Amikacin

Pronunciation

(am i KAY sin)

U.S. Brand Names

Amikin®

Synonyms

Amikacin Sulfate

Generic Available

Yes

Canadian Brand Names

Amikin®

Use

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

Pregnancy Risk Factor

Lactation

Enters breast milk/compatible

Contraindications

Hypersensitivity to amikacin sulfate or any component of the formulation; cross-sensitivity may exist with other aminoglycosides

Warnings/Precautions

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

Adverse Reactions

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, allergic reaction

Overdosage/Toxicology

Symptoms of overdose include ototoxicity, nephrotoxicity, and neuromuscular toxicity. Treatment of choice following a single acute overdose appears to be maintenance of urine output of at least 3 mL/kg/hour during the acute treatment phase. Dialysis is of questionable value in enhancing aminoglycoside elimination. If required, hemodialysis is preferred over peritoneal dialysis in patients with normal renal function.

Drug Interactions

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 effect of neuromuscular-blocking agents and polypeptide antibiotics with administration of aminoglycosides

Stability

Stable for 24 hours at room temperature and 2 days at refrigeration when mixed in D5W, D5¹ /4NS, D5¹ /2NS, NS, LR

Compatibility

Stable in dextran 75 6% in NS, D5LR, D5¹ /4NS, D5¹ /3NS, D5¹ /2NS, D5NS, D10NS, D5W, D10W, D20W, mannitol 20%, ¹ /4NS, ¹ /2NS, NS; variable stability (consult detailed reference) in peritoneal dialysis solutions

Y-site administration: Compatible: Acyclovir, alatrofloxacin, amifostine, amiodarone, amsacrine, aztreonam, cefpirome, cisatracurium, cyclophosphamide, dexamethasone sodium phosphate, diltiazem, docetaxel, enalaprilat, esmolol, etoposide, filgrastim, fluconazole, fludarabine, foscarnet, furosemide, gatifloxacin, gemcitabine, granisetron, idarubicin, IL-2, labetalol, levofloxacin, linezolid, lorazepam, magnesium sulfate, melphalan, midazolam, morphine, ondansetron, paclitaxel, perphenazine, remifentanil, sargramostim, teniposide, thiotepa, vinorelbine, warfarin, zidovudine. Incompatible: Allopurinol, amphotericin B cholesteryl sulfate complex, hetastarch, propofol

Compatibility in syringe: Compatible: Clindamycin, doxapram. Incompatible: Heparin

Compatibility when admixed: Compatible: Amobarbital, ascorbic acid injection, bleomycin, calcium chloride, calcium gluconate, cefepime, cefoxitin, chloramphenicol, chlorpheniramine, cimetidine, ciprofloxacin, clindamycin, colistimethate, dimenhydrinate, diphenhydramine, epinephrine, ergonovine, fluconazole, furosemide, hyaluronidase, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, lincomycin, metaraminol, metronidazole, metronidazole with sodium bicarbonate, norepinephrine, pentobarbital, phenobarbital, phytonadione, polymyxin B sulfate, prochlorperazine edisylate, promethazine, ranitidine, sodium bicarbonate, succinylcholine, vancomycin, verapamil. Incompatible: Amphotericin B, ampicillin, cefazolin, chlorothiazide, heparin, phenytoin, thiopental, vitamin B complex with C. Variable (consult detailed reference): Aminophylline, dexamethasone sodium phosphate, oxacillin, penicillin G potassium, potassium chloride

Mechanism of Action

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

Pharmacodynamics/Kinetics

Absorption: I.M.: May be delayed in the bedridden patient

Distribution: Primarily into extracellular fluid (highly hydrophilic); penetrates blood-brain barrier when meninges inflamed; crosses placenta

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

CSF:blood level ratio: Normal meninges: 10% to 20%; Inflamed meninges: 15% to 24%

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

Infants: Low birth weight (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: I.M.: 45-120 minutes

Excretion: Urine (94% to 98%)

Dosage

Individualization is critical because of the low therapeutic index

Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW)

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 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 effects: Dose as for Clcr 10-40 mL/minute and follow levels

Administration

Administer I.M. injection in large muscle mass

Monitoring Parameters

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

Reference Range

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 mcg/mL

Serious infections: 20-25 mcg/mL

Urinary tract infections: 15-20 mcg/mL

Trough:

Serious infections: 1-4 mcg/mL

Life-threatening infections: 4-8 mcg/mL

Toxic concentration: Peak: >35 mcg/mL; Trough: >10 mcg/mL

Timing of serum samples: Draw peak 30 minutes after completion of 30-minute infusion or at 1 hour following initiation of infusion or I.M. injection; draw trough within 30 minutes prior to next dose

Test Interactions

Penicillin may decrease aminoglycoside serum concentrations in vitro

Dietary Considerations

Sodium content of 1 g: 29.9 mg (1.3 mEq)

Patient Education

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. This drug can only be administered by I.V. or I.M. injection. It is important to maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. Report immediately any 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; or change in urinary pattern or decrease in urine. Report 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 precaution: Inform prescriber if you are or intend to become pregnant.

Additional Information

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)

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

May cause drowsiness; case reports of delirium and psychosis

Mental Health: Effects on Psychiatric Treatment

None reported

Oncology: Emetic Potential

Very low (<10%)

Oncology: Vesicant

Dosage Forms

Injection, solution, as sulfate: 50 mg/mL (2 mL, 4 mL); 62.5 mg/mL (8 mL); 250 mg/mL (2 mL, 4 mL) [contains metabisulfite]

References

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.

Flandrois JP, Bouletreau P, Auboyer R, et al, "Accidental Amikacin Overdose in Man: Emergency Therapy by Extrarenal Dialysis," Infection , 1979, 7:190-1.

Gilbert DN, "Once-Daily Aminoglycoside Therapy," Antimicrob Agents Chemother , 1991, 35(3):399-405.

Green FJ, Lavelle KJ, and Arnoff GR, "Management of Amikacin Overdose," Am J Kidney Dis , 1981, 1:110-2.

Ho PW, Pien FD, and Kominami N, "Massive Amikacin Overdose," Ann Intern Med , 1979, 91:227-8.

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.

International Brand Names

Akacin® (MX, TH); Akamin® (EC); Akicin® (TH); Akim® (EC); Alostil® (ID); Amicacina® (BR); Amicacina Northia® (AR); Amicasil® (IT); Amicin® (IN); Amikacina Ahimsa® (AR); Amikacina Biocrom® (AR); Amikacina Braun® (ES); Amikacina® (CL, CO); Amikacina Combino Pharm® (ES); Amikacina Duncan® (AR); Amikacina Fabra® (AR); Amikacina Klonal® (AR); Amikacina Larjan® (AR); Amikacina L.CH.® (CL); Amikacina Medical® (ES); Amikacina Normon® (CR, DO, ES, GT, HN, PA, SV); Amikacina Richet® (AR); Amikacina Teva® (IT); Amikacin® (AU, GB, NZ, RO, YU); Amikacin DBL® (SG); Amikacine Aguettant® (FR); Amikacine Faulding® (BE); Amikacine® (YU); Amikacin Fresenius® (DE, ZA); Amikacin Injection Meiji® (TH); Amikacin Sulphate Injection® (GB); Amikafur® (MX); Amikalem® (MX); Amikan® (IT); Amikasol® (TH); Amikason's® [inj.] (MX); Amikaver® [inj.] (TR); Amikayect® (MX); Amiketem® [inj.] (TR); Amikin® (AU, BG, BR, CA, CH, CN, CO, CR, CZ, EC, GB, GT, HN, HR, HU, ID, IE, IL, MX, NZ, PA, PL, RO, SG, SV, TH, YU, ZA); Amiklin® (FR); Amikozit® [inj.] (RO, TR); AMK-500® (EC); A.M.K.® (MX); Amukin® (BE, LU, NL); Anibikin® (TH); BB-K8® (IT); Biclin® (ES, MX, PT); Biklin® (AR, AT, DE, FI, SE); Biodacyna® (PL); Biomikin® (HN, SV); Chemacin® (IT); Cinkamin® (AR); Dramigel® (IT); Farcyclin® (YU); Gamikal® [inj.] (MX); Glukamin® (EC); Greini® (AR); Kacinth-A® (ZA); Kanbine® (ES); Likacin® (HU, IL, IT, RU); Lukadin® (IT); Mediamik® (IT); Miacin® (EG, JO, KW, LB, RO, SY); Migracin® (IT); Mikan® (IT); Mikasin® (ID, TR); Mikavir® (IT); Negasin® (RO); Nekacin® (IT); Novamin® (BR); Oprad® (MX); Orlobin® (RO); Pierami® (IT, RO); Riklinak® (AR); Selemycin® (RU); Siamik® (TH); Sulfato de Amicacina® (BR); Tipkin® (TH); Tybikin® (TH); Vijomikin® (GT, HN, PA, SV); Yectamid® (MX)

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