCUTANEOUS	NDA	19 sections
NUVARING	HUMAN PRESCRIPTION DRUG LABEL	2	50090-1008	INSERT, EXTENDED RELEASE	0.12 mg	VAGINAL	NDA	21 sections
NuvaRing	HUMAN PRESCRIPTION DRUG LABEL	2	54868-4832	INSERT, EXTENDED RELEASE	11.70 mg	VAGINAL	NDA	13 sections
EluRyng	HUMAN PRESCRIPTION DRUG LABEL	2	65162-469	RING	0.12 mg	VAGINAL	ANDA	20 sections
Etonogestrel/Ethinyl Estradiol	HUMAN PRESCRIPTION DRUG LABEL	2	66993-605	INSERT, EXTENDED RELEASE	11.70 mg	VAGINAL	NDA AUTHORIZED GENERIC	21 sections
NuvaRing	HUMAN PRESCRIPTION DRUG LABEL	2	76413-131	INSERT, EXTENDED RELEASE	0.12 mg	VAGINAL	NDA	20 sections