Details of the Drug

General Information of Drug (ID: DMTAJQE)

• Drug Name: Amphotericin B
• Synonyms: ABLC; Abelcet; Abelecet; Ambisome; Amphocin; Amphomoronal; Amphotec; Amphotericin; Amphotericinum; Amphotherizin; Amphozone; Fungilin; Fungisome; Fungisone; Fungizone; Halizon; SinuNase; Amfotericina B; Amophotericin B; Amphortericin B; Amphotericin B Cholesterol Dispersion; Amphotericin B Colloidal Dispersion; Amphotericin B liposomal; Amphotericin BETA; Amphotericine B; Amphotericinum B; Amphotherizin [German]; Liposomal Amphotericin B; NCI527017; NS 718; AMPH-B; Abelcet (TN); AmBisome (TN); Amfotericina B [INN-Spanish]; Ampho-Moronal; Amphocil (TN); Amphotec (TN); Amphotericin-B; Amphotericine B [INN-French]; Amphotericinum B [INN-Latin]; Fungilin (TN); Fungisome (TN); Fungizone (TN); LNS-AmB; Mysteclin-F; NKTR-024; Amphotericin B [USAN:INN:JAN]; Amphotericin B, Lipid-based; Amphotericin B, Streptomyces sp.; Amphotericin B (JP15/USP/INN)

Indication

Disease Entry	ICD 11	Status	REF
Acne vulgaris	ED80	Approved	[1]
Actinomycosis	N.A.	Approved	[1]
Acute gonococcal cervicitis	N.A.	Approved	[1]
Aspergillosis	1F20	Approved	[1]
Blastomycosis	1F22	Approved	[1]
Bronchitis	CA20	Approved	[1]
Brucellosis	N.A.	Approved	[1]
Candidiasis	1F23	Approved	[1]
Coccidioidomycosis	1F25	Approved	[1]
Cryptococcal meningitis	N.A.	Approved	[1]
Cryptococcosis	N.A.	Approved	[1]
Cutaneous candidiasis	1F23.14	Approved	[1]
Disseminated sporotrichosis	N.A.	Approved	[1]
Fungal infection	1F29-1F2F	Approved	[2]
Histoplasmosis	N.A.	Approved	[1]
Invasive candidiasis	1F23	Approved	[1]
Leishmaniasis	1F54	Approved	[1]
Lymphogranuloma venereum	N.A.	Approved	[1]
Mycotic endocarditis	N.A.	Approved	[1]
Oral candidiasis	1F23.0	Approved	[1]
Ornithosis	N.A.	Approved	[1]
Pneumonia	CA40	Approved	[1]
Q fever	N.A.	Approved	[1]
Relapsing fever	N.A.	Approved	[1]
Rickettsialpox	N.A.	Approved	[1]
Rocky mountain spotted fever	N.A.	Approved	[1]
Syphilis	N.A.	Approved	[1]
Trachoma	N.A.	Approved	[1]
Typhus	N.A.	Approved	[1]
Urinary tract infection	GC08	Approved	[1]
Yaws	N.A.	Approved	[1]
Candidemia	1F23.3Y	Investigative	[1]
Esophageal candidiasis	N.A.	Investigative	[1]
Mycoses	1F2Z	Investigative	[3]
Pelvic inflammatory disease	GA05	Investigative	[1]
Sinusitis	CA0A.Z	Investigative	[1]

• Therapeutic Class: Antifungal Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 3:
  Molecular Weight (mw); 924.1
  Logarithm of the Partition Coefficient (xlogp); 0
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 12
  Hydrogen Bond Acceptor Count (hbondacc); 18
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [4]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 0.17 mL/min/kg [5]
  Elimination: 3.5% of drug is excreted from urine in the unchanged form [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 40 hours [5]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 4.32852 micromolar/kg/day [6]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.03% [5]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.62 L/kg [5]
  Water Solubility: The ability of drug to dissolve in water is measured as 0.1 mg/mL [4]

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Cell death	Not Available	DDT	OTF5HTYL	[7]
Cell death	Not Available	MIF?	OTUCMVCX	[7]
Neurotoxicity	Not Available	NFKB1	OTNRRD8I	[7]
Neurotoxicity	Not Available	IL1A	OTPSGILV	[7]

• Chemical Identifiers:
  Formula: C47H73NO17
  IUPAC Name: (1R,3S,5R,6R,9R,11R,15S,16R,17R,18S,19E,21E,23E,25E,27E,29E,31E,33R,35S,36R,37S)-33-[(2R,3S,4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid
  Canonical SMILES: C[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@@H](C[C@H]2[C@@H]([C@H](C[C@](O2)(C[C@H](C[C@H]([C@@H](CC[C@H](C[C@H](CC(=O)O[C@H]([C@@H]([C@@H]1O)C)C)O)O)O)O)O)O)O)C(=O)O)O[C@H]3[C@H]([C@H]([C@@H]([C@H](O3)C)O)N)O
  InChI: InChI=1S/C47H73NO17/c1-27-17-15-13-11-9-7-5-6-8-10-12-14-16-18-34(64-46-44(58)41(48)43(57)30(4)63-46)24-38-40(45(59)60)37(54)26-47(61,65-38)25-33(51)22-36(53)35(52)20-19-31(49)21-32(50)23-39(55)62-29(3)28(2)42(27)56/h5-18,27-38,40-44,46,49-54,56-58,61H,19-26,48H2,1-4H3,(H,59,60)/b6-5+,9-7+,10-8+,13-11+,14-12+,17-15+,18-16+/t27-,28-,29-,30+,31+,32+,33-,34-,35+,36+,37-,38-,40+,41-,42+,43+,44-,46-,47+/m0/s1
  InChIKey: APKFDSVGJQXUKY-INPOYWNPSA-N
• Cross-matching ID:
  PubChem CID: 5280965
  CAS Number: 1397-89-3
  DrugBank ID: DB00681
  TTD ID: D02DWM
  VARIDT ID: DR01468
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fungal Cell membrane ergosterol (Fung CME)	TTQKWA4	NOUNIPROTAC	Modulator	[8]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 (PLCB1)	OT9HYT7A	PLCB1_HUMAN	Gene/Protein Processing	[10]
2-aminomuconic semialdehyde dehydrogenase (ALDH8A1)	OTINY3MW	AL8A1_HUMAN	Gene/Protein Processing	[10]
3',5'-cyclic-AMP phosphodiesterase 4D (PDE4D)	OT1RWFV0	PDE4D_HUMAN	Gene/Protein Processing	[10]
5-hydroxytryptamine receptor 3A (HTR3A)	OTAIV1AK	5HT3A_HUMAN	Gene/Protein Processing	[10]
A disintegrin and metalloproteinase with thrombospondin motifs 12 (ADAMTS12)	OTG7HEA2	ATS12_HUMAN	Gene/Protein Processing	[10]
Acrosomal protein SP-10 (ACRV1)	OTUTG7PL	ASPX_HUMAN	Gene/Protein Processing	[10]
Adenosine receptor A3 (ADORA3)	OTHO1BLK	AA3R_HUMAN	Gene/Protein Processing	[10]
Adenylate cyclase type 2 (ADCY2)	OTYCBR8I	ADCY2_HUMAN	Gene/Protein Processing	[10]
ALK tyrosine kinase receptor (ALK)	OTV3P4V8	ALK_HUMAN	Gene/Protein Processing	[10]
Alpha-2A adrenergic receptor (ADRA2A)	OTZFGOTP	ADA2A_HUMAN	Gene/Protein Processing	[10]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Amphotericin B

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Pentamidine	DMHZJCG	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Pentamidine.	Fungal infection [1F29-1F2F]	[11]

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Decreased renal excretion of Amphotericin B caused by Remdesivir mediated nephrotoxicity.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[12]
Uracil mustard	DMHL7OB	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Uracil mustard.	Acute myeloid leukaemia [2A60]	[12]
Framycetin	DMF8DNE	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Framycetin.	Alcoholic liver disease [DB94]	[13]
Inotersen	DMJ93CT	Major	Increased risk of nephrotoxicity by the combination of Amphotericin B and Inotersen.	Amyloidosis [5D00]	[14]
Dronedarone	DMA8FS5	Major	Increased risk of ventricular arrhythmias by the combination of Amphotericin B and Dronedarone.	Angina pectoris [BA40]	[15]
Kanamycin	DM2DMPO	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Kanamycin.	Bacterial infection [1A00-1C4Z]	[13]
Streptomycin	DME1LQN	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Streptomycin.	Bacterial infection [1A00-1C4Z]	[13]
Gentamicin	DMKINJO	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Gentamicin.	Bacterial infection [1A00-1C4Z]	[13]
Rabeprazole	DMMZXIW	Moderate	Increased risk of hypomagnesemia by the combination of Amphotericin B and Rabeprazole.	Bacterial infection [1A00-1C4Z]	[16]
Netilmicin	DMRD1QK	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Netilmicin.	Bacterial infection [1A00-1C4Z]	[13]
Tobramycin	DMUI0CH	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Tobramycin.	Bacterial infection [1A00-1C4Z]	[13]
Etidronic acid	DM1XHYJ	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Etidronic acid.	Bone paget disease [FB85]	[17]
Iodipamide	DMXIQYS	Major	Increased risk of nephrotoxicity by the combination of Amphotericin B and Iodipamide.	Cholelithiasis [DC11]	[18]
Atracurium	DM42HXN	Moderate	Additive neuromuscular blocking effects by the combination of Amphotericin B and Atracurium.	Corneal disease [9A76-9A78]	[19]
Mivacurium	DM473VD	Moderate	Additive neuromuscular blocking effects by the combination of Amphotericin B and Mivacurium.	Corneal disease [9A76-9A78]	[19]
Pancuronium	DMB0VY8	Moderate	Additive neuromuscular blocking effects by the combination of Amphotericin B and Pancuronium.	Corneal disease [9A76-9A78]	[19]
Tubocurarine	DMBZIVP	Moderate	Additive neuromuscular blocking effects by the combination of Amphotericin B and Tubocurarine.	Corneal disease [9A76-9A78]	[19]
Methoxyflurane	DML0RAE	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Methoxyflurane.	Corneal disease [9A76-9A78]	[14]
Dexlansoprazole	DM1DBV5	Moderate	Increased risk of hypomagnesemia by the combination of Amphotericin B and Dexlansoprazole.	Gastro-oesophageal reflux disease [DA22]	[16]
Givosiran	DM5PFIJ	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Givosiran.	Inborn porphyrin/heme metabolism error [5C58]	[12]
Balsalazide	DM7I1T9	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Balsalazide.	Indeterminate colitis [DD72]	[20]
Ibandronate	DM0QZBN	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Ibandronate.	Low bone mass disorder [FB83]	[21]
Arsenic trioxide	DM61TA4	Major	Increased risk of ventricular arrhythmias by the combination of Amphotericin B and Arsenic trioxide.	Mature B-cell lymphoma [2A85]	[22]
Exjade	DMHPRWG	Major	Increased risk of nephrotoxicity by the combination of Amphotericin B and Exjade.	Mineral absorption/transport disorder [5C64]	[23]
Melphalan	DMOLNHF	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Melphalan.	Multiple myeloma [2A83]	[12]
Levomethadyl Acetate	DM06HG5	Major	Increased risk of ventricular arrhythmias by the combination of Amphotericin B and Levomethadyl Acetate.	Opioid use disorder [6C43]	[24]
Esomeprazole	DM7BN0X	Moderate	Increased risk of hypomagnesemia by the combination of Amphotericin B and Esomeprazole.	Peptic ulcer [DA61]	[16]
Estramustine	DMWTAOI	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Estramustine.	Prostate cancer [2C82]	[12]
Everolimus	DM8X2EH	Major	Increased risk of nephrotoxicity by the combination of Amphotericin B and Everolimus.	Renal cell carcinoma [2C90]	[25]
Temsirolimus	DMS104F	Major	Increased risk of nephrotoxicity by the combination of Amphotericin B and Temsirolimus.	Renal cell carcinoma [2C90]	[25]
Sulfasalazine	DMICA9H	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Sulfasalazine.	Rheumatoid arthritis [FA20]	[20]
Paliperidone	DM7NPJS	Moderate	Increased risk of ventricular arrhythmias by the combination of Amphotericin B and Paliperidone.	Schizophrenia [6A20]	[12]
Trifluoperazine	DMKBYWI	Moderate	Increased risk of ventricular arrhythmias by the combination of Amphotericin B and Trifluoperazine.	Schizophrenia [6A20]	[12]
Risperidone	DMN6DXL	Moderate	Increased risk of ventricular arrhythmias by the combination of Amphotericin B and Risperidone.	Schizophrenia [6A20]	[12]
Amisulpride	DMSJVAM	Moderate	Increased risk of ventricular arrhythmias by the combination of Amphotericin B and Amisulpride.	Schizophrenia [6A20]	[12]
Pimozide	DMW83TP	Major	Increased risk of ventricular arrhythmias by the combination of Amphotericin B and Pimozide.	Schizophrenia [6A20]	[26]
Ifosfamide	DMCT3I8	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Ifosfamide.	Solid tumour/cancer [2A00-2F9Z]	[12]
Pipecuronium	DM5F84A	Moderate	Additive neuromuscular blocking effects by the combination of Amphotericin B and Pipecuronium.	Tonus and reflex abnormality [MB47]	[19]
Doxacurium	DMKE7L9	Moderate	Additive neuromuscular blocking effects by the combination of Amphotericin B and Doxacurium.	Tonus and reflex abnormality [MB47]	[19]
Vecuronium	DMP0UK2	Moderate	Additive neuromuscular blocking effects by the combination of Amphotericin B and Vecuronium.	Tonus and reflex abnormality [MB47]	[19]
Rocuronium	DMY9BMK	Moderate	Additive neuromuscular blocking effects by the combination of Amphotericin B and Rocuronium.	Tonus and reflex abnormality [MB47]	[19]
Sirolimus	DMGW1ID	Major	Increased risk of nephrotoxicity by the combination of Amphotericin B and Sirolimus.	Transplant rejection [NE84]	[25]
Tacrolimus	DMZ7XNQ	Major	Increased risk of nephrotoxicity by the combination of Amphotericin B and Tacrolimus.	Transplant rejection [NE84]	[25]
Olsalazine	DMZW9HA	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Olsalazine.	Ulcerative colitis [DD71]	[20]
Plazomicin	DMKMBES	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Plazomicin.	Urinary tract infection [GC08]	[13]
Amiodarone	DMUTEX3	Major	Increased risk of ventricular arrhythmias by the combination of Amphotericin B and Amiodarone.	Ventricular tachyarrhythmia [BC71]	[27]
Ganciclovir	DM1MBYQ	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Ganciclovir.	Virus infection [1A24-1D9Z]	[12]
Valganciclovir	DMS2IUH	Moderate	Increased risk of nephrotoxicity by the combination of Amphotericin B and Valganciclovir.	Virus infection [1A24-1D9Z]	[12]

References

• [1] Amphotericin B FDA Label
• [2] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 050724.
• [3] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [4] BDDCS applied to over 900 drugs
• [5] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [6] 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
• [7] 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.
• [8] Comparative molecular dynamics simulations of amphotericin B-cholesterol/ergosterol membrane channels. Biochim Biophys Acta. 2002 Dec 23;1567(1-2):63-78.
• [9] Carotenoids reverse multidrug resistance in cancer cells by interfering with ABC-transporters. Phytomedicine. 2012 Aug 15;19(11):977-87.
• [10] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [11] Antoniskis D, Larsen RA "Acute, rapidly progressive renal failure with simultaneous use of amphotericin B and pentamidine." Antimicrob Agents Chemother 34 (1990): 470-2. [PMID: 2334159]
• [12] Cerner Multum, Inc. "Australian Product Information.".
• [13] Churchill DN, Seely J "Nephrotoxicity associated with combined gentamicin - amphotericin B therapy." Nephron 19 (1977): 176-81. [PMID: 268496]
• [14] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [15] Product Information. Multaq (dronedarone). sanofi-aventis , Bridgewater, NJ.
• [16] FDA. U.S. Food and Drug Administration "FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of proton pump inhibitor drugs (PPIs).".
• [17] Chang JT, Green L, Beitz J "Renal failure with the use of zoledronic acid." N Engl J Med 349 (2003): 1676-9 discussion 1676-9. [PMID: 14573746]
• [18] Wong GT, Lee EY, Irwin MG. Contrast induced nephropathy in vascular surgery.?Br J Anaesth. 2016;117 Suppl 2:ii63-ii73. [PMID: 27566809]
• [19] Cushard WG, Kohanim M, Lantis LR "Blastomycosis of bone." J Bone Joint Surg Am 51A (1969): 704-12. [PMID: 5819086]
• [20] Novis BH, Korzets Z, Chen P, Bernheim J "Nephrotic syndrome after treatment with 5-aminosalicylic acid." Br Med J (Clin Res Ed) 296 (1988): 1442. [PMID: 3132281]
• [21] Banerjee D, Asif A, Striker L, Preston RA, Bourgoignie JJ, Roth D "Short-term, high-dose pamidronate-induced acute tubular necrosis: The postulated mechanisms of bisphosphonate nephrotoxicity." Am J Kidney Dis 41 (2003): E18. [PMID: 12778436]
• [22] Ohnishi K, Yoshida H, Shigeno K, et al. "Prolongation of the QT interval and ventricular tachycardia in patients treated with arsenic trioxide for acute promyelocytic leukemia." Ann Intern Med 133 (2000): 881-5. [PMID: 11103058]
• [23] Product Information. Exjade (deferasirox). Novartis Pharmaceuticals, East Hanover, NJ.
• [24] Cohen J "Long-term efficacy and safety of terazosin alone and in combination with other antihypertensive agents." Am Heart J 122 (1991): 919-25. [PMID: 1678923]
• [25] Product Information. Prograf (tacrolimus). Fujisawa, Deerfield, IL.
• [26] Product Information. Orap Tablets (pimozide). Gate Pharmaceuticals, Sellersville, PA.
• [27] Antonelli D, Atar S, Freedberg NA, Rosenfeld T "Torsade de pointes in patients on chronic amiodarone treatment: contributing factors and drug interactions." Isr Med Assoc J 7 (2005): 163-5. [PMID: 15792261]