Details of the Drug

General Information of Drug (ID: DMTGBAX)

• Drug Name: Pomalidomide
• Synonyms: Actimid (TN); Pomalidomide (Immunomodulator)

Indication

Disease Entry	ICD 11	Status	REF
Systemic sclerosis	4A42	Approved	[1], [2], [3]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 273.24
  Topological Polar Surface Area (xlogp); 0.2
  Rotatable Bond Count (rotbonds); 1
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 5
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 400 mcgh/L [4]
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 75 mcg/L [4]
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 2-3 h [4]
  Clearance: The total body clearance of drug is 7-10 L/h [5]
  Half-life: The concentration or amount of drug in body reduced by one-half in 9.4 hours [6]
  Metabolism: The drug is metabolized via the hepatic [4]
  Vd: The volume of distribution (Vd) of drug is 62 - 138 L [5]
• Chemical Identifiers:
  Formula: C13H11N3O4
  IUPAC Name: 4-amino-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione
  Canonical SMILES: C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)N
  InChI: InChI=1S/C13H11N3O4/c14-7-3-1-2-6-10(7)13(20)16(12(6)19)8-4-5-9(17)15-11(8)18/h1-3,8H,4-5,14H2,(H,15,17,18)
  InChIKey: UVSMNLNDYGZFPF-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 134780
  ChEBI ID: CHEBI:72690
  CAS Number: 19171-19-8
  DrugBank ID: DB08910
  TTD ID: D0A3ZU
  VARIDT ID: DR00151
  INTEDE ID: DR1313
  ACDINA ID: D00540

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Angiogenesis/myeloma cell growth (AMCG)	TTDIBYJ	NOUNIPROTAC	Modulator	[2], [3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[8]
Cytochrome P450 1A2 (CYP1A2) Main DME	DEJGDUW	CP1A2_HUMAN	Substrate	[9]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Pomalidomide (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Arn-509	DMT81LZ	Moderate	Accelerated clearance of Pomalidomide due to the transporter induction by Arn-509.	Acute myeloid leukaemia [2A60]	[35]
Troleandomycin	DMUZNIG	Moderate	Decreased metabolism of Pomalidomide caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[36]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Pomalidomide caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[37]
Tucatinib	DMBESUA	Moderate	Decreased clearance of Pomalidomide due to the transporter inhibition by Tucatinib.	Breast cancer [2C60-2C6Y]	[36]
Lumacaftor	DMCLWDJ	Moderate	Increased metabolism of Pomalidomide caused by Lumacaftor mediated induction of CYP450 enzyme.	Cystic fibrosis [CA25]	[38]
MK-8228	DMOB58Q	Moderate	Decreased metabolism of Pomalidomide caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[39]
Stiripentol	DMMSDOY	Moderate	Decreased metabolism of Pomalidomide caused by Stiripentol mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[40]
Cobicistat	DM6L4H2	Moderate	Decreased metabolism of Pomalidomide caused by Cobicistat mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[36]
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of Pomalidomide caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[41]
Ceritinib	DMB920Z	Moderate	Decreased clearance of Pomalidomide due to the transporter inhibition by Ceritinib.	Lung cancer [2C25]	[36]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Pomalidomide caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[42]
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of Pomalidomide caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[43]
Idelalisib	DM602WT	Moderate	Decreased metabolism of Pomalidomide caused by Idelalisib mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[36]
IPI-145	DMWA24P	Moderate	Decreased metabolism of Pomalidomide caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[44]
Dabrafenib	DMX6OE3	Moderate	Increased metabolism of Pomalidomide caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[45]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Pomalidomide and Siponimod.	Multiple sclerosis [8A40]	[36]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Pomalidomide and Ocrelizumab.	Multiple sclerosis [8A40]	[46]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Pomalidomide and Ozanimod.	Multiple sclerosis [8A40]	[45]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Pomalidomide caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[45]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Pomalidomide caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[47]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Pomalidomide caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[48]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Pomalidomide when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[49]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Pomalidomide caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[45]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Pomalidomide caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[36]
Fostamatinib	DM6AUHV	Moderate	Decreased clearance of Pomalidomide due to the transporter inhibition by Fostamatinib.	Thrombocytopenia [3B64]	[50]

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

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Sodium stearyl fumarate	E00545	23665634	lubricant

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Pomalidomide 1 mg capsule	1 mg	Oral Capsule	Oral
Pomalidomide 2 mg capsule	2 mg	Oral Capsule	Oral
Pomalidomide 3 mg capsule	3 mg	Oral Capsule	Oral
Pomalidomide 4 mg capsule	4 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: 7348).
• [2] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
• [5] An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
• [6] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [7] DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB08910)
• [8] Pomalidomide: evaluation of cytochrome P450 and transporter-mediated drug-drug interaction potential in vitro and in healthy subjects. J Clin Pharmacol. 2015 Feb;55(2):168-78.
• [9] Population pharmacokinetics of pomalidomide. J Clin Pharmacol. 2015 May;55(5):563-72.
• [10] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [11] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [12] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [13] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [14] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [15] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [16] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [17] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [18] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [19] Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
• [20] Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase-mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells. Mol Carcinog. 2004 Jul;40(3):180-8.
• [21] Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
• [22] Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
• [23] PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
• [24] The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
• [25] The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
• [26] Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
• [27] Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.
• [28] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [29] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [30] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [31] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [32] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [33] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [34] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
• [35] Product Information. Pomalyst (pomalidomide). QLT Phototherapeutics Inc, Vancouver, AZ.
• [36] Cerner Multum, Inc. "Australian Product Information.".
• [37] Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
• [38] Patel S, Robinson R, Burk M "Hypertensive crisis associated with St. John's Wort." Am J Med 112 (2002): 507-8. [PMID: 11959071]
• [39] Product Information. Prevymis (letermovir). Merck & Company Inc, Whitehouse Station, NJ.
• [40] EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports.".
• [41] Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
• [42] Product Information. Lorbrena (lorlatinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
• [43] Product Information. Retevmo (selpercatinib). Lilly, Eli and Company, Indianapolis, IN.
• [44] Product Information. Copiktra (duvelisib). Verastem, Inc., Needham, MA.
• [45] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [46] Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
• [47] Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
• [48] Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
• [49] CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]
• [50] Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.