Identification

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Name
Isotretinoin
Accession Number
DB00982  (APRD00140)
Type
Small Molecule
Groups
Approved
Description

Isotretinoin is a retinoid derivative of vitamin A used in the treatment of severe recalcitrant acne.Label It was most widely marketed under the brand name Accutane, which has since been discontinued.10 Isotretinoin is associated with major risks in pregnancy and so it is only available under the iPLEDGE program in the United States.12 The first isotretinoin containing product was FDA approved on 7 May 1982.10

Structure
Thumb
Synonyms
  • (7E,9E,11E,13Z)-retinoic acid
  • 13-cis-retinoic acid
  • 13-cis-Vitamin A acid
  • 13-RA
  • cis-RA
  • Isotretinoin
  • Isotretinoína
  • Isotrétinoine
  • Isotretinoino
  • Isotretinoinum
  • Neovitamin A acid
External IDs
RO 4-3780 / RO-4-3780
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AbsoricaCapsule40 mg/1OralSun Pharmaceutical Industries, Inc.2012-06-08Not applicableUs
AbsoricaCapsule30 mg/1OralSun Pharmaceutical Industries, Inc.2012-06-08Not applicableUs
AbsoricaCapsule20 mg/1OralSun Pharmaceutical Industries, Inc.2012-06-08Not applicableUs
AbsoricaCapsule35 mg/1OralSun Pharmaceutical Industries, Inc.2015-02-17Not applicableUs
AbsoricaCapsule10 mg/1OralSun Pharmaceutical Industries, Inc.2012-06-08Not applicableUs
AbsoricaCapsule25 mg/1OralSun Pharmaceutical Industries, Inc.2015-02-17Not applicableUs
AccutaneCapsule, liquid filled40 mg/1OralPhysicians Total Care, Inc.1995-08-072010-12-29Us
AccutaneCapsule, liquid filled40 mg/1OralGenentech, Inc.1982-05-072010-12-22Us
AccutaneCapsule, liquid filled20 mg/1OralGenentech, Inc.1982-05-072010-12-22Us
AccutaneCapsule, liquid filled10 mg/1OralGenentech, Inc.1982-05-072010-12-22Us
Additional Data Available
  • Application Number
    Application Number

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  • Product Code
    Product Code

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AmnesteemCapsule10 mg/1OralMylan Pharmaceuticals Inc.2002-11-11Not applicableUs
AmnesteemCapsule40 mg/1OralPhysicians Total Care, Inc.2009-07-14Not applicableUs
AmnesteemCapsule10 mg/1OralPhysicians Total Care, Inc.2005-05-202008-09-16Us
AmnesteemCapsule20 mg/1OralPhysicians Total Care, Inc.2009-09-14Not applicableUs
AmnesteemCapsule40 mg/1OralMylan Pharmaceuticals Inc.2002-11-11Not applicableUs
AmnesteemCapsule10 mg/1OralPhysicians Total Care, Inc.2010-11-02Not applicableUs
AmnesteemCapsule20 mg/1OralMylan Pharmaceuticals Inc.2002-11-11Not applicableUs
ClaravisCapsule, liquid filled20 mg/1OralTeva2003-05-09Not applicableUs0555 105520180913 8702 nacjh
ClaravisCapsule, liquid filled10 mg/1OralTeva2003-05-09Not applicableUs00555 1054 86 nlmimage10 d5306ae3
ClaravisCapsule40 mg/1OralPhysicians Total Care, Inc.2011-09-20Not applicableUs00555 1057 86 nlmimage10 de306f63
Additional Data Available
  • Application Number
    Application Number

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  • Product Code
    Product Code

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Categories
UNII
EH28UP18IF
CAS number
4759-48-2
Weight
Average: 300.4351
Monoisotopic: 300.20893014
Chemical Formula
C20H28O2
InChI Key
SHGAZHPCJJPHSC-XFYACQKRSA-N
InChI
InChI=1S/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18-17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3,(H,21,22)/b9-6+,12-11+,15-8+,16-14-
IUPAC Name
(2Z,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid
SMILES
C\C(\C=C\C1=C(C)CCCC1(C)C)=C/C=C/C(/C)=C\C(O)=O

Pharmacology

Indication

Isotretinoin is indicated to treat severe recalcitrant nodular acne and patients ≥12 years enrolled in the iPLEDGE program.Label,12

Associated Conditions
Pharmacodynamics

The pharmacodynamics of isotretinoin are poorly understood.Label

Mechanism of action

Isotretinoin produces its effects through altering progress through the cell cycle, cell differentiation, survival, and apoptosis.4 These actions reduce sebum production, preventing the blockage of pores, and growth of acne causing bacteria.4 Isotretinoin and 4-oxo-isotretinoin both significantly reduce the production of sebum.4,Label Isotretinoin has little to no affinity for retinol binding proteins (RBPs) and retinoic acid nuclear receptors (RARs).4 Tretinoin and 4-oxo-tretinion bind to the RAR-γ receptor, which is suspected to be part of the action of acne treatment by isotretinoin.4 Isotretinoin induces apoptosis in sebocytes, leading to a decrease in sebum production.4 Isotretinoin also reduces the formation of comedones by reducing hyperkeratinization through an unknown mechanism.4 Isotretinoin does not directly kill bacteria but it does reduce the size of sebum ducts and makes the microenvironment less hospitable to acne causing bacteria.4 It may also increase immune mechanisms and alter chemotaxis of monocytes to reduce inflammation.4

There is preliminary evidence suggesting isotretinoin may interact with FoxO1, which may explain a substantial number of isotretinoin's unexplained actions.9

TargetActionsOrganism
URetinoic acid receptor alpha
other/unknown
Humans
URetinoic acid receptor gammaNot AvailableHumans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Blackbox Warnings

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Absorption

Patients reach a maximum concentration of 74-511ng/mL after 1-4 hours following a 100mg oral dose.1 Isotretinoin is better absorbed with a high fat meal and bioavailability may change from one brand to another.Label

Following a 40mg oral dose, fasted subjects reached a maximum concentration of 314ng/mL in 2.9 hours with an area under the curve of 4055ng/mL*hr.Label Subjects given a high fat meal and a 40mg oral doses reached a maximum concentration of 395ng/mL in 6.4 hours with an area under the curve of 6095ng/mL*mL.Label

Volume of distribution

The volume of distribution in humans is unknown because there is no intravenous preparation.13 In a study of pediatric patients with neuroblastoma the volume of distribution was found to be 85L.6 The volume of distribution was also found to be 2432mL/kg in guinea pigs and 1716mL/kg in obese rats.5

Protein binding

Isotretinoin is >99.9% protein bound, mainly to serum albumin.Label

Metabolism

Isotretinoin, or 13-cis-retinoic acid can undergo reversible cis-trans isomerization to all-trans-retinoic acid.8 Isotretinoin undergoes 4-hydroxylation to 4-hydroxy-13-cis-retinoic acid, which is oxidized to the main metabolite 4-oxo-13-cis-retinoic acid.8,3. All-trans-retinoic acid undergoes 4-hydroxylation to 4-hydroxy-all-trans-retinoic acid, which is oxidized to 4-oxo-all-trans-retinoic acid.8 4-oxo-13-cis-retinoic acid can undergo reversible cis-trans isomerization to 4-oxo-all-trans-retinoic acid.8

Route of elimination

Isotretinoin and its metabolites are conjugated and excreted in the urine and feces in similar amounts.Label 53-74% of an oral dose is eliminated as unchanged isotretinoin in the feces.1

Half life

The half life ranges from 7-39 hours13 with a mean elimination half life of 20 hours.1 The half life of 4-oxo-13-cis-retinoic acid ranges from 17-50 hours with a mean elimination half life of 25 hours.13

Clearance

The clearance of isotretinoin is 15.9L/h in pediatric patients with neuroblastoma.6 Clearance is also 21.3mL/min/kg in guinea pigs and 7.2mL/min/kg in obese rats.5

Toxicity

Patients experiencing an overdose may present with vomiting, facial flushing, cheilosis, abdominal pain, headache, dizziness, and ataxia.Label These symptoms may rapidly resolve.Label Generally no treatment is required for these overdoses.7

The oral lowest dose causing toxic effect (TDLO) for children is 30mg/kg/21W, oral TDLO for men is 24mg/kg/4W, oral TDLO for women is 56mg/kg/8W.14 The intraperitoneal LD50 for rats is 901mg/kg, oral LD50 for mice is 3389mg/kg, oral LD50 for rats is >4000mg/kg.14

Isotretinoin is associated with major congenital malformations, spontaneous abortion, and premature birth.Label It is unknown if isotretinoin is expressed in breast milk but due to the associated hazards a decision should be made to either stop nursing or stop taking isotretinoin.Label

In animal studies, isotretinoin was associated with an increased risk of pheochromocytoma and adrenal medullary hyperplasia at doses above the recommended clinical dose.Label Isotretinoin was negative for the Ames test of mutagenicity once and weakly positive a second time.Label It has not been shown to be clastogenic.Label A study in dogs noted testicular atrophy after doses of 10-30 times the recommended clinical dose for 30 weeks.Label In trials with men there were no effects seen on sperm count, motility, morphology, ejaculate volume, and seminal plasma fructose.Label

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of Isotretinoin which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Isotretinoin which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Isotretinoin which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Isotretinoin which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Isotretinoin which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Isotretinoin which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Isotretinoin which could result in a higher serum level.
AcipimoxThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Isotretinoin is combined with Acipimox.
AclidiniumAclidinium may decrease the excretion rate of Isotretinoin which could result in a higher serum level.
AcrivastineAcrivastine may decrease the excretion rate of Isotretinoin which could result in a higher serum level.
Additional Data Available
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Food Interactions
  • Avoid alcohol.
  • Take with a full glass of water Do not take supplements containing Vitamin A.
  • Take with high-fat meal to increase absorption.

References

Synthesis Reference

Ashok Kumar, Dharmendra Singh, Ganesh Devidas Mahale, Ragnesh Kumar Rana, Mahesh Kharade, "PROCESS FOR PREPARATION OF HIGHLY PURE ISOTRETINOIN." U.S. Patent US20080207946, issued August 28, 2008.

US20080207946
General References
  1. Khoo KC, Reik D, Colburn WA: Pharmacokinetics of isotretinoin following a single oral dose. J Clin Pharmacol. 1982 Aug-Sep;22(8-9):395-402. [PubMed:6957421]
  2. Miastkowska M, Sikora E, Ogonowski J, Zielina M, Łudzik A: The kinetic study of isotretinoin release from nanoemulsion Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2016 Dec 5;510:63-68.
  3. Vane FM, Bugge CJ: Identification of 4-oxo-13-cis-retinoic acid as the major metabolite of 13-cis-retinoic acid in human blood. Drug Metab Dispos. 1981 Nov-Dec;9(6):515-20. [PubMed:6120808]
  4. Layton A: The use of isotretinoin in acne. Dermatoendocrinol. 2009 May;1(3):162-9. doi: 10.4161/derm.1.3.9364. [PubMed:20436884]
  5. Chien DS, Sandri RB, Tang-Liu DS: Systemic pharmacokinetics of acitretin, etretinate, isotretinoin, and acetylenic retinoids in guinea pigs and obese rats. Drug Metab Dispos. 1992 Mar-Apr;20(2):211-7. [PubMed:1352212]
  6. Veal GJ, Cole M, Errington J, Pearson AD, Foot AB, Whyman G, Boddy AV: Pharmacokinetics and metabolism of 13-cis-retinoic acid (isotretinoin) in children with high-risk neuroblastoma - a study of the United Kingdom Children's Cancer Study Group. Br J Cancer. 2007 Feb 12;96(3):424-31. doi: 10.1038/sj.bjc.6603554. Epub 2007 Jan 16. [PubMed:17224928]
  7. Aubin S, Lorette G, Muller C, Vaillant L: Massive isotretinoin intoxication. Clin Exp Dermatol. 1995 Jul;20(4):348-50. [PubMed:8548998]
  8. Brazzell RK, Colburn WA: Pharmacokinetics of the retinoids isotretinoin and etretinate. A comparative review. J Am Acad Dermatol. 1982 Apr;6(4 Pt 2 Suppl):643-51. [PubMed:6461675]
  9. Melnik BC: Isotretinoin and FoxO1: A scientific hypothesis. Dermatoendocrinol. 2011 Jul;3(3):141-65. doi: 10.4161/derm.3.3.15331. Epub 2011 Jul 1. [PubMed:22110774]
  10. FDA Approved Drug Products: Accutane Oral Capsule [Link]
  11. FDA Approved Drug Products: Absorica [Link]
  12. iPLEDGE Program Home Page [Link]
  13. New Zealand Drug Data Sheet: Oratane [Link]
  14. Isotretinoin MSDS [Link]
External Links
Human Metabolome Database
HMDB0006219
KEGG Drug
D00348
PubChem Compound
5282379
PubChem Substance
46508729
ChemSpider
4445539
BindingDB
50031459
ChEBI
6067
ChEMBL
CHEMBL547
Therapeutic Targets Database
DAP000009
PharmGKB
PA450128
Wikipedia
Isotretinoin
ATC Codes
D10AD04 — IsotretinoinD10AD54 — Isotretinoin, combinationsD10BA01 — Isotretinoin
AHFS Codes
  • 84:92.00 — Misc. Skin and Mucous Membrane Agents
FDA label
Download (175 KB)
MSDS
Download (37.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentAcute Myelogenous Leukaemia (AML) / Juvenile Myelomonocytic Leukemia / Myelodysplastic Syndrome1
1Active Not RecruitingTreatmentAdult Solid Neoplasm1
1Active Not RecruitingTreatmentRecurrent Neuroblastoma / Refractory Neuroblastoma / Stage 4 Neuroblastoma1
1CompletedNot AvailableSkin Infections (Acne)1
1CompletedTreatmentAcne1
1CompletedTreatmentAdult Grade III Lymphomatoid Granulomatosis / Anaplastic Large Cell Lymphoma / Angioimmunoblastic T-Cell Lymphoma / Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Intraocular Lymphoma / Nodal marginal zone B-cell lymphomas / Primary Central Nervous System Non-Hodgkin Lymphoma / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Adult Diffuse Small Cleaved Cell Lymphoma / Recurrent Adult Grade III Lymphomatoid Granulomatosis / Recurrent Adult Hodgkin's Lymphoma / Recurrent Adult Immunoblastic Large Cell Lymphoma / Recurrent Adult Lymphoblastic Lymphoma / Recurrent Adult T-Cell Leukemia/Lymphoma / Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Mycosis Fungoides/Sezary Syndrome / Recurrent Small Lymphocytic Lymphoma / Small Intestine Lymphoma / Splenic Marginal Zone Lymphoma / Stage IV Adult Burkitt Lymphoma / Stage IV Adult Diffuse Large Cell Lymphoma / Stage IV Adult Diffuse Mixed Cell Lymphoma / Stage IV Adult Diffuse Small Cleaved Cell Lymphoma / Stage IV Adult Hodgkin Lymphoma / Stage IV Adult Immunoblastic Large Cell Lymphoma / Stage IV Adult Lymphoblastic Lymphoma / Stage IV Adult T-Cell Leukemia/Lymphoma / Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage IV Grade 1 Follicular Lymphoma / Stage IV Grade 2 Follicular Lymphoma / Stage IV Grade 3 Follicular Lymphoma / Stage IV Mantle Cell Lymphoma / Stage IV Marginal Zone Lymphoma / Stage IV Mycosis Fungoides/Sezary Syndrome / Stage IV Small Lymphocytic Lymphoma / Unspecified Adult Solid Tumor, Protocol Specific / Waldenström's Macroglobulinemia (WM)1
1CompletedTreatmentAnus Neoplasms / Human Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentChildhood Acute Promyelocytic Leukemia (M3) / Childhood Atypical Teratoid/Rhabdoid Tumor / Childhood Burkitt Lymphoma / Childhood Chronic Myelogenous Leukemia / Childhood Diffuse Large Cell Lymphoma / Childhood Immunoblastic Large Cell Lymphoma / Juvenile Myelomonocytic Leukemia / Recurrent Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood Acute Myeloid Leukemia / Recurrent Childhood Grade III Lymphomatoid Granulomatosis / Recurrent Childhood Large Cell Lymphoma / Recurrent Childhood Lymphoblastic Lymphoma / Recurrent Childhood Medulloblastoma / Recurrent Childhood Small Noncleaved Cell Lymphoma / Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor / Recurrent Neuroblastoma / Recurrent/Refractory Childhood Hodgkin Lymphoma / Relapsing Chronic Myelogenous Leukemia / Unspecified Childhood Solid Tumor, Protocol Specific1
1CompletedTreatmentDisseminated Neuroblastoma / Recurrent Neuroblastoma / Regional Neuroblastoma1
1CompletedTreatmentEpidermolysis Bullosa1
1CompletedTreatmentHealthy Volunteers5
1CompletedTreatmentLocalized Unresectable Neuroblastoma / Recurrent Neuroblastoma / Regional Neuroblastoma / Stage 4 Neuroblastoma / Stage 4S Neuroblastoma1
1CompletedTreatmentNeuroblastomas1
1RecruitingTreatmentTumors, Solid1
1TerminatedTreatmentAdult Anaplastic Astrocytoma / Adult Anaplastic Oligodendroglioma / Adult Diffuse Astrocytoma / Adult Giant Cell Glioblastoma / Adult Glioblastoma / Adult Gliosarcoma / Adult Mixed Glioma / Adult Oligodendroglioma / Recurrent Adult Brain Tumor1
1TerminatedTreatmentNeuroblastomas1
1WithdrawnTreatmentNeuroblastomas1
1, 2Active Not RecruitingTreatmentAnaplastic Gliomas / Glioblastoma Multiforme (GBM)1
1, 2CompletedTreatmentChronic Myeloproliferative Disorders / Leukemias / Myelodysplastic Syndromes / Thrombocytopenias1
1, 2CompletedTreatmentNeuroblastomas1
1, 2CompletedTreatmentRenal Cancers1
1, 2Not Yet RecruitingOtherNeuroblastomas1
1, 2TerminatedTreatmentAlzheimer's Disease (AD)1
1, 2TerminatedTreatmentLeukemias1
1, 2TerminatedTreatmentRenal Cell Cancer, Recurrent / Stage III Renal Cell Cancer / Stage IV Renal Cell Cancer1
1, 2Unknown StatusTreatmentNeuroblastomas1
2Active Not RecruitingTreatmentEffects of Immunotherapy / Neoplasm, Residual / Neuroblastomas1
2Active Not RecruitingTreatmentKlinefelter's Syndrome / Male Infertility / Y-chromosome Microdeletions1
2Active Not RecruitingTreatmentNeuroblastomas1
2CompletedPreventionActinic Keratosis (AK)1
2CompletedPreventionLung Cancers / Therapeutic Agent Toxicity1
2CompletedTreatmentBrain and Central Nervous System Tumors1
2CompletedTreatmentCervical Cancers / Esophageal Cancers / Head and Neck Carcinoma / Lung Cancers / Non-Melanomatous Skin Cancer / Penile Cancer1
2CompletedTreatmentCollapsing Glomerulopathy / Glomerulosclerosis, Focal Segmental1
2CompletedTreatmentEpidermal p53 Expression / Solar Elastosis1
2CompletedTreatmentInfection, Human Immunodeficiency Virus I1
2CompletedTreatmentJuvenile Myelomonocytic Leukemia1
2CompletedTreatmentLung Cancers1
2CompletedTreatmentMultiple Myeloma and Plasma Cell Neoplasm1
2CompletedTreatmentMycosis Fungoides (MF) / Neoplasms, Hematologic / T-Cell Lymphomas1
2CompletedTreatmentNeuroblastomas5
2CompletedTreatmentProstate Cancer1
2CompletedTreatmentRecurrent Neuroblastoma1
2Not Yet RecruitingTreatmentTinea infections1
2RecruitingTreatmentGanglioneuroblastoma / High-Risk Neuroblastoma / NMYC Gene Amplification1
2RecruitingTreatmentMale Infertility, Azoospermia1
2RecruitingTreatmentNeuroblastomas2
2RecruitingTreatmentNewly Diagnosed High Risk Neuroblastoma1
2TerminatedTreatmentCervical Cancers1
2TerminatedTreatmentNeuroblastomas2
2TerminatedTreatmentProstate Cancer1
2TerminatedTreatmentRefractory, primary Neuroblastoma1
2Unknown StatusTreatmentLeukemias1
2Unknown StatusTreatmentPhotodamage / Solar Elastosis1
3CompletedTreatmentAcne1
3CompletedTreatmentCervix, Dysplasia / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentDisseminated Neuroblastoma / Localized Resectable Neuroblastoma / Localized Unresectable Neuroblastoma / Regional Neuroblastoma / Stage 4 Neuroblastoma / Stage 4S Neuroblastoma1
3CompletedTreatmentHead and Neck Carcinoma1
3CompletedTreatmentLocalized Resectable Neuroblastoma / Localized Unresectable Neuroblastoma / Recurrent Neuroblastoma / Regional Neuroblastoma / Stage 4 Neuroblastoma / Stage 4S Neuroblastoma2
3CompletedTreatmentNeoplasms, Brain / Tumors, Central Nervous System1
3CompletedTreatmentNeuroblastomas2
3CompletedTreatmentPapulopustular Rosacea (PPR)1
3CompletedTreatmentRenal Cancers1
3CompletedTreatmentSevere Nodular Acne1
3RecruitingTreatmentChildhood Ganglioneuroblastoma / Childhood Neuroblastoma / INRG Stage L2 / INRG Stage M / INRG Stage MS / NMYC Gene Amplification / Recurrent Neuroblastoma1
3SuspendedTreatmentAnaplastic Medulloblastoma / Medulloblastomas / Untreated Childhood Medulloblastoma / Untreated Childhood Pineoblastoma / Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor1
3Unknown StatusTreatmentNeuroblastomas2
3WithdrawnPreventionLung Cancers1
3WithdrawnTreatmentBrain and Central Nervous System Tumors1
4Active Not RecruitingTreatmentAcne1
4CompletedBasic ScienceAdverse Effects of Medical Drugs1
4CompletedPreventionVitreoretinopathy, Proliferative1
4CompletedTreatmentAcne Vulgaris1
4RecruitingBasic ScienceAcne Vulgaris1
4RecruitingOtherCYP2D6 Polymorphism1
4Unknown StatusTreatmentQuality of Life / Seborrheic Dermatitis1
Not AvailableActive Not RecruitingTreatmentMedulloblastomas / Pinealoblastoma / Supratentorial Embryonal Tumor, Not Otherwise Specified / Untreated Childhood Medulloblastoma / Untreated Childhood Pineoblastoma / Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor1
Not AvailableCompletedNot AvailableAcne1
Not AvailableCompletedPreventionMelanoma (Skin) / Non-Melanomatous Skin Cancer1
Not AvailableCompletedTreatmentAcne Scars - Mixed Atrophic and Hypertrophic1
Not AvailableCompletedTreatmentDisseminated Neuroblastoma / Ganglioneuroblastoma / Localized Resectable Neuroblastoma / Localized Unresectable Neuroblastoma / Regional Neuroblastoma / Stage 4S Neuroblastoma1
Not AvailableCompletedTreatmentNeuroblastomas1
Not AvailableRecruitingTreatmentNeuroblastomas2
Not AvailableRecruitingTreatmentToxic Epidermal Necrolysis1
Not AvailableUnknown StatusTreatmentNeuroblastomas1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Barr Pharmaceuticals
  • Catalent Pharma Solutions
  • F Hoffmann-La Roche Ltd.
  • Mylan
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Ranbaxy Laboratories
Dosage forms
FormRouteStrength
CapsuleOral25 mg/1
CapsuleOral35 mg/1
Capsule, liquid filledOral10 mg/1
Capsule, liquid filledOral40 mg/1
CapsuleOral10 mg
CapsuleOral40 mg
CapsuleOral10 mg/1
CapsuleOral20 mg/1
CapsuleOral40 mg/1
CapsuleOral30 mg/1
Capsule, liquid filledOral30 mg/1
CapsuleOral20 mg
CapsuleOral30 mg
GelTopical0.05 %
Capsule, gelatin coatedOral10 mg/1
Capsule, gelatin coatedOral30 mg/1
Capsule, gelatin coatedOral40 mg/1
Capsule, liquid filledOral20 mg/1
Capsule, gelatin coatedOral20 mg/1
Prices
Unit descriptionCostUnit
Accutane 20 mg capsule23.77USD capsule
Amnesteem 40 mg capsule22.6USD capsule
Claravis 40 mg capsule22.6USD capsule
Amnesteem 20 mg capsule19.45USD capsule
Claravis 20 mg capsule18.7USD capsule
Claravis 30 mg capsule16.45USD capsule
Amnesteem 10 mg capsule16.4USD capsule
Claravis 10 mg capsule15.77USD capsule
Accutane 40 mg capsule14.88USD capsule
Accutane 10 mg capsule10.55USD capsule
Sotret 40 mg capsule10.08USD capsule
Sotret 20 mg capsule8.67USD capsule
Sotret 30 mg capsule8.44USD capsule
Sotret 10 mg capsule7.31USD capsule
Clarus 40 mg Capsule2.14USD capsule
Clarus 10 mg Capsule1.05USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8367102No2013-02-052021-09-21Us
US9089534No2015-07-282021-09-21Us
US7435427No2008-10-142021-09-21Us
US9078925No2015-07-142021-09-21Us
US8952064No2015-02-102021-09-21Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)189-190MSDS
boiling point (°C)462.8http://www.chemspider.com/Chemical-Structure.4445539.html
water solubility0.00477mg/mLhttps://www.sciencedirect.com/science/article/pii/S0927775716305817
logP5.66https://www.sciencedirect.com/science/article/pii/S0927775716305817
pKa~4https://www.rochecanada.com/content/dam/rochexx/roche-ca/products/ConsumerInformation/MonographsandPublicAdvisories/Accutane/Accutane_PM_E.pdf
Predicted Properties
PropertyValueSource
Water Solubility0.00477 mg/mLALOGPS
logP5.66ALOGPS
logP5.01ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)5ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity97.79 m3·mol-1ChemAxon
Polarizability36.15 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9925
Blood Brain Barrier+0.9311
Caco-2 permeable+0.7603
P-glycoprotein substrateNon-substrate0.6144
P-glycoprotein inhibitor INon-inhibitor0.8912
P-glycoprotein inhibitor IINon-inhibitor0.8088
Renal organic cation transporterNon-inhibitor0.8639
CYP450 2C9 substrateNon-substrate0.8221
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateSubstrate0.6025
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.8831
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9301
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9252
Ames testNon AMES toxic0.8944
CarcinogenicityNon-carcinogens0.7081
BiodegradationReady biodegradable0.5554
Rat acute toxicity2.1455 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9562
hERG inhibition (predictor II)Non-inhibitor0.9538
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
MS/MS Spectrum - Quattro_QQQ 10V, PositiveLC-MS/MSsplash10-0udi-0009000000-12dbd83959268dee6dbf
MS/MS Spectrum - Quattro_QQQ 25V, PositiveLC-MS/MSsplash10-066r-4900000000-31c9262cbbf0bad5b738
MS/MS Spectrum - Quattro_QQQ 40V, PositiveLC-MS/MSsplash10-0fsl-9600000000-c6681587f0a9ae7a712e
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
1H NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as retinoids. These are oxygenated derivatives of 3,7-dimethyl-1-(2,6,6-trimethylcyclohex-1-enyl)nona-1,3,5,7-tetraene and derivatives thereof.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Prenol lipids
Sub Class
Retinoids
Direct Parent
Retinoids
Alternative Parents
Diterpenoids / Medium-chain fatty acids / Methyl-branched fatty acids / Unsaturated fatty acids / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Retinoic acid / Diterpenoid / Retinoid skeleton / Medium-chain fatty acid / Branched fatty acid / Methyl-branched fatty acid / Fatty acyl / Unsaturated fatty acid / Fatty acid / Monocarboxylic acid or derivatives
Molecular Framework
Aliphatic homomonocyclic compounds
External Descriptors
retinoic acid (CHEBI:6067) / Retinoids (LMPR01090021)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Other/unknown
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RARA
Uniprot ID
P10276
Uniprot Name
Retinoic acid receptor alpha
Molecular Weight
50770.805 Da
References
  1. Dahl AR, Grossi IM, Houchens DP, Scovell LJ, Placke ME, Imondi AR, Stoner GD, De Luca LM, Wang D, Mulshine JL: Inhaled isotretinoin (13-cis retinoic acid) is an effective lung cancer chemopreventive agent in A/J mice at low doses: a pilot study. Clin Cancer Res. 2000 Aug;6(8):3015-24. [PubMed:10955779]
  2. Zouboulis CC: Isotretinoin revisited: pluripotent effects on human sebaceous gland cells. J Invest Dermatol. 2006 Oct;126(10):2154-6. [PubMed:16983322]
  3. Vu-Dac N, Gervois P, Torra IP, Fruchart JC, Kosykh V, Kooistra T, Princen HM, Dallongeville J, Staels B: Retinoids increase human apo C-III expression at the transcriptional level via the retinoid X receptor. Contribution to the hypertriglyceridemic action of retinoids. J Clin Invest. 1998 Aug 1;102(3):625-32. [PubMed:9691099]
  4. Taylor LE, Bennett GD, Finnell RH: Altered gene expression in murine branchial arches following in utero exposure to retinoic acid. J Craniofac Genet Dev Biol. 1995 Jan-Mar;15(1):13-25. [PubMed:7601910]
  5. Shroot B, Michel S: Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103. [PubMed:9204085]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RARG
Uniprot ID
P13631
Uniprot Name
Retinoic acid receptor gamma
Molecular Weight
50341.405 Da
References
  1. Layton A: The use of isotretinoin in acne. Dermatoendocrinol. 2009 May;1(3):162-9. doi: 10.4161/derm.1.3.9364. [PubMed:20436884]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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
  1. Hendrix CW, Jackson KA, Whitmore E, Guidos A, Kretzer R, Liss CM, Shah LP, Khoo KC, McLane J, Trapnell CB: The effect of isotretinoin on the pharmacokinetics and pharmacodynamics of ethinyl estradiol and norethindrone. Clin Pharmacol Ther. 2004 May;75(5):464-75. doi: 10.1016/j.clpt.2004.01.003. [PubMed:15116059]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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
  1. Layton A: The use of isotretinoin in acne. Dermatoendocrinol. 2009 May;1(3):162-9. doi: 10.4161/derm.1.3.9364. [PubMed:20436884]
  2. Tsukada M, Schroder M, Seltmann H, Orfanos CE, Zouboulis CC: High albumin levels restrict the kinetics of 13-cis retinoic acid uptake and intracellular isomerization to all-trans retinoic acid and inhibit its anti-proliferative effect on SZ95 sebocytes. J Invest Dermatol. 2002 Jul;119(1):182-5. doi: 10.1046/j.1523-1747.2002.01816.x. [PubMed:12164942]

Drug created on June 13, 2005 07:24 / Updated on May 23, 2019 16:49