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

Stem definitionDrug idCAS RN
retinol derivatives 2722 302-79-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • tretinoin potassium
  • trans-Retinoic acid
  • tretinoin sodium
  • retinoic acid
  • tretinoin
An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).
  • Molecular weight: 300.44
  • Formula: C20H28O2
  • CLOGP: 6.74
  • LIPINSKI: 1
  • HAC: 2
  • HDO: 1
  • TPSA: 37.30
  • ALOGS: -4.80
  • ROTB: 5

  • Status: OFP

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

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0.50 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 3.70 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD

Approvals:

DateAgencyCompanyOrphan
Oct. 20, 1971 FDA VALEANT INTL

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Differentiation syndrome 516.34 16.66 90 5432 821 46679719
Idiopathic intracranial hypertension 118.17 16.66 32 5490 2477 46678063
Product use in unapproved indication 84.22 16.66 76 5446 90197 46590343
Leukaemia recurrent 82.30 16.66 21 5501 1288 46679252
Intracranial pressure increased 43.50 16.66 17 5505 4203 46676337
Haematopoietic neoplasm 41.88 16.66 7 5515 48 46680492
Lower respiratory tract infection fungal 37.10 16.66 8 5514 234 46680306
Dry skin 35.19 16.66 33 5489 40983 46639557
Polyarteritis nodosa 34.16 16.66 8 5514 342 46680198
Erythema 30.59 16.66 58 5464 142762 46537778
Chromosomal deletion 29.23 16.66 5 5517 40 46680500
Neutropenic sepsis 28.73 16.66 18 5504 12306 46668234
Febrile neutropenia 27.52 16.66 44 5478 94583 46585957
Chloroma 27.33 16.66 6 5516 191 46680349
Myelodysplastic syndrome 27.06 16.66 19 5503 15692 46664848
Acute myeloid leukaemia 26.98 16.66 19 5503 15759 46664781
Acute promyelocytic leukaemia 26.49 16.66 8 5514 913 46679627
Disseminated intravascular coagulation 25.99 16.66 20 5502 18985 46661555
Oesophageal mass 21.41 16.66 4 5518 55 46680485
Gambling 21.19 16.66 5 5517 221 46680319
Neutropenia 21.16 16.66 50 5472 143154 46537386
Skin irritation 20.48 16.66 12 5510 7275 46673265
Xerosis 20.11 16.66 6 5516 657 46679883
Skin warm 19.87 16.66 10 5512 4493 46676047
Dysphoria 19.69 16.66 10 5512 4579 46675961
Oral herpes 19.37 16.66 17 5505 19373 46661167
Haemorrhagic diathesis 18.64 16.66 9 5513 3699 46676841
Sweat gland tumour 18.61 16.66 4 5518 115 46680425
Mucosal inflammation 18.61 16.66 23 5499 38953 46641587
Thrombocytopenia 17.41 16.66 43 5479 126538 46554002
Gastrointestinal toxicity 17.31 16.66 9 5513 4322 46676218
Application site dryness 17.22 16.66 4 5518 165 46680375
Lip dry 17.02 16.66 8 5514 3096 46677444
Acne 17.02 16.66 16 5506 19903 46660637

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Differentiation syndrome 617.53 29.05 102 2226 1058 29949092
Idiopathic intracranial hypertension 178.46 29.05 32 2296 546 29949604
Leukaemia recurrent 97.86 29.05 23 2305 1538 29948612
Acute myeloid leukaemia 92.48 29.05 39 2289 17967 29932183
Product use in unapproved indication 89.69 29.05 61 2267 73632 29876518
Haematopoietic neoplasm 82.89 29.05 12 2316 45 29950105
Acute promyelocytic leukaemia 72.31 29.05 15 2313 561 29949589
Hyperleukocytosis 71.64 29.05 18 2310 1591 29948559
Electrocardiogram QT prolonged 67.00 29.05 39 2289 35796 29914354
Cytogenetic abnormality 56.65 29.05 13 2315 781 29949369
Scrotal ulcer 49.09 29.05 10 2318 341 29949809
Hypokalaemia 41.55 29.05 33 2295 50159 29899991
Febrile neutropenia 38.00 29.05 44 2284 106649 29843501
Neutropenia 37.64 29.05 48 2280 128492 29821658
Myelodysplastic syndrome 36.54 29.05 21 2307 18757 29931393
IIIrd nerve paralysis 35.49 29.05 8 2320 443 29949707
Lymphopenia 31.86 29.05 17 2311 13146 29937004
Large granular lymphocytosis 31.77 29.05 6 2322 137 29950013

Pharmacologic Action:

SourceCodeDescription
ATC D10AD01 DERMATOLOGICALS
ANTI-ACNE PREPARATIONS
ANTI-ACNE PREPARATIONS FOR TOPICAL USE
Retinoids for topical use in acne
ATC D10AD51 DERMATOLOGICALS
ANTI-ACNE PREPARATIONS
ANTI-ACNE PREPARATIONS FOR TOPICAL USE
Retinoids for topical use in acne
ATC L01XF01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Retinoids for cancer treatment
FDA CS M0018962 Retinoids
FDA EPC N0000175607 Retinoid
MeSH PA D000970 Antineoplastic Agents
MeSH PA D003879 Dermatologic Agents
MeSH PA D007641 Keratolytic Agents
CHEBI has role CHEBI:22586 antioxidants
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:50176 desquamating agent
CHEBI has role CHEBI:62488 signaling molecules
CHEBI has role CHEBI:63794 retinoid x receptor agonists
CHEBI has role CHEBI:67079 antiinflammatory agents
CHEBI has role CHEBI:67198 retinoic acid receptor agonists
CHEBI has role CHEBI:67199 ap-1 antagonists
CHEBI has role CHEBI:77746 h. sapiens metabolites

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Chloasma indication 36209000
Acne vulgaris indication 88616000
Acute promyelocytic leukemia, FAB M3 indication 110004001
Hyperkeratosis indication 396228006
Facial Fine Wrinkling indication
Solar Lentigines indication
Fine Wrinkling indication
Severe Recalcitrant Nodular Acne indication
Kaposi's Sarcoma Skin Lesions indication
Mottle Hyperpigmentation indication
Keratosis follicularis off-label use 48611009 DOID:2734
Lamellar ichthyosis off-label use 205550003
Plane wart off-label use 240539000
Primary cutaneous T-cell lymphoma off-label use 400122007
Severe Recalcitrant Nodular Rosacea off-label use
Osteomalacia contraindication 4598005 DOID:10573
Suicidal thoughts contraindication 6471006
Alcoholism contraindication 7200002
Rectal hemorrhage contraindication 12063002
Hypercholesterolemia contraindication 13644009
Hearing loss contraindication 15188001
Agranulocytosis contraindication 17182001 DOID:12987
Myocardial infarction contraindication 22298006 DOID:5844
Sunburn contraindication 23346002
Atopic dermatitis contraindication 24079001 DOID:3310
Inflammatory bowel disease contraindication 24526004 DOID:0050589
Crohn's disease contraindication 34000006
Depressive disorder contraindication 35489007
Eczema contraindication 43116000
Disorder of cardiovascular system contraindication 49601007 DOID:1287
Vitiligo contraindication 56727007 DOID:12306
Anorexia nervosa contraindication 56882008 DOID:8689
Tinnitus contraindication 60862001
Corneal opacity contraindication 64634000
Ulcerative colitis contraindication 64766004 DOID:8577
Osteoporosis contraindication 64859006 DOID:11476
Benign intracranial hypertension contraindication 68267002 DOID:11459
Psychotic disorder contraindication 69322001
Diabetes mellitus contraindication 73211009 DOID:9351
Disorder of bone contraindication 76069003 DOID:0080001
Congenital neutropenia contraindication 89655007
Kidney disease contraindication 90708001 DOID:557
Venous thrombosis contraindication 111293003
Leukocytosis contraindication 111583006
Mycosis fungoides contraindication 118618005
Inflammatory disease of liver contraindication 128241005
Bleeding contraindication 131148009
Liver function tests abnormal contraindication 166603001
Acute pancreatitis contraindication 197456007 DOID:2913
Disease of liver contraindication 235856003 DOID:409
Telangiectasia disorder contraindication 247479008
Dyspnea contraindication 267036007
Edema contraindication 267038008
Pregnancy, function contraindication 289908002
Hypertriglyceridemia contraindication 302870006
Keratoconjunctivitis sicca contraindication 302896008 DOID:12895
Neutropenic disorder contraindication 303011007 DOID:1227
Pericardial effusion contraindication 373945007 DOID:118
Adrenal cortical hypofunction contraindication 386584007 DOID:10493
Fever contraindication 386661006
Pseudomembranous enterocolitis contraindication 397683000
Atrophoderma contraindication 399979006
Peripheral vascular disease contraindication 400047006
Severe diarrhea contraindication 409587002
Breastfeeding (mother) contraindication 413712001
Obesity contraindication 414916001 DOID:9970
Denuded skin contraindication 418242004
Retinoic acid syndrome contraindication 450887006
Pulmonary Infiltrates contraindication
Pleural Effusions contraindication
Predisposition To Hypertriglyceridemia contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 4.17 acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
0.05% ALTRENO DOW PHARM N209353 Aug. 23, 2018 RX LOTION TOPICAL Aug. 23, 2021 NEW DOSAGE FORM

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Retinoic acid receptor gamma Nuclear hormone receptor AGONIST EC50 6.70 WOMBAT-PK CHEMBL
Retinoic acid receptor beta Nuclear hormone receptor AGONIST EC50 6.70 WOMBAT-PK CHEMBL
Retinoic acid receptor alpha Nuclear hormone receptor AGONIST EC50 6.70 WOMBAT-PK CHEMBL
5-hydroxytryptamine receptor 2B GPCR Ki 6.64 DRUG MATRIX
Adenosine receptor A3 GPCR Ki 5.53 DRUG MATRIX
Mitogen-activated protein kinase 1 Kinase IC50 6.24 DRUG MATRIX
Retinoic acid receptor RXR-alpha Nuclear hormone receptor Ki 9.40 CHEMBL
Retinoic acid receptor RXR-beta Nuclear hormone receptor Ki 9.30 CHEMBL
Retinoic acid receptor RXR-gamma Nuclear hormone receptor Ki 8.85 CHEMBL
11-cis retinol dehydrogenase Enzyme Ki 7 WOMBAT-PK
Nuclear receptor ROR-beta Nuclear hormone receptor ANTAGONIST IC50 9.82 IUPHAR
Peroxisome proliferator-activated receptor delta Nuclear hormone receptor AGONIST Kd 7.80 IUPHAR
Nuclear receptor ROR-gamma Nuclear hormone receptor IC50 6.70 CHEMBL
Nuclear receptor ROR-alpha Nuclear hormone receptor IC50 6.70 CHEMBL
Nuclear receptor subfamily 2 group C member 2 Unclassified AGONIST EC50 4.62 IUPHAR
Retinoic acid receptor alpha Transcription factor Kd 7.82 CHEMBL
Retinoic acid receptor RXR-gamma Transcription factor Kd 6.46 CHEMBL
Retinoic acid receptor RXR-beta Transcription factor Kd 6.51 CHEMBL
Retinoic acid receptor gamma Transcription factor Kd 7.74 CHEMBL
Cellular retinoic acid-binding protein 1 Cytosolic other IC50 6.43 CHEMBL
Retinoic acid receptor RXR-alpha Transcription factor Kd 6 CHEMBL
Cellular retinoic acid-binding protein 1 Cytosolic other Kd 9.40 CHEMBL
Retinoic acid receptor beta Transcription factor Kd 7.89 CHEMBL
Indoleamine 2,3-dioxygenase 2 Enzyme IC50 4.54 CHEMBL
Cellular retinoic acid-binding protein 2 Cytosolic other Kd 8.70 CHEMBL

External reference:

IDSource
4018550 VUID
N0000146871 NUI
D00094 KEGG_DRUG
4018550 VANDF
C0040845 UMLSCUI
CHEBI:15367 CHEBI
REA PDB_CHEM_ID
CHEMBL38 ChEMBL_ID
D014212 MESH_DESCRIPTOR_UI
DB00755 DRUGBANK_ID
2875 INN_ID
5688UTC01R UNII
444795 PUBCHEM_CID
2644 IUPHAR_LIGAND_ID
10753 RXNORM
46802 MMSL
5610 MMSL
d03863 MMSL
001954 NDDF
387305002 SNOMEDCT_US
54972005 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Altreno HUMAN PRESCRIPTION DRUG LABEL 1 0187-0005 LOTION 0.50 mg TOPICAL NDA 24 sections
Retin-A MICRO HUMAN PRESCRIPTION DRUG LABEL 1 0187-5140 GEL 1 mg TOPICAL NDA 26 sections
Retin-A MICRO HUMAN PRESCRIPTION DRUG LABEL 1 0187-5144 GEL 0.40 mg TOPICAL NDA 26 sections
Retin-A MICRO HUMAN PRESCRIPTION DRUG LABEL 1 0187-5146 GEL 0.60 mg TOPICAL NDA 26 sections
Retin-A MICRO HUMAN PRESCRIPTION DRUG LABEL 1 0187-5148 GEL 0.80 mg TOPICAL NDA 26 sections
Renova HUMAN PRESCRIPTION DRUG LABEL 1 0187-5150 CREAM 0.20 mg TOPICAL NDA 25 sections
Retin-A HUMAN PRESCRIPTION DRUG LABEL 1 0187-5160 CREAM 0.25 mg TOPICAL NDA 21 sections
Retin-A HUMAN PRESCRIPTION DRUG LABEL 1 0187-5162 CREAM 0.50 mg TOPICAL NDA 21 sections
Retin-A HUMAN PRESCRIPTION DRUG LABEL 1 0187-5164 CREAM 1 mg TOPICAL NDA 21 sections
Retin-A HUMAN PRESCRIPTION DRUG LABEL 1 0187-5170 GEL 0.25 mg TOPICAL NDA 21 sections
Retin-A HUMAN PRESCRIPTION DRUG LABEL 1 0187-5172 GEL 0.10 mg TOPICAL NDA 21 sections
TRI-LUMA HUMAN PRESCRIPTION DRUG LABEL 3 0299-5950 CREAM 0.50 mg TOPICAL NDA 24 sections
Avita HUMAN PRESCRIPTION DRUG LABEL 1 0378-6140 GEL 0.25 mg TOPICAL NDA 22 sections
Avita HUMAN PRESCRIPTION DRUG LABEL 1 0378-6141 CREAM 0.25 mg TOPICAL NDA 21 sections
Tretinoin HUMAN PRESCRIPTION DRUG LABEL 1 0378-8082 CREAM 0.25 mg TOPICAL NDA authorized generic 20 sections
Tretinoin HUMAN PRESCRIPTION DRUG LABEL 1 0378-8083 CREAM 0.50 mg TOPICAL NDA authorized generic 20 sections
Tretinoin HUMAN PRESCRIPTION DRUG LABEL 1 0378-8084 CREAM 1 mg TOPICAL NDA authorized generic 20 sections
Tretinoin HUMAN PRESCRIPTION DRUG LABEL 1 0378-8085 GEL 0.10 mg TOPICAL NDA authorized generic 20 sections
Tretinoin HUMAN PRESCRIPTION DRUG LABEL 1 0378-8086 GEL 0.25 mg TOPICAL NDA authorized generic 20 sections
Tretinoin HUMAN PRESCRIPTION DRUG LABEL 1 0378-8090 GEL 0.50 mg TOPICAL ANDA 24 sections
Tretinoin HUMAN PRESCRIPTION DRUG LABEL 1 0378-8092 GEL 0.40 mg TOPICAL NDA authorized generic 25 sections
Tretinoin HUMAN PRESCRIPTION DRUG LABEL 1 0378-8093 GEL 1 mg TOPICAL NDA authorized generic 25 sections
Tretinoin HUMAN PRESCRIPTION DRUG LABEL 1 0472-0117 CREAM 0.25 mg TOPICAL NDA AUTHORIZED GENERIC 22 sections
Clindamycin Phosphate and Tretinoin HUMAN PRESCRIPTION DRUG LABEL 2 0472-1790 GEL 0.25 mg TOPICAL ANDA 16 sections
Tretinoin HUMAN PRESCRIPTION DRUG LABEL 1 0555-0808 CAPSULE, LIQUID FILLED 10 mg ORAL ANDA 24 sections
TRETINOIN HUMAN PRESCRIPTION DRUG LABEL 1 0574-2201 CREAM 1 mg TOPICAL ANDA 23 sections
TRETINOIN HUMAN PRESCRIPTION DRUG LABEL 1 0574-2205 CREAM 0.50 mg TOPICAL ANDA 23 sections
TRETINOIN HUMAN PRESCRIPTION DRUG LABEL 1 0574-2225 CREAM 0.25 mg TOPICAL ANDA 23 sections
TRETINOIN HUMAN PRESCRIPTION DRUG LABEL 1 0574-2301 GEL 0.10 mg TOPICAL ANDA 23 sections
TRETINOIN HUMAN PRESCRIPTION DRUG LABEL 1 0574-2325 GEL 0.25 mg TOPICAL ANDA 23 sections