Kanamycin (Mode of Administration) Date: 1/2/2011

Kanamycin

Pharmacology
Kanamycin interacts with the 30S subunit of prokaryotic ribosomes. It induces substantial amounts of
mistranslation and indirectly inhibits translocation during protein synthesis

Side effects

Serious side effects include tinnitus or loss of hearing, toxicity to kidneys, and allergic reactions
to the drug.[4]

DOSAGE AND ADMINISTRATION

Kanamycin Injection may be given intramuscularly or intravenously. The patient’s pretreatment

body weight should be obtained for calculation of the correct dosage. The dosage of an
aminoglycoside in obese patients should be based on an estimate of the lean body mass. The
status of renal function should be determined by measurement of serum creatinine concentration
or calculation of the endogenous creatinine clearance rate. The blood urea nitrogen (BUN) level
is much less reliable for this purpose. Renal function should be reassessed frequently during
therapy.

It is desirable to measure both peak and trough serum concentrations intermittently during
therapy since both concentrations are used to determine the adequacy and safety of the dose and
to adjust the dosage during treatment. Peak serum concentrations (30 to 90 minutes after
injection) above 35 µg per mL and trough concentrations (just prior to the next dose) above 10
µg per mL should be avoided.

Intramuscular Route

Inject deeply into the upper outer quadrant of the gluteal muscle. The recommended dose for
adults or children is 15 mg/kg/day in two equally divided dosages administered at equally
divided intervals; ie, 7.5 mg/kg q 12h. If continuously high blood levels are desired, the daily
dose of 15 mg/kg may be given in equally divided doses every 6 or 8 hours. Treatment of
patients in the heavier weight classes, ie, 100 kg, should not exceed 1.5 g/day.

In patients with impaired renal function, it is desirable to follow therapy by appropriate serum
assays. If this is not feasible, a suggested method is to reduce the frequency of administration in
patients with renal dysfunction. The interval between doses may be calculated with the following
formula:

   Serum creatinine (mg/100 mL) x 9 = Dosage Interval (in hours); eg, if the serum
   creatinine is 2 mg, the recommended dose (7.5 mg/kg) should be administered every
   18 hours. Changes in creatinine concentration during therapy would, of course,
   necessitate changes in the dosage frequency.

It is desirable to limit the duration of treatment with kanamycin to short term. The usual duration
of treatment is 7 to 10 days. Total daily dose by all routes of administration should not exceed
1.5 g/day. If longer therapy is required, measurement of kanamycin peak and trough serum
concentrations is particularly important as a basis for determining the adequacy and safety of the
dose. These patients should be carefully monitored for changes in renal, auditory, and vestibular
function. Dosage should be adjusted as needed. The risks of toxicity multiply as the length of
treatment increases.

At the recommended dosage level, uncomplicated infections due to kanamycin-susceptible

organisms should respond to therapy in 24 to 48 hours. If definite clinical response does not
occur within 3 to 5 days, therapy should be stopped and the antibiotic susceptibility pattern of the
invading organism should be rechecked. Failure of the infection to respond may be due to
resistance of the organism or to the presence of septic foci requiring surgical drainage.

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Kanamycin (Mode of Administration) Date: 1/2/2011

Intravenous Administration

The dose should not exceed 15 mg/kg per day and must be administered slowly. The solution for
intravenous use is prepared by adding the contents of a 500-mg vial to 100 to 200 mL of sterile
diluent such as Normal Saline or 5% Dextrose in Water, or the contents of a 1.0-g vial to 200 to
400 mL of sterile diluent. The appropriate dose is administered over a 30- to 60-minute period.
The total daily dose should be divided into 2 or 3 equally divided doses.

In pediatric patients the amount of diluent used should be sufficient to infuse the kanamycin
sulfate over a 30- to 60-minute period.

Kanamycin Injection, USP should not be physically mixed with other antibacterial agents but
each should be administered separately in accordance with its recommended route of
administration and dosage schedule.

Management of drug-resistant TB varies with the pattern of drug resistance. Generally, MDR-
TB requires prolonged (eg, 18 to 24 mo) treatment with the remaining active first-line drugs
(including PZA, if susceptible) with addition of an injectable, a fluoroquinolone, and other 2nd-
line drugs as needed to build a 4- or 5-drug regimen that the infecting strain is known or likely to
be susceptible to (ie, based on testing, a known source-case, prior treatment, or drug
susceptibility patterns in the community). Managing the adverse effects of these long, complex
regimens is challenging. MDR-TB should always be treated by a TB specialist experienced with
these cases. Fully supervised treatment is essential to avoid additional drug resistance through
nonadherance.

MULTI DRUG RESISTANT - TUBERCULOSIS

Second-line drugs: Other antibiotics are active against TB and are used primarily when patients
have MDR-TB or do not tolerate one of the first-line drugs. The 2 most important classes are
aminoglycosides (and the closely related polypeptide drug, capreomycin Some Trade Names
CAPASTAT and fluoroquinolones.

Streptomycin, the most commonly used aminoglycoside, is very effective and bactericidal.
Resistance is still relatively uncommon in the US but is more common globally. CSF penetration
is poor, and intrathecal administration should not be used if other effective drugs are available.
Dose-related adverse effects include renal tubular damage, vestibular damage, and ototoxicity.
The dose is about 15 mg/kg IM (maximum: usually 1 g for adults, reduced to 0.75 g [10 mg/kg]
for those ≥ 60 yr). To limit dose-related adverse effects, clinicians give one dose only 5 days/wk
for > 2 mo. Then it may be given twice/wk for another 2 mo if necessary. In patients with renal
insufficiency, dosing frequency should be reduced (eg, 12 to 15 mg/kg/ dose 2 or 3 times/wk).
Patients should be monitored with appropriate testing of balance, hearing, and serum creatinine
levels. Adverse effects include rash, fever, agranulocytosis, and serum sickness. Flushing and
tingling around the mouth commonly accompany injection but subside quickly. Streptomycin
Some Trade Names
No US trade name Click for Drug Monograph is contraindicated during pregnancy because it
may damage the 8th cranial nerve in the fetus.

Kanamycin and amikacin may remain effective even if streptomycin Some Trade Names
No US trade name Click for Drug Monograph resistance has developed. Their renal and neural
toxicities are similar to those of streptomycin Some Trade Names
No US trade name Click for Drug Monograph
. Capreomycin, a related nonaminoglycoside parenteral bactericidal drug, has dosage,
effectiveness, and adverse effects similar to those of aminoglycosides. It is an important drug for
MDR-TB because isolates resistant to streptomycin Some Trade Names
No US trade name Click for Drug Monograph are often susceptible to capreomycin Some Trade
Names CAPASTAT Click for Drug Monograph , and it is somewhat better tolerated than
aminoglycosides when prolonged administration is required.

Drug resistance: Treatment with any single antibiotic always results in survival of a very few
(about 1 in a million) organisms that have acquired spontaneous resistance mutations.

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Kanamycin (Mode of Administration) Date: 1/2/2011

Incomplete or erratic therapy selects for these resistant organisms, making treatment adherence
particularly important in prevention of resistance. Multiple drugs are used concurrently for TB so
that organisms resistant to one drug are killed by the others; simultaneous spontaneous mutations
to multiple drugs are unlikely. However, once a strain resistant to a single drug has developed
and proliferated, it may acquire resistance to additional drugs through the same process; thus,
MDR-TB can occur by stepwise acquired resistance to INH, RIF, and often other drugs. Some
resistant strains appear to be less fit (ie, less transmissible and virulent); others have acquired
compensatory mutations that restore fitness, allowing disease progression and transmission to
occur.

Once a drug-resistant strain develops in a patient, it can spread from person to person (primary
drug resistance). Uninhibited transmission of drug-resistant strains in congregate settings, such
as hospitals, clinics, prisons, shelters, and refugee camps, is a major barrier to global control.

Several new anti-TB drugs that may be active against resistant strains are in preclinical or
clinical development but will not be available for several more years. Furthermore, unless
treatment programs are strengthened (eg, by full supervision of each dose), stepwise resistance to
new drugs is likely.

MDR-TB is TB resistant in vitro to both isoniazid Some Trade Names

INH
NYDRAZID
Click for Drug Monograph and rifampin Some Trade Names
RIFADIN
RIMACTANE
Click for Drug Monograph
, with or without resistance to other drugs. Numerous outbreaks of MDR-TB have been reported,
and the global burden is rising. The Stop TB Partnership estimates that 780,000 new cases of
MDR-TB will occur between 2006 and 2015. In parts of the world where resistance testing is
inadequate or unavailable, many patients who do not respond to first-line therapy probably have
MDR-TB that is undiagnosed. MDR-TB has major negative implications for TB control;
alternative treatments require a longer treatment course with less effective, more toxic, and more
expensive 2nd-line drugs.

XDR-TB is MDR-TB that is also resistant to fluoroquinolones and injectable drugs (eg,
streptomycin Some Trade Names
No US trade name
Click for Drug Monograph
, amikacin Some Trade Names
AMIKIN
Click for Drug Monograph
, kanamycin Some Trade Names
KANTREX
Click for Drug Monograph
, capreomycin Some Trade Names
CAPASTAT
Click for Drug Monograph
). TB strains resistant to other drug combinations that do not meet the definitions of MDR or
XDR are termed polyresistant. Because the fluoroquinolones and injectables are important for
treatment of MDR-TB, XDR-TB has dire therapeutic implications. Although some patients can
be cured, mortality is higher and depends on the number of effective drugs remaining and the
extent of lung destruction. Surgery to remove localized areas of lung destruction plays an
important role in the treatment of advanced cases of MDR-TB or XDR-TB but is not widely
available in high-burden regions.

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