- Accession Number
- DB00479 (APRD00550)
- Small Molecule
- Approved, Investigational, Vet approved
Amikacin is a semi-synthetic aminoglycoside antibiotic that is derived from kanamycin A [Label]. Amikacin is synthesized by acylation with the l-(-)-γ-amino-α-hydroxybutyryl side chain at the C-1 amino group of the deoxystreptamine moiety of kanamycin A .
Amikacin's unique property is that it exerts activity against more resistant gram-negative bacilli such as Acinetobacter baumanii and Pseudomonas aeruginosa. Amikacin also exerts excellent activity against most aerobic gram-negative bacilli from the Enterobacteriaceae family, including Nocardia and some Mycobacterium (M. avium-intracellulare, M. chelonae, and M. fortuitum). M. avium-intracellulare (MAC) is a type of nontuberculous mycobacteria (NTM) found in water and soil. Symptoms of this disease include a persistent cough, fatigue, weight loss, night sweats, and shortness of breath and the coughing up of blood .
Several forms of amikacin are used currently, including an intravenous (IV) or intramuscular (IM) injection . In September 2018, a liposomal inhalation suspension of this drug was approved by the FDA for the treatment of lung disease caused by Mycobacterium avium complex (MAC) bacteria in a small population of patients with the disease who do not respond to traditional treatment ,.
- 1-N-(L(−)-γ-amino-α-hydroxybutyryl)kanamycin A
- External IDs
- BAY 41-6551
- Product Ingredients
Ingredient UNII CAS InChI Key Amikacin sulfate N6M33094FD 39831-55-5 FXKSEJFHKVNEFI-GCZBSULCSA-N
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Amikacin Sulfate Injection USP Liquid 250 mg Intramuscular; Intravenous Sandoz Canada Incorporated 2001-01-29 Not applicable Amikin Solution 250 mg Intramuscular; Intravenous Bristol Myers Squibb 1977-12-31 2006-05-29 Arikayce Suspension 590 mg/8.4mL Respiratory (inhalation) Insmed Incorporated 2018-10-12 Not applicable
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Amikacin Sulfate Injection, solution 50 mg/1mL Intramuscular; Intravenous Bedford Pharmaceuticals 1997-07-10 2009-12-31 Amikacin Sulfate Injection, solution 250 mg/1mL Intramuscular; Intravenous Heritage 2013-12-24 Not applicable Amikacin Sulfate Injection 250 mg/1mL Intramuscular; Intravenous West-Ward Pharmaceuticals Corp. 2015-08-01 Not applicable Amikacin Sulfate Injection, solution 50 mg/1mL Intramuscular; Intravenous Bedford Pharmaceuticals 1994-05-31 2010-03-31 AMIKACIN Sulfate Injection, solution 1 g/4mL Intramuscular; Intravenous Hospira, Inc. 2005-09-30 2010-10-01 Amikacin Sulfate Injection, solution 1 g/4mL Intramuscular; Intravenous Teva Parenteral Medicines, Inc. 1993-10-01 Not applicable AMIKACIN Sulfate Injection, solution 100 mg/2mL Intramuscular; Intravenous Hospira, Inc. 2005-02-28 2010-10-01 Amikacin Sulfate Injection, solution 50 mg/1mL Intramuscular; Intravenous Fresenius Kabi USA, LLC 2015-12-09 2015-12-14 AMIKACIN Sulfate Injection, solution 500 mg/2mL Intramuscular; Intravenous Hospira, Inc. 2005-09-12 2012-11-01 Amikacin Sulfate Injection, solution 500 mg/2mL Intramuscular; Intravenous Teva Parenteral Medicines, Inc. 1993-10-01 Not applicable
- International/Other Brands
- Amexel (Abbott) / Amukin (Bristol-Myers Squibb) / Biklin (Bristol-Myers Squibb) / Erkacin (Brown & Burk) / Farcyclin (Faran Laboratories) / Flexelite (Bros) / Kamin (Bosch) / Novamin (Bristol-Myers Squibb) / Selaxa (Proel) / Selemycin (Medochemie) / Sikacin (Shiteh Organic) / Tipkin (T P Drug) / Tybikin (M & H) / Ukaject (Unimed Pharm) / Unikin (Union) / Uzix (Rafarm) / Xylanal (Epsilon)
- CAS number
- Average: 585.6025
- Chemical Formula
- InChI Key
- IUPAC Name
The amikacin sulfate injection is indicated in the short-term treatment of serious bacterial infections due to susceptible strains of gram-negative bacteria, including Pseudomonas species, Escherichia coli, species of indole-positive and indole-negative Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, as well as Acinetobacter (Mima-Herellea) species .
Clinical studies have shown amikacin sulfate injection to be effective in bacterial septicemia (including neonatal sepsis); in serious infections of the respiratory tract, bones and joints, central nervous system (including meningitis) and skin and soft tissue; intra-abdominal infections (including peritonitis); and in burns and postoperative infections (including post-vascular surgery) .
Clinical studies have shown amikacin also to be effective in serious, complicated, and recurrent urinary tract infections due to the above organisms. Aminoglycosides, including amikacin, are not indicated in uncomplicated first-time episodes of urinary tract infections unless the causative organisms are not susceptible to antibiotics which are less toxic .
In September 2018, a new indication with a new dosage route was approved for this drug. Amikacin liposome inhalation suspension was approved for the treatment of lung disease caused by a group of bacteria, Mycobacterium avium complex (MAC) in a limited population of patients with the disease who do not respond to conventional treatment (refractory disease) . This indication is approved under accelerated approval based on achieving sputum culture conversion (defined as 3 consecutive negative monthly sputum cultures) by Month 6 of treatment. Clinical benefit has not yet been established [Label].
Important notes regarding Staphylococcus and Sensitivity testing:
Staphylococcus aureus, including methicillin-resistant strains, is the principal Gram-positive organism sensitive to amikacin. The use of amikacin in the treatment of staphylococcal infections should be restricted only to second-line therapy, and should be limited to only those patients suffering from severe infections caused by susceptible strains of staphylococcus species who have failed to show sensitivity to other available antibiotics .
Bacteriologic studies should be performed to identify causative organisms and their susceptibilities to amikacin. Amikacin may be used as initial therapy in suspected gram-negative infections and therapy may be initiated before obtaining the results of susceptibility testing [Label], , .
- Associated Conditions
- Bacterial Sepsis
- Bone and Joint Infections
- Central Nervous System Infections
- Infection caused by staphylococci
- Infective pulmonary exacerbation of cystic fibrosis
- Intra-Abdominal Infections
- Lung Infection
- Meningitis, Bacterial
- Mycobacterium avium complex infection
- Neonatal Sepsis
- Peritonitis bacterial
- Postoperative Infections
- Respiratory Tract Infection Bacterial
- Skin and Subcutaneous Tissue Bacterial Infections
- Tuberculosis Infection
- Hospital-acquired bacterial pneumonia
- Minor burns
- Severe Bacterial Infections
- Severe Urinary tract infection
Amikacin is an aminoglycoside antibiotic. Aminoglycosides bind to the bacteria, causing misreading of t-RNA, leaving bacteria unable to synthesize proteins vital to their growth. Aminoglycosides are useful mainly in the treatment infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, however, other antibiotics may be more potent and less toxic to humans [Label], .
- Mechanism of action
The primary mechanism of action of amikacin is the same as that for all aminoglycosides. It binds to bacterial 30S ribosomal subunits and interferes with mRNA binding and tRNA acceptor sites, interfering with bacterial growth. This leads to disruption of normal protein synthesis and production of non-functional or toxic peptides. Other actions have been postulated for drugs of this class [Label], , . Amikacin, as well as the rest of the aminoglycosides, are generally bacteriocidal against gram-positive and gram-negative bacteria , .
Target Actions Organism A30S ribosomal protein S12inhibitor Escherichia coli (strain K12)
Rapidly absorbed after intramuscular administration. Rapid absorption occurs from the peritoneum and pleura. Poor oral and topical absorption. Poorly absorbed from bladder irrigations and intrathecal administration , [Label].
The bioavailability of this drug is expected to vary primarily from individual differences in nebulizer efficiency and airway pathology [Label].
Following IM administration of a single dose of amikacin of 7.5 mg/kg in adults with normal renal function, peak plasma amikacin concentrations of 17-25 micrograms/mL are attained within 45 minutes to 2 hours .
Following IV infusion of the same dose given over 1 hour peak plasma concentrations of the drug average 38 micrograms/mL immediately following the infusion, 5.5 micrograms/mL at 4 hours, and 1.3 micrograms/mL at 8 hours .
- Volume of distribution
- 24 L (28% of body weight healthy adult subjects) .
Following administration of usual dosages of amikacin, amikacin has been found in bone, heart, gallbladder, and lung tissue. Amikacin is also distributed into bile, sputum, bronchial secretions, and interstitial, pleural, and synovial fluids .
- Protein binding
The protein binding of amikacin in serum is ≤ 10% [Label].
Amikacin's structure has been altered to reduce the possible route of enzymatic deactivation, thus reducing bacterial resistance. Many strains of Gram-negative organisms resistant to gentamicin and tobramycin have shown to be sensitive to amikacin in vitro .
- Route of elimination
This drug is eliminated by the kidneys. In adults with normal renal function, 94-98% of a single IM or IV dose of amikacin is excreted unchanged by glomerular filtration in the kidney within 24 hours. Amikacin can be completely recovered within approximately 10-20 days in patients with normal, healthy renal function .
In patients with impaired renal function, the clearance of amikacin is found to be decreased; the more severe the impairment, the slower the clearance. The interval between doses of amikacin should be adjusted according to the level of renal impairment. Endogenous creatinine clearance rate and serum creatinine which have a high correlation with serum half-life of amikacin, may be used as a guide for dosing .
- Half life
The plasma elimination half-life of amikacin is usually 2-3 hours in adults with normal renal function and is reported to range from 30-86 hours in adults with severe renal impairment [Label].
The mean serum clearance rate is about 100 mL/min and the renal clearance rate is 94 mL/min in subjects with normal renal function .
Mild and reversible nephrotoxicity may be observed in 5 - 25% of patients. Amikacin accumulates in the proximal renal tubular cells. Tubular cell regeneration occurs despite continued drug exposure. Toxicity most commonly occurs several days following initiation of therapy. Amikacin may exacerbate pre-existing renal disease [Label].
May cause irreversible ototoxicity [Label]. Ototoxicity appears to be correlated to cumulative exposure. Drug accumulation in the endolymph and perilymph of the inner ear causes irreversible damage to hair cells of the cochlea or summit of ampullar cristae in the vestibular complex. High- frequency hearing is lost first with progression leading to loss of low-frequency hearing. Further toxicity may lead to retrograde degeneration of the 8th cranial (vestibulocochlear) nerve. Vestibular toxicity may cause vertigo, nausea, vomiting, dizziness, and loss of balance , [Label].
Use in Pregnancy
Category D. Gentamicin and other aminoglycosides are known to cross the placenta. There is evidence of selective uptake of gentamicin by the fetal kidney resulting in damage to immature nephrons. Eighth cranial nerve damage has also been reported after in-utero exposure to some of the aminoglycosides. Because of the chemical similarity, all aminoglycosides should be considered potentially nephrotoxic and ototoxic to the developing fetus. Therapeutic blood amikacin levels in the mother do not equate with safety for the fetus. In reproductive toxicity studies in mice and rats, no effects on fertility or fetal toxicity were observed .
Use in Lactation
It is not known whether amikacin is excreted in breast milk. Since the possible harmful effect on the infant is not known, it is recommended that if nursing mothers must be given amikacin, the infants should not be breastfed during therapy .
- Affected organisms
- Humans and other mammals
- Enteric bacteria and other eubacteria
Pathway Category Amikacin Action Pathway Drug action
- Pharmacogenomic Effects/ADRs
- Not Available
- Drug Interactions
Drug Interaction (R)-warfarin The risk or severity of bleeding can be increased when Amikacin is combined with (R)-warfarin. (S)-Warfarin The risk or severity of bleeding can be increased when Amikacin is combined with (S)-Warfarin. 1,10-Phenanthroline The therapeutic efficacy of 1,10-Phenanthroline can be decreased when used in combination with Amikacin. 4-hydroxycoumarin The risk or severity of bleeding can be increased when Amikacin is combined with 4-hydroxycoumarin. Abacavir Amikacin may decrease the excretion rate of Abacavir which could result in a higher serum level. Acarbose Amikacin may decrease the excretion rate of Acarbose which could result in a higher serum level. Aceclofenac The risk or severity of nephrotoxicity can be increased when Aceclofenac is combined with Amikacin. Acemetacin The risk or severity of nephrotoxicity can be increased when Acemetacin is combined with Amikacin. Acenocoumarol The risk or severity of bleeding can be increased when Amikacin is combined with Acenocoumarol. Acetaminophen Amikacin may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
- Food Interactions
- Not Available
- Synthesis Reference
Alberto Mangia, Vicenzo Giobbio, Giorgio Ornato, "Novel process for the synthesis of amikacin." U.S. Patent US4902790, issued August, 1984.US4902790
- General References
- Edson RS, Terrell CL: The aminoglycosides. Mayo Clin Proc. 1999 May;74(5):519-28. [PubMed:10319086]
- Ramirez MS, Tolmasky ME: Amikacin: Uses, Resistance, and Prospects for Inhibition. Molecules. 2017 Dec 19;22(12). pii: molecules22122267. doi: 10.3390/molecules22122267. [PubMed:29257114]
- FDA Approves Arikayce [Link]
- Stat Pearls: Amikacin [Link]
- FDA approves a new antibacterial drug to treat a serious lung disease using a novel pathway to spur innovation [Link]
- MedSafe NZ: Amikacin Injection [File]
- EMA Withdrawal document, Arikayce [File]
- Amikacin, DailyMed [File]
- External Links
- ATC Codes
- S01AA21 — AmikacinD06AX12 — Amikacin
- D06AX — Other antibiotics for topical use
- D06A — ANTIBIOTICS FOR TOPICAL USE
- D06 — ANTIBIOTICS AND CHEMOTHERAPEUTICS FOR DERMATOLOGICAL USE
- D — DERMATOLOGICALS
- J01GB — Other aminoglycosides
- J01G — AMINOGLYCOSIDE ANTIBACTERIALS
- J01 — ANTIBACTERIALS FOR SYSTEMIC USE
- J — ANTIINFECTIVES FOR SYSTEMIC USE
- AHFS Codes
- 08:12.02 — Aminoglycosides
- PDB Entries
- 4p20 / 6cgd
- FDA label
- Download (3.36 MB)
- Download (73.4 KB)
- Clinical Trials
- Abbott laboratories
- Abbott laboratories hosp products div
- Astrazeneca lp
- Baxter healthcare corp anesthesia and critical care
- Bedford laboratories div ben venue laboratories inc
- Hospira inc
- Teva parenteral medicines inc
- Apothecon inc div bristol myers squibb
- Bedford Labs
- Ben Venue Laboratories Inc.
- Bristol-Myers Squibb Co.
- Hospira Inc.
- Mead Johnson and Co.
- Medisca Inc.
- Sicor Pharmaceuticals
- Teva Pharmaceutical Industries Ltd.
- Dosage forms
Form Route Strength Injection Intramuscular; Intravenous 250 mg/1mL Injection, solution Intramuscular; Intravenous 1 g/4mL Injection, solution Intramuscular; Intravenous 100 mg/2mL Injection, solution Intramuscular; Intravenous 500 mg/2mL Liquid Intramuscular; Intravenous 250 mg Injection, solution Intramuscular; Intravenous 250 mg/1mL Injection, solution Intramuscular; Intravenous 50 mg/1mL Solution Intramuscular; Intravenous 250 mg Suspension Respiratory (inhalation) 590 mg/8.4mL
Unit description Cost Unit Amikacin sulfate powder 26.01USD g Amikacin (pf) 500 mg/2 ml 2.53USD ml Amikacin 250 mg/ml vial 2.19USD ml Amikacin (pf) 100 mg/2 ml 1.8USD mlDrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patent Number Pediatric Extension Approved Expires (estimated) US8802137 No 2004-04-08 2024-04-08 US7718189 No 2005-06-06 2025-06-06 US8679532 No 2006-12-05 2026-12-05 US9566234 No 2014-01-18 2034-01-18 US9895385 No 2015-05-15 2035-05-15 US8632804 No 2006-12-05 2026-12-05 US9827317 No 2004-04-08 2024-04-08 US8642075 No 2006-12-05 2026-12-05 US8226975 No 2008-08-15 2028-08-15
- Experimental Properties
Property Value Source melting point (°C) 214 MSDS boiling point (°C) 632.23 https://www.chemicalbook.com/ChemicalProductProperty_US_CB8146049.aspx water solubility 50 mg/ml https://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma/Product_Information_Sheet/a1774pis.pdf logS -0.5 ADME Research, USCD: https://pubchem.ncbi.nlm.nih.gov/compound/amikacin#section=Solubility pKa 8.1 http://www.druginfosys.com/drug.aspx?drugcode=45&type=1
- Predicted Properties
Property Value Source Water Solubility 49.7 mg/mL ALOGPS logP -3.2 ALOGPS logP -8.6 ChemAxon logS -1.1 ALOGPS pKa (Strongest Acidic) 12.1 ChemAxon pKa (Strongest Basic) 9.79 ChemAxon Physiological Charge 4 ChemAxon Hydrogen Acceptor Count 17 ChemAxon Hydrogen Donor Count 13 ChemAxon Polar Surface Area 331.94 Å2 ChemAxon Rotatable Bond Count 10 ChemAxon Refractivity 129.84 m3·mol-1 ChemAxon Polarizability 58.06 Å3 ChemAxon Number of Rings 3 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
Property Value Probability Human Intestinal Absorption - 0.9405 Blood Brain Barrier - 0.9659 Caco-2 permeable - 0.7583 P-glycoprotein substrate Substrate 0.5129 P-glycoprotein inhibitor I Non-inhibitor 0.7336 P-glycoprotein inhibitor II Non-inhibitor 0.8383 Renal organic cation transporter Non-inhibitor 0.8614 CYP450 2C9 substrate Non-substrate 0.816 CYP450 2D6 substrate Non-substrate 0.8309 CYP450 3A4 substrate Non-substrate 0.5664 CYP450 1A2 substrate Non-inhibitor 0.9381 CYP450 2C9 inhibitor Non-inhibitor 0.9237 CYP450 2D6 inhibitor Non-inhibitor 0.9249 CYP450 2C19 inhibitor Non-inhibitor 0.9128 CYP450 3A4 inhibitor Non-inhibitor 0.9434 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8866 Ames test Non AMES toxic 0.6813 Carcinogenicity Non-carcinogens 0.9635 Biodegradation Not ready biodegradable 0.5512 Rat acute toxicity 1.7506 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9926 hERG inhibition (predictor II) Non-inhibitor 0.6366
- Mass Spec (NIST)
- Not Available
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
- This compound belongs to the class of organic compounds known as 4,6-disubstituted 2-deoxystreptamines. These are 2-deoxystreptamine aminoglycosides that a glycosidically linked to a pyranose of furanose unit at the C4- and C6-positions.
- Organic compounds
- Super Class
- Organic oxygen compounds
- Organooxygen compounds
- Sub Class
- Carbohydrates and carbohydrate conjugates
- Direct Parent
- 4,6-disubstituted 2-deoxystreptamines
- Alternative Parents
- Gamma amino acids and derivatives / O-glycosyl compounds / Aminocyclitols and derivatives / Cyclohexanols / Cyclohexylamines / Oxanes / Monosaccharides / N-acyl amines / 1,3-aminoalcohols / 1,2-aminoalcoholsSecondary carboxylic acid amides / Acetals / Polyols / Oxacyclic compounds / Monoalkylamines / Hydrocarbon derivatives / Primary alcohols / Carbonyl compounds / Organic oxides / Organopnictogen compounds show 10 more
- 4,6-disubstituted 2-deoxystreptamine / Gamma amino acid or derivatives / Glycosyl compound / O-glycosyl compound / Aminocyclitol or derivatives / Cyclohexanol / Cyclohexylamine / Fatty acyl / Monosaccharide / N-acyl-amineCyclitol or derivatives / Fatty amide / Oxane / 1,3-aminoalcohol / Cyclic alcohol / Carboxamide group / Secondary alcohol / Secondary carboxylic acid amide / Amino acid or derivatives / 1,2-aminoalcohol / Carboxylic acid derivative / Polyol / Organoheterocyclic compound / Oxacycle / Acetal / Organic nitrogen compound / Primary aliphatic amine / Organonitrogen compound / Carbonyl group / Primary alcohol / Primary amine / Hydrocarbon derivative / Amine / Alcohol / Organic oxide / Organopnictogen compound / Aliphatic heteromonocyclic compound show 27 more
- Molecular Framework
- Aliphatic heteromonocyclic compounds
- External Descriptors
- alpha-D-glucoside, aminoglycoside, carboxamide, amino cyclitol glycoside (CHEBI:2637)
- Escherichia coli (strain K12)
- Pharmacological action
- General Function
- Trna binding
- Specific Function
- With S4 and S5 plays an important role in translational accuracy.Interacts with and stabilizes bases of the 16S rRNA that are involved in tRNA selection in the A site and with the mRNA backbone. Lo...
- Gene Name
- Uniprot ID
- Uniprot Name
- 30S ribosomal protein S12
- Molecular Weight
- 13736.995 Da
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
- Tolmasky ME: Bacterial resistance to aminoglycosides and beta-lactams: the Tn1331 transposon paradigm. Front Biosci. 2000 Jan 1;5:D20-9. [PubMed:10702385]
- Amikacin, DailyMed [File]
- MedSafe NZ: Amikacin Injection [File]
Drug created on June 13, 2005 07:24 / Updated on January 22, 2019 17:56