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Pronunciation |
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(am
i KAY
sin) |
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U.S. Brand
Names |
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Amikin®
Injection |
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Generic
Available |
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No |
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Canadian Brand
Names |
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Amikin® |
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Synonyms |
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Amikacin Sulfate |
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Pharmacological Index |
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Antibiotic, Aminoglycoside |
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Use |
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Treatment of serious infections due to organisms resistant to gentamicin and
tobramycin including Pseudomonas, Proteus, Serratia, and
other gram-positive bacilli (bone infections, respiratory tract infections,
endocarditis, and septicemia); documented infection of mycobacterial organisms
susceptible to amikacin |
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Pregnancy Risk
Factor |
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C |
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Contraindications |
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Hypersensitivity to amikacin sulfate or any component; cross-sensitivity may
exist with other aminoglycosides |
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Warnings/Precautions |
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Dose and/or frequency of administration must be monitored and modified in
patients with renal impairment; drug should be discontinued if signs of
ototoxicity, nephrotoxicity, or hypersensitivity occur; ototoxicity is
proportional to the amount of drug given and the duration of treatment; tinnitus
or vertigo may be indications of vestibular injury and impending bilateral
irreversible damage; renal damage is usually reversible |
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Adverse
Reactions |
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1% to 10%:
Central nervous system: Neurotoxicity
Otic: Ototoxicity (auditory), ototoxicity (vestibular)
Renal: Nephrotoxicity
<1%: Hypotension, headache, drowsiness, drug fever, rash, nausea,
vomiting, eosinophilia, paresthesia, tremor, arthralgia, weakness, dyspnea
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Overdosage/Toxicology |
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Symptoms of overdose include ototoxicity, nephrotoxicity, and neuromuscular
toxicity
Treatment of choice following a single acute overdose appears to be the
maintenance of good urine output of at least 3 mL/kg/hour. Dialysis is of
questionable value in the enhancement of aminoglycoside elimination. If
required, hemodialysis is preferred over peritoneal dialysis in patients with
normal renal function. |
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Drug
Interactions |
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Decreased effect of aminoglycoside: High concentrations of penicillins and/or
cephalosporins ( in vitro data)
Increased toxicity of aminoglycoside: Indomethacin I.V., amphotericin, loop
diuretics, vancomycin, enflurane, methoxyflurane; increased toxicity of
depolarizing and nondepolarizing neuromuscular blocking agents and polypeptide
antibiotics with administration of aminoglycosides |
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Stability |
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Stable for 24 hours at room temperature and 2 days at refrigeration when
mixed in D5W,
D51/4
NS, D51/2
NS, NS, LR |
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Mechanism of
Action |
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Inhibits protein synthesis in susceptible bacteria by binding to 30S
ribosomal subunits |
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Pharmacodynamics/Kinetics |
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Absorption: I.M.: May be delayed in the bedridden patient
Distribution: Crosses the placenta; primarily distributes into extracellular
fluid (highly hydrophilic); penetrates the blood-brain barrier when meninges are
inflamed
Relative diffusion of antimicrobial agents from blood into cerebrospinal
fluid (CSF): Good only with inflammation (exceeds usual MICs); ratio of CSF to
blood level (%):
Normal meninges: 10-20
Inflamed meninges: 15-24
Half-life (dependent on renal function):
Infants: Low birthweight (1-3 days): 7-9 hours; Full term >7 days: 4-5
hours
Children: 1.6-2.5 hours
Adults: Normal renal function: 1.4-2.3 hours; Anuria: End-stage renal
disease: 28-86 hours
Time to peak serum concentration: I.M.: Within 45-120 minutes
Elimination: 94% to 98% excreted unchanged in urine via glomerular filtration
within 24 hours; clearance dependent on renal function and patient age
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Usual Dosage |
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Individualization is critical because of the low therapeutic index
In morbid obesity, dosage requirement may best be estimated using a dosing
weight of IBW + 0.4 (TBW - IBW)
Initial and periodic peak and trough plasma drug levels should be determined,
particularly in critically ill patients with serious infections or in disease
states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic
fibrosis, burns, or major surgery)
Infants, Children, and Adults: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours
Some clinicians suggest a daily dose of 15-20 mg/kg for all patients with
normal renal function. This dose is at least as efficacious with similar, if not
less, toxicity than conventional dosing.
Dosing interval in renal impairment: Some patients may require larger
or more frequent doses if serum levels document the need (ie, cystic fibrosis or
febrile granulocytopenic patients)
Clcr greater than or equal to 60 mL/minute: Administer every 8
hours
Clcr 40-60 mL/minute: Administer every 12 hours
Clcr 20-40 mL/minute: Administer every 24 hours
Clcr <20 mL/minute: Loading dose, then monitor levels
Hemodialysis: Dialyzable (50% to 100%); administer dose postdialysis or
administer 2/3
normal dose as a supplemental dose postdialysis and follow levels
Peritoneal dialysis: Dose as Clcr <20 mL/minute: Follow levels
Continuous arteriovenous or venovenous hemodiafiltration (CAVH) effects: Dose
as for Clcr 10-40 mL/minute and follow levels |
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Monitoring
Parameters |
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Urinalysis, BUN, serum creatinine, appropriately timed peak and trough
concentrations, vital signs, temperature, weight, I & O, hearing
parameters |
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Reference Range |
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Sample size: 0.5-2 mL blood (red top tube) or 0.1-1 mL serum (separated)
Therapeutic levels:
Peak:
Life-threatening infections: 25-30 mg/mL
Serious infections: 20-25 mg/mL
Urinary tract infections: 15-20 mg/mL
Trough:
Serious infections: 1-4 mg/mL
Life-threatening infections: 4-8 mg/mL
Toxic concentration: Peak: >35 mg/mL; Trough:
>10
mg/mL
Timing of serum samples: Draw peak 30 minutes after completion of 30-minute
infusion or at 1 hour following initiation of infusion or I.M. injection; draw
trough within 30 minutes prior to next dose |
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Test
Interactions |
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Penicillin may decrease aminoglycoside serum concentrations in
vitro |
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Mental Health: Effects
on Mental Status |
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May cause drowsiness; case reports of delirium and
psychosis |
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Mental Health:
Effects on Psychiatric
Treatment |
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None reported |
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Dental Health: Local
Anesthetic/Vasoconstrictor
Precautions |
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No information available to require special precautions |
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Dental Health:
Effects on Dental Treatment |
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No effects or complications reported |
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Patient
Information |
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This drug can only be administered I.V. or I.M. It is important to maintain
adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid
intake). Report change in hearing acuity, ringing or roaring in ears, alteration
in balance, vertigo, feeling of fullness in head; pain, tingling, or numbness of
any body part; change in urinary pattern or decrease in urine; signs of
opportunistic infection (eg, white plaques in mouth, vaginal discharge, unhealed
sores, sore throat, unusual fever, chills); pain, redness, or swelling at
injection site; or other adverse reactions. Pregnancy precautions:
Inform prescriber if you are or intend to be pregnant. |
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Nursing
Implications |
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Aminoglycoside levels measured from blood taken from
Silastic® central catheters can sometimes give falsely
high readings (draw levels from alternate lumen or peripheral stick, if
possible) |
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Dosage Forms |
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Injection, as sulfate: 50 mg/mL (2 mL, 4 mL); 250 mg/mL (2 mL, 4
mL) |
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References |
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Bauer LA and Blouin RA,
"Influence of Age on Amikacin Pharmacokinetics in Patients Without Renal Disease. Comparison With Gentamicin and Tobramycin,"
Eur J Clin Pharmacol, 1983, 24(5):639-42.
Begg EJ and Barclay ML, "Aminoglycosides - 50 Years On," Br J Clin
Pharmacol, 1995, 39(6):597-603.
Cunha BA, "Aminoglycosides: Current Role in Antimicrobial Therapy,"
Pharmacotherapy, 1988, 8(6):334-50.
Edson RS and Terrell CL, "The Aminoglycosides," Mayo Clin Proc, 1999,
74(5):519-28.
Gilbert DN, "Once-Daily Aminoglycoside Therapy," Antimicrob Agents
Chemother, 1991, 35(3):399-405.
Iseman MD, "Treatment of Multidrug-Resistant Tuberculosis," N Engl J
Med, 1993, 329(11):784-91.
Kenyon CF, Knoppert DC, Lee SK, et al,
"Amikacin Pharmacokinetics and Suggested Dosage Modifications for the Preterm Infant,"
Antimicrob Agents Chemother, 1990, 34(2):265-8.
Lortholary O, Tod M, Cohen Y, et al, "Aminoglycosides," Med Clin North
Am, 1995, 79(4):761-87.
McCormack JP and Jewesson PJ, "A Critical Re-evaluation of the "Therapeutic
Range" of Aminoglycosides," Clin Infect Dis, 1992, 14(1):320-39
Nicolau DP, Freeman CD, Belliveau PP, et al,
"Experience With a Once-Daily Aminoglycoside Program Administered to 2184 Adult Patients,"
Antimicrob Agents Chemother, 1995, 39(3):650-5.
Preston SL and Briceland LL, "Single Daily Dosing of Aminoglycosides,"
Pharmacotherapy, 1995, 15(3):297-316.
Public Health Service Task Force on Prophylaxis and Therapy for
Mycobacterium avium Complex,
"Recommendations on Prophylaxis and Therapy for Disseminated Mycobacterium avium Complex Disease in Patients Infected With the Human Immunodeficiency Virus,"
N Engl J Med, 1993, 329(12):898-904.
Starke JR and Correa AG,
"Management of Mycobacterial Infection and Disease in Children," Pediatr
Infect Dis J, 1995, 14(6):455-69.
Van der Auwera P,
"Pharmacokinetic Evaluation of Single Daily Dose Amikacin," J Antimicrob
Chemother, 1991, 27(Suppl C):63-71.
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(3):153-6.
Vogelstein B, Kowarski A, and Lietman PS,
"The Pharmacokinetics of Amikacin in Children," J Pediatr, 1977,
91(2):333-9.
Yasuhara H, Kobayashi S, Sakamoto K, et al,
"Pharmacokinetics of Amikacin and Cephalothin in Bedridden Elderly Patients,"
J Clin Pharmacol, 1982, 22(8-9):403-9. |
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