Version May 2024
Neurotoxicity, manifested as vestibular and permanent bilateral auditory ototoxicity, can occur in patients with preexisting renal damage and in patients with normal renal function treated at higher doses and/or periods longer than those recommended. The risk of aminoglycoside-induced ototoxicity is greater in patients with renal damage. High frequency deafness usually occurs first and can be detected only by audiometric testing. Vertigo may occur and may be evidence of vestibular injury. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching, and convulsions. The risk of hearing loss due to aminoglycosides increases with the degree of exposure to either high peak or high trough serum concentrations. Patients developing cochlear damage may not have symptoms during therapy to warn them of developing eighth-nerve toxicity, and total or partial irreversible bilateral deafness may occur after the drug has been discontinued. Aminoglycoside-induced ototoxicity is usually irreversible. Patients treated with parenteral aminoglycosides should be under close clinical observation because of the potential ototoxicity associated with their use. Safety for treatment periods which are longer than 14 days has not been established.
Aminoglycosides are potentially nephrotoxic. The risk of nephrotoxicity is greater in patients with impaired renal function and in those who receive high doses or prolonged therapy. Patients treated with parenteral aminoglycosides should be under close clinical observation because of the potential nephrotoxicity associated with their use. Safety for treatment periods which are longer than 14 days has not been established.
Neuromuscular blockade and respiratory paralysis have been reported following parenteral injection, topical instillation (as in orthopedic and abdominal irrigation or in local treatment of empyema), and following oral use of aminoglycosides. The possibility of these phenomena should be considered if aminoglycosides are administered by any route, especially in patients receiving anesthetics, neuromuscular blocking agents such as tubocurarine, succinylcholine, decamethonium, or in patients receiving massive transfusions of citrate-anticoagulated blood. If blockage occurs, calcium salts may reverse these phenomena, but mechanical respiratory assistance may be necessary.
Renal and eighth-nerve function should be closely monitored especially in patients with known or suspected renal impairment at the onset of therapy and also in those whose renal function is initially normal but who develop signs of renal dysfunction during therapy. Serum concentrations of amikacin should be monitored when feasible to assure adequate levels and to avoid potentially toxic levels and prolonged peak concentrations above 35 mcg/mL. Urine should be examined for decreased specific gravity, increased excretion of proteins, and the presence of cells or casts. Blood urea nitrogen, serum creatinine, or creatinine clearance should be measured periodically. Serial audiograms should be obtained where feasible in patients old enough to be tested, particularly high-risk patients. Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, and hearing loss) or nephrotoxicity requires discontinuation of the drug or dosage adjustment.
Concurrent and/or sequential systemic, oral, or topical use of other neurotoxic or nephrotoxic products, particularly bacitracin, cisplatin, amphotericin B, cephaloridine, paromomycin, viomycin, polymyxin B, colistin, vancomycin, or other aminoglycosides should be avoided. Other factors that may increase risk of toxicity are advanced age and dehydration.
The concurrent use of amikacin with potent diuretics (ethacrynic acid, or furosemide) should be avoided because diuretics by themselves may cause ototoxicity. In addition, when administered intravenously, diuretics may enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.
Dosing guidance:
Dosing: For patients who are underweight (ie, total body weight [TBW] < ideal body weight [IBW]), calculate dose based on TBW. For patients who are nonobese (ie, TBW 1 to 1.25 × IBW), calculate the dose based on TBW or IBW. TBW may be preferred in patients who are nonobese who may have increased Vd (eg, critically ill). For patients with obesity (ie, TBW >1.25 × IBW), use adjusted body weight ([0.4 × (TBW - IBW)] + IBW) for initial weight-based dosing and for estimating kidney function with Cockcroft-Gault (CrCl) (Ref).
Clinical considerations: Therapeutic drug monitoring is recommended to ensure efficacy and avoid toxicity, particularly in patients who are critically ill with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, major surgery). Timing and frequency of concentration monitoring is individualized based on dosing and monitoring strategy (Ref).
Usual dosage range:
Conventional/traditional dosing: IM, IV: 5 mg/kg every 8 hours or 7.5 mg/kg every 12 hours. Target peak concentration depends on indication, site of infection, and minimum inhibitory concentration (MIC) of pathogen; in general, adjust dose to achieve peak of 20 to 40 mg/L. Target trough concentrations should be <8 mg/L; ideal target trough is 1 to 4 mg/L (Ref).
High - dose extended-interval dosing: IV: 15 to 20 mg/kg once daily; use with caution in patients with CrCl <40 mL/minute (Ref). Some experts recommend doses up to 30 mg/kg once daily in critically ill patients (Ref). Adjust amikacin dose and interval to achieve a peak concentration of ~40 mg/L (60 mg/L may be needed in critically ill patients) and trough concentration <2 mg/L (Ref). Note: Published nomograms for dosage adjustment may not apply to patients with altered pharmacokinetics (eg, patients with ascites, burns covering >20% total BSA, end-stage renal disease on dialysis, pregnancy) (Ref); some experts prefer traditional intermittent dosing in such populations (Ref).
Bloodstream infection: Adjunctive empiric therapy for patients with sepsis/septic shock and concern for resistant gram-negative bacteria (eg, immunosuppression, prevalent local resistance, recent antibiotic exposure): IV: 15 to 30 mg/kg once daily in combination with a second gram-negative active agent; once culture and susceptibility results are available, can generally discontinue and use a single agent with documented activity. Amikacin should not be used as monotherapy (Ref).
Cerebrospinal fluid (CSF) shunt infection (susceptible gram-negative organisms):
IV: 5 mg/kg every 8 hours in combination with other appropriate agents (Ref).
Intraventricular/intrathecal (adjunct to systemic therapy; use a preservative-free preparation): 5 to 50 mg/day; usual dose: 30 mg/day (Ref). Some experts recommend adjusting dosage and administration interval based on CSF amikacin concentrations (goal: 10 to 20 times MIC of causative organism), ventricle size, and daily output from ventricular drain (Ref). When intraventricular amikacin is administered via a ventricular drain, clamp drain for 15 to 60 minutes after administration (allows solution to equilibrate in CSF). Duration is individualized according to clinical and microbiologic response (Ref). Note: Intraventricular/intrathecal administration is generally reserved for use in patients who fail parenteral therapy despite removal of CSF shunt or when CSF shunt cannot be removed (Ref).
Cystic fibrosis, acute pulmonary exacerbation (off-label use): IV: 30 to 35 mg/kg once daily in combination with other appropriate agents; adjust dose and interval to achieve a target peak of 80 to 120 mg/L and trough <1 mg/L (Ref).
Meningitis, bacterial (susceptible gram-negative organisms): IV: 5 mg/kg every 8 hours in combination with other appropriate agents (Ref).
Mycobacterial (nontuberculous) infection:
M. avium complex (off-label use):
Disseminated disease in patients with HIV, adjunct therapy: IV: 10 to 15 mg/kg daily as part of an appropriate combination regimen. Note: Some experts recommend addition of amikacin in patients with high mycobacterial loads (ie, >2 log CFU/mL of blood) or in the absence of effective antiretroviral therapy (Ref).
Pulmonary disease (severe nodular/bronchiectatic or cavitary disease) (adjunctive agent): IV: 10 to 15 mg/kg once daily or 15 to 25 mg/kg 3 times weekly for first 2 to 3 months as part of an appropriate combination regimen (Ref).
Rapidly growing mycobacteria (eg, M. abscessus) (off-label use):
Initial therapy: IV: 10 to 15 mg/kg once daily or 15 to 25 mg/kg 3 times weekly as part of an appropriate combination regimen. The optimal duration of therapy is unknown, but generally the duration of parenteral therapy is ≤12 weeks depending on pathogen, severity of infection, tolerability, and other patient-specific factors, followed by long-term oral maintenance therapy; consult an infectious diseases specialist for specific recommendations (Ref).
Maintenance therapy: Inhalation for nebulization (using injection solution): 250 to 500 mg once or twice daily as part of an appropriate combination regimen; consult an infectious diseases specialist for specific recommendations including duration (Ref).
Nocardiosis, severe (off-label use):
Note: Due to concerns for resistance, susceptibility testing should be performed on isolates (Ref).
IV: 10 to 15 mg/kg once daily as part of an appropriate combination regimen (Ref). Prolonged treatment is required (range 6 months to ≥1 year [at least several weeks of parenteral therapy followed by oral therapy]) (Ref). Consult an infectious diseases specialist for specific treatment recommendations.
Plague (Yersinia pestis), treatment (alternative agent) (off-label use):
Note: Consult public health officials for event-specific recommendations.
IV, IM: 15 to 20 mg/kg once daily for 7 to 14 days and for at least a few days after clinical resolution (Ref).
Pneumonia, hospital-acquired or ventilator-associated (alternative agent):
Note: Some experts reserve for patients with risk for multidrug-resistant pathogens (Ref).
IV: 15 to 20 mg/kg once daily in combination with a second gram-negative agent; once culture and susceptibility results are available, can generally discontinue amikacin and use a single agent with documented activity (Ref). Note: Avoid use of amikacin monotherapy (Ref).
Inhalation for nebulization (using injectable solution): 400 to 500 mg every 12 hours in combination with IV antimicrobial therapy. Note: Efficacy is uncertain and bronchospasm may limit use (Ref).
Sepsis or septic shock, adjunctive empiric gram-negative coverage:
Note: Some experts reserve for patients at high risk for multidrug resistant gram-negative pathogens (Ref).
IV: 15 to 30 mg/kg once daily in combination with a second gram-negative agent; once culture and susceptibility tests are available, can generally discontinue and use a single agent with documented activity. Amikacin should not be used as monotherapy (Ref).
Tuberculosis, drug resistant (alternative agent) (off-label use):
Note: Expert consultation for optimal regimen and duration of treatment is advised.
IM, IV: 15 mg/kg once daily or 25 mg/kg 3 times weekly in combination with additional appropriate antituberculosis agents (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
High-dose, extended-interval dosing: IV:
Note: Use with caution in patients with CrCl <40 mL/minute (Ref), although high-dose extended-interval dosing may still be considered, especially in patients with severe sepsis/shock or those infected with multidrug-resistant gram-negative organisms (Ref).
Initial dose: 15 to 20 mg/kg; up to 30 mg/kg once daily in critically ill patients. Subsequent doses and frequency of administration should be determined based on therapeutic drug monitoring. Regimens may vary; nomograms exist to guide dose adjustments, although individualized calculations may be necessary in patients with highly variable or altered aminoglycoside pharmacokinetics (ie, critical illness, pregnancy, etc) (Ref). Also refer to institutional-specific policies. The following recommendations may serve as a general guideline after the initial dose:
CrCl ≥60 mL/minute: Administer every 24 hours; adjust dose and/or interval based on amikacin serum concentrations.
CrCl 40 to <60 mL/minute: Administer every 36 hours; adjust dose and/or interval based on amikacin serum concentrations.
CrCl 20 to <40 mL/minute: Administer every 48 hours; adjust dose and/or interval based on amikacin serum concentrations.
CrCl <20 mL/minute: Administer usual dose once, then determine subsequent dose and interval based on amikacin serum concentrations. Some published protocols would recommend conventional/traditional dosing in these patients (Ref).
Conventional/traditional dosing: IM, IV:
Note: High-dose, extended-interval dosing is generally preferred for treatment of gram-negative infections.
Regimens may vary based on individualized pharmacokinetic calculations and pharmacodynamic targets; also refer to institutional-specific policies. The following recommendations are expert opinion derived from Leroy 1978:
|
CrCl |
If the usual indication-specific dose is 7.5 mg/kg every 12 hours or 5 mg/kg every 8 hours |
|---|---|
|
≥60 mL/minute |
No dosage adjustment necessary. |
|
40 to <60 mL/minute |
5 to 7.5 mg/kg every 12 hours. |
|
20 to <40 mL/minute |
5 to 7.5 mg/kg every 24 hours. |
|
<20 mL/minute |
5 to 7.5 mg/kg once; subsequent doses should be based on amikacin serum concentrations. |
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2):
Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
High-dose, extended-interval dosing: IV: Initial: 20 to 30 mg/kg once daily for known/suspected sepsis; adjust dose and/or interval based on close monitoring of amikacin serum concentrations and individualized pharmacokinetic calculations and pharmacodynamic targets; use of nomograms for dosage adjustment are not recommended in this population (expert opinion derived from Aréchiga-Alvarado 2020).
Hemodialysis, intermittent (thrice weekly):
Dialyzable (~20% to 65% (Ref) dependent on filter and duration): Note: Postdialysis concentrations should be drawn ≥2 and up to 4 hours after hemodialysis to allow for redistribution (Ref).
IM, IV: 5 to 12.5 mg/kg/dose 3 times weekly after dialysis on dialysis days (Ref). Redose when prehemodialysis amikacin concentration <10 mg/L or when posthemodialysis amikacin concentration <6 to 8 mg/L (Ref).
Peritoneal dialysis: IM, IV: Initial: 5 to 12.5 mg/kg/dose (depending on infection site, severity, and susceptibility of infecting organisms) every 48 to 72 hours; adjust dose and/or interval based on amikacin serum concentrations (Ref).
CRRT:
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) and minimal residual kidney function unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, nephrotoxicity) due to drug accumulation is important.
CVVH/CVVHD/CVVHDF: IV: Initial: 15 to 25 mg/kg (depending on infection site, severity, and susceptibility of infecting organisms) every 48 hours. Adjust dose and/or interval, as needed, based upon amikacin serum concentrations (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration):
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, nephrotoxicity) due to drug accumulation is important. The following dosing assumes daily use of PIRRT.
IV: Initial: 15 to 25 mg/kg (depending on infection site, severity, and susceptibility of infecting organisms) every 48 hours. Adjust dose and/or interval, as needed, based upon amikacin serum concentrations. Note: Administer each dose 30 to 60 minutes prior to PIRRT session on PIRRT days (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
The recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.
Class 1, 2, or 3 obesity (BMI ≥30 kg/m2):
IV: Use adjusted body weight for initial weight-based dosing when targeting Cmax/minimum inhibitory concentration (MIC) goals with either loading dose equation (based on target aminoglycoside concentration and estimated Vd) or mg/kg approach and when estimating kidney function with Cockcroft-Gault (CrCl) (Ref). Alternatively, use adjusted body weight to estimate CrCl and aminoglycoside dosing with the Bayesian approach when targeting AUC/MIC goals (Ref). Note: If aminoglycoside therapy is continued, use Cmax/MIC or AUC/MIC goals to optimize therapy, especially in the critically ill where weight and kidney function may be poor surrogates of Vd and clearance (Ref).
Rationale for recommendations: Aminoglycosides are hydrophilic medications with a low Vd and clearance that is proportional to GFR. Pharmacokinetic studies have observed adjusted body weight, using a correction factor of 0.4, is the most appropriate weight metric to correct Vd in the setting of obesity. However, there is wide variation in the correction factors reported, which could lead to under- or over-dosing in clinical practice (Ref). Early use of therapeutic drug monitoring is recommended (Ref).
Refer to adult dosing.
(For additional information see "Amikacin (systemic): Pediatric drug information")
Note: Routes of administration may vary (including IM, IV, intraperitoneal, intrathecal, and intraventricular); dosing presented as mg/kg/dose and mg/kg/day; use caution. Initial dosing recommendations presented. Monitoring of serum concentrations is recommended to ensure efficacy and avoid toxicity, particularly in critically ill patients with serious infection or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, major surgery). Timing and frequency of aminoglycoside concentration monitoring is individualized based on dosing and monitoring strategy (Ref).
Dosing consideration for obesity: In obese pediatric patients, consider use of adjusted body weight (IBW + 0.4 [TBW – IBW]) to calculate initial dosage, based on experience with other aminoglycosides and in adult patients (Ref). Alternatively, adjusted body weight for obese pediatric patients may be calculated using the equation 0.7 x TBW (Ref)). With other aminoglycosides (gentamicin), fat-free mass has been used to calculate the initial dose in pediatric patients ≥2 years of age regardless of body habitus (Ref). Dosage should then be individualized based upon serum concentration monitoring.
General dosing: Infants, Children, and Adolescents: Note: Extended-interval dosing is typically preferred (Ref):
Extended-interval dosing: Limited data available: IV, IM: 15 to 30 mg/kg/dose every 24 hours (Ref). Doses on the higher end of the range may be necessary in patients with critical illness, malignancy, cystic fibrosis, or burn injury, or for bacterial pathogens with minimum inhibitory concentration (MIC) ≥4 mg/L (Ref).
Conventional dosing: IV, IM: 15 to 22.5 mg/kg/day divided every 8 to 12 hours (Ref).
CNS infection:
Meningitis, including health care-associated meningitis: Limited data available: Infants, Children, and Adolescents: IV: 20 to 30 mg/kg/day divided every 8 hours; individualize duration based on patient characteristics, infecting bacteria, and response (Ref).
Ventriculitis (including health care-associated ventriculitis and cerebrospinal fluid [CSF] shunt infections): Limited data available:
Intraventricular/intrathecal (use a preservative-free preparation): Infants, Children, and Adolescents: 5 to 50 mg/day; usual dose: 30 mg/day (Ref). Due to the smaller CSF volume in infants, some guidelines recommend decreasing the infant dose; dosage and administration interval can also be adjusted based on CSF amikacin concentrations, ventricle size, and daily output from ventricular drain (Ref). Duration is individualized according to clinical and microbiological response (Ref).
Cystic fibrosis, acute pulmonary exacerbation:
Note: Extended-interval dosing is preferred over traditional dosing. Use as part of appropriate combination therapy (Ref). Treatment duration varies and is dependent on patient-specific factors including response to therapy; typical duration is 10 to 21 days (Ref).
Extended-interval dosing: Infants, Children, and Adolescents: IV, IM: 30 to 35 mg/kg/dose every 24 hours (Ref). Higher doses (eg, 40 mg/kg/dose every 24 hours) may be necessary when MIC is ≥8 mg/L (Ref).
Traditional dosing: Infants, Children, and Adolescents: IV, IM: 10 mg/kg/dose every 8 hours (Ref).
Endocarditis, treatment: Children and Adolescents: IV: 15 mg/kg/day divided every 8 to 12 hours; use in combination with other antibiotics dependent upon pathogen and source of infection (Ref).
Intra-abdominal infection, complicated: Infants, Children, and Adolescents: IV: 15 to 22.5 mg/kg/day divided every 8 to 24 hours (Ref).
Mycobacterial (nontuberculous) infection: Limited data available:
Mycobacterium avium complex infection in persons that are HIV-exposed/-infected (adjunct therapy):
Infants and Children: IV: 15 to 30 mg/kg/day divided every 12 to 24 hours as part of an appropriate combination regimen; maximum daily dose: 1,500 mg/day; total duration of therapy for M. avium complex infection is ≥12 months (Ref).
Adolescents: IV: 10 to 15 mg/kg/dose every 24 hours as part of an appropriate combination regimen; maximum daily dose: 1,500 mg/day; total duration of therapy for M. avium complex infection is ≥12 months (Ref).
Pulmonary infection in patients with cystic fibrosis (eg, Mycobacterium abscessus, M. avium complex) (Ref): Note: Use as part of an appropriate combination regimen. The duration of parenteral therapy is generally 3 to 12 weeks depending on clinical response, followed by transition to oral and/or inhaled therapy; total treatment duration is ≥12 months after culture conversion.
Infants and Children: IV: 15 to 30 mg/kg/dose every 24 hours; maximum dose: 1,500 mg/dose.
Adolescents: IV: 10 to 15 mg/kg/dose every 24 hours; maximum dose: 1,500 mg/dose.
Tuberculosis, active (drug-resistant); treatment (alternative agent): Limited data available: Note: Use as part of an appropriate combination regimen; duration should be individualized based on extent of disease, rapidity of culture conversion, clinical response, and toxicity (Ref).
Infants, Children, and Adolescents: IM, IV: 15 to 20 mg/kg/dose every 24 hours (Ref).
Peritonitis (CAPD): Infants, Children, and Adolescents: Intraperitoneal: Continuous: Loading dose: 25 mg per liter of dialysate; maintenance dose: 12 mg per liter (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants, Children, and Adolescents: IM, IV:
The following adjustments have been recommended (Ref); Note: 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 adjustment required.
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 <10 mL/minute/1.73 m2: 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.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined:
Nervous system: Neurotoxicity (including muscle twitching, numbness, seizure, tingling of skin)
Otic: Auditory ototoxicity, vestibular ototoxicity
Renal: Nephrotoxicity
Respiratory: Respiratory paralysis
Postmarketing:
Cardiovascular: Hypotension
Dermatologic: Skin rash
Endocrine & metabolic: Albuminuria, hypomagnesemia
Gastrointestinal: Clostridium difficile-associated diarrhea, nausea, vomiting
Genitourinary: Azotemia, hematuria, oliguria, toxic nephrosis
Hematologic & oncologic: Anemia, eosinophilia, leukocyturia
Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms (Bensaid 2012)
Nervous system: Drug fever, headache, paresthesia, tremor
Neuromuscular & skeletal: Arthralgia, state of neuromuscular blockade (Hashimoto 1978)
Renal: Acute kidney injury, casts in urine, increased serum creatinine
Hypersensitivity to amikacin, other aminoglycosides, or any component of the formulation
Concerns related to adverse effects:
• Hypersensitivity: Cross-sensitivity to other aminoglycosides may occur.
• Nephrotoxicity: [US Boxed Warning]: 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: [US Boxed Warning]: May cause neuromuscular blockade and respiratory paralysis; especially when given soon after anesthesia or muscle relaxants.
• Neurotoxicity: [US Boxed Warning]: 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.
Special populations:
• Patients with genomic variants in MT-RNR1: Carriers of certain variants in the MT-RNR1 gene (eg, m.1555A>G) may be at increased risk for aminoglycoside-induced ototoxicity, including potentially significant hearing loss that may be irreversible, even when serum levels are within the normal range.
Concurrent drug therapy issues:
• Neurotoxic and/or nephrotoxic drugs: [US Boxed Warning]: 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: [US Boxed Warning]: 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).
Use with caution in pediatric patients on extracorporeal membrane oxygenation (ECMO); pharmacokinetics of aminoglycosides may be altered; dosage adjustment and close monitoring necessary.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Injection, as sulfate:
Generic: 1 g/4 mL (4 mL [DSC])
Solution, Injection, as sulfate [preservative free]:
Generic: 500 mg/2 mL (2 mL); 1 g/4 mL (4 mL)
Yes
Solution (Amikacin Sulfate Injection)
1 g/4 mL (per mL): $3.31 - $7.35
500 mg/2 mL (per mL): $3.31 - $7.36
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection, as sulfate:
Generic: 250 mg/mL (2 mL); 500 mg/2 mL (2 mL)
IM: Administer IM injection in large muscle mass.
IV: Infuse over 30 to 60 minutes.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
Intrathecal/Intraventricular (off-label route): Reconstitute with preservative-free diluent (NS) only to a final volume of 3 mL (Ref). When administered through a ventricular drain, clamp drain for 15 to 60 minutes before opening the drain to allow amikacin solution to equilibrate in the CSF (Ref).
Inhalation (injection formulation; off-label route): Nebulization: Use with standard jet nebulizer connected to an air compressor or ultrasonic nebulizer; administer with mouthpiece or face mask (Ref). Dilute with NS up to total volume of 4 mL (Ref).
Parenteral:
IM: Administer undiluted into a large muscle mass.
IV: Intermittent IV infusion: Administer by intermittent infusion over 30 to 60 minutes (Ref). Shorter infusion times of 20 minutes have been reported in neonates and slow IV bolus (eg, over 1 to 5 minutes) has also been reported in pediatric patients, including preterm and term neonates (Ref). Avoid infusing concomitantly with penicillins or cephalosporins if feasible; consult drug interactions database for more information.
Intrathecal/intraventricular: Use preservative-free preparations only. No specific administration information available; it has been suggested that instillation of small volumes (<3 mL) over 1 to 2 minutes is safe (Ref). When administered through a ventricular drain, clamp drain for 15 to 60 minutes to allow solution to equilibrate in the cerebrospinal fluid (Ref).
Serious infections: Treatment of serious infections (eg, bloodstream infection, bone infection, respiratory tract infection, endocarditis) due to gram-negative organisms, including Pseudomonas, Escherichia coli, Proteus, Providencia, Klebsiella, Enterobacter, Serratia, and Acinetobacter.
Cystic fibrosis, acute pulmonary exacerbation; Mycobacterium avium complex infection; Mycobacterium (nontuberculous, rapidly growing) infection; Nocardiosis, severe; Plague (Yersinia pestis), treatment; Tuberculosis
Amikacin may be confused with Amicar, anakinra
Amikin may be confused with Amicar, Kineret
The Institute for Safe Medication Practices (ISMP) includes this medication (intrathecal administration) among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Aminoglycosides: May enhance the nephrotoxic effect of other Aminoglycosides. Aminoglycosides may enhance the neurotoxic effect of other Aminoglycosides. Risk X: Avoid combination
Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Amphotericin B may enhance the neurotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Ataluren: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, an increased risk of nephrotoxicity may occur with the concomitant use of ataluren and aminoglycosides. Risk X: Avoid combination
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
Bacitracin (Systemic): May enhance the nephrotoxic effect of Aminoglycosides. Bacitracin (Systemic) may enhance the neurotoxic effect of Aminoglycosides. Risk X: Avoid combination
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Aminoglycosides may enhance the nephrotoxic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy
Botulinum Toxin-Containing Products: Aminoglycosides may enhance the neuromuscular-blocking effect of Botulinum Toxin-Containing Products. Risk C: Monitor therapy
Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Risk C: Monitor therapy
CARBOplatin: May enhance the nephrotoxic effect of Aminoglycosides. Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Risk C: Monitor therapy
Cephalosporins: May enhance the nephrotoxic effect of Aminoglycosides. Cephalosporins may decrease the serum concentration of Aminoglycosides. Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. CISplatin may enhance the neurotoxic effect of Aminoglycosides. Risk X: Avoid combination
Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Management: Avoid coadministration of colistimethate and aminoglycosides whenever possible due to the risk of nephrotoxicity and neuromuscular blockade. If coadministration cannot be avoided, monitor renal and neuromuscular function. Risk D: Consider therapy modification
Cyclizine: May enhance the ototoxic effect of Aminoglycosides. Risk C: Monitor therapy
CycloSPORINE (Systemic): Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Risk C: Monitor therapy
Distigmine: Aminoglycosides may diminish the therapeutic effect of Distigmine. Risk C: Monitor therapy
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Foscarnet: May enhance the nephrotoxic effect of Aminoglycosides. Risk X: Avoid combination
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Risk C: Monitor therapy
Mannitol (Systemic): May enhance the nephrotoxic effect of Aminoglycosides. Risk X: Avoid combination
Mecamylamine: Aminoglycosides may enhance the neuromuscular-blocking effect of Mecamylamine. Risk X: Avoid combination
Methoxyflurane: Aminoglycosides may enhance the nephrotoxic effect of Methoxyflurane. Risk X: Avoid combination
Netilmicin (Ophthalmic): Aminoglycosides may enhance the nephrotoxic effect of Netilmicin (Ophthalmic). Risk X: Avoid combination
Neuromuscular-Blocking Agents: Aminoglycosides may enhance the therapeutic effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy
Oxatomide: May enhance the ototoxic effect of Aminoglycosides. Risk C: Monitor therapy
Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Risk C: Monitor therapy
Polymyxin B: May enhance the nephrotoxic effect of Aminoglycosides. Polymyxin B may enhance the neurotoxic effect of Aminoglycosides. Risk X: Avoid combination
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Tacrolimus (Systemic): Aminoglycosides may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy
Tenofovir Products: Aminoglycosides may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Vancomycin may enhance the neurotoxic effect of Aminoglycosides. Management: Consider avoiding coadministration of aminoglycosides and vancomycin unless clinically indicated. If coadministered, monitor closely for signs of nephrotoxicity and neurotoxicity. Risk D: Consider therapy modification
Evaluate pregnancy status prior to treatment of multidrug-resistant tuberculosis in patients who could become pregnant. Patients who could become pregnant should use effective contraception during treatment for multidrug-resistant tuberculosis (Esmail 2018).
Amikacin crosses the placenta.
Aminoglycosides may cause fetal harm if administered during pregnancy. There are several reports of total irreversible bilateral congenital deafness in children whose mothers received a different 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 intravenous amikacin may be altered. Thirty patients between 6 to 20 weeks' gestation were given a single IM dose of amikacin 7.5 mg/kg within 24 hours prior to elective hysterectomy and therapeutic abortion. Mean peak concentrations and half-life of amikacin were slightly lower than in nonpregnant adults but still within the normal therapeutic range (Bernard 1977).
Amikacin is recommended off label as part of a multiantibiotic treatment regimen of nontuberculosis Mycobacterium avium complex (MAC) in patients with cystic fibrosis in certain situations; route of administration (IV or nebulized) may be dependent upon severity and location of infection (CFF/ECFS [Floto 2016]). Use of the IV route should be reserved for life-threatening infections in pregnant patients due to the potential risk of fetal toxicity (Panchaud 2016).
Amikacin is used off label for the treatment of multidrug-resistant tuberculosis. Tuberculosis (TB) disease (active TB) is associated with adverse fetal outcomes, including intrauterine growth restriction, low birth weight, preterm birth, and perinatal death (Esmail 2018; Miele 2020), as well as adverse maternal outcomes, including increased risks for anemia and cesarean delivery. Placental transmission may rarely occur with active maternal disease (Miele 2020). The treatment of multidrug-resistant tuberculosis in pregnant patients should be individualized; evidence to support a specific regimen is not available (ATS/CDC/ERS/IDSA [Nahid 2019]; WHO 2020). When second-line agents are needed for the treatment of multidrug-resistant tuberculosis during pregnancy, aminoglycosides should be avoided when alternative agents are effective (ATS/CDC/ERS/IDSA [Nahid 2019]). Amikacin may be considered when an aminoglycoside is needed (HHS [OI adult 2020]).
Amikacin is used in the management of plague (Yersinia pestis). Untreated infections in pregnant patients may result in hemorrhage (including postpartum hemorrhage), maternal and fetal death, preterm birth, and stillbirth. Limited data suggest maternal-fetal transmission of Y. pestis can occur if not treated. Pregnant patients should be treated for Y. pestis; parenteral antibiotics are preferred for initial treatment when otherwise appropriate. Amikacin is an alternative aminoglycoside recommended for use (in combination with a fluoroquinolone) for treating pregnant patients with bubonic, pharyngeal, pneumonic, or septicemic plague (CDC [Nelson 2021]).
Amikacin is present in breast milk (Matsuda 1984).
Following a single IM dose of amikacin 100 mg given on days 5 to 7 postpartum, only trace amounts of amikacin were seen in breast milk after 4 and 6 hours. Amikacin was not detectable at 1 and 2 hours postdose (Matsuda 1984). In general, antibiotics that are present in breast milk may cause nondose-related modification of bowel flora. Monitor infants for GI disturbances, such as thrush and diarrhea (WHO 2002).
Due to the potential for serious adverse reactions in the breastfeeding infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, considering the importance of treatment to the mother.
Aminoglycosides have poor oral bioavailability and therefore, use may be considered in breastfeeding patients following treatment for cystic fibrosis (Panchaud 2016).
Patients with multidrug-resistant tuberculosis and a sputum smear-positive test should avoid breastfeeding when possible (Esmail 2018).
Some products may contain sodium.
Urinalysis, urine output, BUN, serum creatinine, plasma amikacin concentrations (as appropriate to dosing method), vital signs, temperature, weight; test hearing before, during and after treatment, particularly in those at risk for ototoxicity or who will be receiving prolonged therapy (>2 weeks).
Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro. This may be clinically-significant for certain penicillin (ticarcillin, piperacillin, carbenicillin) and aminoglycoside (gentamicin, tobramycin) combination therapy in patients with significant renal impairment. Close monitoring of aminoglycoside levels is warranted.
Conventional/traditional dosing:
Timing of serum samples: Draw peak 30 minutes after 30-minute infusion has been completed or 1 hour following initiation of infusion or IM injection; draw trough within 30 minutes before next dose. Obtain drug levels after the third dose unless renal dysfunction/toxicity suspected.
Target concentrations: Peak: 20 to 40 mg/L; trough: <8 mg/L (ideal target 1 to 4 mg/L) (Bertino 1994; Drew 2023).
High-dose extended-interval (once-daily) dosing: Obtain a random amikacin level between 6 and 14 hours after the start of the amikacin infusion. Refer to institution-specific nomogram/policies to determine appropriate dosing interval. If an amikacin-specific nomogram is not available, the amikacin level should be divided by 2 and the result evaluated using a gentamicin or tobramycin dosing nomogram. Alternatively, obtain 2 random amikacin levels with the first level ≥1 to 2 hours after the end of infusion and the second level 6 to 12 hours later (≥1 to 2 half-lives apart); adjust dose and interval to achieve goal concentrations below. When therapy is continued for 5 days or more, monitor the amikacin level once or twice weekly (Bailey 1997; Mueller 2009; Nicolau 1995; Prescott 2010).
Target concentrations:
Peak: ~40 mg/L (Leggett 2015; Nicolau 1995); some experts recommend a target peak of 60 mg/L may be needed in critically ill patients (Galvez 2011) or 80 to 120 mg/L in treatment of acute pulmonary exacerbations of cystic fibrosis (Young 2013).
Trough: <2 mg/L (Nicolau 1995).
Intermittent (thrice-weekly) dosing for mycobacterial infection: Target peak: 65 to 80 mcg/mL; target trough: <5 mcg/mL (ATS/ERS/ESCMID/IDSA [Daley 2020]; Peloquin 2004).
Intrathecal/intraventricular (off-label route): Limited data available (IDSA [Tunkel 2017]): Prior to administration of the next intrathecal/intraventricular dose, withdraw a sample of cerebrospinal fluid (CSF). This trough CSF concentration divided by the amikacin minimum inhibitory concentration for the isolated bacterial pathogen (inhibitory quotient) should exceed 10 to 20.
Inhibits protein synthesis in susceptible bacteria by binding to 30S ribosomal subunits
Absorption:
IM: Rapid.
Oral: Poorly absorbed.
Distribution: Primarily into extracellular fluid (highly hydrophilic); poor penetration into the blood-brain barrier even when meninges are inflamed.
Vd: Varies with age; increased by edema, ascites, and fluid overload; decreased with dehydration:
Neonates and Infants ≤6 months: 0.58 L/kg (range: 0.32 to 0.98 L/kg) (Marik 1991).
Infants ≥6 months: 0.5 L/kg (range: 0.22 to 0.73 L/kg) (Marik 1991).
Children and Adolescents ≤15 years: 0.36 ± 0.08 L/kg (Belfayol 1996).
Adults: 0.25 L/kg (Vozeh 1988).
Relative diffusion of antimicrobial agents from blood into CSF: Good only with inflammation (exceeds usual minimum inhibitory concentrations).
CSF:blood level ratio:
Adults: Normal meninges: <10%; Inflamed meninges: ≤25% (MacDougall 2011).
Infants: Normal meninges: 10% to 20%; Inflamed meninges: up to 50%.
Lung:
Bronchial secretions Cmax (peak): serum Cmax (peak) ratio: ~30% to 40%, varies with time (Santré 1995).
Epithelial lining fluid Cmax (peak): Cmax (peak) ratio: ~10% to 18%, likely varies with time (Heffernan 2019; Najmeddin 2020).
Protein binding: 0% to 11%.
Half-life elimination (renal function and age dependent):
Neonates (Howard 1975):
Birth weight <2 kg:
PNA 1 to 3 days: 7.1 hours.
PNA 4 to 7 days: 6.1 hours.
PNA >7 days: 5.5 hours.
Birth weight ≥2 kg:
PNA 1 to 4 days: 6.5 hours.
PNA 4 to 7 days: 5.1 hours.
PNA >7 days: 4.9 hours.
Infants <6 months: 5.02 hours (range: 1.46 to 11.89 hours) (Marik 1991).
Infants ≥6 months: 2.86 hours (range: 0.63 to 6.28 hours) (Marik 1991).
Children and Adolescents ≤15 years: 2 ± 1 hours (Belfayol 1996).
Adults: Normal renal function: ~2 hours; Anuria/end-stage renal disease: 17 to 150 hours (Aronoff 2007).
Time to peak, serum: IM: 60 minutes; IV: Within 30 minutes following a 30-minute infusion; Note: Distribution is prolonged after larger doses (≥60 minutes after 30-minute infusion of 20 mg/kg [Tod 1998]; ≥90 minutes after 60-minute infusion of a high-dose aminoglycoside [gentamicin 7 mg/kg] [Demczar 1997]).
Excretion: Urine (94% to 98% unchanged).
Altered kidney function: Clearance is decreased in renal impairment.
Anti-infective considerations:
Parameters associated with efficacy: Gram-negative bacilli: Concentration-dependent, associated with Cmax/minimum inhibitory concentration (MIC), goal: ≥8 to 10 (Kato 2017; Moore 1987; Ruiz 2018; White 2015) or AUC24/MIC, goal: 30 to 50 (mild/moderate infection) or 80 to 100 (severe infection) (Bland 2018; Craig 2011; Drusano 2007; Noel 2019; White 2015).
Expected drug exposure in patients with normal renal function:
Cmax (peak), postdistributional:
Infants and Children:
15 mg/kg: ~24 mg/L (Yu 2015).
7.5 mg/kg: ~15 to 20 mg/L (Alqahtani 2018; Kafetzis 1979).
Adults: 15 mg/kg: ~43 mg/L (Maller 1993).
AUC24: 15 mg/kg: 110 to 145 mg•hour/L (Craig 2011).
Parameters associated with toxicity: Nephrotoxicity is associated with more frequent administration and elevated Cmin (trough) concentrations leading to renal accumulation (Rybak 1999); AUC >300 mg/L has also been found to be predictive (Ruiz 2018).
Postantibiotic effect: Bacterial killing continues after amikacin concentration drops below the MIC of targeted pathogen; generally 0.5 to 7.5 hours, though the actual time of postantibiotic effect varies based on multiple factors including organism, amikacin Cmax (peak), and concomitant antimicrobial therapy (Craig 2011; Lacy 1998; Renneberg 1989).
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