Skip to main content

Amikacin (Monograph)

Drug class: Aminoglycosides
VA class: AM300
CAS number: 39831-55-5

Medically reviewed by Drugs.com on Jun 8, 2023. Written by ASHP.

Warning

  • Patients should be under close clinical observation because of potential ototoxicity and nephrotoxicity.1 2 3 Safety of treatment for >14 days not established.1 2 3

  • Neurotoxicity (manifested as vestibular and permanent bilateral auditory ototoxicity) can occur in patients with preexisting renal damage and in those with normal renal function who receive doses higher or treatment longer than recommended.1 2 3 Risk of aminoglycoside-induced ototoxicity is greater in patients with renal damage.1 2 3

  • High-frequency deafness usually occurs first (detectable only by audiometric testing); vertigo may occur (may indicate vestibular injury).1 2 3 Other neurotoxicity manifestations include numbness, skin tingling, muscle twitching, and seizures.1 2 3

  • Risk of hearing loss increases with degree of exposure to either high peak or high trough serum concentrations.1 2 3 Patients developing cochlear damage may not have symptoms during aminoglycoside treatment to warn them of developing eighth nerve toxicity and total or partial irreversible bilateral deafness may occur after drug discontinued.1 2 3 Aminoglycoside-induced ototoxicity usually is irreversible.1 2 3

  • Potentially nephrotoxic.1 2 3 Risk of nephrotoxicity is greater in patients with impaired renal function and in those who receive high dosage or prolonged treatment.1 2 3

  • Neuromuscular blockade and respiratory paralysis reported following parenteral, topical instillation (e.g., in orthopedic and abdominal irrigation, local treatment of empyema), or oral administration of aminoglycosides.1 2 3 Consider possibility of neuromuscular blockade when any route is used, especially in patients receiving anesthetics or neuromuscular blocking agents (e.g., tubocurarine, succinylcholine, decamethonium) or in those receiving massive transfusions of citrate-anticoagulated blood.1 2 3 Calcium salts may reverse neuromuscular blockade, but mechanical respiratory assistance may be necessary.1 2 3

  • Monitor renal and eighth-nerve function closely, especially in patients with known or suspected renal impairment at start of treatment and also in those whose renal function is initially normal but develop renal dysfunction during treatment.1 2 3 Monitor serum amikacin concentrations when feasible to assure adequate concentrations and avoid potentially toxic and prolonged peak concentrations (>35 mcg/mL).1 2 3 Evaluate urine for decreased specific gravity and periodically determine BUN, serum creatinine, or Clcr.1 2 3

  • Obtain serial audiograms if feasible in patients old enough to be tested, particularly high-risk patients.1 2 3 Discontinue or adjust dosage if there is evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, hearing loss) or nephrotoxicity.1 2 3

  • Avoid concurrent and/or sequential use of other neurotoxic or nephrotoxic drugs (systemic, oral, or topical).1 2 3 Other factors that may increase risk of toxicity are advanced age and dehydration.1 2 3

  • Avoid concurrent use of potent diuretics since diuretics themselves may cause ototoxicity and may enhance toxicity by altering serum and tissue aminoglycoside concentrations.1 2 3

Introduction

Antibacterial; aminoglycoside derived from kanamycin.1 2 3 4

Uses for Amikacin

Bone and Joint Infections

Treatment of serious bone and joint infections caused by susceptible gram-negative bacteria.1 2 3

Intra-abdominal Infections

Treatment of serious intra-abdominal infections (including peritonitis) caused by susceptible gram-negative bacteria.1 2 3 5 57 Used as an adjunct to other appropriate anti-infectives (e.g., clindamycin, metronidazole, piperacillin and tazobactam, ampicillin and sulbactam).5 57

Meningitis and Other CNS Infections

Treatment of meningitis caused by susceptible gram-negative bacteria.1 2 3 4 5 15 33 37 38 39 64 77

Aminoglycosides should not be used alone for treatment of meningitis;4 33 usually used as an adjunct to other anti-infectives in initial treatment.6 i

Used in conjunction with ampicillin for initial empiric treatment of neonatal S. agalactiae meningitis or for Listeria monocytogenes meningitis in children.6 Used in conjunction with a third-generation cephalosporin for neonatal gram-negative bacterial meningitis, including infections caused by E. coli.15 Has been used concomitantly with imipenem in adults for treatment of meningitis caused by E. coli,33 concomitantly with meropenem for treatment of meningitis caused by Pseudomonas, or concomitantly with imipenem or colistin (commercially available as colistimethate sodium) for treatment of meningitis caused by Acinetobacter.37 38

Respiratory Tract Infections

Treatment of serious respiratory tract infections caused by susceptible gram-negative bacteria.1 2 3 4 5

Used as an adjunct to an appropriate β-lactam (e.g., ceftriaxone, cefotaxime, cefepime, piperacillin and tazobactam, ticarcillin and clavulanate) or carbapenem (e.g., imipenem, meropenem) for empiric treatment of nosocomial pneumonia.5

Septicemia

Treatment of septicemia caused by susceptible gram-negative bacteria.1 2 3 4 5

Used as an adjunct to an appropriate β-lactam (e.g., ceftriaxone, cefotaxime, cefepime, piperacillin and tazobactam, ticarcillin and clavulanate) or carbapenem (e.g., imipenem, meropenem) for empiric treatment of life-threatening septicemia.5

Skin and Skin Structure Infections

Treatment of serious skin and skin structure infections caused by susceptible gram-negative bacteria.1 2 3

Urinary Tract Infections (UTIs)

Treatment of serious complicated and recurrent UTIs caused by susceptible gram-negative bacteria, including Enterobacteriaceae or Pseudomonas aeruginosa.1 2 3 4 5 Used as an adjunct to other appropriate anti-infectives.5

Not indicated for uncomplicated UTIs unless causative organism is resistant to other less-toxic alternatives.1 2 3

Mycobacterial Infections

Second-line agent for use in multiple-drug regimens for treatment of active tuberculosis† [off-label] in patients with relapse, treatment failure, or Mycobacterium tuberculosis resistant to isoniazid and/or rifampin or when first-line drugs cannot be tolerated.218

Alternative for use in multiple-drug regimens for treatment of M. avium complex† [off-label] (MAC) infections.5 9 58 59 60 61

Treatment of nonpulmonary infections caused by M. abscessus† [off-label],6 9 M. chelonae† [off-label],4 or M. fortuitum† [off-label].4 5 6 9

Nocardia Infections

Treatment of infections caused by Nocardia†.4 5 6 41 42 65 66 67 68 69

Sulfonamides (usually co-trimoxazole) are treatment of choice for most Nocardia infections;4 5 6 42 65 69 concomitant use of amikacin, imipenem, and/or ceftriaxone recommended for initial treatment of severe or disseminated infections.6 65 When sulfonamides cannot be used, regimens containing amikacin, a carbapenem (imipenem or meropenem), a third-generation cephalosporin (ceftriaxone), a tetracycline (doxycycline, minocycline), fixed combination of amoxicillin and clavulanate, clarithromycin, cycloserine, or linezolid are recommended.4 5 6 65 69

Rhodococcus Infections

Treatment of infections caused by Rhodococcus equi†.5

Empiric Therapy in Febrile Neutropenic Patients

Empiric anti-infective therapy of presumed bacterial infections in febrile neutropenic patients†.4 5 8 62 63 75 Used in conjunction with an appropriate antipseudomonal cephalosporin (e.g., ceftazidime, ceftriaxone, cefepime), extended-spectrum penicillin (e.g., piperacillin and tazobactam, ticarcillin and clavulanate), or carbapenem (e.g., imipenem, meropenem).5 8 62 63 75 75

Consult published protocols for the treatment of infections in febrile neutropenic patients for specific recommendations regarding selection of the initial empiric regimen, when to change the initial regimen, possible subsequent regimens, and duration of therapy in these patients.8 Consultation with an infectious disease expert knowledgeable about infections in immunocompromised patients also is advised.8

Amikacin Dosage and Administration

Administration

Administer by IV infusion or IM injection.1 2 3

Has been given intrathecally† or intraventricularly† as an adjunct to IV or IM administration for treatment of meningitis and other CNS infections.4 19 33 34 35 37 38 39

Patients should be well hydrated to minimize chemical irritation of renal tubules which may occur as the result of high urine amikacin concentrations.1 2 3

Renal function should be assessed prior to and daily during therapy.1 2 3

For solution and drug compatibility information, see Compatibility under Stability.

IV Infusion

If a β-lactam (e.g., cephalosporin, penicillin) is administered concomitantly, the drugs should not be admixed and should be administered separately.1 2 3 HID

Dilution

IV solutions are prepared by adding 500 mg to 100–200 mL of 0.9% sodium chloride, 5% dextrose, or other compatible IV solution (see Solution Compatibility under Stability).1 2 3

For pediatric patients, the volume of infusion fluid depends on the patient's needs, but should be sufficient to allow an infusion period of 1–2 hours in infants or 30–60 minutes in older children.1 2 3

Rate of Administration

In adults, administer appropriate dose by IV infusion over 30–60 minutes.1 2 3

In infants, administer appropriate dose by IV infusion over 1–2 hours;1 2 3 in older children, administer by IV infusion over 30–60 minutes.1 2 3

IM Injection

Appropriate dose of commercially available injection containing amikacin in a concentration of 50 or 250 mg/mL should be given undiluted.1 2 3 IM injections have been given into the upper outer quadrant of the buttocks.16

Dosage

Available as amikacin sulfate; dosage expressed in terms of amikacin.1 2 3

IV and IM dosage is identical.1 2 3

Dosage should be individualized taking into consideration patient’s pretreatment body weight, renal status, severity of infection, and susceptibility of the causative organisms.1 2 3 4 11 200 201 202 203 204 216

Many clinicians recommend that dosage be determined using appropriate pharmacokinetic methods for calculating dosage requirements and patient-specific pharmacokinetic parameters (e.g., elimination rate constant, volume of distribution) derived from serum concentration-time data.11 200 201 202 203 204 216

Whenever possible, especially in patients with life-threatening infections, suspected toxicity or nonresponse to treatment, decreased or varying renal function, and/or when increased aminoglycoside clearance (e.g., patients with cystic fibrosis, burns) or prolonged therapy is likely, peak and trough serum concentrations of amikacin should be determined periodically and dosage should be adjusted to maintain desired serum concentrations.4 11 207 216 219 222 223 228 236 237

When conventional dosage regimens (i.e., multiple daily doses) are used, many clinicians recommend that dosage be adjusted to maintain peak and trough serum concentrations of 15–30 and <5–10 mcg/mL, respectively.4 11 14 216 222 225 226 227 238 239 Amikacin serum concentrations >30–35 mcg/mL may be associated with toxicity.14 The manufacturers state that peak serum concentrations (obtained 30–90 minutes after administration) of >35 mcg/mL and trough serum concentrations (obtained just before the next dose) of >10 mcg/mL should be avoided.1 2 3

Once-daily administration† of aminoglycosides is at least as effective as, and may be less toxic than, conventional dosage regimens employing multiple daily doses.11 48 49 50 52 56 62 74 75 76 205 206 207 208 209 210 211 212 213 214 215 216 217 228 229 230 231 232 233 234 235 243 245 246 247 248

Usual duration of treatment is 7–10 days.1 2 3 Safety of aminoglycoside treatment for >14 days not established.1 2 3 If clinical response does not occur within 3–5 days, in vitro susceptibility should be reassessed.1 2 3 In difficult and complicated infections, use of amikacin should be re-evaluated if treatment >10 days is being considered.1 2 3 If the drug is continued, serum amikacin concentrations and renal, auditory, and vestibular functions should be monitored closely.1 2 3

Pediatric Patients

General Dosage for Neonates
IV or IM

Manufacturer recommends an initial loading dose of 10 mg/kg followed by 7.5 mg/kg every 12 hours.1 2 3

Neonates <1 week of age: AAP recommends 7.5 mg/kg every 18–24 hours for those weighing <1.2 kg, 7.5 mg/kg every 12 hours for those weighing 1.2–2 kg, and 7.5–10 mg/kg every 12 hours in those weighing >2 kg.6

Neonates 1–4 weeks of age: AAP recommends 7.5 mg/kg every 18–24 hours for those weighing <1.2 kg, 7.5–10 mg/kg every 8 or 12 hours for those weighing 1.2–2 kg, and 10 mg/kg every 8 hours for those weighing >2 kg.6

AAP states the drug is inappropriate for treatment of mild to moderate infections.6

Once-daily† regimen: Full-term neonates have received 15 mg/kg once daily.48 56 76

General Dosage for Infants and Children
IV or IM

Older infants and children: Manufacturers recommend 15 mg/kg daily given in 2 or 3 equally divided doses (i.e., 7.5 mg/kg every 12 hours or 5 mg/kg every 8 hours).1 2 3

Children ≥1 month of age: AAP recommends 15–22 mg/kg given in 3 divided doses for severe infections.6

AAP states the drug is inappropriate for treatment of mild to moderate infections.6

Once-daily† regimen: Children have received 15–20 mg/kg once daily.50 54 62 74 76

Mycobacterial Infections†
Active Tuberculosis†
IV or IM

Children <15 years of age: 15–30 mg/kg (up to 1 g) once daily or twice weekly.6 218

Children ≥15 years of age: 15 mg/kg daily (up to 1 g) as a single daily dose (usually 750–1000 mg daily) 5–7 times weekly for the first 2–4 months or until culture conversion; dosage can then be reduced to 15 mg/kg daily (up to 1 g) given 2 or 3 times weekly, depending on efficacy of the other drugs in the regimen.218

Must be used in conjunction with other antituberculosis agents.218 Multiple-drug regimen usually given for 12–18 months when rifampin-resistant M. tuberculosis are involved; for 18–24 months when isoniazid- and rifampin-resistant strains are involved; or for 24 months when the strain is resistant to isoniazid, rifampin, ethambutol, and/or pyrazinamide.218

Meningitis
IV or IM

15–20 mg/kg daily given in 2 divided doses for neonates ≤7 days of age and 20–30 mg/kg daily given in 3 divided doses in older neonates and children.64 77 Smaller doses and longer intervals between doses may be indicated in neonates weighing <2 kg.64 77

Empiric Therapy in Febrile Neutropenic Patients†
IV

Children 1–17 years of age: 20 mg/kg once daily or 6.5 mg/kg 3 times daily has been given in conjunction with IV ceftazidime.62

Adults

General Adult Dosage
IV or IM

15 mg/kg daily given in 2 or 3 equally divided doses (i.e., 5 mg/kg every 8 hours or 7.5 mg/kg every 12 hours).1 2 3

Once-daily† regimen: 15 mg/kg once daily has been used.11 49

Meningitis and Other CNS Infections
IV

15 mg/kg daily given in 3 divided doses.77

Intrathecal† or Intraventricular†

4–20 mg as a single daily dose in conjunction with IM or IV administration of the drug (7.5 mg/kg every 12 hours).4 19 33 35 37

Urinary Tract Infections (UTIs)
Uncomplicated Infections
IV or IM

250 mg twice daily.1 2 3

Mycobacterial Infections†
Active Tuberculosis†
IV or IM

15 mg/kg daily (up to 1 g) as a single daily dose (usually 750–1000 mg daily) 5–7 times weekly for the first 2–4 months or until culture conversion; dosage can then be reduced to 15 mg/kg daily (up to 1 g) given 2 or 3 times weekly, depending on efficacy of the other drugs in the regimen.218

Adults >59 years of age: 10 mg/kg (up to 750 mg) daily.218

Must be used in conjunction with other antituberculosis agents.218 Multiple-drug regimen usually given for 12–18 months when rifampin-resistant M. tuberculosis are involved; for 18–24 months when isoniazid- and rifampin-resistant strains are involved; or for 24 months when the strain is resistant to isoniazid, rifampin, ethambutol, and/or pyrazinamide.218

Other Mycobacterial Infections†
IV or IM

Mycobacterium avium complex† (MAC) infections: 7.5–15 mg/kg daily in conjunction with other antimycobacterial anti-infectives.58 59 60 61

IV

M. abscessus† or M. fortuitum† infections: 10–15 mg/kg daily in 2 divided doses in conjunction with other antimycobacterial anti-infectives.9

Nocardia Infections†
IV or IM

5–7.5 mg/kg every 12 hours.69

Empiric Therapy in Febrile Neutropenic Patients†
IV

7.5 mg/kg twice daily has been given in conjunction with IV ceftazidime or IV cefepime.63

Prescribing Limits

Pediatric Patients

IV or IM

Daily dosage should not exceed 15 mg/kg or 1.5 g.1 2 3

Adults

IV or IM

Daily dosage should not exceed 15 mg/kg or 1.5 g.1 2 3

Special Populations

Renal Impairment

Dosage adjustments necessary in patients with renal impairment.4 6 11 14 24

One method suggested by manufacturer is an initial loading dose of 7.5 mg/kg followed by 7.5 mg/kg given at intervals (in hours) calculated by multiplying the patient's steady-state serum creatinine (in mg/dL) by 9.1 2 3 The dosing method of Sarubbi and Hull, which is based on corrected creatinine clearance, also has been recommended.h

The above dosage calculation methods should not be used in patients undergoing hemodialysis or peritoneal dialysis.h In adults with renal failure undergoing hemodialysis, some clinicians recommend supplemental doses of 50–75% of the initial loading dose at the end of each dialysis period.14 Others suggest supplemental doses may not be necessary in patients undergoing short-term hemodialysis.51 Serum concentrations of the drug should be monitored in dialysis patients and dosage adjusted to maintain desired serum concentrations.14 51

Active Tuberculosis†
IV or IM

ATS, CDC, and IDSA recommend that usual doses be given at less frequent intervals since use of lower doses may reduce efficacy of the drug.218 These experts recommend 12–15 mg/kg 2 or 3 times weekly.218 In addition, if the patient is receiving hemodialysis, the dose should be given after the procedure is finished and serum concentrations of the drug should be monitored to avoid toxicity.218

Geriatric Patients

Select dosage with caution and closely monitor renal function because of age-related decreases in renal function.1 2 3 4

No dosage adjustments except those related to renal impairment.1 2 3 (See Renal Impairment under Dosage and Administration.)

Detailed Amikacin dosage information

Cautions for Amikacin

Contraindications

Warnings/Precautions

Warnings

Ototoxicity

Patients receiving aminoglycosides should be under close clinical observation because of possible ototoxicity.1 2 3

Vestibular and permanent bilateral auditory ototoxicity occurs most frequently in those with past or present history of renal impairment, those receiving other ototoxic drugs, and those who receive high dosage or prolonged treatment.1 2 3

High-frequency deafness usually occurs first.1 2 3 Serial audiograms should be obtained if feasible in patients old enough to be tested, particularly in high risk patients.1 2 3

Discontinue amikacin or adjust dosage if there is evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, hearing loss) or nephrotoxicity.1 2 3

Some aminoglycoside have caused fetal ototoxicity when administered to pregnant women.1 2 3 (See Pregnancy under Cautions.)

Nephrotoxicity

Patients receiving aminoglycosides should be under close clinical observation because of possible nephrotoxicity.1 2 3 Renal function should be assessed prior to and daily during therapy.1 2 3

Nephrotoxicity occurs most frequently in those with past or present history of renal impairment, those receiving other nephrotoxic drugs, and those who receive high dosage or prolonged treatment.1 2 3

Patients should be well hydrated.1 2 3 If patients are well-hydrated and renal function is normal, the risk of nephrotoxic effects is low if usual dosage is not exceeded.1 2 3

If evidence of renal irritation occurs (casts, white or red cells, or albumin in urine), increase hydration.1 2 3 Dosage reduction may be desirable if other evidence of renal dysfunction occurs (e.g., decreased Clcr, decreased urine specific gravity, increased BUN or serum creatinine, oliguria).1 2 3

If azotemia increases or if a progressive decrease in urinary output occurs, discontinue amikacin.1 2 3

Neuromuscular Blockade

Risk of neuromuscular blockade and respiratory paralysis.1 2 3 Acute muscular paralysis and apnea can occur.1 2 3

Possibility of neuromuscular blockade should be considered, especially in patients receiving anesthetics or neuromuscular blocking agents (e.g., tubocurarine, succinylcholine, decamethonium) or in those receiving massive transfusions of citrate-anticoagulated blood.1 2 3

Calcium salts may reverse neuromuscular blockade, but mechanical respiratory assistance may be necessary.1 2 3

Sensitivity Reactions

Cross-hypersensitivity

Cross-allergenicity occurs among the aminoglycosides.1 2 3

Sulfite Sensitivity

Contains sodium metabisulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.1 2 3

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of amikacin and other antibacterials, use only for treatment of infections proven or strongly suspected to be caused by susceptible bacteria.1 2

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1 2 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.1 2

Superinfection

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.1 2 3 Discontinue drug and institute appropriate therapy if superinfection occurs.1 2 3

Interactions

Because of possible additive toxicity, avoid concurrent and/or sequential use of other neurotoxic or nephrotoxic drugs (systemic, oral, or topical), particularly bacitracin, cisplatin, amphotericin B, cephaloridine (no longer available in US), paromomycin, viomycin, polymyxin B, colistin, vancomycin, or other aminoglycosides.1 2 3 Do not administer concurrently with potent diuretics.1 2 3 (See Specific Drugs under Interactions.)

Consider possibility of neuromuscular blockade and respiratory paralysis in patients receiving anesthetics or neuromuscular blocking agents (e.g., tubocurarine, succinylcholine, decamethonium).1 2 3 (See Specific Drugs under Interactions.)

Use with caution in patients with muscular disorders such as myasthenia gravis or parkinsonism since drugs used in these patients may aggravate muscle weakness because of their potential curare-like effect on the neuromuscular junction.1 2 3

Topical Instillation

Irreversible deafness, renal failure, and death caused by neuromuscular blockade has occurred when an aminoglycoside was used for topical instillation†; toxicity occurred with irrigation of both small and large surgical fields.1 2 3

Specific Populations

Pregnancy

Category D.1 2 3

Possibility of fetal harm if administered to a pregnant woman.1 2 3 Complete, irreversible, bilateral congenital deafness reported when another aminoglycoside (i.e., streptomycin) was used during pregnancy.1 2 3

If used during pregnancy or if patient becomes pregnant while receiving amikacin, the patient should be apprised of the potential hazard to the fetus.1 2 3

Lactation

Low concentrations distributed into milk.259 Use with caution.1 2 3

Pediatric Use

Use with caution in neonates and premature infants because renal immaturity in these patients may result in prolonged serum half-life.1 2 3

Geriatric Use

Select dosage with caution and closely monitor renal function because of age-related decreases in renal function.1 2 3 4

Monitoring renal function during aminoglycoside therapy is particularly important in geriatric patients.1 2 3 4 Clcr may be more useful than determining BUN or serum creatinine.1 2 3 4

Renal Impairment

Risk of neurotoxicity (manifested as vestibular and permanent bilateral auditory ototoxicity) is greater in patients with renal damage than in other patients.1 2 3

Renal function should be assessed prior to and daily during therapy.1 2 3

Renal eighth-nerve function should be monitored closely, especially in patients who have known or suspected renal impairment at the start of treatment and also in those whose renal function is initially normal but who develop signs of renal dysfunction during treatment.1 2 3

Common Adverse Effects

Ototoxicity or nephrotoxicity.1 2 3 i

Drug Interactions

Neurotoxic, Ototoxic, or Nephrotoxic Drugs

Concomitant or sequential use with other systemic, oral, or topical drugs that have neurotoxic, ototoxic, or nephrotoxic effects (e.g., aminoglycosides, acyclovir, amphotericin B, bacitracin, capreomycin, certain cephalosporins, colistin, cisplatin, methoxyflurane, polymyxin B, vancomycin) may result in additive toxicity and should be avoided, if possible.1 2 3 i In addition, because of the possibility of an increased risk of ototoxicity due to additive effects or altered serum and tissue aminoglycoside concentrations, aminoglycosides should not be given concurrently with ethacrynic acid, furosemide, mannitol, urea.1 2 3 i

Specific Drugs

Drug

Interaction

Comments

Acyclovir

Possible increased risk of neurotoxic, ototoxic, or nephrotoxic effects 1 2 3

Avoid concomitant and/or sequential use if possible1 2 3

Amphotericin B

Possible increased risk of neurotoxic, ototoxic, or nephrotoxic effects 1 2 3

Avoid concomitant and/or sequential use if possible1 2 3

β-Lactam antibiotics (cephalosporins, penicillins)

In vitro evidence of additive or synergistic antibacterial effects between penicillins and aminoglycosides against some enterococci, Enterobacteriaceae, or Ps. aeruginosa;i used to therapeutic advantagei

Possible increased incidence of nephrotoxicity reported with some cephalosporins; cephalosporins may spuriously elevate creatinine concentrations1 2 3

Potential in vitro and in vivo inactivation of aminoglycosides;1 2 3 i HID amikacin may be inactivated by β-lactams to a lesser extent than some other aminoglycosidesi

Do not admix; administer IV solutions of the drugs separatelyHID i

Monitor serum aminoglycoside concentrations, especially when high penicillin doses are used or patient has renal impairmenti

Bacitracin

Possible increased risk of neurotoxic, ototoxic, or nephrotoxic effects 1 2 3

Avoid concomitant and/or sequential use if possible1 2 3

Capreomycin

Possible increased risk of neurotoxic, ototoxic, or nephrotoxic effects 1 2 3

Avoid concomitant and/or sequential use if possible1 2 3

Carbapenems (imipenem)

In vitro evidence of additive or synergistic antibacterial effects with aminoglycosides against some gram-positive bacteria ( E. faecalis, S. aureus, L. monocytogenes)i

Chloramphenicol

Some in vitro evidence of antagonism with aminoglycosides;i in vivo antagonism has not been demonstrated and the drugs have been administered concomitantly with no apparent decrease in activityi

Cisplatin

Possible increased risk of neurotoxic, ototoxic, or nephrotoxic effects 1 2 3

Avoid concomitant and/or sequential use if possible1 2 3

Clindamycin

Some in vitro evidence of antagonism with aminoglycosides;i in vivo antagonism has not been demonstrated and the drugs have been administered concomitantly with no apparent decrease in activityi

Colistimethate/Colistin

Possible increased risk of neurotoxic, ototoxic, or nephrotoxic effects 1 2 3

Avoid concomitant and/or sequential use if possible1 2 3

Diuretics (ethacrynic acid, furosemide, mannitol, urea)

Possible increased risk of ototoxicity (diuretics themselves may cause ototoxicity) or increased risk of other aminoglycoside-related adverse effects (diuretics may alter aminoglycoside serum or tissue concentrations)1 2 3

Neuromuscular blocking agents and general anesthetics (succinylcholine, tubocurarine)

Possible potentiation of neuromuscular blockade and respiratory paralysisi

Use concomitantly with caution; observe closely for signs of respiratory depressioni

NSAIAs

Possible increased serum aminoglycoside concentrations reported with indomethacin in premature neonates; may be related to indomethacin-induced decreases in urine outputi

Closely monitor aminoglycoside concentrations and adjust dosage accordinglyi

Polymyxin B

Possible increased risk of neurotoxic, ototoxic, or nephrotoxic effects 1 2 3

Avoid concomitant and/or sequential use if possible1 2 3

Tetracyclines

Some in vitro evidence of antagonism with aminoglycosides;i in vivo antagonism has not been demonstrated and the drugs have been administered concomitantly with no apparent decrease in activityi

Vancomycin

Possible increased risk of neurotoxic, ototoxic, or nephrotoxic effects 1 2 3

Avoid concomitant and/or sequential use if possible1 2 3
Amikacin drug interactions (more detail)

Amikacin Pharmacokinetics

Absorption

Bioavailability

Not absorbed orally; must be given parenterally.4 11

Rapidly absorbed following IM injection;1 2 3 11 peak serum concentrations attained within 0.5–2 hours.1 2 3 13 16

Distribution

Extent

Distributed into bone, heart, gallbladder, lung tissue, bile, sputum, bronchial secretions, and interstitial, pleural, and synovial fluids.1 2 3 4 h

Only low concentrations distributed into CSF following IM or IV administration.i Intraventricular administration usually produces high CNS concentrations.i

Crosses the placenta.1 2 3 4

Distributed into milk in low concentrations.259

Plasma Protein Binding

≤11%.1 2 3 4

Elimination

Elimination Route

94–98% of a single IM or IV dose excreted unchanged by glomerular filtration within 24 hours.1 2 3 4 17

Half-life

2–3 hours in adults with normal renal function.1 2 3 4 13 14 16 17 20

Special Populations

Increased serum concentrations and prolonged half-life in patients with renal impairment.1 2 3 4 h Half-life ranges from 28–86 hours in adults with severe renal impairment.4 14 21 22 24

Stability

Storage

Parenteral

Injection

15–30°C.1 2 3

Diluted solutions containing 0.25 or 5 mg/mL prepared using 5% dextrose, 5% dextrose and 0.2 or 0.45% sodium chloride, 0.9% sodium chloride, lactated Ringer's, Normosol-M and 5% dextrose, or Normosol-R and 5% dextrose are stable for 24 hours at room temperature.1 2 3

Compatibility

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in Ringer’s injection

Dextrose 5% in Ringer’s injection, lactated

Dextrose 2.5% in sodium chloride 0.45 or 0.9%

Dextrose 5% in sodium chloride 0.2, 0.45, or 0.9%

Dextrose 10% in sodium chloride 0.9%

Dextrose 5, 10, or 20% in water

Mannitol 20% in water

Normosol M or R in dextrose 5% in water

Normosol R

Ringer’s injection

Ringer’s injection, lactated

Sodium chloride 0.25, 0.45, or 0.9%

Sodium lactate (1/6) M
Drug Compatibility
Admixture CompatibilityHID

Compatible

Ascorbic acid injection

Bleomycin sulfate

Calcium chloride

Calcium gluconate

Cefepime HCl

Cefoxitin sodium

Ceftriaxone sodium

Chloramphenicol sodium succinate

Ciprofloxacin

Clindamycin phosphate

Colistimethate sodium

Dimenhydrinate

Diphenhydramine HCl

Epinephrine HCl

Fluconazole

Hyaluronidase

Hydrocortisone sodium succinate

Lincomycin HCl

Norepinephrine bitartrate

Pentobarbital sodium

Phenobarbital sodium

Phytonadione

Polymyxin B sulfate

Potassium chloride

Prochlorperazine edisylate

Promethazine HCl

Ranitidine HCl

Sodium bicarbonate

Succinylcholine chloride

Vancomycin HCl

Verapamil HCl

Incompatible

Amphotericin B

Ampicillin sodium

Cefazolin sodium

Ceftazidime

Chlorothiazide sodium

Heparin sodium

Phenytoin sodium

Variable

Aminophylline

Cefotaxime sodium

Dexamethasone sodium phosphate

Oxacillin sodium

Penicillin G potassium
Y-Site CompatibilityHID

Compatible

Acyclovir sodium

Amifostine

Amiodarone HCl

Anidulafungin

Aztreonam

Bivalirudin

Caspofungin acetate

Cefepime HCI

Ceftaroline fosamil

Ceftazidime

Cisatracurium besylate

Cyclophosphamide

Dexamethasone sodium phosphate

Dexmedetomidine HCl

Diltiazem HCl

Docetaxel

Doripenem

Enalaprilat

Esmolol HCl

Etoposide phosphate

Fenoldopam mesylate

Filgrastim

Fluconazole

Fludarabine phosphate

Foscarnet sodium

Furosemide

Gemcitabine HCl

Granisetron HCl

Hetastarch in lactated electrolyte injection (Hextend)

Hydromorphone HCI

Idarubicin HCI

Labetalol HCl

Levofloxacin

Linezolid

Lorazepam

Magnesium sulfate

Melphalan HCl

Meperidine HCI

Midazolam HCl

Milrinone lactate

Morphine sulfate

Nicardipine HCl

Ondansetron HCl

Paclitaxel

Pemetrexed sodium

Remifentanil HCl

Sargramostim

Teniposide

Thiotepa

Tigecycline

Vinorelbine tartrate

Warfarin sodium

Zidovudine

Incompatible

Allopurinol sodium

Amphotericin B cholesteryl sulfate complex

Azithromycin

Hetastarch in sodium chloride 0.9%

Propofol

Actions and Spectrum

Advice to Patients

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Amikacin Sulfate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

50 mg (of amikacin) per mL*

Amikacin Sulfate Injection

250 mg (of amikacin) per mL*

Amikacin Sulfate Injection

AHFS DI Essentials™. © Copyright 2024, Selected Revisions June 18, 2013. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Hospira. Amikacin sulfate injection, USP fliptop vial prescribing information. Lake Forest, IL; 2004 Apr.

2. Bedford. Amikacin sulfate injection, USP prescribing information. Bedford, OH; 2004 Jan.

3. Sicor. Amikacin sulfate injection USP. Irvine, CA; 2005 Jun.

4. Kucers A, Crowe S, Grayson ML et al, eds. The use of antibiotics. A clinical review of antibacterial, antifungal, and antiviral drugs. 5th ed. Jordan Hill, Oxford: Butterworth-Heinemann; 1997: 504-21.

5. Anon. The choice of antibacterial drugs. Med Lett Treat Guid. 2004; 2:13-26.

6. American Academy of Pediatrics. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006.

8. Hughes WT, Armstrong D, Bodey GP et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002; 34:730-51. http://www.ncbi.nlm.nih.gov/pubmed/11850858?dopt=AbstractPlus

9. American Thoracic Society. Supplement: American Thoracic Society—Diagnosis and treatment of disease caused by nontuberculous mycobacteria. Am J Respir Crit Care Med. 1997; 156(2 Part 2):S1-19.

10. The United States pharmacopoeia, 29th rev, and The national formulary, 24th ed. Rockville, MD: The United States Pharmacopeial Convention; 2005:127-8,3192.

11. Chambers HF. Aminoglycosides. In: Brunton LL, Lazo JS, Parker KL et al, eds. Goodman and Gillman's the pharmacological basis of therapeutics. 11th ed. New York, NY: McGraw-Hill; 2006:1155-71.

12. Kawaguchi H. Discovery, chemistry, and activity of amikacin. J Infect Dis. 1978; 134(Suppl):242-8.

13. Kaplan MA, Coppola WP, Nunning BC et al. Pharmaceutical properties and stability of amikacin. Curr Ther Res Clin Exp. 1976; 20:352-8. http://www.ncbi.nlm.nih.gov/pubmed/12916?dopt=AbstractPlus

14. Barza M, Scheife RT. Drug therapy reviews: antimicrobial spectrum, pharmacology and therapeutic use of antibiotics, part 4: aminoglycosides. Am J Hosp Pharm. 1977; 34:723-37. http://www.ncbi.nlm.nih.gov/pubmed/407790?dopt=AbstractPlus

15. Dellagrammaticas HD, Christodoulou C, Megaloyanni E et al. Treatment of gram-negative bacterial meningitis in term neonates with third generation cephalosporins plus amikacin. Biol Neonate. 2000; 77:139-46. http://www.ncbi.nlm.nih.gov/pubmed/10729716?dopt=AbstractPlus

16. Clarke JR, Libke RD, Regamey C et al. Comparative pharmacokinetics of amikacin and kanamycin. Clin Pharmacol Ther. 1974; 15:610-6. http://www.ncbi.nlm.nih.gov/pubmed/4210297?dopt=AbstractPlus

17. Lode H, Grunert K, Koeppe P et al. Pharmacokinetic and clinical studies with amikacin, a new aminoglycoside antibiotic. J Infect Dis. 1976; 134(Suppl):316-22.

18. Howard JB, McCracken GH, Trujillo H et al. Amikacin in newborn infants: comparative pharmacology with kanamycin and clinical efficacy in 45 neonates with bacterial diseases. Antimicrob Agents Chemother. 1976; 10:205-10. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=429721&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/984762?dopt=AbstractPlus

19. Hamory B, Ignatiadis P, Sande MA. Intrathecal amikacin administration–use in the treatment of gentamicin-resistant Klebsiella pneumoniae meningitis. J AMA. 1976; 236:1973-4.

20. Bodey GP, Valdivieso M, Feld R et al. Pharmacology of amikacin in humans. Antimicrob Agents Chemother. 1974; 5:508-12. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=429003&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/4462465?dopt=AbstractPlus

21. Appel GB, Neu HC. The nephrotoxicity of antimicrobial agents, part 2. N Engl J Med. 1977; 296:722-8. http://www.ncbi.nlm.nih.gov/pubmed/190540?dopt=AbstractPlus

22. Bennett WM, Muther RS, Parker RA et al. Drug therapy in renal failure: dosing guidelines for adults. Ann Intern Med. 1980; 93:62-89. http://www.ncbi.nlm.nih.gov/pubmed/6994534?dopt=AbstractPlus

23. Howard JB, McCracken GH. Pharmacological evaluation of amikacin in neonates. Antimicrob Agents Chemother. 1975; 8:86-90. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=429265&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/1164009?dopt=AbstractPlus

24. Pijck J, Hallynck T, Soep H et al. Pharmacokinetics of amikacin in patients with renal insufficiency: relation of half-life and creatinine clearance. J Infect Dis. 1976; 134(Suppl):S331-41.

25. Gaillard JL, Silly C, Le Masne A et al. Cerebrospinal fluid penetration of amikacin in children with community-acquired bacterial meningitis. Antimicrob Agents Chemother. 1995; 39:253-5. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=162520&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/7695318?dopt=AbstractPlus

26. Santre C, Georges H, Jacquier JM et al. Amikacin levels in bronchial secretions of 10 pneumonia patients with respiratory support treated once daily versus twice daily. Antimicrob Agents Chemother. 1995; 39:264-7. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=162523&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/7695320?dopt=AbstractPlus

27. Canis F, Husson MO, Turck D et al. Pharmacokinetics and bronchial diffusion of single daily dose amikacin in cystic fibrosis patients. J Antimicrob Chemother. 1997; 39:431-3. http://www.ncbi.nlm.nih.gov/pubmed/9096197?dopt=AbstractPlus

28. Kihara M, Ikeda Y, Takagi N et al. Pharmacokinetics of single-dose intravenous amikacin in critically ill patients undergoing slow hemodialysis. Intensive Care Med. 1995; 21:348-51. http://www.ncbi.nlm.nih.gov/pubmed/7650258?dopt=AbstractPlus

30. Smeltzer BD, Schwartzman MS, Bertino JS. Amikacin pharmacokinetics during continuous ambulatory peritoneal dialysis. Antimicrob Agents Chemother. 1988; 32:236-40. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=172141&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/3364945?dopt=AbstractPlus

31. Bermudez RH, Lugo A, Ramirez-Ronda CH et al. Amikacin sulfate levels in human serum and bile. Antimicrob Agents Chemother. 1981; 19:352-4. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=181428&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/7347566?dopt=AbstractPlus

32. Hansbrough JF, Clark JE, Reimer LG. Concentrations of kanamycin and amikacin in human gallbladder bile and wall. Antimicrob Agents Chemother. 1981; 20:515-7. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=181734&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/7342877?dopt=AbstractPlus

33. Preston SL, Briceland LL. Intrathecal administration of amikacin for treatment of meningitis secondary to cephalosporin-resistant Escherichia coli. Ann Pharmacother. 1993; 27:870-3. http://www.ncbi.nlm.nih.gov/pubmed/8364266?dopt=AbstractPlus

34. Wright PF, Kaiser AB, Bowman CM et al. The pharmacokinetics and efficacy of an aminoglycoside administered into the cerebral ventricles in neonates: implications for further evaluation of this route of therapy in meningitis. J Infect Dis. 1981; 143:141-7. http://www.ncbi.nlm.nih.gov/pubmed/7012246?dopt=AbstractPlus

35. Block CS, Cassel R, Koornhof HJ. Klebsiella meningitis treated with intrathecal amikacin. Lancet. 1977; 1:1371-2. http://www.ncbi.nlm.nih.gov/pubmed/69095?dopt=AbstractPlus

36. Kafetzis DA, Sinaniotis CA, Papadatos CJ et al. Pharmacokinetics of amikacin in infants and pre-school children. Acta Paediatr Scand. 1979; 68:419-22. http://www.ncbi.nlm.nih.gov/pubmed/443042?dopt=AbstractPlus

37. Fulnecky EJ, Wright D, Scheld WM et al. Amikacin and colistin for treatment of Acinetobacter baumannii meningitis. J Infect. 2005; 51:e249-51. http://www.ncbi.nlm.nih.gov/pubmed/15913780?dopt=AbstractPlus

38. Nguyen MH, Harris SP, Muder RR et al. Antibiotic-resistant Acinetobacter meningitis in neurosurgical patients. Neurosurgery. 1994; 35:851-5. http://www.ncbi.nlm.nih.gov/pubmed/7838333?dopt=AbstractPlus

39. Corpus KA, Weber KB, Zimmerman CR. Intrathecal amikacin for the treatment of pseudomonal meningitis. Ann Pharmacother. 2004; 38:992-5. http://www.ncbi.nlm.nih.gov/pubmed/15122005?dopt=AbstractPlus

40. Torres-Tortosa M, Arrizabalaga J, Villanueva JL et al. Prognosis and clinical evaluation of infection caused by Rhodococcus equi in HIV-infected patients. Chest. 2003; 123:1970-6. http://www.ncbi.nlm.nih.gov/pubmed/12796176?dopt=AbstractPlus

41. Kashima M, Kano R, Mikami Y et al. A successfully treated case of mycetoma due to Nocardia veterana. Br J Dermatol. 2005; 142:1349-52.

42. Hitti W, Wolff M. Two cases of multidrug-resistant Nocardia farcinica infection in immunosuppressed patients and implications for empiric therapy. Eur J Clin Microbiol Infect Dis. 2005; 24:142-4. http://www.ncbi.nlm.nih.gov/pubmed/15692815?dopt=AbstractPlus

43. Autret E, Marchand S, Breteau M et al. Pharmacokinetics of amikacin in cystic fibrosis: a study of bronchial diffusion. Eur J Clin Pharmacol. 1986; 31:79-83. http://www.ncbi.nlm.nih.gov/pubmed/3780832?dopt=AbstractPlus

44. Mombelli G, Coppens L, Thys JP et al. Anti-Pseudomonas activity in bronchial secretions of patients receiving amikacin or tobramycin as a continuous infusion. Antimicrob Agents Chemother. 1981; 19:72-5. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=181359&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/7247362?dopt=AbstractPlus

45. Dull WL, Alexander MR, Kasik JE. Bronchial secretion levels of amikacin. Antimicrob Agents Chemother. 1979; 16:767-71. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=352950&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/533258?dopt=AbstractPlus

46. Honda DH, Adams HG, Barriere SL. Amikacin penetration into synovial fluid during treatment of septic arthritis. Drug Intell Clin Pharm. 1981; 15:284-6. http://www.ncbi.nlm.nih.gov/pubmed/7023898?dopt=AbstractPlus

47. Kenyon CF, Knoppert DC, Lee SK et al. Amikacin pharmacokinetics and suggested dosage modifications for the preterm infant. Antimicrob Agents Chemother. 1990; 34:265-8. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=171570&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/2327775?dopt=AbstractPlus

48. Langhendries JP, Battisti O, Bertrand JM et al. Once-a-day administration of amikacin in neonates: assessment of nephrotoxicity and ototoxicity. Dev Pharmacol Ther. 1993; 20:220-30. http://www.ncbi.nlm.nih.gov/pubmed/7828457?dopt=AbstractPlus

49. Karachalios GN, Houpas P, Tziviskou E et al. Prospective randomized study of once-daily versus twice-daily amikacin regimens in patients with systemic infections. Int J Clin Pharmacol Ther. 1998; 36:561-4. http://www.ncbi.nlm.nih.gov/pubmed/9799062?dopt=AbstractPlus

50. Krivoy N, Postovsky S, Elhasid R et al. Pharmacokinetic analysis of amikacin twice and single daily dosage in immunocompromised pediatric patients. Infection. 1998; 26:396-8. http://www.ncbi.nlm.nih.gov/pubmed/9861567?dopt=AbstractPlus

51. Armstrong DK, Hodgman T, Visconti JA et al. Hemodialysis of amikacin in critically ill patients. Crit Care Med. 1988; 16:517-20. http://www.ncbi.nlm.nih.gov/pubmed/3359790?dopt=AbstractPlus

52. Vic P, Ategbo S, Turck D et al. Tolerance, pharmacokinetics and efficacy of once daily amikacin for treatment of Pseudomonas aeruginosa pulmonary exacerbations in cystic fibrosis patients. Eur J Pediatr. 1996; 155:948-53. http://www.ncbi.nlm.nih.gov/pubmed/8911895?dopt=AbstractPlus

53. Izquierdo M, Lanao JM, Cervero L et al. A comparative study of the population pharmacokinetics of gentamicin and amikacin in newborn patients. J Clin Pharmacol Ther. 1993; 18:411-3,

54. El Desoky ES, Shoreit AH. Once- versus twice-daily administration of amikacin in pediatric patients with bronchopneumonia: plasma drug concentration and Bayesian pharmacokinetics estimation. Ann Pharmacother. 1999; 33:749-50. http://www.ncbi.nlm.nih.gov/pubmed/10410192?dopt=AbstractPlus

55. O'Brien MA, Mason NA. Systemic absorption of intraperitoneal antimicrobials in continuous ambulatory peritoneal dialysis. Clin Pharm. 1992; 11:246-54. http://www.ncbi.nlm.nih.gov/pubmed/1611814?dopt=AbstractPlus

56. Kotze A, Bartel PR, Sommers DK. Once versus twice daily amikacin in neonates: prospective study on toxicity. J Paediatr Child Health. 1999; 35:283-6. http://www.ncbi.nlm.nih.gov/pubmed/10404451?dopt=AbstractPlus

57. Solomkin JS, Mazuski JE, Baron EJ et al. Guidelines for the selection of anti-infective agents for complicated intra-abdominal infections. Clin Infect Dis. 2003; 37:997-1005. http://www.ncbi.nlm.nih.gov/pubmed/14523762?dopt=AbstractPlus

58. Horsburgh CR. Mycobacterium avium complex infection in the acquired immunodeficiency syndrome. N Engl J Med. 1991; 324:1332-8. http://www.ncbi.nlm.nih.gov/pubmed/2017230?dopt=AbstractPlus

59. Roger PM, Carles M, Agussol-Foin I et al. Efficacy and safety of an intravenous induction therapy for treatment of disseminated Mycobacterium avium complex infection in AIDS patients: a pilot study. J Antimicrob Chemother. 1999; 44:129-31. http://www.ncbi.nlm.nih.gov/pubmed/10459822?dopt=AbstractPlus

60. Chiu J, Nussbaum J, Bozzette S et al. Treatment of disseminated Mycobacterium avium complex infection in AIDS with amikacin, ethambutol, rifampin, and ciprofloxacin. Ann Intern Med. 1990; 113:358-61. http://www.ncbi.nlm.nih.gov/pubmed/2382918?dopt=AbstractPlus

61. Parenti DM, Williams PL, Hafner R et al. A phase II/III trial of antimicrobial therapy with or without amikacin in the treatment of disseminated Mycobacterium avium infection in HIV-infected individuals. AIDS. 1998; 12:2439-46. http://www.ncbi.nlm.nih.gov/pubmed/9875582?dopt=AbstractPlus

62. Charnas R, Luthi AR, Ruch W et al. Once daily ceftriaxone plus amikacin vs. three times daily ceftazidime plus amikacin for treatment of febrile neutropenic children with cancer. Pediatr Infect Dis J. 1997; 16:346-53. http://www.ncbi.nlm.nih.gov/pubmed/9109134?dopt=AbstractPlus

63. Cordonnier C, Herbrecht R, Pico JL et al et al. Cefepime/amikacin versus ceftazidime/amikacin as empirical therapy for febrile episodes in neutropenic patients: a comparative study. Clin Infect Dis. 1997; 24:41-51. http://www.ncbi.nlm.nih.gov/pubmed/8994754?dopt=AbstractPlus

64. Feigin RD, McCracken GH, Klein JO. Diagnosis and management of meningitis. Pediatr Infect Dis J. 1992; 11:785-814. http://www.ncbi.nlm.nih.gov/pubmed/1448332?dopt=AbstractPlus

65. Sorrell TC, Iredell JR, Mitchell DH. Nocardia species. In: Mandell GL, Bennett JE, Dolin R eds. Principles and practices of infectious diseases. 5th ed. New York: Churchill Livingstone; 2000:2637-45.

66. Ortiz AM, Rabagliati R, Machuca E. Successful treatment of Nocardia asteroides peritonitis in a patient undergoing automated peritoneal dialysis and receiving immunosuppressive therapy. Adv Perit Dial. 2005; 21:66-8. http://www.ncbi.nlm.nih.gov/pubmed/16686287?dopt=AbstractPlus

67. Tripodi MF, Adinolfi LE, Andreana A et al. Treatment of pulmonary nocardiosis in heart-transplant patients: importance of susceptibility studies. Clin Transp. 2001; 15:415-20.

68. Kilincer C, Hamamcioglu MK, Simsek O et al. Nocardial brain abscess: review of clinical management. J Clin Neurosci. 2006; 13:481-5. http://www.ncbi.nlm.nih.gov/pubmed/16678731?dopt=AbstractPlus

69. Filice GA. Nocardiosis. In: Kasper DL, Braunwald E, Fauci AS et al, eds. Harrison's principles of internal medicine. 16th ed. New York: McGraw-Hill; 2006.

70. Kirby WMM, Clarke JT, Libke RD et al. Clinical pharmacology of amikacin and kanamycin. J Infect Dis. 1976; 134(Suppl):s312-5. http://www.ncbi.nlm.nih.gov/pubmed/993624?dopt=AbstractPlus

71. Matsuda S, Mori S, Tanno M et al. Evaluation of amikacin in the obstetric and gynecologic fields. Jpn J Antibiot. 1974; 27:633-6. http://www.ncbi.nlm.nih.gov/pubmed/4617009?dopt=AbstractPlus

73. Shah S, Ohlsson A, Shah V. Intraventricular antibiotics for bacterial meningitis in neonates (review). Cochrane Database Syst Rev. 2004; CD004496.

74. Forsyth NB, Botha JH, Hadley GP. A comparison of two amikacin dosing regimens in paediatric surgical patients. Ann Trop Paediatr. 1997; 17:253-61. http://www.ncbi.nlm.nih.gov/pubmed/9425382?dopt=AbstractPlus

75. Ariffin H, Arasu A, Mahfuzah M et al. Single-daily ceftriaxone plus amikacin versus thrice-daily ceftazidime plus amikacin as empirical treatment of febrile neutropenia in children with cancer. J Paediatr Child Health. 2001; 37:38-43. http://www.ncbi.nlm.nih.gov/pubmed/11168867?dopt=AbstractPlus

76. Contopoulos-Ioannidis DG, Giotis ND, Baliatsa DV et al. Extended-interval aminoglycoside administration for children: a meta-analysis. Pediatrics. 2004; 114:111-8.

77. Tunkel AR, Hartman BJ, Kaplan SL et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004; 39:1267-84. http://www.ncbi.nlm.nih.gov/pubmed/15494903?dopt=AbstractPlus

99. Dee TH, Kozin F. Gentamicin and tobramycin penetration into synovial fluid. Antimicrob Agents Chemother. 1977; 12:548-9. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=429965&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/921252?dopt=AbstractPlus

200. Schentag JJ. Aminoglycosides. In: Evans WE, Schentag JJ, Jusko WJ, eds. Applied pharmacokinetics: principles of therapeutic drug monitoring. San Francisco: Applied Therapeutics, Inc.; 1980:174-209.

201. Zaske DE. Aminoglycosides: counterpoint discussion. In: Evans WE, Schentag JJ, Jusko WJ, eds. Applied pharmacokinetics: principles of therapeutic drug monitoring. San Francisco: Applied Therapeutics, Inc.; 1980:210-39.

202. Barclay ML, Begg EJ, Hickling KG. What is the evidence for once-daily aminoglycoside therapy? Clin Pharmacokinet. 1994; 27:32-48.

203. Rotschafer JC, Rybak MJ. Single daily dosing of aminoglycosides: a commentary. Ann Pharmacother. 1994; 28:797-801. http://www.ncbi.nlm.nih.gov/pubmed/7919572?dopt=AbstractPlus

204. Klotz U, Godel A. Once-daily dosing of gentamicin: experience with therapeutic drug monitoring and Bayesian pharmacokinetics. Ther Drug Monit. 1994; 16:534-5. http://www.ncbi.nlm.nih.gov/pubmed/7846756?dopt=AbstractPlus

205. Hustinx WN, Hoepelman IM. Aminoglycoside dosage regimens. Is once a day enough? Clin Pharmacokinet. 1993; 25:427-32.

206. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer. Efficacy and toxicity of single daily doses of amikacin and ceftriaxone versus multiple daily doses of amikacin and ceftazidime for infection in patients with cancer and granulocytopenia. Ann Intern Med. 1993; 119:584-93. http://www.ncbi.nlm.nih.gov/pubmed/8363169?dopt=AbstractPlus

207. Rodman DP, Maxwell AJ, McKnight JT. Extended dosage intervals for aminoglycosides. Am J Hosp Pharm. 1994; 51:2016-21. http://www.ncbi.nlm.nih.gov/pubmed/7977422?dopt=AbstractPlus

208. Bates RD, Nahata MC. Once-daily administration of aminoglycosides. DICP. 1994; 28:757-66.

209. Levison ME. New dosing regimens for aminoglycoside antibiotics. Ann Intern Med. 1992; 117:693-4. http://www.ncbi.nlm.nih.gov/pubmed/1530203?dopt=AbstractPlus

210. Zhanel GG. Changing strategies in aminoglycoside dosing; the result of research on antimicrobial pharmacodynamics. Int J Med Microbiol Virol Parasitol Infect Dis. 1993; 279:447-9.

211. Gilbert DN. Once-daily aminoglycoside therapy. Antimicrob Agents Chemother. 1991; 35:399-405. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=245022&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/2039189?dopt=AbstractPlus

212. Prins JM, Buller HR, Kuijper EJ et al. Once versus thrice daily gentamicin in patients with serious infections. Lancet. 1993; 341:335-9. http://www.ncbi.nlm.nih.gov/pubmed/8094114?dopt=AbstractPlus

213. Parker SE, Davey PG. Once-daily aminoglycoside dosing. Lancet. 1993; 341:346-7. http://www.ncbi.nlm.nih.gov/pubmed/8094120?dopt=AbstractPlus

214. Craig WA. Post-antibiotic effects in experimental infection models: relationship to in-vitro phenomena and to treatment of infections in man. J Antimicrob Chemother. 1993; 31(Suppl D):149-58. http://www.ncbi.nlm.nih.gov/pubmed/8335516?dopt=AbstractPlus

215. Vanhaeverbeek M, Siska G, Douchamps J et al. Comparison of the efficacy and safety of amikacin once or twice-a-day in the treatment of severe gram-negative infections in the elderly. Int J Clin Pharmacol Ther Toxicol. 1993; 31:153-6. http://www.ncbi.nlm.nih.gov/pubmed/8468114?dopt=AbstractPlus

216. Gilbert DN. Aminoglycosides. In: Mandell GL, Bennett JE, Dolin R eds. Principles and practices of infectious diseases. 5th ed. New York: Churchill Livingstone; 2000:307-36.

217. Powell SH, Thompson WL, Luthe MA et al. Once-daily vs. continuous aminoglycoside dosing: efficacy and toxicity in animal and clinical studies of gentamicin, netilmicin, and tobramycin. J Infect Dis. 1983; 147:918-32. http://www.ncbi.nlm.nih.gov/pubmed/6860416?dopt=AbstractPlus

218. Centers for Disease Control and Prevention. Treatment of tuberculosis, American Thoracic Society, CDC, and Infectious Diseases Society of America. MMWR Morb Mortal Wkly Rep. 2003; 52(No. RR-11):1-77. http://www.cdc.gov/mmwr/PDF/rr/rr5211.pdf http://www.ncbi.nlm.nih.gov/pubmed/12549898?dopt=AbstractPlus

219. McCormack JP, Jewesson PJ. A critical reevaluation of the therapeutic range of aminoglycosides. Clin Infect Dis. 1992; 14:320-39. http://www.ncbi.nlm.nih.gov/pubmed/1571447?dopt=AbstractPlus

220. Viscoli C, Dudley M, Ferrea G et al. Serum concentrations and safety of single daily dosing of amikacin in children undergoing bone marrow transplantation. J Antimicrob Chemother 1991; 27 (Suppl C):113-20.

221. Tulkens PM. Efficacy and safety of aminoglycosides once-a-day: experimental and clinical data. Scand J Infect Dis. 1991; 74:249-57.

222. Reviewers’ comments (personal observations).

223. Zhanel GG, Craig WA. Pharmacokinetic contributions to postantibiotic effects. Clin Pharmacokinet. 1994; 27:377-92. http://www.ncbi.nlm.nih.gov/pubmed/7851055?dopt=AbstractPlus

224. Moore RD, Lietman PS, Smith CR. Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis. 1987; 155:93-9. http://www.ncbi.nlm.nih.gov/pubmed/3540140?dopt=AbstractPlus

225. Moore RD, Smith CR, Lietman PS. The association of aminoglycoside plasma levels with mortality in patients with gram-negative bacteremia. J Infect Dis. 1984; 149:443-8. http://www.ncbi.nlm.nih.gov/pubmed/6715900?dopt=AbstractPlus

226. Moore RD, Smith CR, Lietman PS. Association of aminoglycoside plasma levels with therapeutic outcome in gram-negative pneumonia. Am J Med. 1984; 77:657-62. http://www.ncbi.nlm.nih.gov/pubmed/6385693?dopt=AbstractPlus

227. Sarubbi FA Jr, Hull JH. Amikacin serum concentrations: prediction of levels and dosage guidelines. Ann Intern Med. 1978; 89:612-8. http://www.ncbi.nlm.nih.gov/pubmed/717929?dopt=AbstractPlus

228. Parker SE, Davey PG. Serum monitoring and practicalities of once-daily aminoglycoside dosing. J Antimicrob Chemother. 1994; 33:351.

229. Hansen M, Achen F, Carstensen C et al. Once- versus thrice-daily dosing of netilmicin in febrile immunocompromised patients: a randomized, controlled study of efficacy and safety. J Drug Dev. 1988; 1(Suppl 3):119-24.

230. Maller R, Ahrne H, Holmen C et al. Once- versus twice-daily amikacin regimen: efficacy and safety in systemic Gram-negative infections. J Antimicrob Chemother. 1993; 31:939-48. http://www.ncbi.nlm.nih.gov/pubmed/8360131?dopt=AbstractPlus

231. Marik PE, Lipman J, Kobilski S et al. A prospective randomized study comparing once- versus twice-daily amikacin dosing in critically ill adult and paediatric patients. J Antimicrob Chemother. 1991; 28:753-64. http://www.ncbi.nlm.nih.gov/pubmed/1778878?dopt=AbstractPlus

232. Norström L, Lerner SA. Single daily dose therapy with aminoglycosides. J Hosp Infect. 1991; 18(Suppl A):117-29. http://www.ncbi.nlm.nih.gov/pubmed/1679774?dopt=AbstractPlus

233. Parker SE, Davey PG. Practicalities of once-daily aminoglycoside dosing. J Antimicrob Chemother. 1993; 31:4-8. http://www.ncbi.nlm.nih.gov/pubmed/8018114?dopt=AbstractPlus

234. Pechère JC, Craig WA, Meunier F. Once daily dosing of aminoglycoside: one step forward. J Antimicrob Chemother. 1991; 27(Suppl C):149-52. http://www.ncbi.nlm.nih.gov/pubmed/1856144?dopt=AbstractPlus

235. Viganò A, Principi N, Brivio L et al. Comparison of 5 milligrams of netilmicin per kilogram of body weight once daily versus 2 milligrams per kilogram thrice daily for treatment of gram-negative pyelonephritis in children. Antimicrob Agents Chemother. 1992; 36:1499-1503. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=191611&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/1510446?dopt=AbstractPlus

236. MacGowan AP, Reeves DS. Serum monitoring and practicalities of once-daily aminoglycoside dosing. J Antimicrob Chemother. 1994; 33:349-50. http://www.ncbi.nlm.nih.gov/pubmed/8182018?dopt=AbstractPlus

237. O’Shaughnessy EM, Das SS. Serum monitoring and practicalities of once-daily aminoglycoside dosing. J Antimicrob Chemother. 1994; 33:350. http://www.ncbi.nlm.nih.gov/pubmed/8182019?dopt=AbstractPlus

238. Smith CR, Maxwell RR, Edwards CQ et al. Nephrotoxicity induced by gentamicin and amikacin. Johns Hopkins Med J. 1978; 142:85-90. http://www.ncbi.nlm.nih.gov/pubmed/342789?dopt=AbstractPlus

239. Konrad F, Wagner R, Neumeister B et al. Studies on drug monitoring in thrice and once daily treatment with aminoglycosides. Intensive Care Med. 1993; 19:215-20. http://www.ncbi.nlm.nih.gov/pubmed/8366230?dopt=AbstractPlus

243. Nicolau DP, Freeman CD, Belliveau PP et al. Experience with a once-daily aminoglycoside program administered to 2,184 adult patients. Antimicrob Agents Chemother. 1995; 39:650-5. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=162599&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/7793867?dopt=AbstractPlus

244. Skopnik H, Heimann G. Once daily aminoglycoside dosing in full term neonates. Pediatr Infect Dis J. 1995; 14:71-2. http://www.ncbi.nlm.nih.gov/pubmed/7715998?dopt=AbstractPlus

245. Hatala R, Dinh T, Cook DJ. Once-daily aminoglycoside dosing in immunocompetent adults: a meta-analysis. Ann Intern Med. 1996; 124:717-25. http://www.ncbi.nlm.nih.gov/pubmed/8633831?dopt=AbstractPlus

246. Barza M, Ioannidis JPA, Cappelleri JC et al. Single or multiple daily doses of aminoglycosides: a meta-analysis. BMJ. 1996; 312:338-45. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2350289&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/8611830?dopt=AbstractPlus

247. Ferriols-Lisart R, Alòs-Almiñana M. Effectiveness and safety of once-daily aminoglycosides: a meta-analysis. Am J Health-Syst Pharm. 1996; 53:1141-50. http://www.ncbi.nlm.nih.gov/pubmed/8734674?dopt=AbstractPlus

248. McLean AJ, Ioannides-Demos LL, Spicer WJ et al. Aminoglycoside dosing: one, two or three times a day? Med J Aust. 1996; 164:39-42.

249. Garrelts JC. Exploration of once-daily dosing of aminoglycosides through Bayesian simulation. Pharmacotherapy. 1996; 16:286-94. http://www.ncbi.nlm.nih.gov/pubmed/8820474?dopt=AbstractPlus

250. Gilbert DN, Meta-analyses are no longer required for determining the efficacy of single daily dosing of aminoglycosides. Clin Infect Dis. 1997; 24:816-9. Editorial.

251. Barclay ML, Kirkpatrick CMJ, Begg EJ. Once daily aminoglycoside therapy. Is it less toxic than multiple daily doses and how should it be monitored? Clin Pharmacokinet. 1999; 36:89-98.

252. Freeman CD, Nicolau DP, Belliveau PP et al. Once-daily dosing of aminoglycosides: review and recommendations for clinical practice. J Antimicrob Chemother. 1997; 39:677-86. http://www.ncbi.nlm.nih.gov/pubmed/9222035?dopt=AbstractPlus

253. Tod MM, Padoin C, Petitjean O. Individualising aminoglycoside dosage regimens after therapeutic drug monitoring: simple or complex pharmacokinetic methods? Clin Pharmacokinet. 2001; 40:803-14.

254. Reimann IR, Meier-Hellmann A, Traut T et al. Monitoring of a single post-infusion blood sample to estimate the actual peak and trough concentration of tobramycin in critically ill patients. Exp Toxicol Pathol. 2003; 54:493-8. http://www.ncbi.nlm.nih.gov/pubmed/12877363?dopt=AbstractPlus

255. Wallace AW, Jones M, Bertino JS. Evaluation of four once-daily aminoglycoside dosing nomograms. Pharmacotherapy. 2002; 22:1077-83. http://www.ncbi.nlm.nih.gov/pubmed/12222541?dopt=AbstractPlus

256. Coulthard KP, Peckham DG, Conway SP et al. Therapeutic drug monitoring of once daily tobramycin in cystic fibrosis–caution with trough concentrations. J Cyst Fibros. 2006; epub.

257. Prins JM, Weverling GJ, de Block K et al. Validation and nephrotoxicity of a simplified once-daily aminoglycoside dosing schedule and guidelines for monitoring therapy. Antimicrob Agents Chemother. 1996; 40:2494-9. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=163563&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/8913452?dopt=AbstractPlus

258. Boyle EM, Brookes I, Nye K et al. Random gentamicin concentrations do not predict trough levels in neonates receiving once daily fixed dose regimens. BMC Pediatrics. 2006; 6:1-17. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1413531&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/16457711?dopt=AbstractPlus

259. Matsuda S. Transfer of antibiotics into maternal milk. Biol Res Pregnancy Perinatol. 1984;5:57-60.

h. AHFS Drug Information 2004. McEvoy GK, ed. Amikacin Sulfate. Bethesda, MD: American Society of Health-System Pharmacists; 2004:62-3.

i. AHFS Drug Information 2004. McEvoy GK, ed. Aminoglycosides General Statement. Bethesda, MD: American Society of Health-System Pharmacists; 2004: 56-62.

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:27-37.

Frequently asked questions

Medical Disclaimer