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Kanamycin

Pronunciation

(kan a MYE sin)

Index Terms

  • Kanamycin Sulfate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Injection, solution:

Generic: 1 g/3 mL (3 mL) [DSC]

Pharmacologic Category

  • Antibiotic, Aminoglycoside

Pharmacology

Interferes with protein synthesis in bacterial cell by binding to ribosomal subunit

Absorption

IM: Rapid

Oral: Minimal

Distribution

Vd: ~0.3 L/kg:

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

CSF:blood level ratio: Normal meninges: Nil; Inflamed meninges: 43%

Excretion

Urine (as unchanged drug)

Time to Peak

Serum: IM: 1-2 hours (decreased in burn patients)

Half-Life Elimination

2-4 hours; Anuria: 80 hours; End-stage renal disease: 40-96 hours

Protein Binding

0%

Special Populations: Renal Function Impairment

Patients with renal function impairment or diminished glomerular pressure excrete kanamycin more slowly. May build up excessively high blood levels that lead to increased risk of ototoxic reactions.

Special Populations Note

Burn patients: Half-life may significantly decrease, resulting in decreased serum concentrations.

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

Contraindications

Hypersensitivity to kanamycin, any component of the formulation, or other aminoglycosides; pregnancy

Dosing: Adult

Note: Kanamycin injection is no longer available in the US.

Note: Dosing should be based on ideal body weight

Susceptible systemic infections: IM, IV: 5-7.5 mg/kg/dose in divided doses every 8-12 hours (<15 mg/kg/day)

Following surgical contamination, peritonitis: Intraperitoneal: 500 mg

Irrigating solution: 0.25%; maximum 1.5 g/day (via all administration routes)

Aerosol: 250 mg 2-4 times/day

Dosing: Geriatric

IM, IV: Initial dose should be 5-7.5 mg/kg based on ideal body weight (except in obese patients); maintenance dose and interval should be adjusted for estimated renal function; dosing interval in most older patients is every 12-24 hours (see Dosing in Renal Impairment).

Dosing: Pediatric

Note: Kanamycin injection is no longer available in the US.

Note: Dosing should be based on ideal body weight

Infections: IM, IV: 15 mg/kg/day in divided doses every 8-12 hours

Dosing: Renal Impairment

Adults: IV: The following adjustments have been recommended (Aronoff, 2007). Note: Renally adjusted dose recommendations are based on a dose of 7.5 mg/kg every 12 hours.

CrCl >50 mL/minute: Administer every 12-24 hours

CrCl 10-50 mL/minute: Administer every 24-72 hours; monitor levels.

CrCl <10 mL/minute: Administer every 48-72 hours; monitor levels.

Intermittent hemodialysis (IHD): One-half the dose administered after hemodialysis on dialysis days.

Peritoneal dialysis (PD): Administration via PD fluid: 15-20 mg/L/day of PD fluid

Continuous renal replacement therapy (CRRT): Administer every 24-72 hours; monitor levels. Note: Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate).

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling.

Reconstitution

IV: Must be further diluted prior to IV 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.

Administration

IM: Administer deeply in upper outer quadrant of the gluteal muscle.

IV: 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.

Compatibility

Stable in D5NS, D5W, D10W, LR, NS.

Compatibility in syringe: Incompatible with ampicillin, heparin.

Storage

Store vial at controlled room temperature. Darkening of vials does not indicate loss of potency.

Drug Interactions

AbobotulinumtoxinA: Aminoglycosides may enhance the neuromuscular-blocking effect of AbobotulinumtoxinA. Monitor therapy

Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Arbekacin: May enhance the nephrotoxic effect of Aminoglycosides. Arbekacin may enhance the ototoxic effect of Aminoglycosides. Monitor therapy

Bacitracin (Systemic): Kanamycin may enhance the nephrotoxic effect of Bacitracin (Systemic). Avoid combination

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Monitor therapy

Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Monitor therapy

CARBOplatin: Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Monitor therapy

Cefazedone: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cephalosporins (2nd Generation): May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cephalosporins (3rd Generation): May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cephalosporins (4th Generation): May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cephalothin: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cephradine: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination

CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Consider therapy modification

CycloSPORINE (Systemic): Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Monitor therapy

Distigmine: Aminoglycosides may diminish the therapeutic effect of Distigmine. Monitor therapy

Foscarnet: May enhance the nephrotoxic effect of Aminoglycosides. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Monitor therapy

Mannitol (Systemic): May enhance the nephrotoxic effect of Aminoglycosides. Avoid combination

Mecamylamine: Aminoglycosides may enhance the neuromuscular-blocking effect of Mecamylamine. Avoid combination

Neuromuscular-Blocking Agents: Aminoglycosides may enhance the respiratory depressant effect of Neuromuscular-Blocking Agents. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Monitor therapy

OnabotulinumtoxinA: Aminoglycosides may enhance the neuromuscular-blocking effect of OnabotulinumtoxinA. Monitor therapy

Oxatomide: May enhance the ototoxic effect of Aminoglycosides. 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; Nafcillin; Oxacillin; Penicillin G (Parenteral/Aqueous); Penicillin G Benzathine; Penicillin G Procaine; Penicillin V Potassium. Consider therapy modification

RimabotulinumtoxinB: Aminoglycosides may enhance the neuromuscular-blocking effect of RimabotulinumtoxinB. Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Tenofovir Products: Aminoglycosides may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. Monitor therapy

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Test Interactions

Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro, leading to a potential underestimation of aminoglycoside serum concentration.

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

ALERT: U.S. Boxed Warning

Ototoxicity:

Patients treated with aminoglycosides by any route should be under close clinical observation because of the potential toxicity associated with their use. As with other aminoglycosides, the major toxic effects of kanamycin sulfate are its action on the auditory and vestibular branches of the eighth nerve and the renal tubules. Neurotoxicity is manifested by bilateral auditory toxicity which often is permanent and, sometimes, by vestibular ototoxicity. Loss of high frequency perception usually occurs before there is noticeable clinical hearing loss and can be detected by audiometric testing. There may not be clinical symptoms to warn of developing cochlear damage. 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 increases with the degree of exposure to either high peak or high trough serum concentrations and continues to progress after drug withdrawal.

Renal toxicity:

Renal impairment may be characterized by decreased creatinine clearance, the presence of cells or casts, oliguria, proteinuria, decreased urine specific gravity, or evidence of increasing nitrogen retention (increasing serum urea nitrogen [BUN], nonprotein nitrogen [NPN], or serum creatinine).

The risks of severe ototoxic and nephrotoxic reactions are sharply increased in patients with impaired renal function and in those with normal renal function who receive high doses or prolonged therapy.

Monitoring:

Renal and eighth nerve function should be closely monitored, especially in patients with known or suspected reduced renal function 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 parenterally administered aminoglycosides should be monitored when feasible to assure adequate levels and to avoid potentially toxic levels. Urine should be examined for decreased specific gravity, increased excretion of protein, and the presence of cells or casts. BUN, serum creatinine, or creatinine clearance should be measured periodically. Serial audiograms should be obtained when 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 dosage adjustment or discontinuance of the drug.

Neuromuscular blockade:

Neuromuscular blockade with respiratory paralysis may occur when kanamycin sulfate is instilled intraperitoneally concomitantly with anesthesia and muscle-relaxing drugs. Neuromuscular blockade has been reported following parenteral injection and the oral use of aminoglycosides. The possibility of the occurrence of neuromuscular blockade and respiratory paralysis 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 reduce these phenomena but mechanical respiratory assistance may be necessary.

Concurrent therapy:

The concurrent or sequential systemic, oral, or topical use of kanamycin and other potentially nephrotoxic, or neurotoxic drugs, particularly polymyxin B, bacitracin, colistin, amphotericin B, cisplatin, vancomycin, and all other aminoglycosides (including paromomycin) should be avoided because the toxicity may be additive. Other factors which may increase patient risk of toxicity are advanced age and dehydration.

Kanamycin sulfate should not be given concurrently with potent diuretics (ethacrynic acid, furosemide, meralluride sodium, sodium mercaptomerin, or mannitol). Some diuretics themselves cause ototoxicity, and IV administered diuretics may enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.

Warnings/Precautions

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.

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.

Pregnancy Risk Factor

D

Pregnancy Considerations

Kanamycin crosses the placenta. Aminoglycosides may cause fetal harm if administered to a pregnant woman. There are several reports of total irreversible bilateral congenital deafness in children whose mothers received another aminoglycoside (streptomycin) during pregnancy. Although serious side effects to the fetus/infant have not been reported following maternal use of all aminoglycosides, a potential for harm exists.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, weight gain), change in balance, severe dizziness, passing out, hearing impairment, hearing loss, tinnitus, muscle weakness, burning or numbness feeling, twitching, seizures, shortness of breath, or loss of strength and energy (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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