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Kanamycin Sulfate

Class: Aminoglycosides
VA Class: AM300
CAS Number: 25389-94-0

Warning(s)

  • Neurotoxicity and Ototoxicity
  • Neurotoxicity (manifested as both auditory and vestibular ototoxicity) can occur.1 Other neurotoxicity manifestations include vertigo, numbness, skin tingling, muscle twitching, and seizures.1

  • Eighth-cranial nerve impairment develops principally in patients with preexisting renal damage and in those with normal renal function who receive doses higher or treatment longer than recommended.1

  • Aminoglycoside-induced ototoxicity is irreversible, usually bilateral, and may be partial or total.1

  • Risk of hearing loss increases with degree of exposure to either high peak or high trough serum concentrations.1

  • Adjust dosage or discontinue kanamycin if evidence of ototoxicity (e.g., dizziness, vertigo, tinnitus, roaring in the ears, hearing loss) occurs.1

  • Patients developing cochlear damage may not have symptoms during aminoglycoside treatment to warn them of eighth-cranial nerve toxicity and total or partial, irreversible, bilateral deafness may occur after drug discontinued.1

  • Nephrotoxicity
  • Potentially nephrotoxic.1

  • Oliguria may indicate renal impairment.1

  • Nephrotoxicity develops principally in patients with preexisting renal damage and in those with normal renal function who receive doses higher or treatment longer than recommended.1

  • Patient Monitoring
  • Patients should be under close clinical observation because of potential toxicities.1

  • Closely monitor renal and eighth-cranial nerve function, especially in patients with known or suspected renal impairment at start of treatment and also in those whose renal function is initially normal but who develop renal dysfunction during treatment.1

  • Periodically monitor serum kanamycin concentrations to ensure adequate concentrations and avoid potentially toxic and prolonged peak concentrations (>35 mcg/mL).1

  • Rising trough concentrations (>10 mcg/mL) may indicate tissue accumulation.1 Tissue accumulation, excessive peak concentrations, cumulative dose, advanced age, and dehydration may contribute to ototoxicity and nephrotoxicity.1

  • Evaluate urine for decreased specific gravity and increased excretion of protein, cells, and casts; periodically determine BUN, Scr, and CLcr.1

  • When feasible, perform serial audiograms in patients old enough to be tested, particularly high-risk patients.1

  • Discontinue kanamycin or adjust dosage if there is evidence of impaired renal, vestibular, or auditory function.1

  • Neuromuscular Blockade
  • Concomitant use of an aminoglycoside with anesthesia and muscle-relaxing drugs may cause neuromuscular blockade with respiratory paralysis.1 May occur with aminoglycosides given by any route, including intraperitoneal instillation.1

  • Consider possibility of neuromuscular blockade and respiratory paralysis when administering aminoglycosides, especially concurrently with anesthetics or neuromuscular-blocking agents (e.g., tubocurarine, succinylcholine, decamethonium) or in patients receiving massive transfusions of citrate-anticoagulated blood.1 (See Interactions.)

  • Calcium salts may reduce neuromuscular blockade, but mechanical respiratory assistance may be necessary.1

  • Interactions
  • Avoid concurrent and/or sequential use of other neurotoxic or nephrotoxic drugs, particularly other aminoglycosides (including paromomycin), amphotericin B, bacitracin, cisplatin, colistimethate/colistin, polymyxin B, vancomycin, and viomycin.1 (See Interactions.)

  • Avoid concurrent use of potent diuretics (e.g., ethacrynic acid, furosemide, meralluride sodium [not commercially available in the US], sodium mercaptomerin [not commercially available in the US], mannitol) since diuretics themselves may cause ototoxicity and IV diuretics enhance toxicity by altering serum and tissue aminoglycoside concentrations.1 (See Interactions.)

Introduction

Antibacterial and antituberculosis agent; aminoglycoside antibiotic obtained from cultures of Streptomyces kanamyceticus.1 4 21

Uses for Kanamycin Sulfate

Serious Bacterial Infections

Has been used for short-term treatment of serious bacterial infections caused by susceptible Acinetobacter, Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, Proteus, or Serratia marcescens.1 4 Not a drug of choice; use only when causative agent is susceptible and other anti-infectives are ineffective or contraindicated.21 When a parenteral aminoglycoside is indicated, amikacin, gentamicin, or tobramycin usually is preferred.4 21

Has been used in conjunction with a penicillin or cephalosporin for initial therapy of serious infections when the causative agent is unknown.1 If anaerobic bacteria are suspected, consider using a suitable anti-infective in conjunction with kanamycin.1 Adjust therapy based on in vitro susceptibility testing.1

Slideshow: The Shocking Truth About Antibiotic Resistance

Has been used for treatment of known or suspected staphylococcal infections in certain situations.1 This includes initial treatment of severe infections when the causative organisms may be either gram-negative bacteria or staphylococci, treatment of infections caused by susceptible staphylococci in patients hypersensitive to other more appropriate anti-infectives, and treatment of mixed infections that may involve both gram-negative bacteria and staphylococci.1 Not a drug of choice for staphylococcal infections.1

Mycobacterial Infections

Treatment of active (clinical) tuberculosis (TB) in conjunction with other antituberculosis agents.6 7 21

Second-line agent used in the treatment of TB in patients with relapse, treatment failure, or Mycobacterium tuberculosis resistant to isoniazid and/or rifampin or when first-line drugs cannot be tolerated.6

Patients with treatment failure or drug-resistant M. tuberculosis, including multidrug-resistant (MDR) TB (resistant to both isoniazid and rifampin) or extensively drug-resistant (XDR) TB (resistant to both isoniazid and rifampin and also resistant to a fluoroquinolone and at least one parenteral second-line antimycobacterial such as capreomycin, kanamycin, or amikacin), should be referred to or managed in consultation with experts in the treatment of TB as identified by local or state health departments or CDC.6 e

Kanamycin Sulfate Dosage and Administration

Administration

Administer by IV infusion or IM injection.1

IV administration generally is recommended in patients with life-threatening infections, septicemia, shock, severe hypotension, CHF, hematologic disorders, severe burns, or reduced muscle mass.b

Has been administered by inhalation via a nebulizer.1

Has been administered by intraperitoneal instillation1 4 or irrigation (abscess cavities, pleural space, peritoneal and ventricular cavities).1

Has been administered orally,2 but a preparation for oral administration is no longer commercially available in the US.

Patient should be well hydrated prior to and during therapy to minimize chemical irritation of renal tubules from high urine kanamycin concentrations.1

Assess renal function prior to and daily or more frequently during therapy.1 Keep patients under close clinical observation because of the risk of ototoxicity and nephrotoxicity.1 (See Neurotoxicity and Ototoxicity under Cautions.)

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer concomitant anti-infectives (e.g., cephalosporins, penicillins) separately; do not admix.1

Dilution

Prepare IV infusions by adding 500 mg of kanamycin to 100–200 mL or 1 g to 200–400 mL of compatible diluent (e.g., 0.9% sodium chloride, 5% dextrose).1

Rate of Administration

Administer slowly over 30–60 minutes.1

IM Administration

Inject deeply into the upper outer quadrant of the gluteal muscle.1

Intraperitoneal Instillation

Instill into the peritoneal cavity through a polyethylene catheter sutured into the wound at closure (e.g., following exploration for established peritonitis or after peritoneal contamination due to fecal spill during surgery).1

Consider risk of toxicity with this route; closely monitor serum concentrations.1 If possible, postpone until patient has fully recovered from the effects of anesthesia and skeletal muscle relaxants.1 (See Interactions.)

Dilution

Prepare intraperitoneal solution by diluting 500 mg kanamycin in 20 mL sterile water for injection.1

Irrigation

If used as an irrigating solution in abscess cavities, pleural space, or peritoneal and ventricular cavities, consider risk of toxicity with this route; closely monitor serum concentrations.1

Dilution

Prepare a solution for irrigation containing 2.5 mg kanamycin per mL.1

Nebulization

Monitor serum concentrations carefully during nebulization therapy.1

Dilution

Prepare a solution for nebulization by diluting 1 mL of kanamycin injection (250 mg/mL) in 3 mL of 0.9% sodium chloride injection.1

Dosage

Available as kanamycin sulfate; dosage expressed in terms of kanamycin.1

Dosage is identical for either IV or IM administration.1

Base dosage on patient’s pretreatment body weight and renal status.1 For obese patients, base dosage on lean body mass.1

Many clinicians recommend that dosage be determined using appropriate pharmacokinetic methods for calculating dosage requirements and patient-specific pharmacokinetic parameters (e.g., elimination rate constant, volume of distribution) derived from serum concentration-time data; susceptibility of the causative organism; severity of the infection; and the patient’s immune and clinical status.b Because of potential toxicity, fixed-dosage recommendations not based on patient weight or serum drug concentrations are not advised.b

Determine peak and trough serum kanamycin concentrations periodically during therapy.1 b Adjust dosage to maintain desired serum concentrations whenever possible, especially in patients with life-threatening infections, suspected toxicity or nonresponse to treatment, decreased or varying renal function, and/or when increased aminoglycoside clearance (e.g., patients with cystic fibrosis, burns) or prolonged therapy is likely.4 200 201 202 203

In general, desirable peak kanamycin concentrations (30–60 minutes following IM injection or 15–30 minutes after completion of an IV infusion)b during parenteral therapy are 15–30 mcg/mL1 4 8 b and trough concentrations (just prior to the next dose) should not exceed 5–10 mcg/mL.1 4 8 b Some evidence suggests that an increased risk of toxicity may be associated with prolonged peak kanamycin concentrations >30–35 mcg/mL.4 8 Manufacturer recommends avoiding peak serum concentrations (30–90 minutes after injection) >35 mcg/mL and trough concentrations (just prior to the next dose) >10 mcg/mL.1

Once daily administration of kanamycin is recommended for the treatment of tuberculosis;6 once-daily regimens are rarely used for other indications.4

Usual duration of parenteral treatment for serious bacterial infections is 7–10 days.1 In difficult and complicated infections, reevaluate use of kanamycin if treatment duration >14 days is being considered.1 4 Long-term use is not recommended.1 4

If the drug is continued, closely monitor serum kanamycin concentrations and renal, auditory, and vestibular functions if the drug is continued.1

Well-hydrated patients with normal kidney function who receive a total kanamycin dose of ≤15 g have a low risk of toxic reactions.1

Pediatric Patients

General Pediatric Dosage

Use with caution in premature infants and neonates because renal immaturity may prolong serum half-life.1

AAP states kanamycin is inappropriate for treatment of mild to moderate infections.7

Serious Bacterial Infections

Uncomplicated infections usually respond within 24–48 hours; if definite clinical response does not occur within 3–5 days, discontinue kanamycin and reevaluate susceptibility of the causative organism.1 Failure to respond may be caused by resistance or the presence of septic foci requiring surgical drainage.1

IV

15 mg/kg daily given in 2 or 3 equally divided doses every 8 or 12 hours.1

Infants and children >4 weeks of age: AAP recommends 15–22.5 mg/kg daily given in 3 divided doses;7 some clinicians recommend 30 mg/kg daily given in 3 divided doses.7

IM

15 mg/kg daily given in 2 equally divided doses every 12 hours; alternatively, use 3 or 4 equally divided doses every 6 or 8 hours if continuously high blood concentrations desired.1

Infants and children >4 weeks of age: AAP recommends 15–22.5 mg/kg daily given in 3 divided doses;7 some clinicians recommend 30 mg/kg daily given in 3 divided doses.7

Tuberculosis
Treatment of Active (Clinical) Tuberculosis

Should not be used alone for treatment of TB; must be given in conjunction with other antituberculosis agents.6

IV or IM

Children <15 years of age weighing ≤40 kg: 15–30 mg/kg daily (up to 1 g) given once daily or twice weekly recommended by ATS, CDC, and IDSA.6

Children ≥15 years of age or weighing >40 kg: ATS, CDC, and IDSA recommend 15 mg/kg daily (up to 1 g) given as a single daily dose 5–7 times weekly for the first 2–4 months or until culture conversion;6 dosage can then be reduced to 15 mg/kg daily (up to 1 g) given as a single daily dose 2–3 times weekly.6

AAP recommends 15–30 mg/kg daily (up to 1 g) in infants, children, or adolescents.7

Adults

Serious Bacterial Infections

Uncomplicated infections usually respond within 24–48 hours; if definite clinical response does not occur within 3–5 days, discontinue kanamycin and reevaluate susceptibility of the causative organism.1 Failure to respond may be caused by resistance or the presence of septic foci requiring surgical drainage.1

IV

15 mg/kg daily in 2 or 3 equally divided doses given every 8 or 12 hours for 7–10 days.1

IM

15 mg/kg (up to 1.5 g) daily given in 2 equally divided doses every 12 hours for 7–10 days; alternatively, 3 or 4 equally divided doses every 6 or 8 hours if continuously high blood concentrations desired.1

Intraperitoneal

Instill 500 mg into the peritoneal cavity for established peritonitis or after peritoneal contamination due to fecal spill during surgery.1

Irrigation

Instill 2.5 mg/mL solution into abscess cavities, pleural space, or peritoneal or ventricular cavities.1

Inhalation

250 mg 2–4 times daily.1 Administer diluted in 3 mL of 0.9% sodium chloride using a nebulizer.1

Tuberculosis
Treatment of Active (Clinical) Tuberculosis

Should not be used alone for treatment of TB; must be given in conjunction with other antituberculosis agents.6

IV or IM

ATS, CDC, and IDSA recommend 15 mg/kg (up to 1 g) given once daily 5–7 times weekly for 2–4 months or until culture conversion;6 dosage can then be reduced to 15 mg/kg once daily (up to 1 g) 2–3 times weekly.6

Prescribing Limits

Pediatric Patients

Serious Bacterial Infections
All Routes

Maximum: 1.5 g daily.1 Total dose ≤15 g.1

Treatment of Active (Clinical) Tuberculosis
IV or IM

Maximum 1 g.6

Adults

Serious Bacterial Infections
All Routes

Maximum: 1.5 g daily.1 Total dose ≤15 g.1

Treatment of Active (Clinical) Tuberculosis
IV or IM

Maximum 1 g.6

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.1

Renal Impairment

Serious Bacterial Infections

Dosage adjustments necessary in patients with renal impairment.1 4 8 15 Whenever possible, monitor serum kanamycin concentrations, especially in patients with changing renal function.1

Various methods have been used to determine aminoglycoside dosage for patients with renal impairment, and there is wide variation in dosage recommendations for these patients.1 8 15

Manufacturer recommends an initial dosage of 7.5 mg/kg given at intervals (in hours) calculated by multiplying the patient’s steady-state serum creatinine (in mg/dL) by 9.1

The dosing method of Sarubbi and Hull (based on corrected Clcr) also has been recommended.b Consult specialized references for specific information on dosage for patients with renal impairment.

Dosage calculation methods should not be used in patients undergoing hemodialysis or peritoneal dialysis.a

In adults with renal failure undergoing hemodialysis, some clinicians recommend supplemental doses of 50–75% of the initial loading dose at the end of each dialysis period.8

Dialysis patients: monitor serum kanamycin concentrations and adjust dosage to maintain desired concentrations.a

Treatment of Active (Clinical) Tuberculosis
Adults
IV or IM

ATS, CDC, and IDSA recommend that usual doses be given at less frequent intervals; lower doses may reduce efficacy.6 These experts recommend 12–15 mg/kg daily given 2 or 3 times weekly.6

Hemodialysis patients: Give dose after hemodialysis is finished.6 Monitor serum kanamycin concentrations and adjust dosage to maintain desired concentrations.6

Geriatric Patients

Treatment of Active (Clinical) Tuberculosis
IV or IM

>59 years of age: 10 mg/kg daily (up to 750 mg).6

Select dosage with caution and closely monitor renal function because of age-related decreases in renal function.a

Cautions for Kanamycin Sulfate

Contraindications

  • History of hypersensitivity or serious toxic reactions to kanamycin or other aminoglycosides.1

  • Long-term therapy (e.g., tuberculosis) because of toxic hazards associated with extended administration.1

Warnings/Precautions

Warnings

Neurotoxicity and Ototoxicity

Patients receiving aminoglycosides should be under close clinical observation because of possible ototoxicity.1

Vestibular and permanent bilateral auditory ototoxicity occurs most frequently in those with past or present history of renal impairment, those receiving other ototoxic drugs, and those who receive high dosages or prolonged treatment.1

Serial audiograms should be obtained, if feasible, in patients old enough to be tested, particularly in high-risk patients.1

Discontinue kanamycin or adjust dosage if there is evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, hearing loss).1

Some aminoglycosides have caused fetal ototoxicity when administered to pregnant women.1 (See Pregnancy under Cautions.)

Nephrotoxicity

Patients receiving aminoglycosides should be under close clinical observation because of possible nephrotoxicity.1 Renal function should be assessed prior to therapy and daily, or more frequently, during therapy.1

Nephrotoxicity occurs most frequently in those with past or present history of renal impairment, those receiving other nephrotoxic drugs, and those who receive high dosage or prolonged treatment.1

Monitor urine for increased protein excretion and the presence of cells and casts.1 Obtain Clcr, Scr, and/or BUN at the onset of therapy, frequently during therapy, and at or shortly after the end of therapy.1 If renal function is changing, test more frequently.1

Dosage reduction and increased hydration may be desirable if other evidence of renal dysfunction occurs (e.g., decreased Clcr, decreased urine specific gravity, increased BUN or serum creatinine, oliguria).1

If azotemia increases or if a progressive decrease in urinary output occurs, discontinue kanamycin.1

Aminoglycoside-induced nephrotoxicity usually is reversible.1

Neuromuscular Blockade

Neuromuscular blockade and respiratory paralysis reported with high kanamycin dosage.1

Possibility of neuromuscular blockade should be considered, especially in patients receiving anesthetics or neuromuscular blocking agents (e.g., tubocurarine, succinylcholine, decamethonium) or in those receiving massive transfusions of citrate-anticoagulated blood.1

Calcium salts may reverse neuromuscular blockade, but mechanical respiratory assistance may be necessary.1

Sensitivity Reactions

Hypersensitivity

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, reported with aminoglycosides.1

Cross-sensitivity

Cross-sensitivity occurs among the aminoglycosides.1 b

Sulfite Sensitivity

Kanamycin injection contains sodium metabisulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.1

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of kanamycin and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.1

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.1

Usually used in conjunction with other anti-infectives (e.g., penicillins, cephalosporins) for empiric treatment of serious infections pending results of in vitro susceptibility tests.1 If anaerobic bacteria are suspected, concomitant use of an anti-infective active against anaerobes is necessary.1

Topical Instillation

Aminoglycosides may be absorbed in substantial quantities from body surfaces after topical instillation or local irrigation and may cause neurotoxicity, nephrotoxicity, neuromuscular blockade, or respiratory paralysis.1 b Carefully monitor serum levels during treatment.1

Hydration

Patient should be well hydrated before treatment to prevent irritation of the renal tubules by the high concentrations of kanamycin in the urinary excretory system.1

Risk of toxic reactions is low in well-hydrated patients with normal kidney function who receive a total kanamycin dose ≤15 g.1

Neuromuscular Disorders

Use with caution in patients with neuromuscular disorders such as myasthenia gravis, parkinsonism, or infant botulism; may aggravate muscle weakness because of potential curare-like effect on the neuromuscular junction.1

Superinfection

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.1 Discontinue drug and institute appropriate therapy if superinfection occurs.1

Specific Populations

Pregnancy

Category D.1

Possibility of fetal harm if administered to a pregnant woman.1 Complete, irreversible, bilateral congenital deafness reported when another aminoglycoside (i.e., streptomycin) was used during pregnancy.1

If used during pregnancy or if patient becomes pregnant while receiving kanamycin, patient should be apprised of the potential hazard to the fetus.1

Lactation

Distributed into milk.1 Use with caution.1

Pediatric Use

Use with caution in neonates and premature infants because renal immaturity in these patients may result in prolonged serum half-life.1

Geriatric Use

Increased risk of toxicity; select dosage with caution and closely monitor renal function because of age-related decreases in renal function.1

When assessing renal function in geriatric patients, Clcr may be more useful than BUN or Scr.1

Renal Impairment

Risk of neurotoxicity (manifested as vestibular and permanent bilateral auditory ototoxicity) is greater in patients with renal damage than in other patients.1

Renal function should be assessed prior to and during therapy.1

Eighth-cranial nerve function should be monitored closely, especially in patients who have known or suspected renal impairment at the start of treatment and also in those whose renal function is initially normal but who develop signs of renal dysfunction during treatment.1

Common Adverse Effects

Ototoxicity, neurotoxicity.1

Interactions for Kanamycin Sulfate

Neurotoxic, Ototoxic, or Nephrotoxic Drugs

Concomitant or sequential use with other drugs that have neurotoxic, ototoxic, or nephrotoxic effects may result in additive toxicity and should be avoided, if possible.1 b

Because of the possibility of an increased risk of ototoxicity due to additive effects or altered serum and tissue aminoglycoside concentrations, do not give concurrently with potent diuretics.1 b

Specific Drugs and Laboratory Tests

Drug

Interaction

Comments

Amphotericin B

Possible increased incidence of nephrotoxicity and/or neurotoxicity1

Avoid concurrent or sequential use, if possible1

Anti-emetics (e.g., dimenhydrinate, meclizine)

Anti-emetics that suppress nausea and vomiting of vestibular origin and vertigo may mask symptoms of vestibular ototoxicity8

Bacitracin

Possible increased incidence of nephrotoxicity and/or neurotoxicity1

Avoid concurrent or sequential use, if possible1

β-Lactam antibiotics (cephalosporins, penicillins)

In vitro evidence of additive or synergistic antibacterial effects between penicillins and aminoglycosides against some enterococci, Enterobacteriaceae, or Ps. aeruginosa; used to therapeutic advantage (e.g., treatment of endocarditis)b

Possible increased incidence of nephrotoxicity reported with some cephalosporins; cephalosporins may spuriously elevate creatinine concentrations1 b

Potential in vitro and in vivo inactivation of aminoglycosides1

Do not admix; administer IV solutions of the drugs separately1

Monitor serum aminoglycoside concentrations, especially when high penicillin doses are used or patient has renal impairment1

Promptly assay, freeze, or treat specimens with beta-lactamase1

Carbapenems (imipenem)

In vitro evidence of additive or synergistic antibacterial effects with aminoglycosides against some gram-positive bacteria (Enterococcus faecalis, S. aureus, Listeria monocytogenes)b

Chloramphenicol

Some in vitro evidence of antagonism with aminoglycosides; in vivo antagonism has not been demonstrated and the drugs have been administered concomitantly with no apparent decrease in activityb

Cisplatin

Possible increased incidence of nephrotoxicity and/or neurotoxicity1

Avoid concurrent or sequential use, if possible1

Clindamycin

Some in vitro evidence of antagonism with aminoglycosides; in vivo antagonism has not been demonstrated and the drugs have been administered concomitantly with no apparent decrease in activityb

Colistimethate/Colistin

Possible increased incidence of nephrotoxicity and/or neurotoxicity1

Avoid concurrent or sequential use, if possible1

Diuretics (ethacrynic acid, furosemide, meralluride sodium, sodium mercaptomerin, mannitol)

Possible increased risk of ototoxicity (diuretics themselves may cause ototoxicity) or increased risk of other aminoglycoside-related adverse effects (diuretics may alter aminoglycoside serum or tissue concentrations)1 b

Neuromuscular blocking agents and general anesthetics (succinylcholine, tubocurarine, decamethonium)

Possible potentiation of neuromuscular blockade and respiratory paralysis1

Use concomitantly with caution; closely observe for signs of respiratory depression1

NSAIAs

Possible increased serum aminoglycoside concentrations reported with indomethacin in premature neonates; may be related to indomethacin-induced decreases in urine output

Closely monitor aminoglycoside concentrations and adjust dosage accordingly

Polymyxin B

Possible increased incidence of nephrotoxicity and/or neurotoxicity1

Avoid concurrent or sequential use, if possible1

Tetracyclines

Some in vitro evidence of antagonism with aminoglycosides; in vivo antagonism has not been demonstrated and the drugs have been administered concomitantly with no apparent decrease in activityb

Vancomycin

Possible increased incidence of nephrotoxicity and/or neurotoxicity1

Avoid concurrent or sequential use, if possible1

Kanamycin Sulfate Pharmacokinetics

Absorption

Bioavailability

Poorly absorbed from the GI tract.4 16 17 21

Rapidly absorbed following IM injection;1 13 21 peak serum concentrations attained within 1 hour.1

Aminoglycosides are quickly and almost totally absorbed from body surfaces (except the urinary bladder) after local irrigation or intraoperative topical application in association with medical procedures.1 b Also rapidly absorbed from the bronchial tree, wounds, or denuded skin after local instillation, or when used to irrigate joints; use of large doses at these sites may result in substantial plasma concentrations of the drugs.b

Plasma Concentrations

Following a single IM dose of 7.5 mg/kg in adults with normal renal function, peak plasma concentrations average 22 mcg/mL within 1 hour;1 8 hours after the dose, plasma concentrations average 3.2 mcg/mL.1 Plasma concentrations are similar following IV infusion over 1 hour.1

Premature infants: Single IM dose of 6.3–8.5 mg/kg resulted in peak plasma concentrations averaging 17.5 mcg/mL within 1 hour and 5.8 mcg/mL at 12 hours.18

Neonates 1–7 days of age: Single IM dose of 7.5 mg/kg or 10 mg/kg resulted in peak serum concentrations of 21.8 or 26.8 mcg/mL, respectively, 30 minutes after dose.19 When given by IV infusion over 20 minutes, plasma concentrations were 21.4 or 29.3 mcg/mL, respectively.19

Intraperitoneal instillation of 500 mg in 20 mL of 0.9% sodium chloride: Peak plasma concentration of 19 mcg/mL within 15 minutes.14

Special Populations

Plasma concentrations may be lower in pregnant women.4

Plasma concentrations are higher in patients with renal impairment.1 4 15

Plasma concentrations may be decreased in patients with severe burns.1

Distribution

Extent

Distributed into most body tissues and fluids including pleural fluid, synovial fluid, ascitic fluid, gallbladder, and bile.1 4 Low concentrations in saliva and bronchial secretions.4

Low concentrations in CSF in adults with uninflamed meninges.1 4

Infants: CSF concentration is 10–20% of serum concentrations if normal meninges; may be 50% if meninges are inflamed.1

Crosses the placenta and is distributed into cord blood and amniotic fluid.1 4

Distributed into milk.1

Elimination

Elimination Route

Excreted principally in urine by glomerular filtration; not reabsorbed by renal tubules.1

Removed by hemodialysis4 10 15 and peritoneal dialysis.4 15

Half-life

Adults: 2–4 hours.1 4 8 9 11 13 15

Special Populations

Geriatric patients: Half-life may be prolonged.4

Premature neonates: 9 hours.18

Neonates 1–7 days of age: 4.3–5.1 hours.19

Severe burn patients: Possible decreased half-life.1

Renal impairment: Prolonged half-life.1 4 15

Severe renal impairment: 27–80 hours.4 8 15

Stability

Storage

Parenteral

Injection

20–25°C.1

Stable for 24 hours at room temperature in most IV fluids (e.g., 0.9% sodium chloride, 5% dextrose).5

Solution may darken during storage; does not indicate a loss of potency.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Amino acids 4.25%, dextrose 25%

Dextrose 5% in sodium chloride 0.9%

Dextrose 5 or 10% in water

Isolyte M or P with dextrose 5%

Ringer’s injection, lactated

Sodium chloride 0.9%

Drug Compatibility

Manufacturer states that kanamycin should not be admixed with β-lactam antibiotics because of possible mutual inactivation.1

Admixture CompatibilityHID

Compatible

Ascorbic acid injection

Cefoxitin sodium

Chloramphenicol sodium succinate

Clindamycin phosphate

Dopamine HCl

Furosemide

Penicillin G potassium

Penicillin G sodium

Polymyxin B sulfate

Sodium bicarbonate

Vitamin B complex with C

Incompatible

Amphotericin B

Chlorpheniramine maleate

Colistimethate sodium

Heparin sodium

Methohexital sodium

Variable

Hydrocortisone sodium succinate

Y-Site CompatibilityHID

Compatible

Cyclophosphamide

Furosemide

Heparin sodium with hydrocortisone sodium succinate

Hydromorphone HCl

Magnesium sulfate

Meperidine HCl

Morphine sulfate

Perphenazine

Potassium chloride

Vitamin B complex with C

Actions and Spectrum

  • Usually bactericidal.1

  • Inhibits protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits.1 b

  • In vitro spectrum of activity includes many gram-negative aerobic bacteria (including most Enterobacteriaceae and Pseudomonas aeruginosa), some mycobacteria, and some aerobic gram-positive bacteria.1 b Inactive against fungi, viruses, and most anaerobic bacteria.b

  • Gram-positive aerobes: Active in vitro against penicillinase-producing and nonpenicillinase-producing Staphylococcus aureus,1 S. epidermidis,1 Streptococcus pyogenes (group A β-hemolytic streptococci),1 S. pneumoniae,1 and group D streptococci.1

  • Gram-negative aerobes: Active in vitro and in clinical infections against Acinetobacter,1 Citrobacter,1 Enterobacter aerogenes,1 Escherichia coli,1 Haemophilus influenzae,1 Klebsiella pneumoniae,1 Neisseria gonorrhoeae,1 Proteus,1 Providencia,1 Salmonella,1 Shigella,1 and Serratia marcescens.1

  • Mycobacteria: Active against Mycobacterium tuberculosis4 6 and may be active against multidrug-resistant strains.6 Active in vitro against some strains of M. abscessus.

  • Partial cross-resistance occurs between kanamycin and other aminoglycosides.b

  • Some M. tuberculosis resistant to streptomycin may be susceptible to kanamycin,6 but M. tuberculosis demonstrates complete cross-resistance between kanamycin and amikacin.4 6 Cross-resistance also can occur between kanamycin and capreomycin.f

  • There have been recent reports of extensively drug-resistant (XDR) TB.c d e XDR TB is caused by M. tuberculosis resistant to both rifampin and isoniazid that also are resistant to a fluoroquinolone and at least one parenteral second-line antimycobacterial (capreomycin, kanamycin, amikacin).c d e

Advice to Patients

  • Advise patients that antibacterials (including kanamycin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1

  • Importance of completing full course of therapy, even if feeling better after a few days.1

  • Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with kanamycin or other antibacterials in the future.1

  • Importance of informing clinician if there is evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, hearing loss), other neurotoxicity (numbness, skin tingling, muscle twitching, seizures), or nephrotoxicity (e.g., decreased urine output).1

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Kanamycin Sulfate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

250 mg (of kanamycin) per mL*

Kanamycin Sulfate Injection (with sodium bisulfite and sodium citrate)

Abraxis

333 mg (of kanamycin) per mL*

Kanamycin Sulfate Injection (with sodium bisulfite and sodium citrate)

Abraxis

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions January 1, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

1. Abraxis Pharmaceutical Products. Kanamycin injection, USP prescribing information. Schaumburg, IL; 2006 June.

2. Apothecon. Kantrex (kanamycin sulfate) capsules, USP prescribing information. Princeton, NJ; 1996 Jan.

3. The United States pharmacopoeia, 29th rev, and The national formulary, 24th ed. Rockville, MD: The United States Pharmacopeial Convention; 2005:1212-4,3212.

4. Kucers A, Crowe S, Grayson ML et al, eds. The use of antibiotics. A clinical review of antibacterial, antifungal, and antiviral drugs. 5th ed. Jordan Hill, Oxford: Butterworth-Heinemann; 1997: 439-49.

5. Trissel LA. Handbook on injectable drugs. 12th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2003:819-22.

6. Centers for Disease Control and Prevention. Treatment of tuberculosis, American Thoracic Society, CDC, and Infectious Diseases Society of America. MMWR Recomm Rep. 2003; 52(No. RR-11):1-77.

7. American Academy of Pediatrics. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006:678-98,753.

8. Barza M, Scheife RT. Drug therapy reviews: antimicrobial spectrum, pharmacology and therapeutic use of antibiotics, part 4: aminoglycosides. Am J Hosp Pharm. 1977; 34:723-37. [PubMed 407790]

9. Clarke JR, Libke RD, Regamey C et al. Comparative pharmacokinetics of amikacin and kanamycin. Clin Pharmacol Ther. 1974; 15:610-6. [PubMed 4210297]

10. Danish M, Schultz R, Jusko WJ. Pharmacokinetics of gentamicin and kanamycin during hemodialysis. Antimicrob Agents Chemother. 1974; 6:841-7. [PubMed 4451356]

11. Cabana BE, Taggart JG. Comparative pharmacokinetics of BB-K8 and kanamycin in dogs and humans. Antimicrob Agents Chemother. 1973; 3:478-83. [PubMed 4790604]

12. Howard JB, McCracken GH, Trujillo H et al. Amikacin in newborn infants: comparative pharmacology with kanamycin and clinical efficacy in 45 neonates with bacterial diseases. Antimicrob Agents Chemother. 1976; 10:205-10. [PubMed 984762]

13. Kirby WMM, Clarke JT, Libke RD et al. Clinical pharmacology of amikacin and kanamycin. J Infect Dis. 1976; 134(Suppl):s312-5. [PubMed 993624]

14. Pissiotis CA, Nichols RL, Condon RE. Absorption and excretion of intraperitoneally administered kanamycin sulfate. Surg Gynecol Obstet. 1972; 134:995-8. [PubMed 5032398]

15. Bennett WM, Muther RS, Parker RA et al. Drug therapy in renal failure: dosing guidelines for adults. Ann Intern Med. 1980; 93:62-89. [IDIS 122057] [PubMed 6994534]

16. Kunin CM. Absorption, distribution, excretion and rate of kanamycin. Ann NY Acad Sci. 1966; 132:811-8. [PubMed 5336394]

17. Kunin CM, Chalmers TC, Leevy CM et al. Absorption of orally administered neomycin and kanamycin with special reference to patients with severe hepatic and renal disease. N Engl J Med. 1960; 262:380-5. [PubMed 14412744]

18. Axline SG, Simon HJ. Clinical pharmacology of antimicrobials in premature infants. I. Kanamycin, streptomycin, and neomycin. Antimicrob Agents Chemother. 1964; 10:135-41. [PubMed 14287917]

19. McCracken GH, Threlkeld N, Thomas ML. Intravenous administration of kanamycin and gentamicin in newborn infants. Pediatrics. 1977; 60:463-6. [PubMed 905011]

20. Sweetman S, ed. Martindale: the complete drug reference. London: Pharmaceutical Press. Electronic version. 2006.

21. Chambers HF. Aminoglycosides. In: Brunton LL, Lazo JS, Parker KL et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 11th ed. New York, NY: McGraw-Hill; 2006:1155-71.

200. Rodman DP, Maxwell AJ, McKnight JT. Extended dosage intervals for aminoglycosides. Am J Hosp Pharm. 1994; 51:2016-21. [PubMed 7977422]

201. McCormack JP, Jewesson PJ. A critical reevaluation of the therapeutic range of aminoglycosides. Clin Infect Dis. 1992; 14:320-39. [IDIS 295073] [PubMed 1571447]

202. Reviewers’ comments (personal observations).

203. Zhanel GG, Craig WA. Pharmacokinetic contributions to postantibiotic effects. Clin Pharmacokinet. 1994; 27:377-92. [PubMed 7851055]

204. Hustinx WN, Hoepelman IM. Aminoglycoside dosage regimens. Is once a day enough? Clin Pharmacokinet. 1993; 25:427-32.

205. Viscoli C, Dudley M, Ferrea G et al. Serum concentrations and safety of single daily dosing of amikacin in children undergoing bone marrow transplantation. J Antimicrob Chemother. 1991; 27(Suppl C):113-20. [PubMed 1856140]

206. Tulkens PM. Efficacy and safety of aminoglycosides once-a-day: experimental and clinical data. Scand J Infect Dis. 1991; 74:249-57.

207. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer. Efficacy and toxicity of single daily doses of amikacin and ceftriaxone versus multiple daily doses of amikacin and ceftazidime for infection in patients with cancer and granulocytopenia. Ann Intern Med. 1993; 119:584-93. [IDIS 320672] [PubMed 8363169]

208. MacGowan AP, Reeves DS. Serum monitoring and practicalities of once-daily aminoglycoside dosing. J Antimicrob Chemother. 1994; 33:349-50. [IDIS 326509] [PubMed 8182018]

209. O’Shaughnessy EM, Das SS. Serum monitoring and practicalities of once-daily aminoglycoside dosing. J Antimicrob Chemother. 1994; 33:350. [IDIS 326510] [PubMed 8182019]

210. Parker SE, Davey PG. Serum monitoring and practicalities of once-daily aminoglycoside dosing. J Antimicrob Chemother. 1994; 33:351.

a. AHFS drug information 2007. McEvoy GK, ed. Kanamycin. Bethesda, MD: American Society of Health-System Pharmacists; 2007:70-79.

b. AHFS drug information 2007. McEvoy GK, ed. Aminoglycosides general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2007:60-69.

c. World Health Organization. Extensively drug-resistant tuberculosis (XDR-TB): recommendations for prevention and control. Wkly Epidemiol Rec. 2006; 45:430-2.

d. Gandhi NR, Moll A, Sturm AW et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet. 2006; 368:1575-80. [PubMed 17084757]

e. Centers for Disease Control and Prevention. Extensively drug-resistant tuberculosis–United States, 1993–2006. MMWR Morb Mortal Wkly Rep. 2007; 56:250-3. [PubMed 17380107]

f. Mause CE, Plikaytis BB, Shinnick TM. Molecular analysis of cross-resistance to capreomycin, kanamycin, amikacin, and viomycin in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2005; 49:3192-7. [PubMed 16048924]

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:971-4.

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