Amikacin sulfate: Difference between revisions

Amikacin sulfate
	Black Box Warning
	Adult Indications & Dosage
	Pediatric Indications & Dosage
	Contraindications
	Warnings & Precautions
	Adverse Reactions
	Drug Interactions
	Use in Specific Populations
	Administration & Monitoring
	Overdosage
	Pharmacology
	Clinical Studies
	How Supplied
	Images
	Patient Counseling Information
	Precautions with Alcohol
	Brand Names
	Look-Alike Names

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Revision as of 20:52, 23 December 2014

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alberto Plate [2]

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Black Box Warning

Warning

See full prescribing information for complete Boxed Warning.

Condition Name: Patients treated with parenteral aminoglycosides should be under close clinical observation because of the potential ototoxicity and nephrotoxicity associated with their use. Safety for treatment periods which are longer than 14 days has not been established.

Neurotoxicity, manifested as vestibular and permanent bilateral auditory ototoxicity, can occur in patients with preexisting renal damage and in patients with normal renal function treated at higher doses and/or for periods longer than those recommended. The risk of aminoglycoside-induced ototoxicity is greater in patients with renal damage. High frequency deafness usually occurs first and can be detected only by audiometric testing. Vertigo may occur and may be evidence of vestibular injury. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching and convulsions. The risk of hearing loss due to aminoglycosides increases with the degree of exposure to either high peak or high trough serum concentrations. Patients developing cochlear damage may not have symptoms during therapy to warn them of developing eighth-nerve toxicity, and total or partial irreversible bilateral deafness may occur after the drug has been discontinued. Aminoglycoside-induced ototoxicity is usually irreversible.

Aminoglycosides are potentially nephrotoxic. The risk of nephrotoxicity is greater in patients with impaired renal function and in those who receive high doses or prolonged therapy.

Neuromuscular blockade and respiratory paralysis have been reported following parenteral injection, topical instillation (as in orthopedic and abdominal irrigation or in local treatment of empyema), and following oral use of aminoglycosides. The possibility of these phenomena should be considered if aminoglycosides are administered by any route, especially in patients receiving anesthetics; neuromuscular blocking agents such as tubocurarine, succinylcholine, decamethonium; or in patients receiving massive transfusions of citrate-anticoagulated blood. If blockage occurs, calcium salts may reverse these phenomena, but mechanical respiratory assistance may be necessary.

Renal and eighth-nerve function should be closely monitored especially in patients with known or suspected renal impairment at the onset of therapy and also in those whose renal function is initially normal but who develop signs of renal dysfunction during therapy. Serum concentrations of amikacin should be monitored when feasible to assure adequate levels and to avoid potentially toxic levels and prolonged peak concentrations above 35 micrograms per mL. Urine should be examined for decreased specific gravity, increased excretion of proteins and the presence of cells or casts. Blood urea nitrogen, serum creatinine or creatinine clearance should be measured periodically. Serial audiograms should be obtained where feasible in patients old enough to be tested, particularly high risk patients. Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears and hearing loss) or nephrotoxicity requires discontinuation of the drug or dosage adjustment.

Concurrent and/or sequential systemic, oral or topical use of other neurotoxic or nephrotoxic products, particularly bacitracin, cisplatin, amphotericin B, cephaloridine, paromomycin, viomycin, polymyxin B, colistin, vancomycin or other aminoglycosides should be avoided. Other factors that may increase risk of toxicity are advanced age and dehydration.

The concurrent use of amikacin with potent diuretics (ethacrynic acid or furosemide) should be avoided since diuretics by themselves may cause ototoxicity. In addition, when administered intravenously, diuretics may enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.)

Overview

Amikacin sulfate is an antibiotic that is FDA approved for the treatment of infections due to susceptible strains of Gram-negative bacteria, including Pseudomonas species, Escherichia coli, species of indole-positive and indole-negative Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, Acinetobacter (Mima-Herellea) species, Staphylococcus and Gram-positive organisms, such as streptococcus. Clinical studies have proven efficacy in:

Bacterial Septicemia (including neonatal sepsis)
Severe respiratory tract infections
Bone infections
Joint infections
Central nervous system infections (including meningitis)
Skin and soft tissue infections
Intra-abdominal infections (including peritonitis).
Burns
Post-operative infections (including post-vascular surgery)
Serious complicated and recurrent urinary tract infections. There is a Black Box Warning for this drug as shown here. Common adverse reactions include neuromuscular blockade, ototoxicity, nephrotoxicity and respiratory paralysis..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Infections due to susceptible strains of Gram-negative bacteria, including Pseudomonas species, Escherichia coli, species of indole-positive and indole-negative Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, Acinetobacter (Mima-Herellea) species, Staphylococcus and Gram-positive organisms, such as streptococcus. Clinical studies have proven efficacy in:

Bacterial Septicemia (including neonatal sepsis)
Severe respiratory tract infections
Bone infections
Joint infections
Central nervous system infections (including meningitis)
- Dosage:
  - IV: 15 mg/kg/day IV divided in doses q8h.
  - Intraventricular: 5mg-50 mg/day.
Skin and soft tissue infections
Intra-abdominal infections (including peritonitis).
Burns
Post-operative infections (including post-vascular surgery)
Serious complicated and recurrent urinary tract infections

Dosage

Intramuscular Administration for Patients with Normal Renal Function

The recommended dosage for adults, children and older infants with normal renal function is 15 mg/kg/day divided into 2 or 3 equal doses administered at equally divided intervals, i.e., 7.5 mg/kg q12h or 5 mg/kg q8h. Treatment of patients in the heavier weight classes should not exceed 1.5 g/day. When amikacin is indicated in newborns, it is recommended that a loading dose of 10 mg/kg be administered initially to be followed with 7.5 mg/kg every 12 hours.

The usual duration of treatment is 7 to 10 days. It is desirable to limit the duration of treatment to short-term whenever feasible. The total daily dose by all routes of administration should not exceed 15 mg/kg/day. In difficult and complicated infections where treatment beyond 10 days is considered, the use of amikacin should be reevaluated. If continued, amikacin serum levels and renal, auditory and vestibular functions should be monitored. At the recommended dosage level, uncomplicated infections due to amikacin-sensitive organisms should respond in 24 to 48 hours. If definite clinical response does not occur within 3 to 5 days, therapy should be stopped and the antibiotic susceptibility pattern of the invading organism should be rechecked. Failure of the infection to respond may be due to resistance of the organism or to the presence of septic foci requiring surgical drainage. When amikacin is indicated in uncomplicated urinary tract infections, a dose of 250 mg twice daily may be used.

Intramuscular Administration for Patients with Impaired Renal Function

Whenever possible, serum amikacin concentrations should be monitored by appropriate assay procedures. Doses may be adjusted in patients with impaired renal function either by administering normal doses at prolonged intervals or by administering reduced doses at a fixed interval.

Both methods are based on the patient's creatinine clearance or serum creatinine values since these have been found to correlate with aminoglycoside half-lives in patients with diminished renal function. These dosage schedules must be used in conjunction with careful clinical and laboratory observations of the patient and should be modified as necessary. Neither method should be used when dialysis is being performed.

Normal Dosage at Prolonged Intervals: If the creatinine clearance rate is not available and the patient's condition is stable, a dosage interval in hours for the normal dose can be calculated by multiplying the patient's serum creatinine by 9, e.g., if the serum creatinine concentration is 2 mg/100 mL, the recommended single dose (7.5 mg/kg) should be administered every 18 hours.
Reduced Dosage at Fixed Time Intervals: When renal function is impaired and it is desirable to administer amikacin at a fixed time interval, dosage must be reduced. In these patients, serum amikacin concentrations should be measured to assure accurate administration of amikacin and to avoid concentrations above 35 mcg/mL. If serum assay determinations are not available and the patient's condition is stable, serum creatinine and creatinine clearance values are the most readily available indicators of the degree of renal impairment to use as a guide for dosage. First, initiate therapy by administering a normal dose, 7.5 mg/kg, as a loading dose. This loading dose is the same as the normally recommended dose which would be calculated for a patient with a normal renal function as described above. To determine the size of maintenance doses administered every 12 hours, the loading dose should be reduced in proportion to the reduction in the patient's creatinine clearance rate:

Intravenous Administrations

The individual dose, the total daily dose, and the total cumulative dose of amikacin sulfate are identical to the dose recommended for intramuscular administration. The solution for intravenous use is prepared by adding the contents of a 500 mg vial to 100 or 200 mL of sterile diluent such as 0.9% sodium chloride injection or 5% dextrose injection or any other compatible solutions listed below. The solution is administered to adults over a 30 to 60 minute period. The total daily dose should not exceed 15 mg/kg/day and may be divided into either 2 or 3 equally-divided doses at equally-divided intervals.

In pediatric patients, the amount of fluid used will depend on the amount of amikacin sulfate ordered for the patient. It should be a sufficient amount to infuse the amikacin over a 30 to 60 minute period. Infants should receive a 1 to 2 hour infusion.

Amikacin should not be physically premixed with other drugs but should be administered separately according to the recommended dose and route.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Febrile Neutropenia

2010 Guideline - Treatment of febrile neutropenia in cancer patients ^[1]

Tuberculosis

Used as a second-line drug

Dosage: 15 mg/kg per day (1.0 g/day), intramuscular or intravenous, usually given as a single daily dose (5--7 days/week) ^[2]

Nosocomial Pneumonia

Dosage: 20 mg/kg per day

Non–Guideline-Supported Use

Bacterial Endocarditis

Dosage: Amikacin^[3] 7.5 mg/kg/12h + Cloxacillin 2 g/4h (Duration of therapy: 2 weeks).

Eye Infection

Dosage: 25 mg subconjunctival

Mycobacteriosis

Dosage: 7.5 mg/kg IV administered for 4 weeks in a multidrug regimen including ethambutol, rifampin, and ciprofloxacin^[4].

Nocardiosis

Dosage: 15 mg/kg/day IM dividen in 2 doses every 21 days ^[5]

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Infections due to susceptible strains of Gram-negative bacteria, including Pseudomonas species, Escherichia coli, species of indole-positive and indole-negative Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, Acinetobacter (Mima-Herellea) species, Staphylococcus and Gram-positive organisms, such as streptococcus. Clinical studies have proven efficacy in:

Bacterial Septicemia (including neonatal sepsis)
Severe respiratory tract infections
Bone infections
Joint infections
Central nervous system infections (including meningitis)
- Dosage:
  - IV: 15 mg/kg/day IV divided in doses q8h.
  - Intraventricular: 5mg-50 mg/day.
Skin and soft tissue infections
Intra-abdominal infections (including peritonitis).
Burns
Post-operative infections (including post-vascular surgery)
Serious complicated and recurrent urinary tract infections

Dosage

Intramuscular Administration for Patients with Normal Renal Function

The recommended dosage for adults, children and older infants with normal renal function is 15 mg/kg/day divided into 2 or 3 equal doses administered at equally divided intervals, i.e., 7.5 mg/kg q12h or 5 mg/kg q8h. Treatment of patients in the heavier weight classes should not exceed 1.5 g/day. When amikacin is indicated in newborns, it is recommended that a loading dose of 10 mg/kg be administered initially to be followed with 7.5 mg/kg every 12 hours.

The usual duration of treatment is 7 to 10 days. It is desirable to limit the duration of treatment to short-term whenever feasible. The total daily dose by all routes of administration should not exceed 15 mg/kg/day. In difficult and complicated infections where treatment beyond 10 days is considered, the use of amikacin should be reevaluated. If continued, amikacin serum levels and renal, auditory and vestibular functions should be monitored. At the recommended dosage level, uncomplicated infections due to amikacin-sensitive organisms should respond in 24 to 48 hours. If definite clinical response does not occur within 3 to 5 days, therapy should be stopped and the antibiotic susceptibility pattern of the invading organism should be rechecked. Failure of the infection to respond may be due to resistance of the organism or to the presence of septic foci requiring surgical drainage. When amikacin is indicated in uncomplicated urinary tract infections, a dose of 250 mg twice daily may be used.

Intramuscular Administration for Patients with Impaired Renal Function

Whenever possible, serum amikacin concentrations should be monitored by appropriate assay procedures. Doses may be adjusted in patients with impaired renal function either by administering normal doses at prolonged intervals or by administering reduced doses at a fixed interval.

Both methods are based on the patient's creatinine clearance or serum creatinine values since these have been found to correlate with aminoglycoside half-lives in patients with diminished renal function. These dosage schedules must be used in conjunction with careful clinical and laboratory observations of the patient and should be modified as necessary. Neither method should be used when dialysis is being performed.

Normal Dosage at Prolonged Intervals: If the creatinine clearance rate is not available and the patient's condition is stable, a dosage interval in hours for the normal dose can be calculated by multiplying the patient's serum creatinine by 9, e.g., if the serum creatinine concentration is 2 mg/100 mL, the recommended single dose (7.5 mg/kg) should be administered every 18 hours.
Reduced Dosage at Fixed Time Intervals: When renal function is impaired and it is desirable to administer amikacin at a fixed time interval, dosage must be reduced. In these patients, serum amikacin concentrations should be measured to assure accurate administration of amikacin and to avoid concentrations above 35 mcg/mL. If serum assay determinations are not available and the patient's condition is stable, serum creatinine and creatinine clearance values are the most readily available indicators of the degree of renal impairment to use as a guide for dosage. First, initiate therapy by administering a normal dose, 7.5 mg/kg, as a loading dose. This loading dose is the same as the normally recommended dose which would be calculated for a patient with a normal renal function as described above. To determine the size of maintenance doses administered every 12 hours, the loading dose should be reduced in proportion to the reduction in the patient's creatinine clearance rate:

Intravenous Administrations

The individual dose, the total daily dose, and the total cumulative dose of amikacin sulfate are identical to the dose recommended for intramuscular administration. The solution for intravenous use is prepared by adding the contents of a 500 mg vial to 100 or 200 mL of sterile diluent such as 0.9% sodium chloride injection or 5% dextrose injection or any other compatible solutions listed below. The solution is administered to adults over a 30 to 60 minute period. The total daily dose should not exceed 15 mg/kg/day and may be divided into either 2 or 3 equally-divided doses at equally-divided intervals.

In pediatric patients, the amount of fluid used will depend on the amount of amikacin sulfate ordered for the patient. It should be a sufficient amount to infuse the amikacin over a 30 to 60 minute period. Infants should receive a 1 to 2 hour infusion.

Amikacin should not be physically premixed with other drugs but should be administered separately according to the recommended dose and route.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Tuberculosis

Used as a second-line drug

Dosage: 15-30 mg/kg per day (1 g/day) intramuscular or intravenous as a single daily dose.) ^[6]

Nosocomial Pneumonia

Dosage: 20 mg/kg per day

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Amikacin sulfate in pediatric patients.

Contraindications

A history of hypersensitivity to amikacin is a contraindication for its use. A history of hypersensitivity or serious toxic reactions to aminoglycosides may contraindicate the use of any other aminoglycoside because of the known cross-sensitivities of patients to drugs in this class.

Warnings