Details of the Drug

General Information of Drug (ID: DM4QTBN)

Drug Name

Isotretinoin

Synonyms

Accutane; Amnesteem; Claravis; Isotane; Isotretinoine; Isotretinoino; Isotretinoinum; Isotrex; Roaccutan; Roaccutane; Roacutan; Sotret; Teriosal; Neovitamin A acid; R 3255; Ro 4 3780; Ro 43780; Accutane (TN); Amnesteem (TN); BML2-E07; CIP-Isotretinoin; Claravi (TN); Clarus (TN); Decutan (TN); Isotane (TN); Isotretinoin (USP); Isotretinoin Zinc Salt, 13 cis Isomer; Isotretinoine [INN-French]; Isotretinoino [INN-Spanish]; Isotretinoinum [INN-Latin]; Izotek (TN); Oratane (TN); Ro 4-3780; Ro-43780; Roaccutane (TN); Sotret (TN); Isotretinoin [USAN:INN:BAN]; Ro-4-3780; Isotretinoin Zinc Salt, 13-cis-Isomer; (2Z,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoic acid; (2Z,4E6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid; (7E,9E,11E,13Z)-retinoic acid; 13-RA; 13-cis RA; 13-cis-Vitamin A acid; 3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)2-cis-4-trans-6-trans-8-trans-nonatetraenoic acid

Indication

Disease Entry	ICD 11	Status	REF
Acne vulgaris	ED80	Approved	[1]
Mycosis fungoides	2B01	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[3]
Neuroblastoma	2D11.2	Investigative	[2]
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Therapeutic Class

Antiacne Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

300.4

Logarithm of the Partition Coefficient (xlogp)

6.3

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [4]
Elimination: 0.5% of drug is excreted from urine in the unchanged form [4]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 6.65679 micromolar/kg/day [5]

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Lipids abnormal	Not Available	LDLR	OTEZ79V2	[6]
Lipids abnormal	Not Available	HDLBP	OTKDEEYX	[6]
Low density lipoprotein increased	Not Available	APOB	OTH0UOCZ	[6]
Low density lipoprotein increased	Not Available	PIP1-2	OTN8LSSF	[6]
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Chemical Identifiers

Formula: C20H28O2
IUPAC Name: (2Z,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoic acid
Canonical SMILES: CC1=C(C(CCC1)(C)C)/C=C/C(=C/C=C/C(=C\\C(=O)O)/C)/C
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-
InChIKey: SHGAZHPCJJPHSC-XFYACQKRSA-N

Cross-matching ID

PubChem CID: 5282379
ChEBI ID: CHEBI:6067
CAS Number: 4759-48-2
DrugBank ID: DB00982
TTD ID: D00DKK
INTEDE ID: DR0890
ACDINA ID: D00335

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Retinoic acid receptor (RAR)	TTOD7B3	NOUNIPROTAC	Agonist	[7]
COVID-19 papain-like proteinase (PL-PRO)	TTNHMO8	R1AB_SARS2 (819-2763)	Inhibitor	[3]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[8]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
1,4-alpha-glucan-branching enzyme (GBE1)	OTK2N05B	GLGB_HUMAN	Gene/Protein Processing	[9]
1-acyl-sn-glycerol-3-phosphate acyltransferase gamma (AGPAT3)	OTAUR5TG	PLCC_HUMAN	Gene/Protein Processing	[9]
1-acylglycerol-3-phosphate O-acyltransferase ABHD5 (ABHD5)	OTY829Z3	ABHD5_HUMAN	Gene/Protein Processing	[9]
1-acylglycerol-3-phosphate O-acyltransferase PNPLA3 (PNPLA3)	OTR4990X	PLPL3_HUMAN	Gene/Protein Processing	[9]
11-beta-hydroxysteroid dehydrogenase 1 (HSD11B1)	OTO7FJA9	DHI1_HUMAN	Gene/Protein Processing	[10]
2'-5'-oligoadenylate synthase 1 (OAS1)	OT8ZLOCY	OAS1_HUMAN	Gene/Protein Processing	[9]
2-Hydroxyacid oxidase 2 (HAO2)	OTDWSQ0L	HAOX2_HUMAN	Gene/Protein Processing	[9]
2-oxoisovalerate dehydrogenase subunit beta, mitochondrial (BCKDHB)	OT8OSVYU	ODBB_HUMAN	Gene/Protein Processing	[9]
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1)	OTNAZVKB	3BHS1_HUMAN	Gene/Protein Processing	[9]
3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase (EBP)	OTSMGKXQ	EBP_HUMAN	Gene/Protein Processing	[9]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Isotretinoin

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Sarecycline	DMLZNIQ	Major	Increased risk of pseudotumor cerebri by the combination of Isotretinoin and Sarecycline .	Acne vulgaris [ED80]	[11]
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Coadministration of a Drug Treating the Disease Different from Isotretinoin (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Isotretinoin and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[12]
Arn-509	DMT81LZ	Moderate	Increased metabolism of Isotretinoin caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[13]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Isotretinoin and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[14]
Omadacycline	DMR2J95	Major	Increased risk of pseudotumor cerebri by the combination of Isotretinoin and Omadacycline.	Bacterial infection [1A00-1C4Z]	[11]
Minocycline	DMVN5OH	Major	Increased risk of pseudotumor cerebri by the combination of Isotretinoin and Minocycline.	Bacterial infection [1A00-1C4Z]	[11]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Isotretinoin and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[15]
Alpelisib	DMEXMYK	Moderate	Increased metabolism of Isotretinoin caused by Alpelisib mediated induction of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[16]
Lumacaftor	DMCLWDJ	Moderate	Increased metabolism of Isotretinoin caused by Lumacaftor mediated induction of CYP450 enzyme.	Cystic fibrosis [CA25]	[17]
Ivacaftor	DMZC1HS	Moderate	Decreased metabolism of Isotretinoin caused by Ivacaftor mediated inhibition of CYP450 enzyme.	Cystic fibrosis [CA25]	[18]
MK-8228	DMOB58Q	Moderate	Decreased metabolism of Isotretinoin caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[19]
Cenobamate	DM8KLU9	Moderate	Increased metabolism of Isotretinoin caused by Cenobamate mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[20]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Isotretinoin and Cannabidiol.	Epileptic encephalopathy [8A62]	[13]
Ripretinib	DM958QB	Moderate	Decreased metabolism of Isotretinoin caused by Ripretinib mediated inhibition of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[12]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Isotretinoin and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[21]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Isotretinoin and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[22]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Isotretinoin and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[23]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Isotretinoin and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[24]
TP-434	DM5A31S	Major	Increased risk of pseudotumor cerebri by the combination of Isotretinoin and TP-434.	Infectious gastroenteritis/colitis [1A40]	[11]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Isotretinoin caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[25]
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of Isotretinoin caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[13]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Isotretinoin and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[26]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Isotretinoin and Idelalisib.	Mature B-cell leukaemia [2A82]	[27]
Vemurafenib	DM62UG5	Moderate	Decreased metabolism of Isotretinoin caused by Vemurafenib mediated inhibition of CYP450 enzyme.	Melanoma [2C30]	[12]
Dabrafenib	DMX6OE3	Moderate	Increased metabolism of Isotretinoin caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[13]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of Isotretinoin caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[28]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Isotretinoin caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[29]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Isotretinoin caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[30]
ABIRATERONE	DM8V75C	Moderate	Decreased metabolism of Isotretinoin caused by ABIRATERONE mediated inhibition of CYP450 enzyme.	Prostate cancer [2C82]	[23]
Enzalutamide	DMGL19D	Moderate	Increased metabolism of Isotretinoin caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[31]
Leflunomide	DMR8ONJ	Major	Increased risk of hepatotoxicity by the combination of Isotretinoin and Leflunomide.	Rheumatoid arthritis [FA20]	[23]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Isotretinoin caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[13]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Isotretinoin and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[13]
Pitolisant	DM8RFNJ	Moderate	Increased metabolism of Isotretinoin caused by Pitolisant mediated induction of CYP450 enzyme.	Somnolence [MG42]	[13]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Isotretinoin caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[32]
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⏷ Show the Full List of 34 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Allura red AC dye	E00338	33258	Colorant
Alpha-tocopherol	E00243	14985	Antimicrobial preservative; Antioxidant
D&C red no. 27	E00381	83511	Colorant
D&C red no. 30	E00456	3000709	Colorant
DL-alpha-tocopherol	E00052	2116	Antioxidant
FD&C blue no. 1	E00263	19700	Colorant
FD&C blue no. 2	E00446	2723854	Colorant
Hydrazine yellow	E00409	164825	Colorant
Isopropyl alcohol	E00070	3776	Antimicrobial preservative; Solvent
methylparaben	E00149	7456	Antimicrobial preservative
Propyl 4-hydroxybenzoate	E00141	7175	Antimicrobial preservative
Propyl gallate	E00075	4947	Antimicrobial preservative; Antioxidant
Quinoline yellow WS	E00309	24671	Colorant
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Sunset yellow FCF	E00255	17730	Colorant
Ammonia	E00007	222	Alkalizing agent
Butyl alcohol	E00011	263	Flavoring agent; Solvent
Butylhydroxyanisole	E00308	24667	Antimicrobial preservative; Antioxidant
Edetate disodium	E00186	8759	Complexing agent
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Glycerin	E00026	753	Antimicrobial preservative; Emollient; Flavoring agent; Humectant; Lubricant; Plasticizing agent; Solvent; Suppository base; Tonicity agent; Viscosity-controlling agent
Hexahydric alcohol	E00083	5780	Diluent; Flavoring agent; Humectant; Plasticizing agent
Lithol rubin BCA	E00607	135423095	Colorant
Medium-chain triglyceride	E00640	Not Available	Emollient; Lubricant; Surfactant
Polysorbate 80	E00665	Not Available	Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Potassium hydroxide	E00233	14797	Alkalizing agent
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Sodium hydroxide	E00234	14798	Alkalizing agent
Sorbitan monooleate	E00503	9920342	Dispersing agent; Emulsifying agent; Solubilizing agent; Surfactant; Suspending agent; Vaccine adjuvant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
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⏷ Show the Full List of 33 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Isotretinoin 40 mg capsule	40 mg	Oral Capsule	Oral
Isotretinoin 25 mg capsule	25 mg	Oral Capsule	Oral
Isotretinoin 10 mg capsule	10 mg	Oral Capsule	Oral
Isotretinoin 30 mg capsule	30 mg	Oral Capsule	Oral
Isotretinoin 20 mg capsule	20 mg	Oral Capsule	Oral
Isotretinoin 35 mg capsule	35 mg	Oral Capsule	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7600).
2	Isotretinoin FDA Label
3	ClinicalTrials.gov (NCT04361422) Isotretinoin in Treatment of COVID-19. U.S. National Institutes of Health.
4	BDDCS applied to over 900 drugs
5	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6	ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
7	Retinoid agonist isotretinoin ameliorates obstructive renal injury. J Urol. 2003 Oct;170(4 Pt 1):1398-402.
8	The effect of isotretinoin on the pharmacokinetics and pharmacodynamics of ethinyl estradiol and norethindrone. Clin Pharmacol Ther. 2004 May;75(5):464-75.
9	Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
10	Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005 Jul;125(1):143-53.
11	Gardner K, Cox T, Digre KB "Idiopathic intracranial hypertension associated with tetracycline use in fraternal twins: case reports and review." Neurology 45 (1995): 6-10. [PMID: 7824136]
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16	Product Information. Piqray (alpelisib). Novartis Pharmaceuticals, East Hanover, NJ.
17	Cerner Multum, Inc. "Canadian Product Information.".
18	Product Information. Kalydeco (ivacaftor). Vertex Pharmaceuticals, Cambridge, MA.
19	Product Information. Prevymis (letermovir). Merck & Company Inc, Whitehouse Station, NJ.
20	Product Information. Xcopri (cenobamate). SK Life Science, Inc., Paramus, NJ.
21	Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
22	Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
23	Canadian Pharmacists Association.
24	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
25	Product Information. Lorbrena (lorlatinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
26	Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
27	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
28	EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
29	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
30	Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
31	Benoist G, van Oort I, et al "Drug-drug interaction potential in men treated with enzalutamide: Mind the gap." Br J Clin Pharmacol 0 (2017): epub. [PMID: 28881501]
32	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.