Daptomycin
Identification
- Name
- Daptomycin
- Accession Number
- DB00080 (BTD00111, BIOD00111)
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Description
Daptomycin is a naturally-occurring lipopeptide antibiotic that kills susceptible gram positive bacteria by disrupting their membrane potential. It is found in the soil bacterium called Streptomyces roseosporus. Antibiotics are used in the treatment of infections caused by bacteria. They work by killing bacteria or preventing their growth. Daptomycin will not work for colds, flu, or other virus infections. It was approved in September 2003 for the treatment of complicated skin and soft tissue infections. It has a safety profile similar to other agents commonly administered to treat gram-positive infections.
- Structure
Structure for Daptomycin (DB00080)
- Synonyms
- Daptomicina
- Daptomycin
- Daptomycine
- Daptomycinum
- External IDs
- LY 146032 / LY-146032 / LY-164032
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Unlock Additional DataCubicin Powder, for solution 500 mg Intravenous Cubist Pharmaceuticals, Inc. 2007-12-03 Not applicable Canada 
Cubicin Injection, powder, lyophilized, for solution 500 mg/10mL Intravenous Merck Sharp & Dohme Corp. 2003-09-12 Not applicable US 
Cubicin Injection 350 mg/350mg Intravenous OSO BioPharmaceuticals Manufacturing, LLC 2003-09-12 Not applicable US Cubicin RF Powder, for solution 500 mg Intravenous Cubist Pharmaceuticals, Inc. 2018-01-17 Not applicable Canada Cubicin RF Injection, powder, lyophilized, for solution 500 mg/10mL Intravenous Merck Sharp & Dohme Corp. 2016-07-06 Not applicable US Daptomycin Injection, powder, lyophilized, for solution 350 mg/7mL Intravenous Civica, Inc. 2019-09-03 Not applicable US Daptomycin Injection, powder, lyophilized, for solution 350 mg/7mL Intravenous Fresenius Kabi USA, LLC 2019-06-01 Not applicable US Daptomycin Injection, powder, lyophilized, for solution 350 mg/7mL Intravenous Xellia Pharmaceuticals USA LLC 2019-03-15 Not applicable US Daptomycin Injection, powder, lyophilized, for solution 350 mg/7mL Intravenous Sagent Pharmaceuticals 2020-02-01 Not applicable US Daptomycin Injection, powder, lyophilized, for solution 350 mg/7mL Intravenous Xellia Pharmaceuticals USA, LLC 2018-07-19 Not applicable US Additional Data Available- Application NumberApplication Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Unlock Additional DataDaptomycin Injection, powder, lyophilized, for solution 500 mg/10mL Intravenous Xellia Pharmaceuticals USA LLC 2018-10-01 Not applicable US Daptomycin Injection, powder, lyophilized, for solution 500 mg/10mL Intravenous BE Pharmaceuticals Inc. 2019-06-26 Not applicable US Daptomycin Injection, powder, lyophilized, for solution 350 mg/7mL Intravenous Accord Healthcare, Inc. 2019-07-16 Not applicable US Daptomycin Injection, powder, lyophilized, for solution 500 mg/10mL Intravenous Fresenius Kabi USA, LLC 2016-06-28 Not applicable US Daptomycin Injection, powder, lyophilized, for solution 500 mg/10mL Intravenous Cipla USA Inc. 2019-09-23 Not applicable US Daptomycin Injection, powder, lyophilized, for solution 500 mg/10mL Intravenous Accord Healthcare Inc. 2019-06-24 Not applicable US Daptomycin Injection, powder, lyophilized, for solution 50 mg/1mL Intravenous Sagent Pharmaceuticals 2019-11-15 Not applicable US Daptomycin Injection, powder, lyophilized, for solution 500 mg/10mL Intravenous Fresenius Kabi USA, LLC 2018-04-11 Not applicable US Daptomycin Injection, powder, lyophilized, for solution 500 mg/10mL Intravenous Mylan Institutional LLC 2018-09-04 Not applicable US Daptomycin Injection, powder, lyophilized, for solution 500 mg/10mL Intravenous Jiangsu Hengrui Medicine Co., Ltd. 2019-08-22 Not applicable US Additional Data Available- Application NumberApplication Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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- International/Other Brands
- Cidecin / Cubicin
- Categories
- Agents Causing Muscle Toxicity
- Amino Acids, Peptides, and Proteins
- Anti-Bacterial Agents
- Anti-Infective Agents
- Antibacterials for Systemic Use
- Antiinfectives for Systemic Use
- Cyclic Lipopeptides
- Drugs that are Mainly Renally Excreted
- Lipids
- Lipopeptide Antibacterial
- Lipopeptides
- Peptides
- Peptides, Cyclic
- UNII
- NWQ5N31VKK
- CAS number
- 103060-53-3
- Weight
- Average: 1620.693
Monoisotopic: 1619.71036644 - Chemical Formula
- C72H101N17O26
- InChI Key
- DOAKLVKFURWEDJ-QCMAZARJSA-N
- InChI
- InChI=1S/C72H101N17O26/c1-5-6-7-8-9-10-11-22-53(93)81-44(25-38-31-76-42-20-15-13-17-39(38)42)66(108)84-45(27-52(75)92)67(109)86-48(30-59(102)103)68(110)89-61-37(4)115-72(114)49(26-51(91)40-18-12-14-19-41(40)74)87-71(113)60(35(2)24-56(96)97)88-69(111)50(34-90)82-55(95)32-77-63(105)46(28-57(98)99)83-62(104)36(3)79-65(107)47(29-58(100)101)85-64(106)43(21-16-23-73)80-54(94)33-78-70(61)112/h12-15,17-20,31,35-37,43-50,60-61,76,90H,5-11,16,21-30,32-34,73-74H2,1-4H3,(H2,75,92)(H,77,105)(H,78,112)(H,79,107)(H,80,94)(H,81,93)(H,82,95)(H,83,104)(H,84,108)(H,85,106)(H,86,109)(H,87,113)(H,88,111)(H,89,110)(H,96,97)(H,98,99)(H,100,101)(H,102,103)/t35-,36-,37-,43+,44+,45-,46+,47+,48+,49+,50-,60+,61+/m1/s1
- IUPAC Name
- (3S)-3-{[(3S,6S,9R,15S,18R,21S,24S,30S,31R)-3-[2-(2-aminophenyl)-2-oxoethyl]-24-(3-aminopropyl)-15,21-bis(carboxymethyl)-6-[(2R)-1-carboxypropan-2-yl]-9-(hydroxymethyl)-18,31-dimethyl-2,5,8,11,14,17,20,23,26,29-decaoxo-1-oxa-4,7,10,13,16,19,22,25,28-nonaazacyclohentriacontan-30-yl]carbamoyl}-3-[(2R)-3-carbamoyl-2-[(2S)-2-decanamido-3-(1H-indol-3-yl)propanamido]propanamido]propanoic acid
- SMILES
- CCCCCCCCCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H]1[C@@H](C)OC(=O)[C@H](CC(=O)C2=CC=CC=C2N)NC(=O)[C@@H](NC(=O)[C@@H](CO)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCN)NC(=O)CNC1=O)[C@H](C)CC(O)=O
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Pharmacology
- Indication
For the treatment of complicated skin and skin structure infections caused by susceptible strains of Gram-positive microorganisms.
- Associated Conditions
- Pharmacodynamics
Daptomycin is a 13 member amino acid cyclic lipopeptide antibiotic active against Gram-positive bacteria only. It has proven in vitro activity against enterococci (including glycopeptide-resistant Enterococci (GRE)), staphylococci (including methicillin-resistant Staphylococcus aureus), streptococci and corynebacteria. Daptomycin is derived from the fermentation product of Streptomyces roseosporus.
- Mechanism of action
Daptomycin appears to bind or insert into the outer membrane of gram positive bacteria. The binding and integration of daptomycin into the cell membrane is calcium dependent. Calcium ions cause a conformational change in daptomycin, augmenting its amphipathicity (hydrophilic head group and hydrophobic tail group), leading to incorporation into the cell membrane. This binding causes rapid depolarisation, resulting in a loss of membrane potential leading to inhibition of protein, DNA and RNA synthesis, which results in bacterial cell death. The bactericidal activity of daptomycin is concentration-dependent. There is in vitro evidence of synergy with β-lactam antibiotics.
Target Actions Organism ABacterial outer membrane incorporation into and destabilizationBacteria - Absorption
Generally exhibits linear and time-independent pharmacokinetics at a dosage of 4–12 mg/kg IV once every 24 hours. Steady-state trough serum concentrations are achieved by the third daily dose.
- Volume of distribution
- 0.1 L/Kg [healthy adult subjects]
- Protein binding
Daptomycin is reversibly bound to human plasma proteins, primarily to serum albumin, in a concentration-independent manner. The overall mean binding ranged from 90 to 93%.
- Metabolism
Minor amounts of three oxidative metabolites and one unidentified compound have been detected in urine. The site of metabolism has not been identified.
- Route of elimination
Daptomycin is excreted primarily by the kidney. In a mass balance study of 5 healthy subjects using radiolabeled daptomycin, approximately 78% of the administered dose was recovered from urine based on total radioactivity (approximately 52% of the dose based on microbiologically active concentrations) and 5.7% of the dose was recovered from feces (collected for up to 9 days) based on total radioactivity. Because renal excretion is the primary route of elimination, dosage adjustment is necessary in patients with severe renal insufficiency (CLCR <30 mL/min)
- Half life
Half-life elimination: 8-9 hours (up to 28 hours in renal impairment)
- Clearance
Excreted primarily in the urine as unchanged drug (78%) and in the feces (6%)
- Toxicity
- Not Available
- Affected organisms
- Enteric bacteria and other eubacteria
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.
Learn moreStructured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.
Learn moreStructured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.
Learn moreInteractions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Unlock Additional Data(R)-warfarin The risk or severity of bleeding can be increased when Daptomycin is combined with (R)-warfarin. (S)-Warfarin The risk or severity of bleeding can be increased when Daptomycin is combined with (S)-Warfarin. 4-hydroxycoumarin The risk or severity of bleeding can be increased when Daptomycin is combined with 4-hydroxycoumarin. Abacavir Daptomycin may decrease the excretion rate of Abacavir which could result in a higher serum level. Acarbose Daptomycin may decrease the excretion rate of Acarbose which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Daptomycin which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Daptomycin which could result in a higher serum level. Acenocoumarol The risk or severity of bleeding can be increased when Daptomycin is combined with Acenocoumarol. Acetaminophen Daptomycin may decrease the excretion rate of Acetaminophen which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Daptomycin which could result in a lower serum level and potentially a reduction in efficacy. Additional Data Available- Extended DescriptionExtended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - Severity
- Evidence Level
- ActionAction
An effect category for each drug interaction. Know how this interaction affects the subject drug.
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- Food Interactions
- No interactions found.
References
- Synthesis Reference
Dennis Keith, "Methods for preparing purified daptomycin." U.S. Patent US20030045484, issued March 06, 2003.
US20030045484- General References
- Woodworth JR, Nyhart EH Jr, Brier GL, Wolny JD, Black HR: Single-dose pharmacokinetics and antibacterial activity of daptomycin, a new lipopeptide antibiotic, in healthy volunteers. Antimicrob Agents Chemother. 1992 Feb;36(2):318-25. [PubMed:1318678]
- Tally FP, DeBruin MF: Development of daptomycin for gram-positive infections. J Antimicrob Chemother. 2000 Oct;46(4):523-6. [PubMed:11020247]
- Charles PG, Grayson ML: The dearth of new antibiotic development: why we should be worried and what we can do about it. Med J Aust. 2004 Nov 15;181(10):549-53. [PubMed:15540967]
- Fowler VG Jr, Boucher HW, Corey GR, Abrutyn E, Karchmer AW, Rupp ME, Levine DP, Chambers HF, Tally FP, Vigliani GA, Cabell CH, Link AS, DeMeyer I, Filler SG, Zervos M, Cook P, Parsonnet J, Bernstein JM, Price CS, Forrest GN, Fatkenheuer G, Gareca M, Rehm SJ, Brodt HR, Tice A, Cosgrove SE: Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med. 2006 Aug 17;355(7):653-65. [PubMed:16914701]
- Lee SY, Fan HW, Kuti JL, Nicolau DP: Update on daptomycin: the first approved lipopeptide antibiotic. Expert Opin Pharmacother. 2006 Jul;7(10):1381-97. [PubMed:16805723]
- Link [Link]
- External Links
- KEGG Drug
- D01080
- KEGG Compound
- C12013
- PubChem Compound
- 16134395
- PubChem Substance
- 46504551
- ChemSpider
- 10200644
- RxNav
- 22299
- ChEBI
- 600103
- ChEMBL
- CHEMBL387675
- Therapeutic Targets Database
- DAP001328
- PharmGKB
- PA164768820
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Daptomycin
- ATC Codes
- J01XX09 — Daptomycin
- AHFS Codes
- 08:12.28.12 — Cyclic Lipopeptides
- FDA label
- Download (560 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Cubist pharmaceuticals inc
- Packagers
- Cardinal Health
- Catalent Pharma Solutions
- Cubist Pharmaceuticals Inc.
- Hospira Inc.
- Oso Biopharmaceuticals Manufacturing LLC
- Sepracor Pharmaceuticals Inc.
- Dosage forms
Form Route Strength Injection Intravenous 350 mg/350mg Powder, for solution Intravenous 500 mg Injection, powder, lyophilized, for solution Intravenous 500 mg/10mL Injection, powder, lyophilized, for solution Intravenous 350 mg/7mL Injection, powder, lyophilized, for solution Intravenous 50 mg/1mL Powder, for solution Intravenous - Prices
Unit description Cost Unit Cubicin 500 mg vial 272.7USD vial DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Unlock Additional DataCA2344318 No 2006-07-04 2019-09-24 Canada US6468967 No 2002-10-22 2019-09-24 US US6852689 No 2005-02-08 2019-09-24 US US8003673 No 2011-08-23 2028-09-04 US USRE39071 No 2006-04-18 2016-06-15 US US8058238 No 2011-11-15 2020-11-28 US US8129342 No 2012-03-06 2020-11-28 US US9138456 No 2015-09-22 2030-11-23 US Additional Data Available- Filed On
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0173 mg/mL ALOGPS logP -0.47 ALOGPS logP -9.4 ChemAxon logS -5 ALOGPS pKa (Strongest Acidic) 2.98 ChemAxon pKa (Strongest Basic) 9.59 ChemAxon Physiological Charge -3 ChemAxon Hydrogen Acceptor Count 27 ChemAxon Hydrogen Donor Count 22 ChemAxon Polar Surface Area 702.02 Å2 ChemAxon Rotatable Bond Count 35 ChemAxon Refractivity 393.57 m3·mol-1 ChemAxon Polarizability 158.96 Å3 ChemAxon Number of Rings 4 ChemAxon Bioavailability 0 ChemAxon Rule of Five No ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule Yes ChemAxon - Predicted ADMET features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Taxonomy
- Classification
- Not classified
Targets
References
- Jerala R: Synthetic lipopeptides: a novel class of anti-infectives. Expert Opin Investig Drugs. 2007 Aug;16(8):1159-69. [PubMed:17685866]
- Lee SY, Fan HW, Kuti JL, Nicolau DP: Update on daptomycin: the first approved lipopeptide antibiotic. Expert Opin Pharmacother. 2006 Jul;7(10):1381-97. [PubMed:16805723]
- Guay DR: Daptomycin: the first approved lipopeptide antimicrobial. Consult Pharm. 2004 Jul;19(7):614-28. [PubMed:16553491]
- Jung D, Rozek A, Okon M, Hancock RE: Structural transitions as determinants of the action of the calcium-dependent antibiotic daptomycin. Chem Biol. 2004 Jul;11(7):949-57. [PubMed:15271353]
Drug created on June 13, 2005 07:24 / Updated on February 25, 2020 00:00