KANAMYCIN- kanamycin a sulfate injection, solution
APP Pharmaceuticals, LLC
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Kanamycin Injection, USP and other antibacterial drugs, Kanamycin Injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
BOXED WARNING
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 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 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 BUN, 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.
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. Blood urea nitrogen, 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 with respiratory paralysis may occur when kanamycin 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.
The concurrent and/or sequential systemic, oral, or topical use of kanamycin and other potentially nephrotoxic, and/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 should not be given concurrently with potent diuretics (ethacrynic acid, furosemide, meralluride sodium, sodium mercaptomerin, or mannitol). Some diuretics themselves cause ototoxicity, and intravenously administered diuretics may enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.
DESCRIPTION
Kanamycin sulfate is an aminoglycoside antibiotic produced by Streptomyces kanamyceticus. It is D-Streptamine, 0-3-amino-3-deoxy-?-D-glucopyranosyl � (1?6)-0- [6-amino-6-deoxy-?-D-glucopyranosyl -- (1?4)]-2-deoxy, sulfate 1:1 (salt). It consists of two amino sugars glycosidically linked to deoxystreptamine. Kanamycin Injection, USP, sterile solution for parenteral administration, contains respectively; kanamycin sulfate equivalent to 500 mg and 1g kanamycin; sodium bisulfite, an antioxidant, 0.66% and 0.45%; and sodium citrate, 2.2% and 2.2% with pH of each dosage form adjusted to 4.5 with sulfuric acid.
CLINICAL PHARMACOLOGY
The drug is rapidly absorbed after intramuscular injection and peak serum levels are generally reached within approximately one hour. Doses of 7.5 mg/kg give mean peak levels of 22 mcg/mL. At 8 hours following a 7.5 mg/kg dose, mean serum levels are 3.2 mcg/mL. The serum half-life is 2 1/2 hours. Intravenous administration of kanamycin over a period of one hour resulted in serum concentrations similar to those obtained by intramuscular administration.
