Details of the Drug

General Information of Drug (ID: DMH07Y3)

Drug Name

Letrozole

Synonyms

Femara; Femera; Letoval; Letrozol; Novartis Brand of Letrozole; CGS 20267; CGS-20267; FEM-345; Femara (TN); Letrozole [USAN:INN]; CGS 20267, Femara, Piroxicam, Letrozole; Letrozole (JAN/USP/INN); 1-[Bis-(4-cyanophenyl)methyl]-1,2,4-triazole; 1-[bis(4-cyanophenyl)methyl]-1,2,4-triazole; 4,4'-((1h-1,2,4-triazol-1-yl)methylene)dibenzonitrile; 4,4'-(1H-1,2,4-Triazol-1-ylmethylene)dibenzonitrile; 4,4'-(1H-1,2,4-triazol-1-yl-methylene)-bis(benzonitrile); 4,4'-(1H-1,2,4-triazol-1-ylmethanediyl)dibenzonitrile; 4,4'-(1H-1,2,4-triazol-1-ylmethylene)bis-Benzonitrile Letrozole; 4,4'-(1h-1,2,4-triazol-1-ylmethylene) bis-benzonitrile; 4,4'-(1h-1,2,4-triazol-1-ylmethylene)bis-benzonitrile; 4,4'-(1h-1,2,4-triazol-1-ylmethylene)bisbenzonitrile; 4-[(4-cyanophenyl)-(1,2,4-triazol-1-yl)methyl]benzonitrile

Indication

Disease Entry	ICD 11	Status	REF
Hormonally-responsive breast cancer	2C60-2C65	Approved	[1], [2]

Therapeutic Class

Anticancer Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

285.3

Topological Polar Surface Area (xlogp)

2.7

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 0.104 micromol/L [3]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 8.1 h [3]
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [4]
Bioavailability: The bioavailability of drug is 99.9% [3]
Clearance: The clearance of drug is 1.52 L/h [5]
Elimination: Letrozole is 90% eliminated in the urine [6]
Half-life: The concentration or amount of drug in body reduced by one-half in 42 hours [3]
Metabolism: The drug is metabolized via the CYP2A6 to a ketone analog metabolite and further metabolized by CYP3A4 and CYP2A6 to 4,4'-(hydroxymethylene)dibenzonitrile [7]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.14616 micromolar/kg/day [8]
Unbound Fraction: The unbound fraction of drug in plasma is 0.41% [9]
Vd: The volume of distribution (Vd) of drug is 1.87 L/kg [3]
Water Solubility: The ability of drug to dissolve in water is measured as 0.041 mg/mL [4]

Chemical Identifiers

Formula: C17H11N5
IUPAC Name: 4-[(4-cyanophenyl)-(1,2,4-triazol-1-yl)methyl]benzonitrile
Canonical SMILES: C1=CC(=CC=C1C#N)C(C2=CC=C(C=C2)C#N)N3C=NC=N3
InChI: InChI=1S/C17H11N5/c18-9-13-1-5-15(6-2-13)17(22-12-20-11-21-22)16-7-3-14(10-19)4-8-16/h1-8,11-12,17H
InChIKey: HPJKCIUCZWXJDR-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 3902
ChEBI ID: CHEBI:6413
CAS Number: 112809-51-5
DrugBank ID: DB01006
TTD ID: D0C1WH
INTEDE ID: DR0929
ACDINA ID: D00356

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[10]

------------------------------------------------------------------------------------

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[11]
Cytochrome P450 2A6 (CYP2A6)_{Main DME}	DEJVYAZ	CP2A6_HUMAN	Substrate	[12]
Aromatase (CYP19A1)	DEQX145	CP19A_HUMAN	Substrate	[13]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Letrozole

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Lapatinib	DM3BH1Y	Moderate	Decreased metabolism of Letrozole caused by Lapatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[45]
Tucatinib	DMBESUA	Moderate	Decreased metabolism of Letrozole caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[46]
-----------

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Arn-509	DMT81LZ	Moderate	Increased metabolism of Letrozole caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[47]
Dronedarone	DMA8FS5	Moderate	Decreased metabolism of Letrozole caused by Dronedarone mediated inhibition of CYP450 enzyme.	Angina pectoris [BA40]	[48]
Cilostazol	DMZMSCT	Moderate	Decreased metabolism of Letrozole caused by Cilostazol mediated inhibition of CYP450 enzyme.	Arterial occlusive disease [BD40]	[49]
Ivacaftor	DMZC1HS	Moderate	Decreased metabolism of Letrozole caused by Ivacaftor mediated inhibition of CYP450 enzyme.	Cystic fibrosis [CA25]	[50]
MK-8228	DMOB58Q	Moderate	Decreased metabolism of Letrozole caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[51]
Escitalopram	DMFK9HG	Moderate	Decreased metabolism of Letrozole caused by Escitalopram mediated inhibition of CYP450 enzyme.	Depression [6A70-6A7Z]	[52]
Cenobamate	DMGOVHA	Moderate	Increased metabolism of Letrozole caused by Cenobamate mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[53]
Brivaracetam	DMSEPK8	Minor	Decreased metabolism of Letrozole caused by Brivaracetam mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[47]
Rufinamide	DMWE60C	Moderate	Increased metabolism of Letrozole caused by Rufinamide mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[47]
Phenobarbital	DMXZOCG	Minor	Decreased metabolism of Letrozole caused by Phenobarbital mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[54]
Cannabidiol	DM0659E	Minor	Decreased metabolism of Letrozole caused by Cannabidiol mediated inhibition of CYP450 enzyme.	Epileptic encephalopathy [8A62]	[47]
Boceprevir	DMBSHMF	Moderate	Decreased metabolism of Letrozole caused by Boceprevir mediated inhibition of CYP450 enzyme.	Hepatitis virus infection [1E50-1E51]	[55]
Telaprevir	DMMRV29	Moderate	Decreased metabolism of Letrozole caused by Telaprevir mediated inhibition of CYP450 enzyme.	Hepatitis virus infection [1E50-1E51]	[56]
Rifapentine	DMCHV4I	Moderate	Increased metabolism of Letrozole caused by Rifapentine mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[57]
Etravirine	DMGV8QU	Moderate	Increased metabolism of Letrozole caused by Etravirine mediated induction of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[58]
Darunavir	DMN3GCH	Moderate	Decreased metabolism of Letrozole caused by Darunavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[59]
Pirfenidone	DM6VZFQ	Moderate	Decreased metabolism of Letrozole caused by Pirfenidone mediated inhibition of CYP450 enzyme.	Idiopathic interstitial pneumonitis [CB03]	[47]
Brigatinib	DM7W94S	Moderate	Increased metabolism of Letrozole caused by Brigatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[60]
Ceritinib	DMB920Z	Moderate	Decreased metabolism of Letrozole caused by Ceritinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[61]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Letrozole caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[62]
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of Letrozole caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[47]
Idelalisib	DM602WT	Moderate	Decreased metabolism of Letrozole caused by Idelalisib mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[63]
IPI-145	DMWA24P	Moderate	Decreased metabolism of Letrozole caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[64]
Dabrafenib	DMX6OE3	Moderate	Increased metabolism of Letrozole caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[47]
Exjade	DMHPRWG	Moderate	Decreased metabolism of Letrozole caused by Exjade mediated inhibition of CYP450 enzyme.	Mineral absorption/transport disorder [5C64]	[65]
Flibanserin	DM70DTN	Moderate	Decreased metabolism of Letrozole caused by Flibanserin mediated inhibition of CYP450 enzyme.	Mood disorder [6A60-6E23]	[66]
Thalidomide	DM70BU5	Major	Additive thrombogenic effects by the combination of Letrozole and Thalidomide.	Multiple myeloma [2A83]	[67]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Letrozole caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[47]
Nilotinib	DM7HXWT	Moderate	Decreased metabolism of Letrozole caused by Nilotinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[68]
Dasatinib	DMJV2EK	Moderate	Decreased metabolism of Letrozole caused by Dasatinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[69]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive myelosuppressive effects by the combination of Letrozole and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[70]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of Letrozole caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[71]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Letrozole caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[72]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Letrozole caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[73]
Lonafarnib	DMGM2Z6	Moderate	Decreased metabolism of Letrozole caused by Lonafarnib mediated inhibition of CYP450 enzyme.	Premature ageing appearance [LD2B]	[74]
Enzalutamide	DMGL19D	Moderate	Increased metabolism of Letrozole caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[75]
Temsirolimus	DMS104F	Moderate	Increased plasma concentrations of Letrozole and Temsirolimus due to competitive inhibition of the same metabolic pathway.	Renal cell carcinoma [2C90]	[76]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Letrozole caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[47]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Letrozole caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[61]
Armodafinil	DMGB035	Minor	Increased metabolism of Letrozole caused by Armodafinil mediated induction of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[77]
LEE011	DMMX75K	Moderate	Decreased metabolism of Letrozole caused by LEE011 mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[78]
Pitolisant	DM8RFNJ	Moderate	Increased metabolism of Letrozole caused by Pitolisant mediated induction of CYP450 enzyme.	Somnolence [MG42]	[47]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Letrozole caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[79]
-----------


⏷ Show the Full List of 43 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
D&C red no. 27	E00381	83511	Colorant
FD&C blue no. 2	E00446	2723854	Colorant
Hydrazine yellow	E00409	164825	Colorant
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Sunset yellow FCF	E00255	17730	Colorant
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Carmellose sodium	E00625	Not Available	Disintegrant
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 3350	E00652	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyethylene glycol 400	E00653	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Triacetin	E00080	5541	Humectant; Plasticizing agent; Solvent
Vinylpyrrolidone	E00668	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Water	E00035	962	Solvent
--------------------


⏷ Show the Full List of 25 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Letrozole 2.5 mg tablet	2.5 mg	Oral Tablet	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: 5209).
2	New drugs in development for the treatment of endometriosis. Expert Opin Investig Drugs. 2008 Aug;17(8):1187-202.
3	The discovery and mechanism of action of letrozole. Breast Cancer Res Treat. 2007;105 Suppl 1:7-17. doi: 10.1007/s10549-007-9696-3. Epub 2007 Oct 3.
4	BDDCS applied to over 900 drugs
5	Pfister CU, Martoni A, Zamagni C, Lelli G, De Braud F, Souppart C, Duval M, Hornberger U: Effect of age and single versus multiple dose pharmacokinetics of letrozole (Femara) in breast cancer patients. Biopharm Drug Dispos. 2001 Jul;22(5):191-7. doi: 10.1002/bdd.273.
6	FDA Approved Drug Products: Femara Letrozole Oral Tablets
7	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.
8	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
9	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
10	Aromatase inhibitors--theoretical concept and present experiences in the treatment of endometriosis. Zentralbl Gynakol. 2003 Jul-Aug;125(7-8):247-51.
11	Inhibition of drug metabolizing cytochrome P450s by the aromatase inhibitor drug letrozole and its major oxidative metabolite 4,4'-methanol-bisbenzonitrile in vitro. Cancer Chemother Pharmacol. 2009 Oct;64(5):867-75.
12	Letrozole concentration is associated with CYP2A6 variation but not with arthralgia in patients with breast cancer. Breast Cancer Res Treat. 2018 Nov;172(2):371-379.
13	Double-blind, randomised, multicentre endocrine trial comparing two letrozole doses, in postmenopausal breast cancer patients. Eur J Cancer. 1999 Feb;35(2):208-13.
14	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.
15	Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
16	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.
17	Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
18	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.
19	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.
20	Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
21	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.
22	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.
23	Urinary and serum octopamine in patients with portal-systemic encephalopathy. Lancet. 1975 Nov 15;2(7942):943-6.
24	Bidirectional transfer of methadone across human placenta. Biochem Pharmacol. 2005 Jan 1;69(1):187-97.
25	Aromatization of testosterone and 19-nortestosterone by a single enzyme from equine testicular microsomes. Differences from human placental aromatase. J Steroid Biochem. 1988 Jan;29(1):119-25.
26	N-demethylation of levo-alpha-acetylmethadol by human placental aromatase. Biochem Pharmacol. 2004 Mar 1;67(5):885-92.
27	Loss of aromatase cytochrome P450 function as a risk factor for Parkinson's disease? Brain Res Rev. 2008 Mar;57(2):431-43.
28	Identifying susceptibility genes for prostate cancer--a family-based association study of polymorphisms in CYP17, CYP19, CYP11A1, and LH-beta. Cancer Epidemiol Biomarkers Prev. 2005 Aug;14(8):2035-9.
29	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.
30	Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
31	Genotoxicity of tamoxifen, tamoxifen epoxide and toremifene in human lymphoblastoid cells containing human cytochrome P450s. Carcinogenesis. 1994 Jan;15(1):5-9.
32	Psychotropic drug interactions with valproate. Clin Neuropharmacol. 2005 Mar-Apr;28(2):96-101.
33	The role of human cytochrome P450 enzymes in the formation of 2-hydroxymetronidazole: CYP2A6 is the high affinity (low Km) catalyst. Drug Metab Dispos. 2013 Sep;41(9):1686-94.
34	Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
35	CYP2A6- and CYP2A13-catalyzed metabolism of the nicotine delta-5'(1')iminium ion. J Pharmacol Exp Ther. 2012 Nov;343(2):307-15.
36	Effective aromatase inhibition by anastrozole in a patient with gonadotropin-independent precocious puberty in McCune-Albright syndrome. J Pediatr Endocrinol Metab. 2002;15 Suppl 3:945-8.
37	Aminoglutethimide-induced protein free radical formation on myeloperoxidase: a potential mechanism of agranulocytosis. Chem Res Toxicol. 2007 Jul;20(7):1038-45.
38	Enantioselective nonsteroidal aromatase inhibitors identified through a multidisciplinary medicinal chemistry approach. J Med Chem. 2005 Nov 17;48(23):7282-9.
39	Aromatase inhibitors for male infertility. J Urol. 2002 Feb;167(2 Pt 1):624-9.
40	Toremifene-atamestane; alone or in combination: predictions from the preclinical intratumoral aromatase model. J Steroid Biochem Mol Biol. 2008 Jan;108(1-2):1-7.
41	Pharmacophore modeling strategies for the development of novel nonsteroidal inhibitors of human aromatase (CYP19). Bioorg Med Chem Lett. 2010 May 15;20(10):3050-64.
42	Highly potent first examples of dual aromatase-steroid sulfatase inhibitors based on a biphenyl template. J Med Chem. 2010 Mar 11;53(5):2155-70.
43	Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
44	Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032111)
45	Product Information. Tykerb (lapatinib). Novartis Pharmaceuticals, East Hanover, NJ.
46	Product Information. Tukysa (tucatinib). Seattle Genetics Inc, Bothell, WA.
47	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
48	Product Information. Multaq (dronedarone). sanofi-aventis , Bridgewater, NJ.
49	Hedaya MA, El-Afify DR, El-Maghraby GM "The effect of ciprofloxacin and clarithromycin on sildenafil oral bioavailability in human volunteers." Biopharm Drug Dispos 27 (2006): 103-10. [PMID: 16372380]
50	Product Information. Kalydeco (ivacaftor). Vertex Pharmaceuticals, Cambridge, MA.
51	Product Information. Prevymis (letermovir). Merck & Company Inc, Whitehouse Station, NJ.
52	Canadian Pharmacists Association.
53	Product Information. Xcopri (cenobamate). SK Life Science, Inc., Paramus, NJ.
54	Klotz U "The role of pharmacogenetics in the metabolism of antiepileptic drugs: pharmacokinetic and therapeutic implications." Clin Pharmacokinet 46 (2007): 271-9. [PMID: 17375979]
55	Product Information. Victrelis (boceprevir). Schering-Plough Corporation, Kenilworth, NJ.
56	Product Information. Incivek (telaprevir). Vertex Pharmaceuticals, Cambridge, MA.
57	Product Information. Priftin (rifapentine). Hoechst Marion-Roussel Inc, Kansas City, MO.
58	Product Information. Intelence (etravirine). Ortho Biotech Inc, Bridgewater, NJ.
59	Product Information. Prezista (darunavir). Ortho Biotech Inc, Bridgewater, NJ.
60	Product Information. Alunbrig (brigatinib). Ariad Pharmaceuticals Inc, Cambridge, MA.
61	Cerner Multum, Inc. "Australian Product Information.".
62	Product Information. Lorbrena (lorlatinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
63	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
64	Product Information. Copiktra (duvelisib). Verastem, Inc., Needham, MA.
65	Product Information. Exjade (deferasirox). Novartis Pharmaceuticals, East Hanover, NJ.
66	Product Information. Addyi (flibanserin). Sprout Pharmaceuticals, Raleigh, NC.
67	Bennett CL, Nebeker JR, Samore MH, et al "The Research on Adverse Drug Events and Reports (RADAR) project." JAMA 293 (2005): 2131-40. [PMID: 15870417]
68	Product Information. Tasigna (nilotinib). Novartis Pharmaceuticals, East Hanover, NJ.
69	Product Information. Sprycel (dasatinib). Bristol-Myers Squibb, Princeton, NJ.
70	Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
71	EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
72	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
73	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
74	Product Information. Zokinvy (lonafarnib). Eiger BioPharmaceuticals, Palo Alto, CA.
75	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]
76	Product Information. Prograf (tacrolimus). Fujisawa, Deerfield, IL.
77	Doherty MM, Charman WN "The mucosa of the small intestine: how clinically relevant as an organ of drug metabolism?" Clin Pharmacokinet 41 (2002): 235-53. [PMID: 11978143]
78	DSouza DL, Levasseur LM, Nezamis J, Robbins DK, Simms L, Koch KM "Effect of alosetron on the pharmacokinetics of alprazolam." J Clin Pharmacol 41 (2001): 452-4. [PMID: 11304902]
79	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.