Amikacin

Pharmacologic Category

Dosing: Adult

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.

Indication-specific dosing:

Cerebrospinal fluid (CSF) shunt infection (susceptible gram-negative organisms):

IV: 5 mg/kg every 8 hours in combination with other appropriate agents (IDSA [Tunkel 2004]; IDSA [Tunkel 2017])

Intraventricular/intrathecal (adjunct to systemic therapy; use a preservative-free preparation): 5 to 50 mg/day; usual dose: 30 mg/day (Guardado 2008; IDSA [Tunkel 2004]; IDSA [Tunkel 2017]; Khan 2017; Shofty 2016; Wang 2014). Some experts recommend adjusting dosage and administration interval based on CSF amikacin concentrations (goal: 10 to 20 times MIC of causative organism (IDSA [Tunkel 2017]); data are limited (Smetana 2018). When intraventricular amikacin is administered via a ventricular drain, clamp drain for 15 to 60 minutes after administration (allows solution to equilibrate in CSF) (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]). 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 (Baddour 2018).

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)

Meningitis, bacterial (susceptible gram-negative organisms): IV: 5 mg/kg every 8 hours in combination with other appropriate agents (IDSA [Tunkel 2004]; IDSA [Tunkel 2017])

Mycobacterium avium complex (MAC) (off-label use): IV: Adjunct therapy (with macrolide, rifamycin, and ethambutol): 8 to 25 mg/kg (maximum single dose for age >50 years: 500 mg) 2 to 3 times weekly for first 2 to 3 months for severe disease (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).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

Some patients may require larger or more frequent doses if serum levels document the need (ie, cystic fibrosis or febrile granulocytopenic patients).

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 <10 mL/minute: Administer every 48 to 72 hours based on serum concentrations

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 <10 mg/L; redose when post-HD concentration <6 to 8 mg/L (Heintz 2009). 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 <10 mg/L (Heintz 2009).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Obesity: Adult

In moderate obesity (TBW/IBW ≥1.25) or greater (eg, morbid obesity [TBW/IBW >2]), initial dosage requirement may be estimated using a dosing weight of IBW + 0.4 (TBW - IBW) (Traynor 1995).

Dosing: Pediatric

Note: Individualization is critical because of the low therapeutic index. 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).

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]);

CNS infections:

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: 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.

Endocarditis, treatment: 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: 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), treatment: 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 [OI pediatric 2013])

Adolescents: IV: 10 to 15 mg/kg/dose every 24 hours as part of a multiple drug regimen; maximum daily dose: 1,500 mg/day (HHS [OI adult 2016]; HHS [OI pediatric 2013])

Tuberculosis, drug-resistant:

Infants, Children, and Adolescents ≤14 years:

Non-HIV-exposed/-positive:

Once-daily regimen: IM, IV: 15 to 20 mg/kg/dose once daily as part of a multiple drug regimen (ATS/CDC/IDSA [Nahid 2016]); current guidelines do not provide a maximum daily dose; for HIV-exposed/-positive pediatric patients, a maximum daily dose of 1,000 mg/day has been suggested for similar mg/kg doses (HHS [OI pediatric 2013])

Twice-weekly regimen: IM, IV: 25 to 30 mg/kg/dose administered twice weekly as part of a multiple drug regimen; dosing based on experience in adult patients and pediatric pharmacokinetic considerations (ATS/CDC/IDSA [Nahid 2016]); current guidelines do not provide a maximum daily dose; for HIV-exposed/-positive pediatric patients, a maximum daily dose of 1,000 mg/day has been suggested for similar mg/kg doses (HHS [OI pediatric 2013])

HIV-exposed/-positive: IM, IV: 15 to 30 mg/kg/dose once daily as part of a multiple drug regimen; maximum daily dose: 1,000 mg/day (HHS [OI pediatric 2013])

Adolescents ≥15 years: Independent of HIV status:

Once-daily regimen: IM, IV: 15 mg/kg/dose once daily as part of a multiple drug regimen (ATS/CDC/IDSA [Nahid 2016]; HHS [OI adult 2016]); current guidelines do not provide a maximum daily dose; for HIV-exposed/-positive pediatric patients, a maximum daily dose of 1,000 mg/day has been suggested for similar mg/kg doses (HHS [OI pediatric 2013])

Three-times-weekly regimen: IM, IV: 25 mg/kg/dose 3 times weekly (ATS/CDC/IDSA [Nahid 2016]; HHS [OI adult 2016]). Current guidelines do not provide a maximum dose; for HIV-exposed/-positive pediatric patients, a maximum daily dose of 1,000 mg/day has been suggested for similar mg/kg doses (HHS [OI 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)

Dosing: Renal Impairment: Pediatric

Infants, Children, and Adolescents: IM, IV:

The following adjustments have been recommended (Aronoff 2007); 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

Calculations

Use: Labeled Indications

Serious infections: Treatment of serious infections (eg, bone infections, respiratory tract infections, endocarditis, septicemia) due to gram-negative organisms, including Pseudomonas, Escherichia coli, Proteus, Providencia, Klebsiella, Enterobacter, Serratia, and Acinetobacter

Use: Off-Label: Adult

Cystic fibrosis exacerbation (aerosolized amikacin)Level of Evidence [B]

The use of aerosolized amikacin for cystic fibrosis exacerbations has not been well studied. There is evidence to support the use of aerosolized amikacin to eradicate P. aeruginosa, Mycobacterium abscessus, and Mycobacterium avium complex in patients with cystic fibrosis when used as adjunctive therapy with amikacin IV and ceftazidime. A Society of Infectious Diseases Pharmacists consensus summary does not recommend routine use of aerosolized antibiotics to treat acute cystic fibrosis exacerbations. Ref

Mycobacterium avium complex (MAC)Level of Evidence [G]

Based on an official statement on the diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases from the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA), amikacin (or streptomycin) for the first 2 to 3 months of therapy in combination with a macrolide, rifamycin, and ethambutol is effective and recommended for the treatment of extensive Mycobacterium avium complex (MAC) disease, especially fibrocavitary or severe nodular/bronchiectatic disease, or patients who have failed prior drug therapy.

TuberculosisLevel of Evidence [G]

According to the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America joint guidelines on the treatment of tuberculosis (TB), intravenous (IV) or intramuscular (IM) amikacin can be used as second-line therapy for patients with drug-resistant TB whose isolate has demonstrated presumed susceptibility to amikacin.

Level of Evidence Definitions

Level of Evidence Scale

Clinical Practice Guidelines

Meningitis, Bacterial:

IDSA, “Practice Guidelines for the Management of Bacterial Meningitis,” November 2004

Meningitis and Ventriculitis, Healthcare-Associated:

IDSA, "Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis," February 2017.

Opportunistic Infections:

HHS, Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents

Pneumonia, Hospital-Acquired and Ventilator-Associated:

IDSA/ATS, "Management of Adults with Hospital-Acquired and Ventilator-Associated Pneumonia," July 2016.

Tuberculosis:

ATS/CDC/IDSA, "Treatment of Drug-Susceptible Tuberculosis," 2016 . Note: Information contained within this monograph is pending revision based on these more recent guidelines.

Administration: IM

Administer IM injection in large muscle mass.

Administration: 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.

Administration: Injectable Detail

pH: 3.5 to 5.5

Administration: Inhalation

Nebulization (off-label route): Use with standard jet nebulizer connected to an air compressor or ultrasonic nebulizer; administer with mouthpiece or face mask (Le 2010)

Administration: Intrathecal

Intrathecal/Intraventricular (off-label route): Reconstitute with preservative-free diluent (NS) only to a final volume of 3 mL (Corpus 2004; Preston 1993). 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 (IDSA [Tunkel 2017).

Administration: Pediatric

Parenteral: Administer around-the-clock to promote less variation in peak and trough serum levels.

IM: Administer undiluted into a large muscle mass. Slower absorption and lower peak concentrations, probably due to poor circulation in the atrophic muscle, may occur following IM injection; in paralyzed patients, suggest IV route

Intermittent IV infusion: Infuse over 30 to 60 minutes; in infants infusion over 1 to 2 hours is recommended by the manufacturer.

Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides 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.

Dietary Considerations

Some products may contain sodium.

Storage/Stability

Store intact vials at 20°C to 25°C (68°F to 77°F). Following admixture at concentrations of 0.25 to 5 mg/mL in D5W, NS, D51/4NS, D51/2NS, LR, Normosol M in D5W, Normosol R in D5, Plasma-Lyte 56 in D5 or Plasma-Lyte 148 in D5W, amikacin is stable for 24 hours at room temperature, 60 days at 4°C (39°F), or 30 days at -15°C (5°F). Previously refrigerated or thawed frozen solutions are stable for 24 hours when stored at 25°C (77°F).

Preparation for Administration: Adult

For intravenous administration, dilute in a compatible solution (eg, NS, D5W) to a final concentration of 0.25 to 5 mg/mL.

Preparation for Administration: Pediatric

Parenteral: IV intermittent infusion: Dilute in a compatible solution (eg, NS, D5W) to a final concentration of 0.25 to 5 mg/mL per the manufacturer; concentrations as high as 10 mg/mL have been reported (Murray 2014).

Compatibility

See Trissel’s IV Compatibility Database

Open Trissel's IV Compatibility

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat bacterial infections.

Frequently reported side effects of this drug

• Diarrhea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain

• Noise or ringing in the ears

• Trouble hearing

• Hearing loss

• Change in balance

• Muscle weakness

• Burning or tingling feeling

• Twitching

• Seizures

• Trouble breathing

• Slow breathing

• Shallow breathing

• Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

Contraindications

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

Warnings/Precautions

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.

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: [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).

Geriatric Considerations

The aminoglycosides are important therapeutic interventions for infections due to susceptible organisms and as empiric therapy in seriously ill patients. Their use is not without risk of toxicity whose risks can be minimized if initial dosing is adjusted for estimated renal function and appropriate monitoring performed. High dose, once daily aminoglycosides have been advocated as an alternative to traditional dosing regimens. Once daily or extended interval dosing is as effective and may be safer than traditional dosing.

Warnings: Additional Pediatric Considerations

Use with caution in pediatric patients on extracorporeal membrane oxygenation (ECMO); pharmacokinetics of aminoglycosides may be altered; dosage adjustment and close monitoring necessary.

Pregnancy Risk Factor

Pregnancy Considerations

Amikacin crosses the placenta.

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 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 (Bernard 1977).

Amikacin may be one of the preferred antibiotics when an aminoglycoside is needed for multidrug resistant TB in pregnancy (HHS [OI] 2018). Amikacin is recommended as part of a multiantibiotic treatment regimen of Mycobacterium avium complex (MAC) in patients with cystic fibrosis in certain situations (Floto 2016); use of the IV route should be reserved for life-threatening infections in pregnant females (Panchaud 2016).

Breast-Feeding Considerations

Amikacin is present in breast milk (trace amounts) (Matsuda 1984).

In general, modification of infant bowel flora may occur with any antibiotic exposure (Chung 2002).

Aminoglycosides have poor oral bioavailability and therefore use may be considered in breastfeeding women following maternal injection (Panchaud 2016); also consider indication for therapy as recommendations vary by guideline (HHS [OI] 2018; Nahid 2016; Panchaud 2016; WHO 2014). 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, taking into account the importance of treatment to the mother.

Lexicomp Pregnancy & Lactation, In-Depth

Amikacin

Briggs' Drugs in Pregnancy & Lactation

Amikacin

Adverse Reactions

1% to 10%:

Central nervous system: Neurotoxicity

Genitourinary: Nephrotoxicity

Otic: Auditory ototoxicity, vestibular ototoxicity

<1%, postmarketing, and/or case reports: Arthralgia, drowsiness, drug fever, dyspnea, eosinophilia, headache, hypersensitivity reaction, hypotension, nausea, paresthesia, skin rash, tremor, vomiting, weakness

Allergy and Idiosyncratic Reactions

Aminoglycoside Allergy

Metabolism/Transport Effects

None known.

Drug Interactions Open Interactions

Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy

Arbekacin: May enhance the nephrotoxic effect of Aminoglycosides. Arbekacin may enhance the ototoxic 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

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. 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: Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Risk C: Monitor therapy

Cefazedone: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy

Cephalosporins (2nd Generation): May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy

Cephalosporins (3rd Generation): May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy

Cephalosporins (4th Generation): May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy

Cephalothin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy

Cephradine: May enhance the nephrotoxic effect 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. Risk C: Monitor therapy

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

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

Foscarnet: May enhance the nephrotoxic effect of Aminoglycosides. Risk X: Avoid combination

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

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. Exceptions: Amoxicillin; Ampicillin; Bacampicillin; Cloxacillin; Dicloxacillin; Nafcillin; Oxacillin; Penicillin G (Parenteral/Aqueous); Penicillin G Benzathine; Penicillin G Procaine; Penicillin V Benzathine; Penicillin V Potassium. Risk D: Consider therapy modification

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

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: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Risk D: Consider therapy modification

Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy

Test Interactions

Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro, leading to a potential underestimation of aminoglycoside serum concentration.

Monitoring Parameters

Urinalysis, BUN, serum creatinine, appropriately timed peak and trough concentrations, vital signs, temperature, weight, I & O, hearing parameters

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). Aminoglycoside levels measured from blood taken from Silastic® central catheters can sometimes give falsely high readings (draw levels from alternate lumen or peripheral stick, if possible).

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.

Reference Range

Traditional dosing:

Therapeutic levels:

Peak:

Life-threatening infections: 25 to 40 mcg/mL

Serious infections: 20 to 25 mcg/mL

Urinary tract infections: 15 to 20 mcg/mL

Trough: <8 mcg/mL

The American Thoracic Society (ATS) recommends trough levels of <4 to 5 mcg/mL for patients with hospital-acquired pneumonia.

Toxic concentration: Peak: >40 mcg/mL; Trough: >10 mcg/mL

Timing of serum samples: Draw peak 30 minutes after completion of 30-minute infusion or at 1 hour following initiation of infusion or IM injection; draw trough within 30 minutes prior to next 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. When therapy is continued for 5 days or more, monitor the amikacin level once or twice weekly (Bailey 1997; Nicolau 1995).

Intrathecal/intraventricular (off-label route): Limited data available (IDSA [Tunkel 2017]; Smetana 2018): Prior to administration of the next intrathecal/intraventricular dose, withdraw a sample of CSF. This trough CSF concentration divided by the amikacin MIC for the isolated bacterial pathogen (inhibitory quotient) should exceed 10 to 20.

Advanced Practitioners Physical Assessment/Monitoring

Assess culture/sensitivity tests and patient's allergy history prior to beginning therapy. Obtain BUN, serum creatinine, and serum drug concentrations (peak and trough levels). Obtain vital signs, temperature, weight, and I & O. Order dosage based on ideal body weight. Obtain baseline and periodic hearing tests (audiograms). Assess for effectiveness of treatment. Assess potential for interactions with other nephrotoxic or ototoxic drugs. Assess for ototoxicity, neurotoxicity, and nephrotoxicity on a regular basis; dosage adjustment or discontinuation of therapy may be needed if signs occur. Test for C. difficile if patient develops diarrhea.

Nursing Physical Assessment/Monitoring

Check ordered labs and report any abnormalities. Monitor vital signs, temperature, weight, and I & Os as ordered. Monitor and report any signs or symptoms of ototoxicity (auditory or vestibular), neurotoxicity (drowsiness, paresthesia, headache, dizziness, muscle weakness), and nephrotoxicity (I & O, hematuria, edema) on a regular basis. Monitor for severe or bloody diarrhea and send a specimen to the lab for C. difficile. Monitor for improvement with infection.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection, as sulfate:

Generic: 500 mg/2 mL (2 mL [DSC]); 1 g/4 mL (4 mL)

Solution, Injection, as sulfate [preservative free]:

Generic: 500 mg/2 mL (2 mL); 1 g/4 mL (4 mL)

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection:

Generic: 250 mg/mL (2 mL)

Solution, Injection, as sulfate:

Generic: 500 mg/2 mL (2 mL)

Anatomic Therapeutic Chemical (ATC) Classification

J01GB06

Generic Available (US)

Yes

Pricing: US

Solution (Amikacin Sulfate Injection)

1 g/4 mL (per mL): $2.19 - $7.35

500 mg/2 mL (per mL): $2.22 - $7.36

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

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

Pharmacodynamics/Kinetics

Absorption:

IM: Rapid

Oral: Poorly absorbed

Distribution: Vd: 0.25 L/kg (Vozeh 1988); primarily into extracellular fluid (highly hydrophilic); poor penetration into the blood-brain barrier even when meninges are inflamed; Vd is increased in neonates and patients with edema, ascites, fluid overload; Vd is decreased in patients with dehydration

Relative diffusion of antimicrobial agents from blood into CSF: Good only with inflammation (exceeds usual MICs)

CSF:blood level ratio: Infants: Normal meninges: 10% to 20%; Inflamed meninges: up to 50%

Protein-binding: 0% to 11%

Half-life elimination (renal function and age dependent):

Infants: Low birth weight (1 to 3 days): 7 to 9 hours; Full-term >7 days: 4 to 5 hours (Howard 1975)

Children: 1.6 to 2.5 hours

Adolescents: 1.5 ± 1 hour

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

Excretion: Urine (94% to 98% unchanged)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: Clearance is decreased in renal impairment.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

Index Terms

Amikacin Sulfate

FDA Approval Date

May 18, 1992

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Last Updated 4/8/20

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