FDA label 7d3c33bb-4662-82ba-e053-2991aa0a9d75

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.

WARNINGS: See BOXED WARNING above. Aminoglycosides can cause fetal harm when administered to pregnant women. Aminoglycoside antibiotics cross the placenta and there have been several reports of total, irreversible, bilateral congenital deafness in children whose mothers received streptomycin during pregnancy. Although serious side effects to fetus or newborn have not been reported in treatment of pregnant women with other aminoglycosides, the potential for harm exists. Reproductive studies have been performed in rats and rabbits and have revealed no evidence of impaired fertility or teratogenic effects. Dosages of 200 mg/kg/day in pregnant rats and pregnant guinea pigs led to hearing impairment in the off-spring. There are no well-controlled studies in pregnant women but clinical experience does not include any positive evidence of adverse effects on the fetus. However, if the drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard on the fetus. Contains sodium bisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

ADVERSE REACTIONS: Kanamycin has the potential to induce auditory and sometimes vestibular toxicity, renal toxicity, and neuromuscular blockade. The risks are higher for patients with a present or past history of renal impairment (especially if hemodialysis is required): for those receiving concomitant or sequential treatment with other ototoxic or nephrotoxic drugs or rapid acting diuretic agents given intravenously (ethacrynic acid, furosemide, and mannitol), and for patients treated for longer periods and/or with higher doses than recommended. Ototoxicity Toxic effects of kanamycin on the eighth cranial nerve can result in partially reversible or irreversible bilateral loss of hearing, loss of balance, or both. Tinnitus or vertigo may or may not be experienced. Cochlear damage is usually manifested initially by small changes in audiometric test results at the high frequencies and may not be associated with subjective hearing loss. Vestibular dysfunction is usually manifested by nystagmus, vertigo, nausea, vomiting, or acute Meniere’s syndrome. Nephrotoxicity Albuminuria, presence of red and white cells, and granular casts; azotemia and oliguria have been reported. Renal function changes are usually reversible when the drug is discontinued. Renal impairment may be characterized by a rise in serum creatinine and may be accompanied by oliguria, presence of casts, cells, and protein in the urine, by rising levels of BUN or by decrease in creatinine clearance. Neuromuscular Blockade Acute muscular paralysis and apnea can occur following treatment with aminoglycoside antibiotics. Neurotoxicity can occur after intrapleural and interperitoneal instillation of large doses of an aminoglycoside; however, the reaction has followed intravenous, intramuscular, and even the oral administration of these agents. Other Some local irritation or pain may follow the intramuscular injection of kanamycin. Other adverse reactions of the drug reported on rare occasions are skin rash, drug fever, headache, paresthesia, nausea, vomiting, and diarrhea. The “malabsorption syndrome” characterized by an increase in fecal fat, decrease in serum carotene, and fall in xylose absorption, reportedly has occurred with prolonged therapy.

Ototoxicity Toxic effects of kanamycin on the eighth cranial nerve can result in partially reversible or irreversible bilateral loss of hearing, loss of balance, or both. Tinnitus or vertigo may or may not be experienced. Cochlear damage is usually manifested initially by small changes in audiometric test results at the high frequencies and may not be associated with subjective hearing loss. Vestibular dysfunction is usually manifested by nystagmus, vertigo, nausea, vomiting, or acute Meniere’s syndrome.

Nephrotoxicity Albuminuria, presence of red and white cells, and granular casts; azotemia and oliguria have been reported. Renal function changes are usually reversible when the drug is discontinued. Renal impairment may be characterized by a rise in serum creatinine and may be accompanied by oliguria, presence of casts, cells, and protein in the urine, by rising levels of BUN or by decrease in creatinine clearance.

Neuromuscular Blockade Acute muscular paralysis and apnea can occur following treatment with aminoglycoside antibiotics. Neurotoxicity can occur after intrapleural and interperitoneal instillation of large doses of an aminoglycoside; however, the reaction has followed intravenous, intramuscular, and even the oral administration of these agents.