Amikacin

U.S. BRAND NAMES — Amikin®
PHARMACOLOGIC CATEGORY Antibiotic, Aminoglycoside
DOSING: ADULTS — Individualization is critical because of the low therapeutic index
Note: 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)
Usual dosage range: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours Note: 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.
Hospital-acquired pneumonia (HAP): 20 mg/kg/day with antipseudomonal beta-lactam or carbapenem (American Thoracic Society/ATS guidelines)
Meningitis(Pseudomonas aeruginosa): 5 mg/kg every 8 hours (administered with another bacteriocidal drug)
Mycobacterium fortuitum, M. chelonae, or M. abscessus: 10-15 mg/kg daily for at least 2 weeks with high dose cefoxitin
DOSING: PEDIATRIC — Usual dosage range: Infants and Children: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours
(For additional information see "Amikacin: Pediatric drug information")
Note: 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)
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Individualization is critical because of the low therapeutic index. 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
Dialyzable (50% to 100%)
Administer dose postdialysis or administer 2/3 normal dose as a supplemental dose postdialysis and follow levels.
Peritoneal dialysis effects: Dose as for Clcr <20 mL/minute: Follow levels.
Continuous arteriovenous or venovenous hemodiafiltration effects: Dose as for Clcr 10-40 mL/minute: Follow levels.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Injection, solution, as sulfate: 50 mg/mL (2 mL, 4 mL); 62.5 mg/mL (8 mL) [DSC]; 250 mg/mL (2 mL, 4 mL) Amikin®: 50 mg/mL (2 mL); 250 mg/mL (2 mL, 4 mL) [contains metabisulfite]
DOSAGE FORMS: CONCISE Injection, solution: 50 mg/mL (2 mL, 4 mL); 250 mg/mL (2 mL, 4 mL) Amikin®: 50 mg/mL (2 mL); 250 mg/mL (2 mL, 4 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. Do not mix with other drugs, administer separately.
I.M.: Administer I.M. injection in large muscle mass.
I.V.: Infuse over 30-60 minutes.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
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.
USE — Treatment of serious infections (bone infections, respiratory tract infections, endocarditis, and septicemia) due to organisms resistant to gentamicin and tobramycin, including Pseudomonas, Proteus, Serratia, and other gram-negative bacilli; documented infection of mycobacterial organisms susceptible to amikacin
ADVERSE REACTIONS SIGNIFICANT 1% to 10%: Central nervous system: Neurotoxicity Otic: Ototoxicity (auditory), ototoxicity (vestibular) Renal: Nephrotoxicity
<1% (Limited to important or life-threatening): Allergic reaction, dyspnea, eosinophilia
CONTRAINDICATIONS — Hypersensitivity to amikacin sulfate or any component of the formulation; cross-sensitivity may exist with other aminoglycosides
WARNINGS / PRECAUTIONS Box Warnings: Nephrotoxicity: See "Concerns related to adverse effects" below. Neuromuscular blockade and respiratory paralysis: See "Concerns related to adverse effects" below. Neurotoxicity: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Nephrotoxicity: [U.S. Boxed Warning]: May cause nephrotoxicity; usual risk factors include pre-existing renal impairment, concomitant nephrotoxic medications, advanced age and dehydration. Discontinue treatment if signs of nephrotoxicity occur; renal damage is usually reversible. Neuromuscular blockade and respiratory paralysis: [U.S. Boxed Warning]: May cause neuromuscular blockade and respiratory paralysis; especially when given soon after anesthesia or muscle relaxants. Neurotoxicity: [U.S. Boxed Warning]: May cause neurotoxicity; usual risk factors include pre-existing renal impairment, concomitant neuro-/nephrotoxic medications, advanced age and dehydration. 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. Discontinue treatment if signs of ototoxicity occur. Superinfection: Prolonged use may result in superinfection, including pseudomembranous colitis.
Disease-related concerns: Hearing impairment: Use with caution in patients with pre-existing vertigo, tinnitus, or hearing loss. Hypocalcemia: Use with caution in patients with hypocalcemia. Neuromuscular disorders: Use with caution in patients with neuromuscular disorders, including myasthenia gravis. Renal impairment: Use with caution in patients with pre-existing renal insufficiency; dosage modification required.
Dosage form specific issues: Sulfite: Solution contains sodium metabisulfate; use caution in patients with sulfite allergy.
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
PREGNANCY RISK FACTOR — D (show table)
LACTATION — Enters breast milk/compatible
BREAST-FEEDING CONSIDERATIONS — Amikacin is excreted into breast milk in trace amounts; however, it is not absorbed when taken orally. This limited oral absorption may minimize exposure to the nursing infant. Nondose-related effects could include modification of bowel flora.
Although breast-feeding is not recommended by the manufacturer, based on available data, amikacin is generally considered compatible (low risk to infant) while breast-feeding [human data].
DIETARY CONSIDERATIONS — Sodium content of 1 g: 29.9 mg (1.3 mEq)
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, appropriately timed peak and trough concentrations, vital signs, temperature, weight, I & O, hearing parameters
Some penicillin derivatives may accelerate the degradation of aminoglycosidesin vitro. This may be clinically-significant for certain penicillin (ticarcillin, piperacillin, carbenicillin) and aminoglycoside (gentamicin, tobramycin) combination therapy in patients with significant renal impairment. Close monitoring of aminoglycoside levels is warranted.
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: 25-40 mcg/mL Serious infections: 20-25 mcg/mL Urinary tract infections: 15-20 mcg/mL Trough: Serious infections: <8 mcg/mL Life-threatening infections: <8 mcg/mL The American Thoracic Society (ATS) recommends trough levels of <4-5 mcg/mL for patients with hospital-acquired pneumonia.
Toxic concentration: Peak: >40 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
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms 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.
CANADIAN BRAND NAMES — Amikacin Sulfate Injection, USP; Amikin®
INTERNATIONAL BRAND NAMES — Akacin (TH); Akicin (TH); Akim (EC); Alostil (ID); Amicacina (ES); Amicasil (IT); Amicin (IN); Amikacin Sulfate Injection, USP (CA); Amikacina (CL); Amikafur (MX); Amikan (IT); Amikayect (MX); Amikin (AU, BF, BG, BJ, BR, CA, CH, CI, CO, CZ, EC, EE, ET, GB, GH, GM, GN, HK, HU, ID, IE, KE, KR, LR, MA, ML, MR, MU, MW, MX, MY, NE, NG, PE, PH, PK, PL, SC, SD, SG, SL, SN, TH, TW, TZ, UG, ZA, ZM, ZW); Amiklin (FR); Amikozit (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amiktam (KR); Amukin (BE, NL); Biklin (AR, AT, DE, DK, FI, PH, SE, VE); Biodacyna (PL); Biokacin (PY); Briclin (UY); Briklin (GR); Chemacin (IT); Cidacid (PH); Cinmik (PH); Gamikal (MX); Glukamin (EC); Kacinth-A (ZA); Kamin (PH); Kanbine (ES); Kormakin (PH); Lanomycin (GR); Likacin (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Lukadin (IT); Miacin (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Nica (PH); Novamin (BR); Orlobin (GR); Pierami (TW); Riklinak (AR); Savox (TW); Selaxa (GR); Selemycin (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, MY, OM, QA, SA, SY, YE); Sikacin (TW); Tybikin (TH); Yectamid (MX)
MECHANISM OF ACTION — Inhibits protein synthesis in susceptible bacteria by binding to 30S ribosomal subunits
PHARMACODYNAMICS / KINETICS Absorption: I.M.: Rapid Oral: Poorly absorbed
Distribution: Primarily into extracellular fluid (highly hydrophilic); penetrates blood-brain barrier when meninges inflamed 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%
Protein-binding: 0% to 11%
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%)
PATIENT INFORMATION — Report loss of hearing, ringing or roaring in the ears, or feeling of fullness in head.