|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section and/or refer to product labeling for additional detail.
Medication Safety Issues
Sound-alike/look-alike issues:
Kanamycin may be confused with Garamycin®, gentamicin
Pronunciation
(kan a MYE sin)
U.S. Brand Names
Index Terms
Generic Available
No
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of serious infections caused by susceptible strains of E. coli, Proteus species, Enterobacter aerogenes, Klebsiella pneumoniae, Serratia marcescens, and Acinetobacter species; second-line treatment of Mycobacterium tuberculosis
Pregnancy Risk Factor
D
Pregnancy Considerations
Kanamycin crosses the placenta and produces detectable serum levels in the fetus. There is one case report of hearing impairment in a child with prenatal exposure to kanamycin. Because of several reports of total irreversible bilateral congenital deafness in children whose mothers received streptomycin during pregnancy, kanamycin has been classified by the manufacturer as pregnancy risk category D.
Lactation
Enters breast milk/not recommended (AAP rates “compatible”)
Breast-Feeding Considerations
Kanamycin is excreted into breast milk in minute amounts; however, it is not well absorbed when taken orally. This limited oral absorption may minimize exposure to the nursing infant. Nondose-related effects could include modification of bowel flora. The AAP considers kanamycin to be “usually compatible with breast-feeding.”
Contraindications
Hypersensitivity to kanamycin, any component of the formulation, or other aminoglycosides; pregnancy
Warnings/Precautions
Boxed warnings:
• Nephrotoxicity: 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: 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 fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
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.
Other warnings/precautions:
• Long-term use: Not intended for long-term therapy due to toxic hazards associated with extended administration.
Adverse Reactions
Frequency not defined.
Cardiovascular: Edema
Central nervous system: Neurotoxicity, drowsiness, headache, pseudomotor cerebri
Dermatologic: Skin itching, redness, rash, photosensitivity, erythema
Gastrointestinal: Nausea, vomiting, diarrhea, malabsorption syndrome (with prolonged and high-dose therapy of hepatic coma), anorexia, weight loss, salivation increased, enterocolitis
Hematologic: Granulocytopenia, agranulocytosis, thrombocytopenia
Local: Burning, stinging
Neuromuscular & skeletal: Weakness, tremor, muscle cramps
Otic: Ototoxicity (auditory), ototoxicity (vestibular)
Renal: Nephrotoxicity
Respiratory: Dyspnea
Drug Interactions
Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy
Botulinum Toxin Type A: Aminoglycosides may enhance the neuromuscular-blocking effect of Botulinum Toxin Type A. Risk C: Monitor therapy
Botulinum Toxin Type B: Aminoglycosides may enhance the neuromuscular-blocking effect of Botulinum Toxin Type B. Risk C: Monitor therapy
Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Risk C: Monitor therapy
CARBOplatin: Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Risk C: Monitor therapy
Cardiac Glycosides: Aminoglycosides may decrease the absorption of Cardiac Glycosides. Risk C: Monitor therapy
CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Risk D: Consider therapy modification
CycloSPORINE: Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
Gallium Nitrate: Aminoglycosides may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Risk C: Monitor therapy
Neuromuscular-Blocking Agents: Aminoglycosides may enhance the respiratory depressant effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy
Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Exceptions: Amoxicillin; Ampicillin; Cloxacillin; Dicloxacillin; Methicillin; Nafcillin; Oxacillin; Penicillin G (Parenteral/Aqueous); Penicillin G Benzathine; Penicillin G Procaine; Penicillin V Potassium. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Storage
Store vial at controlled room temperature. Darkening of vials does not indicate loss of potency.
Reconstitution
I.V.: Must be further diluted prior to I.V. infusion. For adults, dilute 500 mg in 100-200 mL of appropriate solution or 1 g in 200-400 mL. For pediatric patients, use sufficient amount to infuse solution over 30-60 minutes.
Intraperitoneal: Dilute dose in 20 mL sterile distilled water.
Aerosol: Dilute 250 mg in 3 mL normal saline.
Compatibility
Stable in D5NS, D5W, D10W, LR, NS; variable stability (consult detailed reference) in TPN.
Y-site administration: Compatible: Cyclophosphamide, furosemide, heparin with hydrocortisone sodium succinate, hydromorphone, magnesium sulfate, meperidine, morphine, perphenazine, potassium chloride, vitamin B complex with C. Variable (consult detailed reference): TPN.
Compatibility in syringe: Compatible: Penicillin G sodium. Incompatible: Ampicillin, heparin, piperacillin.
Compatibility when admixed: Compatible: Ascorbic acid injection, cefoxitin, chloramphenicol, clindamycin, dopamine, furosemide, penicillin G potassium, penicillin G sodium, polymyxin B sulfate, sodium bicarbonate, vitamin B complex with C. Incompatible: Amphotericin B, cefazolin, cefotaxime, cefotetan, chlorpheniramine, colistimethate, heparin, lincomycin, methohexital, phenobarbital, phenytoin, piperacillin. Variable (consult detailed reference): Hydrocortisone sodium succinate.
Mechanism of Action
Interferes with protein synthesis in bacterial cell by binding to ribosomal subunit
Pharmacodynamics/Kinetics
Absorption:
I.M.: Rapid
Oral: Minimal
Distribution:
Relative diffusion from blood into CSF: Good only with inflammation (exceeds usual MICs)
CSF:blood level ratio: Normal meninges: Nil; Inflamed meninges: 43%
Protein binding: 0%
Half-life elimination: 2-4 hours; Anuria: 80 hours; End-stage renal disease: 40-96 hours
Time to peak, serum: I.M.: 1-2 hours (decreased in burn patients)
Excretion: Urine (as unchanged drug)
Dosage
Note: Dosing should be based on ideal body weight
Children: Infections: I.M., I.V.: 15 mg/kg/day in divided doses every 8-12 hours
Adults:
Infections: I.M., I.V.: 5-7.5 mg/kg/dose in divided doses every 8-12 hours (<15 mg/kg/day)
Intraperitoneal: After contamination in surgery: 500 mg
Irrigating solution: 0.25%; maximum 1.5 g/day (via all administration routes)
Aerosol: 250 mg 2-4 times/day
Dosing adjustment/interval in renal impairment:
Clcr 50-80 mL/minute: Administer 60% to 90% of dose or administer every 8-12 hours
Clcr 10-50 mL/minute: Administer 30% to 70% of dose or administer every 12 hours
Clcr <10 mL/minute: Administer 20% to 30% of dose or administer every 24-48 hours
Administration: I.M.
Administer deeply in upper outer quadrant of the gluteal muscle.
Administration: I.V.
Infuse over 30-60 minutes.
Some penicillins (eg, carbenicillin, ticarcillin and piperacillin) have been shown to inactivate aminoglycosides 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.
Monitoring Parameters
Serum creatinine and BUN every 2-3 days; peak and trough concentrations; hearing
Some penicillin derivatives may accelerate the degradation of aminoglycosides in 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
Therapeutic: Peak: 15-30 mcg/mL; Trough: 5-10 mcg/mL; Toxic: Peak: >35 mcg/mL; Trough: >10 mcg/mL
Test Interactions
Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro, leading to a potential underestimation of aminoglycoside serum concentration.
Patient Education
Report persistent diarrhea.
Geriatric Considerations
This is not a drug of choice since elderly may have increased adverse effects (renal).
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Salivation increased.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Infectious Diseases Comment
A well-documented reaction can occur between beta-lactam and aminoglycoside antibiotics in vitro, leading to complexation, opening of the beta-lactam ring and presumably, loss of antibacterial activity for one or both agents. However, the conditions under which this reaction occurs are variable and influenced by (but not limited to) assay methodology, sampling time and storage, and drug selection and concentration. In general, many of the in vitro studies employed artificial conditions that tested high concentrations of the penicillin derivative (equating to serum levels most likely observed only in severe renal impairment) in combination with gentamicin or tobramycin. Incubation of the agents at conditions of 37°C for up to 48 hours has definitely demonstrated inactivation and loss of bactericidal activity. However, some of these studies permitted a considerable time lapse prior to assaying the medium, or stored the samples at higher temperatures (-20°C or greater), which may have allowed continued chemical degradation prior to assay. In general, amikacin was the most resistant to penicillin-mediated chemical degradation, and cephalosporins were much less likely than penicillins to inactivate the aminoglycosides.
The more robust studies have been those which evaluated in vivo effects via rapid and frequent blood sampling during concomitant dosing. In vivo, there are a number of studies documenting significant changes in the half-life of gentamicin in combination with primarily ticarcillin and carbenicillin, but usually only in the setting of end-stage renal disease. A number of literature reports suggest that despite documented changes in gentamicin kinetics, this is not likely to lead to clinically-significant differences in outcomes in patients with normal renal function. Furthermore, there are no published, prospective, outcomes-based studies that provide compelling evidence of changes in rates of clinical or microbiological response as a function of dosing separation.
Based on the weight of evidence to date, coadministration of (but not coadmixture of) a penicillin or cephalosporin antibiotic with an aminoglycoside should not pose a significant concern in patients with even mild renal impairment. However, specific circumstances exist in which this approach should be undertaken with caution. Concurrent administration of either gentamicin or tobramycin with piperacillin, carbenicillin, or ticarcillin (including combinations with beta-lactamase inhibitors), particularly in the face of moderate-to-severe renal failure, would warrant careful monitoring of aminoglycoside serum levels, CBCs and clinical response to avoid potentially-reduced efficacy due to chemical inactivation.
Mental Health: Effects on Mental Status
May cause drowsiness or dizziness; case reports of delirium and psychosis with aminoglycosides
Mental Health: Effects on Psychiatric Treatment
May cause agranulocytosis; use caution with clozapine and carbamazepine
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as sulfate: 1 g/3 mL (3 mL) [contains sodium bisulfate]
References
Begg EJ and Barclay ML, “Aminoglycosides - 50 Years On,” Br J Clin Pharmacol, 1995, 39(6):597-603.
Chow MS, Quintiliani R, and Nightingale CH, ” In Vivo Inactivation of Tobramycin by Ticarcillin. A Case Report," JAMA, 1982, 247(5):658-9.
Cunha BA, “Aminoglycosides: Current Role in Antimicrobial Therapy,” Pharmacotherapy, 1988, 8(6):334-50.
Daly JS, Dodge RA, Glew RH, et al, “Effect of Time and Temperature on Inactivation of Aminoglycosides by Ampicillin at Neonatal Dosages,” J Perinatol, 1997, 17(1):42-5.
Dowell JA, Korth-Bradley J, Milisci M, et al, “Evaluating Possible Pharmacokinetic Interactions Between Tobramycin, Piperacillin, and a Combination of Piperacillin and Tazobactam in Patients With Various Degrees of Renal Impairment,” J Clin Pharmacol, 2001, 41(9):979-86.
“Drugs for Tuberculosis,” Med Lett Drugs Ther, 1993, 35(908):99-101.
Edson RS and Terrell CL, “The Aminoglycosides,” Mayo Clin Proc, 1999, 74(5):519-28.
Farchione LA, “Inactivation of Aminoglycosides by Penicillins,” J Antimicrob Chemother, 1982, 8(Suppl A):27-36.
Fuchs PC, Stickel S, Anderson PH, et al, “In Vitro Inactivation of Aminoglycosides by Sulbactam, Other Beta-Lactams, and Sulbactam-Beta-Lactam Combinations,” Antimicrob Agents Chemother, 1991, 35(1):182-4.
Halstenson CE, Wong MO, Herman CS, et al, “Effect of Concomitant Administration of Piperacillin on the Dispositions on Isepamicin and Gentamicin in Patients With End-Stage Renal Disease,” Antimicrob Agents Chemother, 1992, 36(9):1832-36.
Hitt CM, Patel KB, Nicolau DP, et al, “Influence of Piperacillin-Tazobactam on Pharmacokinetics of Gentamicin Given Once Daily,” Am J Health Syst Pharm, 1997, 54(23):2704-8.
Iseman MD, “Treatment of Multidrug-Resistant Tuberculosis,” N Engl J Med, 1993, 329(11):784-91.
Konishi H, Goto M, Nakamoto Y, et al, “Tobramycin Inactivation by Carbenicillin, Ticarcillin, and Piperacillin,” Antimicrob Agents Chemother, 1983, 23(5):653-57.
Kristensen M, Molholm HJ, Kampmann J, et al, “Letter: Drug Elimination and Renal Function,” J Clin Pharmacol, 1974, 14(5-6):307-8.
Lau A, Lee M, Flascha S, et al, “Effect of Piperacillin on Tobramycin Pharmacokinetics in Patients With Normal Renal Function,” Antimicrob Agents Chemother, 1983, 24(4):533-7.
Russoe ME and Atkins-Thor E, “Gentamicin and Ticarcillin in Subjects With End-Stage Renal Disease. Comparison of Two Assay Methods and Evaluation of Inactivation Rate,” Clin Nephrol, 1981, 15(4):175-80.
Thompson MIB, Russo ME, Saxon BJ, et al, “Gentamicin Inactivation by Piperacillin or Carbenicillin in Patients With End-Stage Renal Disease,” Antimicrob Agents Chemother, 1982, 21(2):268-73.
Viollier AF, Standiford HC, Drusano GL, et al, “Comparative Pharmacokinetics and Serum Bactericidal Activity of Mezlocillin, Ticarcillin and Piperacillin, With and Without Gentamicin,” J Antimicrob Chemother, 1985, 15(5):597-606.
Walterspiel JN, Feldman S, Van R, et al, “Comparative Inactivation of Isepamicin, Amikacin, and Gentamicin by Nine Beta-Lactams and Two Beta-Lactamase Inhibitors, Cilastatin and Heparin,” Antimicrob Agents Chemother, 1991, 35(9):1875-8.
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
Lexi-Comp.com
Last full review/revision August 2008
Content last modified August 2008
| 
