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| legal_UK = POM
| legal_UK = POM
| legal_US = Rx-only
| legal_US = Rx-only
| routes_of_administration = [[Intramuscular injection|Intramuscular]], [[Intravenous therapy|intravenous]]
| routes_of_administration = [[Intramuscular injection|intramuscular]], [[Intravenous therapy|intravenous]]
<!--Pharmacokinetic data-->
<!--Pharmacokinetic data-->
| bioavailability =
| bioavailability =
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| metabolism =
| metabolism =
| elimination_half-life = 2-3 hours
| elimination_half-life = 2-3 hours
| excretion = [[Kidney|Renal]]
| excretion = [[kidney]]
<!--Identifiers-->
<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number_Ref = {{cascite|correct|??}}
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| StdInChIKey = LKCWBDHBTVXHDL-RMDFUYIESA-N
| StdInChIKey = LKCWBDHBTVXHDL-RMDFUYIESA-N
}}
}}
<!-- Definition and medical uses -->
'''Amikacin''', sold under the brandname '''Amikin''', is an [[aminoglycoside]] [[antibiotic]] used to treat different types of [[bacteria]]l [[infection]]s. Amikacin works by binding to the bacterial [[30S]] [[ribosome|ribosomal]] subunit, causing misreading of [[mRNA]] and leaving the bacterium unable to synthesize [[protein]]s vital to its growth.
'''Amikacin''', sold under the brandname '''Amikin''', is an [[antibiotic]] use for a number of [[bacterial infections]].<!-- <ref name=AHFS2016/> --> This includes [[joint infections]], [[intraabdominal infections]], [[meningitis]], [[pneumonia]], [[sepsis]], and [[urinary tract infections]].<ref name=AHFS2016/> It is also used for the treatment of [[multidrug-resistant tuberculosis]].<ref name=WHO2008>{{cite book|title=WHO Model Formulary 2008|date=2009|publisher=World Health Organization|isbn=9789241547659|page=137|url=http://apps.who.int/medicinedocs/documents/s16879e/s16879e.pdf|accessdate= 8 December 2016}}</ref> It is used either by [[intravenous|injection into a vein]] or [[intramuscular|muscle]].<ref name=AHFS2016/>

<!-- Side effects and mechanism -->
Common side effects include hearing loss, balance problems, and [[kidney problems]].<!-- <ref name=AHFS2016/> --> Other side effects include [[paralysis]] resulting in the inability to breath.<!-- <ref name=AHFS2016/> --> If used during [[pregnancy]] it may cause permanent deafness in the baby.<!-- <ref name=AHFS2016/> --> Amikacin is in the [[aminoglycoside]] family of medications.<!-- <ref name=AHFS2016/> --> It works by blocking the function of the bacteria's [[30S ribosomal subunit]], making it unable to make [[protein]].<ref name=AHFS2016/>


<!-- History, society and culture -->
<!-- History, society and culture -->
Amikacin was initially sold in 1976.<ref>{{cite book|title=Oxford Handbook of Infectious Diseases and Microbiology|date=2009|publisher=OUP Oxford|isbn=9780191039621|page=56|url=https://books.google.ca/books?id=5W-WBQAAQBAJ&pg=PT56}}</ref> It is on the [[World Health Organization's List of Essential Medicines]], a list of the most important medication needed in a basic [[health system]].<ref>{{cite web|title=WHO Model List of EssentialMedicines|url=http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?ua=1|work=World Health Organization|accessdate=22 April 2014|date=October 2013}}</ref>
Amikacin patented in 1971 and came into commercial use in 1976.<ref>{{cite book|last1=Fischer|first1=Janos|last2=Ganellin|first2=C. Robin|title=Analogue-based Drug Discovery|date=2006|publisher=John Wiley & Sons|isbn=9783527607495|page=507|url=https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA507|language=en}}</ref><ref>{{cite book|title=Oxford Handbook of Infectious Diseases and Microbiology|date=2009|publisher=OUP Oxford|isbn=9780191039621|page=56|url=https://books.google.ca/books?id=5W-WBQAAQBAJ&pg=PT56}}</ref> It is on the [[World Health Organization's List of Essential Medicines]], the most important medication needed in a basic [[health system]].<ref>{{cite web|title=WHO Model List of EssentialMedicines|url=http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?ua=1|work=World Health Organization|accessdate=22 April 2014|date=October 2013}}</ref> The wholesale cost in the [[developing world]] is 13.8 to 130.50 USD for a month.<ref name=ERC2014>{{cite web|title=X|url=X|website=International Drug Price Indicator Guide|accessdate=8 December 2016}}</ref> In the United States a typical course of treatment costs 25 to 50 USD.<ref name=Ric2015>{{cite book|last1=Hamilton|first1=Richart|title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=9781284057560|page=35}}</ref> It is made from [[kanamycin]].<ref name=AHFS2016>{{cite web|title=Amikacin Sulfate|url=https://www.drugs.com/monograph/amikacin-sulfate.html|publisher=The American Society of Health-System Pharmacists|accessdate= 8 December 2016}}</ref>



==Medical uses==
==Medical uses==

Revision as of 23:07, 10 December 2016

Amikacin
Clinical data
Trade namesAmikin, others
AHFS/Drugs.comMonograph
MedlinePlusa682661
Pregnancy
category
  • AU: D
Routes of
administration		intramuscular, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding0-11%
Elimination half-life2-3 hours
Excretionkidney
Identifiers
  • (2S)-4-Amino-N-[(2S,3S,4R,5S)-5-amino-2-[(2S,3R,4S,5S,6R)-4-amino-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4-[(2R,3R,4S,5R,6R)-6-(aminomethyl)-3,4,5-trihydroxy-oxan-2-yl]oxy-3-hydroxy-cyclohexyl]-2-hydroxybutanamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.048.653 Edit this at Wikidata
Chemical and physical data
FormulaC22H43N5O13
Molar mass585.603 g/mol g·mol−1
3D model (JSmol)
  • O=C(N[C@H]3[C@H](O[C@H]1O[C@@H]([C@@H](O)[C@H](N)[C@H]1O)CO)[C@@H](O)[C@H](O[C@H]2O[C@H](CN)[C@@H](O)[C@H](O)[C@H]2O)[C@@H](N)C3)[C@@H](O)CCN
  • InChI=1S/C22H43N5O13/c23-2-1-8(29)20(36)27-7-3-6(25)18(39-22-16(34)15(33)13(31)9(4-24)37-22)17(35)19(7)40-21-14(32)11(26)12(30)10(5-28)38-21/h6-19,21-22,28-35H,1-5,23-26H2,(H,27,36)/t6-,7+,8-,9+,10+,11-,12+,13+,14+,15-,16+,17-,18+,19-,21+,22+/m0/s1 checkY
  • Key:LKCWBDHBTVXHDL-RMDFUYIESA-N checkY
  (verify)

Amikacin, sold under the brandname Amikin, is an antibiotic use for a number of bacterial infections. This includes joint infections, intraabdominal infections, meningitis, pneumonia, sepsis, and urinary tract infections.[2] It is also used for the treatment of multidrug-resistant tuberculosis.[3] It is used either by injection into a vein or muscle.[2]

Common side effects include hearing loss, balance problems, and kidney problems. Other side effects include paralysis resulting in the inability to breath. If used during pregnancy it may cause permanent deafness in the baby. Amikacin is in the aminoglycoside family of medications. It works by blocking the function of the bacteria's 30S ribosomal subunit, making it unable to make protein.[2]

Amikacin patented in 1971 and came into commercial use in 1976.[4][5] It is on the World Health Organization's List of Essential Medicines, the most important medication needed in a basic health system.[6] The wholesale cost in the developing world is 13.8 to 130.50 USD for a month.[7] In the United States a typical course of treatment costs 25 to 50 USD.[8] It is made from kanamycin.[2]


Medical uses

Amikacin is most often used for treating severe, hospital-acquired infections with multidrug-resistant Gram-negative bacteria such as Pseudomonas aeruginosa, Acinetobacter, and Enterobacter. Serratia marcescens and Providencia stuartii are also included in the spectrum. Amikacin can also be used to treat non-tubercular mycobacterial infections and tuberculosis (if caused by sensitive strains) when first-line drugs fail to control the infection.

Amikacin may be combined with a beta-lactam antibiotic for empiric therapy for people with neutropenia and fever.

Liposomal amikacin for inhalation is currently in late stage clinical trials for the treatment of respiratory diseases, such as cystic fibrosis,[9] Pseudomonas aeruginosa,[10] non-tubercular mycobacterial infections[11] and bronchiectasis.[12][13]

Bacterial susceptibility data

Amikacin is usually used as a last-resort medication against multidrug-resistant bacteria. The following represents susceptibility data on a few medically significant microorganisms.

  • Pseudomonas aeruginosa0.5 μg/mL – 32 μg/mL
  • Pseudomonas aeruginosa (aminoglycoside-resistant) – 32 μg/mL – 64 μg/mL
  • Serratia marcescens – ≤0.25 μg/mL – 8 μg/mL
  • Serratia marcescens (multidrug-resistant) – 32 μg/mL

[14]

Adverse effects

Side-effects of amikacin are similar to those of other aminoglycosides. Kidney damage and hearing loss are the most important effects. Because of this potential, blood levels of the drug and markers of kidney function (creatinine) may be monitored. Moreover, doses are adjusted specifically based upon serum Creatinine clearance in clinical settings. [citation needed]

Administration

Amikacin may be administered once or twice a day but must be given by the intravenous or intramuscular route or via nebulization. There is no oral form available as amikacin is not absorbed orally. In people with kidney failure, dosage must be adjusted according to the creatinine clearance, usually by reducing the dosing frequency.

Resistance

Amikacin evades attacks by most of the antibiotic-inactivating enzymes that are responsible for antibiotic resistance in bacteria. This is accomplished by the L-hydroxyaminobuteroyl amide (L-HABA) moiety attached to N-1 (compare to kanamycin), which inhibits acetylation, phosphorylation, and adenylation in the distant amino sugar ring (C-2,C-3,C-4). To prevent the development of bacterial resistance to this antibiotic, its use is tightly regulated.

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  2. ^ a b c d "Amikacin Sulfate". The American Society of Health-System Pharmacists. Retrieved 8 December 2016.
  3. ^ WHO Model Formulary 2008 (PDF). World Health Organization. 2009. p. 137. ISBN 9789241547659. Retrieved 8 December 2016.
  4. ^ Fischer, Janos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 507. ISBN 9783527607495.
  5. ^ Oxford Handbook of Infectious Diseases and Microbiology. OUP Oxford. 2009. p. 56. ISBN 9780191039621.
  6. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
  7. ^ [X "X"]. International Drug Price Indicator Guide. Retrieved 8 December 2016. {{cite web}}: Check |url= value (help)
  8. ^ Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 35. ISBN 9781284057560.
  9. ^ "Randomized, open-label, active-controlled, multicenter study to assess the efficacy, safety and tolerability of Arikace™ in Cystic Fibrosis patients with chronic infection due to Pseudomonas aeruginosa" is a European Phase III clinical trial, being conducted across multiple sites in the EU, starting at the Royal Brompton Hospital, Department of Respiratory Medicine, in London. https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-000441-20/GB
  10. ^ http://www.clinicaltrials.gov/ct2/show/NCT01315678
  11. ^ "A Randomized, Double-Blind, Placebo-Controlled Study of Liposomal Amikacin for Inhalation (Arikace™) in Patients With Recalcitrant Nontuberculous Mycobacterial Lung Disease" is a Phase II clinical trial in collaboration with the US National Institute of Allergy and Infectious Diseases. http://www.clinicaltrials.gov/ct2/show/NCT01315236
  12. ^ "A Placebo Controlled, Randomized, Parallel Cohort, Safety And Tolerability Study Of 2 Dose Levels Of Liposomal Amikacin For Inhalation (Arikace™) In Patients With Bronchiectasis Complicated By Chronic Infection Due To Pseudomonas Aeruginosa" Phase II (completed). http://www.clinicaltrials.gov/ct2/show/NCT00775138
  13. ^ "A Study to Determine the Safety and Tolerability of Arikace™ Versus Placebo in Patients Who Have Bronchiectasis" is a Phase II clinical trial (as [4]) completed in the UK. http://www.ukctg.nihr.ac.uk/trialdetails/NCT00775138
  14. ^ http://www.toku-e.com/Assets/MIC/Amikacin%20hydrate.pdf
  • Edson RS, Terrell CL. The aminoglycosides. Mayo Clin Proc. 1999 May;74(5):519–28. Review. PMID 10319086
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