Amikacin Sulfate

Class: Aminoglycosides
VA Class: AM300
CAS Number: 39831-55-5

• 
  

  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 Cl_cr.^{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 Sulfate

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† 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† (MAC) infections.^{5 9 58 59 60 61}

Treatment of nonpulmonary infections caused by M. abscessus†,^{6 9} M. chelonae†,⁴ or M. fortuitum†.^{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 Sulfate Dosage and Administration

Administration

Administer by IV infusion or IM injection.^{1 2 3}

Has been given intrathecallly† 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.)

Cautions for Amikacin Sulfate

Contraindications

• 
  

  Hypersensitivity or serious toxic reactions to amikacin or other aminoglycosides.^{1 2 3}

  
  

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 Cl_cr, 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} Cl_cr 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}

Interactions for Amikacin Sulfate

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