Kanamycin is an aminoglycoside antibiotic.
Administration
Kanamycin sulfate is usually administered by deep IM injection, IV infusion, or orally.
The drug has also been administered by intraperitoneal instillation, irrigation, or inhalation.
For adults, IV infusions are prepared by adding 500 mg of kanamycin to 100-200 mL of usual IV infusion fluid such as 0.9% sodium chloride or 5% dextrose injection or by adding 1 g of the drug to 200-400 mL of diluent.
The appropriate dose should be infused over 30-60 minutes.
For pediatric patients, the volume of infusion fluid depends on the patient’s needs, but should be sufficient to allow an infusion period of 30-60 minutes.
Dosage
Dosage of kanamycin sulfate is expressed in terms of kanamycin.
IM and IV dosage are identical and should be based on an estimate of ideal body weight. The manufacturers state that dosage by all routes of administration should not exceed 1.5 g daily.
The usual IM or IV dosage of kanamycin recommended by the manufacturers for adults, children, and infants with normal renal function is 15 mg/kg daily given in equally divided doses at 8- or 12-hour intervals.
The manufacturers state that IM dosage may be given in equally divided doses at 6-hour intervals if continuously high blood concentrations are desired.
Some clinicians recommend kanamycin dosages of 15 mg/kg daily given in equally divided doses at 12-hour intervals in infants 7 days of age or younger who weigh 2 kg or less and 20 mg/kg daily given in equally divided doses every 12 hours in infants 7 days of age or younger who weigh more than 2 kg.
Whenever possible, and 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, peak and trough serum concentrations of kanamycin should be determined periodically and IM or IV dosage should be adjusted to maintain desired serum concentrations.
A causal relationship between maintenance of certain peak or trough serum concentrations or other pharmacodynamic endpoints and clinical response or toxicity has not been established to date for aminoglycoside dosing regimens. However, in general, desirable peak serum concentrations of kanamycin for systemic infections are 15-30 mcg/mL and trough concentrations of the drug should not exceed 5-10 mcg/mL.
An increased risk of toxicity may be associated with prolonged peak kanamycin serum concentrations greater than 30-35 mcg/mL.
As an adjunct in the treatment of hepatic encephalopathy, the usual adult dosage of kanamycin is 8-12 g daily administered orally in divided doses.
For preoperative intestinal antisepsis, the usual adult dosage is 1 g orally every hour for 4 doses followed by 1 g every 6 hours for 36-72 hours. For intraperitoneal instillation in adults, 500 mg of kanamycin is dissolved in 20 mL of sterile water for injection and instilled into the peritoneal cavity through a polyethylene catheter sutured into the wound at closure. A 0.25% solution of kanamycin has been used to irrigate the pleural space, ventricular or abscess cavities, wounds, or surgical sites. For inhalation, 250 mg of kanamycin is diluted with 3 mL of 0.9% sodium chloride and nebulized. This dose may be given 2-4 times daily.
Treatment of Active Tuberculosis
In the treatment of clinical tuberculosis, kanamycin is considered a second-line agent for use in multiple-drug regimens for the treatment of active tuberculosis. Therapy for tuberculosis should be continued long enough to prevent relapse. The minimum duration of treatment currently recommended for patients with culture-positive pulmonary tuberculosis is 6 months (26 weeks), and recommended regimens consist of an initial intensive phase (2 months) and a continuation phase (usually either 4 or 7 months).
The American Thoracic Society (ATS), US Centers for Disease Control and Prevention (CDC), and Infectious Diseases Society of America (IDSA) state that the usual dosage of kanamycin for use in conjunction with other antituberculosis agents for the treatment of active tuberculosis in adults and children 15 years of age or older is 15 mg/kg daily (up to 1 g) given IM or IV as a single daily dose (usually 750-1000 mg daily) 5-7 times weekly for the first 2-4 months or until culture conversion; dosage can then be reduced to 15 mg/kg daily (up to 1 g) given 2 or 3 times weekly, depending on efficacy of the other drugs in the regimen.
However, these experts recommend that adults older than 59 years of age receive a dosage of 10 mg/kg (up to 750 mg) daily.
The dosage of kanamycin recommended by the ATS, CDC, IDSA, and American Academy of Pediatrics (AAP) for the treatment of active tuberculosis in pediatric patients is 15-30 mg/kg daily (up to 1 g) once daily. The ATS, CDC, and IDSA state that pediatric patients also can receive kanamycin in an intermittent regimen using a dosage of 15-30 mg/kg twice weekly.
Dosage in Renal Impairment
In patients with impaired renal function, IM and IV doses and/or frequency of administration of kanamycin must be modified in response to serum concentrations of the drug and the degree of renal impairment.
There are various methods to determine dosage and a wide variation in dosage recommendations for these patients. However, even when one of these methods is used, peak and trough serum concentrations of the drug should be monitored, especially in patients with changing renal function.
The manufacturers recommend that 7.5-mg/kg doses be given at intervals (in hours) calculated by multiplying the patient’s steady-state serum creatinine (in mg/dL) by 9. Alternatively, many clinicians recommend the dosing method of Sarubbi and Hull, which is based on corrected creatinine clearance.
These dosage calculation methods should not be used in patients undergoing hemodialysis or peritoneal dialysis. 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.
However, serum concentrations of the drug should be monitored in dialysis patients and dosage should be adjusted to maintain desired serum concentrations.
Pharmacokinetics
The pharmacokinetics of kanamycin are similar to those of the other aminoglycosides. In all studies described in the Pharmacokinetics section, kanamycin was administered as the sulfate salt; dosages and concentrations of the drug are expressed in terms of kanamycin.
Absorption
Approximately 1% of an oral dose of kanamycin is absorbed from the normal GI tract. Following IM administration of a single kanamycin dose of 7.5 mg/kg in adults with normal renal function, peak kanamycin plasma concentrations averaging 22 mcg/mL are attained within approximately 1 hour; plasma concentrations of the drug average 3.2 mcg/mL at 8 hours.
When the same dose is administered by IV infusion over 1 hour, similar plasma concentrations of kanamycin are attained. In one study in premature infants, peak plasma kanamycin concentrations averaging 17. mcg/mL were attained within 1 hour following IM administration of a single kanamycin dose of 6.3-8. mg/kg; plasma concentrations of the drug averaged 5.8 mcg/mL at 12 hours. In one study, intraperitoneal instillation of 500 mg of kanamycin diluted in 20 mL of 0.9% sodium chloride resulted in peak plasma kanamycin concentrations of 19 mcg/mL within 15 minutes.
Elimination
The plasma elimination half-life of kanamycin is usually 2-4 hours in adults with normal renal function and is reported to range from 27-80 hours in adults with severe renal impairment.
The plasma elimination half-life of kanamycin is reported to average 9 hours in premature infants. In adults with normal renal function, 80-90% of a single IM dose of kanamycin is excreted unchanged by glomerular filtration within 24 hours.
Complete recovery of the dose in urine requires approximately 10-20 days in patients with normal renal function. Following oral administration, unabsorbed kanamycin is excreted unchanged in the feces and that portion of the dose which is absorbed is excreted unchanged in the urine.
Chemistry and Stability
Chemistry
Kanamycin, an aminoglycoside antibiotic obtained from cultures of Streptomyces kanamyceticus, is a complex of 3 components with various degrees of antimicrobial activity—kanamycin A, B, and C.
The commercially available drug is comprised almost entirely of the sulfate salt of kanamycin A and occurs as a white, crystalline powder and is freely soluble in water and practically insoluble in alcohol. Kanamycin sulfate injection is a clear, colorless solution; sulfuric acid is added during manufacture of the injection to adjust the pH to 4.5.
Stability
Kanamycin sulfate capsules should be stored in tight containers at a temperature less than 40°C, preferably between 15-30°C. Kanamycin sulfate injection should be stored at a temperature less than 40°C, preferably between 15-30°C; freezing should be avoided. Kanamycin sulfate is stable for 24 hours at room temperature in most IV infusion fluids including 0.9% sodium chloride or 5% dextrose injection.
The manufacturers state that kanamycin sulfate injection should not be mixed with other drugs. For further information on chemistry and stability, mechanism of action, spectrum, resistance, pharmacokinetics, uses, cautions, drug interactions, and dosage and administration of kanamycin, see the Aminoglycosides General Statement 8:12.02.
Preparations
Kanamycin Sulfate Oral Capsules 500 mg (of kanamycin) Kantrex®, Geneva Parenteral Injection 37. mg (of kanamycin) per Kanamycin Sulfate Injection mL Pediatric, (with sodium bisulfite and sodium citrate) SoloPak Kantrex® Pediatric, (with sodium bisulfite and sodium citrate) Sandoz 250 mg (of kanamycin) per mL Kanamycin Sulfate Injection, (with sodium bisulfite and sodium citrate) SoloPak Kantrex®, (with sodium bisulfite and sodium citrate) Geneva 333 mg (of kanamycin) per mL Kanamycin Sulfate Injection, (with sodium bisulfite and sodium citrate) SoloPak Kantrex®, (with sodium bisulfite and sodium citrate) Sandoz