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

Stem definition	Drug id	CAS RN
retinol derivatives	78	55079-83-9

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: acitretin acitretinoin etretin neotigason soriatane isoacitretin isoetretin	An oral retinoid effective in the treatment of psoriasis. It is the major metabolite of ETRETINATE with the advantage of a much shorter half-life when compared with etretinate. Molecular weight: 326.44 Formula: C21H26O3 CLOGP: 6.07 LIPINSKI: 1 HAC: 3 HDO: 1 TPSA: 46.53 ALOGS: -5.83 ROTB: 6 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

acitretin
acitretinoin
etretin
neotigason
soriatane
isoacitretin
isoetretin

An oral retinoid effective in the treatment of psoriasis. It is the major metabolite of ETRETINATE with the advantage of a much shorter half-life when compared with etretinate.

Molecular weight: 326.44
Formula: C21H26O3
CLOGP: 6.07
LIPINSKI: 1
HAC: 3
HDO: 1
TPSA: 46.53
ALOGS: -5.83
ROTB: 6

Status: OFP

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

Drug dosage:

Dose	Unit	Route
35	mg	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	0 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	3.83 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	59 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

Date	Agency	Company	Orphan
Oct. 28, 1996	FDA	STIEFEL LABS INC

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
Psoriasis	729.35	19.87	311	6594	78293	46600864
Skin exfoliation	93.24	19.87	59	6846	32879	46646278
Skin haemorrhage	91.53	19.87	34	6871	5857	46673300
Psoriatic arthropathy	90.29	19.87	60	6845	36319	46642838
Pruritus	72.68	19.87	129	6776	242223	46436934
Drug ineffective	68.54	19.87	237	6668	677601	46001556
Cutaneous T-cell lymphoma	67.60	19.87	19	6886	1344	46677813
Pregnancy	58.39	19.87	41	6864	27096	46652061
Dry skin	57.48	19.87	48	6857	40968	46638189
Skin plaque	56.71	19.87	24	6881	5811	46673346
Infected dermal cyst	55.25	19.87	13	6892	451	46678706
Pustular psoriasis	54.49	19.87	21	6884	3996	46675161
Rash pustular	52.75	19.87	24	6881	6905	46672252
Erythema	50.61	19.87	82	6823	142738	46536419
Rhesus antigen positive	47.08	19.87	9	6896	111	46679046
Drug exposure before pregnancy	46.77	19.87	12	6893	599	46678558
Wrong technique in device usage process	44.55	19.87	15	6890	1938	46677219
Erythrodermic psoriasis	42.31	19.87	12	6893	877	46678280
Skin fissures	41.42	19.87	21	6884	7659	46671498
Squamous cell carcinoma	38.15	19.87	20	6885	7816	46671341
Burning sensation	37.12	19.87	39	6866	44372	46634785
Guttate psoriasis	36.82	19.87	9	6896	368	46678789
Pregnancy of partner	35.69	19.87	6	6899	33	46679124
Skin lesion	34.82	19.87	30	6875	26683	46652474
Weaning failure	32.97	19.87	8	6897	317	46678840
Blood immunoglobulin M decreased	31.16	19.87	9	6896	702	46678455
Skin atrophy	29.93	19.87	14	6891	4286	46674871
Immunoglobulins decreased	29.61	19.87	9	6896	837	46678320
Type IIb hyperlipidaemia	29.37	19.87	5	6900	30	46679127
Blood albumin increased	29.20	19.87	9	6896	877	46678280
Lipids increased	28.06	19.87	9	6896	999	46678158
Abortion induced	28.06	19.87	18	6887	10242	46668915
Lip dry	27.63	19.87	12	6893	3092	46676065
Ichthyosis	27.30	19.87	5	6900	48	46679109
Onychalgia	27.24	19.87	8	6897	661	46678496
Sunburn	26.65	19.87	11	6894	2501	46676656
Exposure via body fluid	25.01	19.87	7	6898	487	46678670
Tanning	24.66	19.87	5	6900	85	46679072
Injection site bruising	24.07	19.87	28	6877	35608	46643549
Increased bronchial secretion	23.91	19.87	9	6896	1605	46677552
Inappropriate schedule of product administration	23.89	19.87	38	6867	64975	46614182
Rickets	23.79	19.87	4	6901	22	46679135
Blood immunoglobulin G decreased	22.63	19.87	9	6896	1859	46677298
Death	22.16	19.87	11	6894	335537	46343620
Mean cell haemoglobin increased	22.06	19.87	9	6896	1987	46677170
Exposure during pregnancy	21.91	19.87	49	6856	108163	46570994
Cellulitis	21.71	19.87	38	6867	70250	46608907
Keratoacanthoma	21.63	19.87	6	6899	404	46678753
Toxicity to various agents	21.34	19.87	3	6902	211763	46467394
Psoriasis area severity index increased	21.03	19.87	4	6901	48	46679109
Mastitis	20.83	19.87	9	6896	2289	46676868
Maternal exposure before pregnancy	20.57	19.87	11	6894	4470	46674687
Blister	20.56	19.87	29	6876	44602	46634555
Toxic goitre	20.16	19.87	3	6902	6	46679151
Serum ferritin decreased	20.16	19.87	8	6897	1644	46677513

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
Psoriasis	724.72	19.96	278	5324	42228	29904648
Vein rupture	199.20	19.96	41	5561	589	29946287
Drug ineffective	143.63	19.96	239	5363	340148	29606728
Skin plaque	131.72	19.96	42	5560	3620	29943256
Venous injury	111.54	19.96	22	5580	251	29946625
Injection site haemorrhage	100.44	19.96	42	5560	7813	29939063
Injection site papule	85.14	19.96	18	5584	296	29946580
Erythrodermic psoriasis	84.03	19.96	21	5581	741	29946135
Injection site swelling	83.14	19.96	38	5564	8742	29938134
Cutaneous T-cell lymphoma	72.36	19.96	21	5581	1314	29945562
Pityriasis rubra pilaris	69.05	19.96	12	5590	63	29946813
Skin erosion	58.49	19.96	19	5583	1734	29945142
Granuloma annulare	57.93	19.96	11	5591	101	29946775
Squamous cell carcinoma	57.27	19.96	31	5571	10219	29936657
Inappropriate schedule of product administration	56.78	19.96	52	5550	39676	29907200
Dermatitis exfoliative generalised	53.31	19.96	20	5582	2795	29944081
Squamous cell carcinoma of skin	52.19	19.96	28	5574	9067	29937809
Pain in extremity	49.41	19.96	80	5522	110141	29836735
Myalgia	46.30	19.96	64	5538	76603	29870273
Pustular psoriasis	39.86	19.96	14	5588	1621	29945255
Hypercholesterolaemia	39.75	19.96	22	5580	7570	29939306
Hyperkeratosis	39.73	19.96	17	5585	3340	29943536
Muscular weakness	39.72	19.96	54	5548	63591	29883285
Skin exfoliation	38.40	19.96	33	5569	23139	29923737
Dermatitis exfoliative	37.38	19.96	21	5581	7435	29939441
Keratoacanthoma	36.38	19.96	10	5592	513	29946363
Induration	35.70	19.96	11	5591	845	29946031
Basal cell carcinoma	35.34	19.96	27	5575	16041	29930835
Malignant melanoma stage I	34.22	19.96	7	5595	97	29946779
Psoriatic arthropathy	33.60	19.96	26	5576	15735	29931141
Neuroendocrine tumour of the lung metastatic	33.52	19.96	7	5595	108	29946768
Insomnia	32.95	19.96	61	5541	93275	29853601
Myasthenia gravis	31.65	19.96	14	5588	2978	29943898
Therapeutic product effect incomplete	31.27	19.96	35	5567	33799	29913077
Macule	31.10	19.96	10	5592	883	29945993
Retinal disorder	30.10	19.96	10	5592	979	29945897
Skin injury	29.96	19.96	10	5592	993	29945883
Erythema	29.07	19.96	52	5550	77399	29869477
Pruritus	28.47	19.96	66	5536	118138	29828738
Decreased immune responsiveness	27.59	19.96	10	5592	1268	29945608
Pain of skin	25.73	19.96	13	5589	3720	29943156
Hepatic cirrhosis	22.94	19.96	21	5581	15978	29930898
Sticky skin	22.75	19.96	3	5599	0	29946876
Cutaneous symptom	22.61	19.96	6	5596	269	29946607
Type 2 diabetes mellitus	21.75	19.96	19	5583	13603	29933273
Death	20.56	19.96	22	5580	357261	29589615
Hepatic fibrosis	20.47	19.96	11	5591	3569	29943307
Drug intolerance	20.40	19.96	33	5569	45258	29901618
Skin lesion	20.36	19.96	21	5581	18473	29928403
Superficial spreading melanoma stage unspecified	20.21	19.96	5	5597	169	29946707
Skin disorder	20.18	19.96	17	5585	11591	29935285

Pharmacologic Action:

Source	Code	Description
ATC	D05BB02	DERMATOLOGICALS ANTIPSORIATICS ANTIPSORIATICS FOR SYSTEMIC USE Retinoids for treatment of psoriasis
FDA CS	M0018962	Retinoids
FDA EPC	N0000175607	Retinoid
MeSH PA	D003879	Dermatologic Agents
MeSH PA	D007641	Keratolytic Agents
CHEBI has role	CHEBI:50176	desquamating agent

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Severe Recalcitrant Psoriasis	indication
Lichen planus	off-label use	4776004	DOID:9201
Keratosis follicularis	off-label use	48611009	DOID:2734
Lamellar ichthyosis	off-label use	205550003
Ichthyosiform erythroderma	off-label use	268282005
Primary cutaneous T-cell lymphoma	off-label use	400122007
Alcoholism	contraindication	7200002
Hypercholesterolemia	contraindication	13644009
Depressive disorder	contraindication	35489007
Acute nephropathy	contraindication	58574008
Hepatic failure	contraindication	59927004
Night blindness	contraindication	65194006	DOID:8499
Benign intracranial hypertension	contraindication	68267002	DOID:11459
Diabetes mellitus	contraindication	73211009	DOID:9351
Premature epiphyseal closure	contraindication	89493005
Liver function tests abnormal	contraindication	166603001
Hypoalphalipoproteinemia	contraindication	190785000
Acute pancreatitis	contraindication	197456007	DOID:2913
Hypertrophy of bone	contraindication	203514008	DOID:205
Drug-induced hepatitis	contraindication	235876009
Pregnancy, function	contraindication	289908002
Hypertriglyceridemia	contraindication	302870006
Cardiovascular event risk	contraindication	395112001
Visual impairment	contraindication	397540003
Breastfeeding (mother)	contraindication	413712001
Obesity	contraindication	414916001	DOID:9970
Psychiatric Disturbance	contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	4.17	acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Retinoic acid receptor alpha	Nuclear hormone receptor	P10276	RARA_HUMAN	AGONIST			WOMBAT-PK	CHEMBL
Retinoic acid receptor gamma	Nuclear hormone receptor	P13631	RARG_HUMAN	AGONIST			CHEMBL	CHEMBL
Bile salt export pump	Transporter	O95342	ABCBB_HUMAN		IC50	4.74	CHEMBL
Bile salt export pump	Unclassified		ABCBB_RAT		IC50	4.71	CHEMBL

External reference:

ID	Source
LCH760E9T7	UNII
4021061	VUID
N0000148524	NUI
D02754	KEGG_DRUG
69427-46-9	SECONDARY_CAS_RN
C0050559	UMLSCUI
CHEBI:50173	CHEBI
CHEMBL1131	ChEMBL_ID
5284513	PUBCHEM_CID
DB00459	DRUGBANK_ID
D017255	MESH_DESCRIPTOR_UI
5530	INN_ID
7598	IUPHAR_LIGAND_ID
16818	RXNORM
11379	MMSL
117161	MMSL
4128	MMSL
d03836	MMSL
004121	NDDF
108914001	SNOMEDCT_US
386938006	SNOMEDCT_US
4021061	VANDF

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Acitretin	HUMAN PRESCRIPTION DRUG LABEL	1	0093-1135	CAPSULE	10 mg	ORAL	ANDA	24 sections
Acitretin	HUMAN PRESCRIPTION DRUG LABEL	1	0093-1136	CAPSULE	25 mg	ORAL	ANDA	24 sections
Acitretin	HUMAN PRESCRIPTION DRUG LABEL	1	0093-1138	CAPSULE	17.50 mg	ORAL	ANDA	24 sections
Acitretin	HUMAN PRESCRIPTION DRUG LABEL	1	0115-1667	CAPSULE	10 mg	ORAL	ANDA	17 sections
Acitretin	HUMAN PRESCRIPTION DRUG LABEL	1	0115-1668	CAPSULE	17.50 mg	ORAL	ANDA	17 sections
Acitretin	HUMAN PRESCRIPTION DRUG LABEL	1	0115-1669	CAPSULE	25 mg	ORAL	ANDA	17 sections
Acitretin	HUMAN PRESCRIPTION DRUG LABEL	1	0115-1698	CAPSULE	22.50 mg	ORAL	ANDA	17 sections
Acitretin	HUMAN PRESCRIPTION DRUG LABEL	1	0115-1750	CAPSULE	10 mg	ORAL	ANDA	17 sections
Acitretin	HUMAN PRESCRIPTION DRUG LABEL	1	0115-1751	CAPSULE	17.50 mg	ORAL	ANDA	17 sections
Acitretin	HUMAN PRESCRIPTION DRUG LABEL	1	0115-1752	CAPSULE	22.50 mg	ORAL	ANDA	17 sections
Acitretin	HUMAN PRESCRIPTION DRUG LABEL	1	0115-1753	CAPSULE	25 mg	ORAL	ANDA	17 sections
SORIATANE	HUMAN PRESCRIPTION DRUG LABEL	1	0145-0090	CAPSULE	10 mg	ORAL	NDA	27 sections
SORIATANE	HUMAN PRESCRIPTION DRUG LABEL	1	0145-0091	CAPSULE	25 mg	ORAL	NDA	27 sections
Acitretin	HUMAN PRESCRIPTION DRUG LABEL	1	0378-7020	CAPSULE	10 mg	ORAL	ANDA	28 sections
Acitretin	HUMAN PRESCRIPTION DRUG LABEL	1	0378-7023	CAPSULE	25 mg	ORAL	ANDA	28 sections
ACITRETIN	HUMAN PRESCRIPTION DRUG LABEL	1	42291-086	CAPSULE	10 mg	ORAL	ANDA	25 sections
ACITRETIN	HUMAN PRESCRIPTION DRUG LABEL	1	42291-087	CAPSULE	17.50 mg	ORAL	ANDA	25 sections
ACITRETIN	HUMAN PRESCRIPTION DRUG LABEL	1	42291-088	CAPSULE	25 mg	ORAL	ANDA	25 sections
ACITRETIN	HUMAN PRESCRIPTION DRUG LABEL	1	42794-080	CAPSULE	10 mg	ORAL	ANDA	25 sections
ACITRETIN	HUMAN PRESCRIPTION DRUG LABEL	1	42794-081	CAPSULE	17.50 mg	ORAL	ANDA	25 sections
ACITRETIN	HUMAN PRESCRIPTION DRUG LABEL	1	42794-083	CAPSULE	25 mg	ORAL	ANDA	25 sections
ACITRETIN	HUMAN PRESCRIPTION DRUG LABEL	1	66993-894	CAPSULE	10 mg	ORAL	NDA authorized generic	16 sections
ACITRETIN	HUMAN PRESCRIPTION DRUG LABEL	1	66993-896	CAPSULE	25 mg	ORAL	NDA authorized generic	16 sections