tigecycline Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
antibiotics, protein-synthesis inhibitors, tetracycline derivatives	2661	220620-09-7

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: CL-331002 CL 331002 tigecycline tygacil glycylcycline	Tigecycline inhibits protein translation in bacteria by binding to the 30S ribosomal subunit and blocking entry of amino-acyl tRNA molecules into the A site of the ribosome. This prevents incorporation of amino acid residues into elongating peptide chains. In general, tigecycline is considered bacteriostatic; however, tigecycline has demonstrated bactericidal activity against isolates of S. pneumoniae and L. pneumophila. Molecular weight: 585.66 Formula: C29H39N5O8 CLOGP: -0.03 LIPINSKI: 3 HAC: 13 HDO: 7 TPSA: 205.76 ALOGS: -3.11 ROTB: 7 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

CL-331002
CL 331002
tigecycline
tygacil
glycylcycline

Tigecycline inhibits protein translation in bacteria by binding to the 30S ribosomal subunit and blocking entry of amino-acyl tRNA molecules into the A site of the ribosome. This prevents incorporation of amino acid residues into elongating peptide chains. In general, tigecycline is considered bacteriostatic; however, tigecycline has demonstrated bactericidal activity against isolates of S. pneumoniae and L. pneumophila.

Molecular weight: 585.66
Formula: C29H39N5O8
CLOGP: -0.03
LIPINSKI: 3
HAC: 13
HDO: 7
TPSA: 205.76
ALOGS: -3.11
ROTB: 7

Status: OFP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
0.10	g	P

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	3	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	295 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	22 %	Benet LZ, Broccatelli F, Oprea TI
BA (Bioavailability)	0 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	12 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	3.80 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.20 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	48 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
June 15, 2005	FDA	PF PRISM CV

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Pathogen resistance	213.72	30.77	56	3493	6004	46676509
Pancreatitis acute	146.35	30.77	59	3490	24813	46657700
Pancreatitis	120.42	30.77	61	3488	43566	46638947
Drug resistance	97.97	30.77	40	3509	17328	46665185
Klebsiella infection	80.96	30.77	27	3522	6635	46675878
Thrombocytopenia	63.52	30.77	62	3487	126519	46555994
Hypofibrinogenaemia	63.37	30.77	15	3534	1055	46681458
Acinetobacter infection	59.13	30.77	15	3534	1407	46681106
Multiple organ dysfunction syndrome	56.92	30.77	40	3509	51670	46630843
Sepsis	47.55	30.77	55	3494	135959	46546554
Adjusted calcium decreased	46.64	30.77	8	3541	106	46682407
Septic shock	44.20	30.77	36	3513	57857	46624656
Biloma	43.59	30.77	7	3542	60	46682453
Globulins decreased	41.57	30.77	8	3541	207	46682306
Haemodynamic instability	40.84	30.77	17	3532	7708	46674805
Morganella infection	40.81	30.77	9	3540	461	46682052
Haemostasis	40.50	30.77	8	3541	238	46682275
Systemic inflammatory response syndrome	39.50	30.77	15	3534	5356	46677157
Hepatotoxicity	38.82	30.77	24	3525	24985	46657528
Coma hepatic	38.39	30.77	9	3540	607	46681906
Drug ineffective	38.08	30.77	125	3424	677713	46004800
Multiple-drug resistance	37.65	30.77	12	3537	2553	46679960
Immunosuppressant drug level increased	34.75	30.77	12	3537	3270	46679243
Escherichia infection	32.35	30.77	16	3533	10801	46671712
Blood fibrinogen decreased	32.05	30.77	8	3541	702	46681811
Nephropathy toxic	31.49	30.77	14	3535	7440	46675073
Wound haemorrhage	31.42	30.77	10	3539	2117	46680396
Blood urea increased	31.14	30.77	21	3528	25331	46657182

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Pathogen resistance	165.23	25.22	58	4468	8352	29939600
Hypofibrinogenaemia	143.51	25.22	36	4490	1609	29946343
Septic shock	135.38	25.22	96	4430	63511	29884441
Drug ineffective	126.93	25.22	201	4325	340186	29607766
Multiple organ dysfunction syndrome	93.47	25.22	77	4449	63410	29884542
Drug resistance	93.26	25.22	50	4476	20083	29927869
Enterococcal infection	76.57	25.22	33	4493	8191	29939761
Klebsiella infection	71.97	25.22	30	4496	6857	29941095
Mycobacterium chelonae infection	66.76	25.22	16	4510	589	29947363
Sepsis	60.35	25.22	91	4435	146304	29801648
Treatment failure	55.03	25.22	44	4482	34635	29913317
Thrombocytopenia	54.78	25.22	84	4442	136960	29810992
Pancreatitis acute	50.42	25.22	37	4489	25658	29922294
Ototoxicity	49.20	25.22	15	4511	1381	29946571
Pancreatitis	46.91	25.22	41	4485	36449	29911503
Mycobacterium abscessus infection	42.11	25.22	11	4515	577	29947375
Acinetobacter infection	40.55	25.22	12	4514	998	29946954
Klebsiella bacteraemia	40.01	25.22	12	4514	1045	29946907
Multiple-drug resistance	38.25	25.22	15	4511	2926	29945026
Gallstone ileus	37.55	25.22	6	4520	22	29947930
Coagulopathy	34.85	25.22	26	4500	18461	29929491
Fungaemia	31.22	25.22	12	4514	2219	29945733
Deafness neurosensory	30.40	25.22	12	4514	2381	29945571
Anuria	30.10	25.22	19	4507	10297	29937655
Flavobacterium infection	29.98	25.22	6	4520	93	29947859
Candida infection	29.84	25.22	22	4504	15340	29932612
Product use in unapproved indication	29.11	25.22	45	4481	73648	29874304
Haematological malignancy	29.04	25.22	6	4520	110	29947842
Acoustic neuroma	27.91	25.22	6	4520	134	29947818
Staphylococcal infection	27.40	25.22	28	4498	30196	29917756
Bacteraemia	27.37	25.22	21	4505	15539	29932413
Hepatotoxicity	26.60	25.22	22	4504	18123	29929829
Nausea	25.35	25.22	100	4426	296857	29651095

Pharmacologic Action:

Source	Code	Description
ATC	J01AA12	ANTIINFECTIVES FOR SYSTEMIC USE ANTIBACTERIALS FOR SYSTEMIC USE TETRACYCLINES Tetracyclines
FDA CS	M0021223	Tetracyclines
MeSH PA	D000900	Anti-Bacterial Agents
MeSH PA	D000890	Anti-Infective Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D011500	Protein Synthesis Inhibitors
FDA EPC	N0000175938	Tetracycline-class Antibacterial

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Pneumonia due to Streptococcus	indication	34020007
Haemophilus influenzae pneumonia	indication	70036007
Abdominal abscess	indication	75100008
Infectious disease of abdomen	indication	128070006
Complicated appendicitis	indication	418171008
Complicated Skin and Skin Structure E. Coli Infection	indication
Complicated Skin and Skin Structure Staphylococcus Aureus Infection	indication
Complicated Skin and Skin Structure Infection	indication
Complicated Skin and Skin Structure Streptococcus Pyogenes Infection	indication
Legionella Pneumophila Pneumonia	indication
Complicated Bacterial Peritonitis	indication
Complicated Skin and Skin Structure Enterococcus Faecalis Infection	indication
Complicated Skin and Skin Structure Streptococcus Agalactiae Infection	indication
Hyperbilirubinemia	contraindication	14783006	DOID:2741
Gastrointestinal perforation	contraindication	51875005
Hepatic failure	contraindication	59927004
Pancreatitis	contraindication	75694006	DOID:4989
Pregnancy, function	contraindication	289908002
Pseudomembranous enterocolitis	contraindication	397683000
Antibiotic-Induced Hypoprothrombinemia	contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	3.13	acidic
pKa2	8.64	acidic
pKa3	11.14	acidic
pKa4	11.96	acidic
pKa5	13.08	acidic
pKa6	13.93	acidic
pKa7	9.41	Basic
pKa8	7.96	Basic
pKa9	7.31	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

None

External reference:

ID	Source
4024922	VUID
N0000171604	NUI
D01079	KEGG_DRUG
4024922	VANDF
C0255348	UMLSCUI
CHEBI:142708	CHEBI
T1C	PDB_CHEM_ID
CHEMBL376140	ChEMBL_ID
D000078304	MESH_DESCRIPTOR_UI
C087533	MESH_SUPPLEMENTAL_RECORD_UI
54686193	PUBCHEM_CID
8115	INN_ID
DB00560	DRUGBANK_ID
70JE2N95KR	UNII
10929	IUPHAR_LIGAND_ID
384455	RXNORM
20166	MMSL
230306	MMSL
69774	MMSL
d05537	MMSL
010833	NDDF
418313005	SNOMEDCT_US
418631002	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Tygacil	HUMAN PRESCRIPTION DRUG LABEL	1	0008-4990	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	50 mg	INTRAVENOUS	NDA	33 sections
Tygacil	HUMAN PRESCRIPTION DRUG LABEL	1	0008-4994	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	50 mg	INTRAVENOUS	NDA	30 sections
Tigecycline	HUMAN PRESCRIPTION DRUG LABEL	1	0781-3481	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	50 mg	INTRAVENOUS	ANDA	26 sections
TIGECYCLINE	HUMAN PRESCRIPTION DRUG LABEL	1	16729-364	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	50 mg	INTRAVENOUS	NDA	31 sections
Tigecycline	Human Prescription Drug Label	1	55150-228	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	50 mg	INTRAVENOUS	ANDA	28 sections
Tigecycline	HUMAN PRESCRIPTION DRUG LABEL	1	60505-6098	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	50 mg	INTRAVENOUS	ANDA	27 sections
Tigecycline	Human Prescription Drug Label	1	63323-960	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	50 mg	INTRAVENOUS	NDA	27 sections
Tigecycline	HUMAN PRESCRIPTION DRUG LABEL	1	70121-1647	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	50 mg	INTRAVENOUS	NDA	22 sections
Tigecycline	HUMAN PRESCRIPTION DRUG LABEL	1	70594-035	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	50 mg	INTRAVENOUS	ANDA	33 sections
Tigecycline	HUMAN PRESCRIPTION DRUG LABEL	1	71288-019	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	50 mg	INTRAVENOUS	ANDA	30 sections