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Amikacin

J01G - Aminoglycoside antibacterials ATC J01GB06 Small molecule approved 1981 Parenteral Topical Natural product Orphan Narrow therapeutic index Black-box warning

🧬 Cross-allergy: Aminoglycosides

JFDA label: Likacin Inj

⚠ Black-Box Warning
  • Ototoxicity:
  • Nephrotoxicity:
  • Neuromuscular blockade:
  • Monitoring:
  • Concurrent therapy:
  • Nephrotoxicity

Mechanism of Action

Inhibits protein synthesis in susceptible bacteria by binding to 30S ribosomal subunits

Indications

Approved

  • Serious infections

Off-label

  • Bacterial endophthalmitis
  • Cystic fibrosis exacerbation (aerosolized amikacin)
  • Mycobacterium avium complex (MAC)
  • Tuberculosis

Antimicrobial Spectrum

Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: EUCAST v16 · curated · openfda-label.

Bacteria

OrganismActivityMIC
Acinetobacter baumannii Susceptible 8.0 mg/L
Acinetobacter spp. Susceptible 81.0 mg/L
Citrobacter freundii Active
Enterobacterales Susceptible 81.0 mg/L
Escherichia coli Susceptible 8.0 mg/L
Klebsiella pneumoniae Susceptible 8.0 mg/L
Mycobacterium tuberculosis Susceptible 1.0 mg/L
Proteus rettgeri Active
Providencia stuartii Active
Pseudomonas aeruginosa Susceptible 8.0 mg/L
Pseudomonas aeruginosa Susceptible 161.0 mg/L
Serratia marcescens Active
Acinetobacter baumannii Resistant 16.0 mg/L
Escherichia coli Resistant 16.0 mg/L
Klebsiella pneumoniae Resistant 16.0 mg/L
Pseudomonas aeruginosa Resistant 16.0 mg/L

Class profile

gramStatusBoth
spectrumBreadthModerate
atypicalCoverageNo
isBactericidal1
moaCategoryProtein synthesis inhibitor (30S ribosomal)
pdIndexConcentration-dependent
postAntibioticEffectProlonged
mrsaCoverage0
resistanceMechanismsAminoglycoside-modifying enzymes,Ribosomal methylation (16S rRNA),Reduced outer membrane permeability

Contraindications

Source: Lexicomp

  • Hypersensitivity to amikacin, other aminoglycosides, or any component of the formulation Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (1)

Common Neurotoxicity

Ear and labyrinth disorders (2)

Common Auditory ototoxicity · vestibular ototoxicity

Dosing

Source: Lexicomp

Individualization is critical because of the low therapeutic index In underweight and nonobese patients, use of total body weight (TBW) instead of ideal body weight for determining the initial mg/kg/dose is widely accepted (Nicolau, 1995). Ideal body weight (IBW) also may be used to determine doses for patients who are neither underweight nor obese (Gilbert 2009). Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Manufacturer recommends a maximum daily dose of 15 mg/kg/day (or 1.5 g/day in heavier patients). Higher doses may be warranted based on therapeutic drug monitoring or susceptibility information. Usual dosage range: IM, IV: 5 to 7.5 mg/kg/dose every 8 hours; Note: Some clinicians suggest a daily dose of 15 to 20 mg/kg/day for all patients with normal renal function. This dose is at least as efficacious with similar, if not less, toxicity than conventional dosing. Intrathecal/intraventricular (off-label route): Meningitis (susceptible gram-negative organisms): 5 to 50 mg/day (Gilbert, 1986; Guardado 2008; IDSA 2004; Kasiakou 2005) Indication-specific dosing: Cystic fibrosis exacerbation (off-label use/route): Inhalation for nebulization: Monotherapy: 500 mg twice daily (Le 2010) Adjunctive therapy: 100 mg twice daily with concomitant IV amikacin and ceftazidime (Schaad 1987) Endophthalmitis, bacterial (off-label use): Intravitreal: 0.4 mg/0.1 mL NS in combination with vancomycin Meningitis (susceptible gram-negative organisms): IV: 5 mg/kg every 8 hours (administered with another bactericidal drug) (IDSA 2004) Intrathecal/intraventricular (off-label route): Usual dose: 30 mg/day (IDSA 2004); Range: 5 to 50 mg/day (with concurrent systemic antimicrobial therapy) (Gilbert, 1986; Guardado 2008; IDSA 2004; Kasiakou 2005) Mycobacterium avium complex (MAC) (off-label use): IV: Adjunct therapy (with macrolide, rifamycin, and ethambutol): 8 to 25 mg/kg 2 to 3 times weekly for first 2 to 3 months for severe disease (maximum single dose for age >50 years: 500 mg) (Griffith 2007) Mycobacterium fortuitum, M. chelonae, or M. abscessus: IV: 10 to 15 mg/kg daily for at least 2 weeks with high dose cefoxitin Pneumonia, hospital-acquired (HAP) or ventilator-associated (VAP) (alternative therapy) (off-label dose): IV: 15 to 20 mg/kg/dose once every 24 hours for 7 days; may consider shorter or longer durations depending on rate of clinical improvement. When used as empiric therapy, use in combination with an agent active against S. aureus and an additional antipseudomonal agent. Note: Aminoglycosides are not recommended as monotherapy in patients with HAP or VAP due to P. aeruginosa (Kalil 2016).
(For additional information see "Amikacin: Pediatric drug information") General dosing, severe, susceptible infections: Infants, Children, and Adolescents: IM, IV: 15 to 22.5 mg/kg/day divided every 8 hours or 15 to 20 mg/kg/dose every 24 hours (Red Book [AAP 2015]) Dosage should be based on an estimate of ideal body weight. In morbidly obese children and adolescents, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW). Initial dosing recommendation presented; dosage should be individualized based upon serum concentration monitoring. Initial and periodic plasma drug concentrations (eg, peak and trough with conventional dosing, post dose level at a prespecified time with extended-interval dosing) should be determined, particularly in critically ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Indication-specific dosing: CNS infections (off-label dose): Meningitis (Tunkel 2004): Infants and Children: IV: 20 to 30 mg/kg/day divided every 8 hours Adolescents: IV: 15 mg/kg/day divided every 8 hours VP-shunt infection, ventriculitis: Limited data available: Intraventricular/intrathecal (use a preservative free preparation): Infants, Children, and Adolescents: 5 to 50 mg/day; usual dose: 30 mg/day Cystic fibrosis, pulmonary infection (systemic use) (off-label use): Infants, Children, and Adolescents: Traditional dosing: IV, IM: 10 mg/kg/dose every 8 hours (Wallace 1993) Extended-interval dosing: IV: 30 mg/kg/dose every 24 hours (Flume 2009); Note: The CF Foundation recommends extended-interval dosing as preferred over traditional dosing. Cystic fibrosis, pulmonary infection (inhalational use; off-label use/route): Inhalation for nebulization: Adolescents ≥14 years: Monotherapy: Refer to adult dosing Children ≥3 years and Adolescents: Adjunctive therapy: Refer to adult dosing Endocarditis, treatment (off-label dose): Children and Adolescents: IV: 15 mg/kg/day divided every 8 to 12 hours; use in combination with other antibiotics dependent upon organism and source of infection (ie, valve-type) (AHA [Baltimore 2015]) Intra-abdominal infection, complicated (off-label dose): Infants, Children and Adolescents: IV: 15 to 22.5 mg/kg/day divided every 8 to 24 hours (Solomkin 2010) Mycobacterium, avium complex infection (MAC) (off-label use): HIV-exposed/-positive: Infants and Children: IV: 15 to 30 mg/kg/day divided every 12 to 24 hours as part of a multiple drug regimen; maximum daily dose: 1,500 mg/day (HHS [pediatric] 2013) Adolescents: IV: 10 to 15 mg/kg/day every 24 hours as part of a multiple drug regimen (HHS [adult] 2015; HHS [pediatric] 2013) Peritonitis (CAPD): Infants, Children, and Adolescents: Intraperitoneal: Continuous: Loading dose: 25 mg per liter of dialysate; maintenance dose: 12 mg per liter (Warady 2012) Tuberculosis, drug-resistant (off-label use): Infants, Children, and Adolescents ≤14 ye
Refer to adult dosing.
Some patients may require larger or more frequent doses if serum levels document the need (ie, cystic fibrosis or febrile granulocytopenic patients). Adults: The following adjustments have been recommended: Note: Renally adjusted dose recommendations are based on a dose of 7.5 mg/kg every 12 hours (Aronoff 2007). GFR >50 mL/minute: No dosage adjustment necessary. GFR 10 to 50 mL/minute: Administer every 24 to 72 hours based on serum concentrations GFR Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days): Dialyzable (20%; variable; dependent on filter, duration, and type of HD): 5 to 7.5 mg/kg every 48 to 72 hours. Follow levels. Redose when pre-HD concentration Note: Dosing dependent on the assumption of 3 times/week, complete IHD sessions. Peritoneal dialysis (PD) (Li 2010): Intermittent dosing: 2 mg/kg per exchange once daily; allow to dwell ≥6 hours Continuous dosing (all exchanges): Loading dose: 25 mg/L; maintenance dose: 12 mg/L Continuous renal replacement therapy (CRRT) (Heintz 2009; Trotman 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and minimal residual renal function) and should not supersede clinical judgment: CVVH/CVVHD/CVVHDF: Loading dose of 10 mg/kg followed by maintenance dose of 7.5 mg/kg every 24 to 48 hours Note: For severe gram-negative rod infections, target peak concentration of 15 to 30 mg/L; redose when concentration Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer’s labeling; however, the following adjustments have been recommended (Aronoff 2007): Renally adjusted dose recommendations are based on doses of 5 to 7.5 mg/kg/dose every 8 hours. GFR >50 mL/minute/1.73 m2: No dosage adjustment necessary GFR 30 to 50 mL/minute/1.73 m2: Administer every 12 to 18 hours GFR 10 to 29 mL/minute/1.73 m2: Administer every 18 to 24 hours GFR 2: Administer every 48 to 72 hours Intermittent hemodialysis: 5 mg/kg/dose; redose as indicated by serum concentrations Peritoneal dialysis (PD): 5 mg/kg/dose; redose as indicated by serum concentrations Continuous renal replacement therapy (CRRT): 7.5 mg/kg/dose every 12 hours, monitor serum concentrations
There are no dosage adjustments provided in the manufacturer’s labeling.

Warnings & Precautions

Source: Lexicomp

Hypersensitivity

Cross-sensitivity to other aminoglycosides may occur.

Nephrotoxicity

May cause nephrotoxicity; usual risk factors include preexisting renal impairment, concomitant nephrotoxic medications, advanced age and dehydration. Discontinue treatment if signs of nephrotoxicity occur; renal damage is usually reversible.

Neuromuscular blockade and respiratory paralysis

May cause neuromuscular blockade and respiratory paralysis; especially when given soon after anesthesia or muscle relaxants.

Neurotoxicity

May cause neurotoxicity; usual risk factors include preexisting renal impairment, concomitant neuro-/nephrotoxic medications, advanced age and dehydration. Ototoxicity is proportional to the amount of drug given and the duration of treatment. Tinnitus or vertigo may be indications of vestibular injury and impending bilateral irreversible damage. Discontinue treatment if signs of ototoxicity occur.

Superinfection

Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment. Disease-related concerns:

Hearing impairment

Use with caution in patients with preexisting vertigo, tinnitus, or hearing loss.

Hypocalcemia

Use with caution in patients with hypocalcemia.

Neuromuscular disorders

Use with caution in patients with neuromuscular disorders, including myasthenia gravis or parkinsonism.

Renal impairment

Use with caution in patients with preexisting renal insufficiency; dosage modification required. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Neurotoxic and/or nephrotoxic drugs

Avoid concomitant or sequential use of other neurotoxic and/or nephrotoxic drugs (eg, bacitracin, cisplatin, amphotericin B, paromomycin, polymyxin B, colistin, vancomycin, other aminoglycosides).

Potent diuretics

Avoid concomitant use with potent diuretics (eg, ethacrynic acid, furosemide) since diuretics themselves may cause ototoxicity and may enhance aminoglycoside toxicity. Dosage form specific issues:

Sulfites

May contain sulfites which may cause allergic-type reactions (including anaphylaxis) as well as life-threatening or less severe asthmatic episodes in certain individuals. Other warnings/precautions:

Surgical irrigation

Irreversible deafness, renal failure, and death due to neuromuscular blockade have been reported following use of aminoglycosides as surgical irrigation; rapid systemic absorption occurs with topical application (except to the urinary bladder).

Pregnancy & Lactation

Pregnancy

FDA category D

Adverse events were not observed in the initial animal reproduction studies. Amikacin crosses the placenta and produces detectable concentrations in the fetus. Aminoglycosides may cause fetal harm if administered to a pregnant woman. There are several reports of total irreversible bilateral congenital deafness in children whose mothers received another aminoglycoside (streptomycin) during pregnancy. Although serious side effects to the fetus/infant have not been reported following maternal use of all aminoglycosides, a potential for harm exists. Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of amikacin may be altered (Bernard 1977).

Lactation

Amikacin is excreted into breast milk (trace amounts) (Matsuda 1984). Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother. As a class, aminoglycosides are expected to be poorly distributed into breast milk, limiting systemic exposure to a nursing infant. In general, modification of bowel flora may occur with

LactMed: monitor the infant.

Monitoring

EfficacyPeak 20–30 mg/L (30 min post-infusion); trough < 5 mg/L (once-daily: trough < 1 mg/L); renal function; audiogram for prolonged therapy
ToxicityNephrotoxicity; ototoxicity (auditory and vestibular); check SCr every 2–3 days in at-risk patients
Clinical pearlLike gentamicin but used for resistant organisms including MDR-TB. AUC-guided dosing is increasingly preferred.
CounselingReport hearing changes, dizziness, or decreased urination immediately.

Chemistry & Properties

2D structure
FormulaC22H43N5O13
Molecular weight585.61 g/mol
IUPAC name(2S)-4-amino-N-[(1R,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,5S,6R)-6-(aminomethyl)-3,4,5-trihydroxyoxan-2-yl]oxy-3-hydroxycyclohexyl]-2-hydroxybutanamide
CAS37517-28-5
PubChem CID37768
InChIKeyLKCWBDHBTVXHDL-RMDFUYIESA-N
logP-8.42 (XLogP -7.9)
Polar surface area331.94 Ų
H-bond acceptors / donors17 / 13
Drug-likeness (QED)0.11
Lipinski violations3
SMILESNCC[C@H](O)C(=O)N[C@@H]1C[C@H](N)[C@@H](O[C@H]2O[C@H](CN)[C@@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@H]1O[C@H]1O[C@H](CO)[C@@H](O)[C@H](N)[C@H]1O

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability70.0%
Half-life2.921 h
Volume of distribution0.2 L/kg
Protein binding10.9%
BBB penetrantNo

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drugSeverityManagement
Atracurium major
Bacitracin major
Botulinum Toxin Type B major
Botulinum toxin type A major
Bumetanide major
Capreomycin major
Cidofovir major
Cisatracurium major
Colistimethate major
Deferasirox major
Diatrizoate major
Doxacurium major
Etacrynic acid major
Everolimus major
Foscarnet major
Furosemide major
Gallium nitrate major
Human Rho(D) immune globulin major
Human botulinum neurotoxin A/B immune globulin major
Human cytomegalovirus immune globulin major
Human immunoglobulin G (intravenous and subcutaneous) major
Human immunoglobulin G (intravenous) major
Inotersen major
Iodipamide major
Iodixanol major
Iohexol major
Iopamidol major
Iopromide major
Iothalamic acid major
Ioversol major
Ioxilan major
Magnesium sulfate major
Mannitol major
Metocurine major
Mivacurium major
Pancuronium major
Pipecuronium major
Polymyxin B major
Rapacuronium major
Rocuronium major

Showing 40 of 100+.

Registered Products (11)

BrandForm / strengthPackAgentCitizen (JOD)
Amiswiss Vial 500 mg/2 ml 1 vial Argon drug store 0.460
Likacin Inj Injection 500 mg/2 ml 1 vial pack varies AL Rahma Drug Store 3.480
Likacin Gel Gel 5 % 30 g tube AL Rahma Drug Store 4.620
Miacin 100 Ampoules Ampoule (as Sulphate) 100 mg/2 ml 6 amp Hikma Pharmaceuticals Co.Ltd/Jordan 4.930
Amicine 250mg/2ml Solution for Inj Injection 250 mg/2 ml 5 vial MS PHARMA/JORDAN 18.610
Amicine 500mg/2ml Solution for Inj Injection 500 mg/2 ml 5 vial MS PHARMA/JORDAN 18.610
Miacin 500 Ampoules Ampoule 500 mg/2 ml 6 amp Hikma Pharmaceuticals Co.Ltd/Jordan 24.000
Selemycin Ampoule 250 mg/2 ml 10 amp Al Hilal Drug Store 27.680
Selemycin Ampoule 500 mg/2 ml 10 amp Al Hilal Drug Store 45.200
Likacin Inj Injection 500 mg/2 ml 50 vial pack varies AL Rahma Drug Store 147.900
Amikam Vial 250 mg/ml 2 ml مستودع أدوية الليليوÙ