Kanamycin warnings and precautions

Kanamycin
KANAMYCIN® Package Insert
Description
Clinical Pharmacology
Microbiology
Indications and Usage
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Overdosage
Dosage and Administration
How Supplied
Labels and Packages

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Warnings and Precautions

Warnings

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 cranial 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.

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.

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.

Precautions

General

Prescribing Kanamycin Injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Neurotoxic and nephrotoxic antibiotics may be almost completely absorbed from body surfaces (except the urinary bladder) after local irrigation and after topical application during surgical procedures. The potential toxic effects of antibiotics administered in this fashion (otoand nephrotoxicity, neuromuscular blockade, respiratory paralysis) should be considered (see WARNING box).

Increased nephrotoxicity has been reported following concomitant administration of aminoglycoside antibiotics and with some cephalosporins.

Aminoglycosides should be used with caution in patients with neuromuscular disorders such as myasthenia gravis, Parkinsonism, or infant botulism, since these drugs may aggravate muscle weakness because of their potential curare-like effect on neuromuscular function.

Elderly patients may have a decrease in renal function which may not be evident in the results of routine screening tests, such as BUN or serum creatinine levels. Measurement of creatinine clearance or an estimate based on published nomograms or equations may be more useful. Monitoring of renal function during treatment with kanamycin, as with other aminoglycosides, is particularly important in such patients.

Because of high concentrations of kanamycin in the urinary excretory system, patients should be well hydrated before treatment to prevent irritation of the renal tubules.

NOTE: The risk of toxic reactions is low in well-hydrated patients with normal Kidney function, who receive a total dose of 15 g of kanamycin or less.

Treatment with kanamycin may result in overgrowth of nonsusceptible organisms. If this occurs kanamycin should be discontinued and appropriate therapy initiated.

Information for Patients

Patients should be counseled that antibacterial drugs including Kanamycin Injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Kanamycin Injection is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Kanamycin Injection or other antibacterial drugs in the future.

Laboratory Tests

Tests of eighth cranial nerve functions: Serial audiometric tests are suggested, particularly when renal function is impaired and/or prolonged aminoglycoside therapy is required; such tests should also be repeated periodically after treatment if there is evidence of a hearing deficit or vestibular abnormalities before or during therapy, or when consecutive or concomitant use of other potentially ototoxic drug is unavoidable.

Test of renal function: It should be emphasized that since renal function may alter appreciably during therapy, renal function should be tested daily or more frequently. Urine should be examined for increased excretion of protein and for presence of cells and casts, keeping in mind the effects of the primary illness on these tests. One or more of the following laboratory measurements should be obtained at the onset of therapy, frequently during therapy, and at, or shortly after, the end of therapy:

• Creatinine clearance rate (either carefully measured or estimated from published nomograms or equations based on patient’s age, sex, body weight, and serial creatinine concentrations) (preferred over BUN).

• Serum creatinine concentration (preferred over BUN).

• Blood urea nitrogen (BUN).

More frequent testing is desirable if renal function is changing. If signs of renal irritation appear, such as casts, white or red cells, and albumin, hydration should be increased and a reduction in dosage may be desirable (see DOSAGE AND ADMINISTRATION). These signs usually disappear when treatment is completed. However, if azotemia or a progressive decrease of urine output occurs, treatment should be stopped.

Laboratory Test Interactions

Concomitant cephalosporin therapy may spuriously elevate creatinine determinations.

The inactivation between aminoglycosides and beta-lactam antibiotics described in Drug Interactions may continue in specimens of body fluids collected for assay, resulting in inaccurate, false low aminoglycoside readings. Such specimens should be properly handled, i.e., assayed promptly, frozen, or treated with beta-lactamase.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies have not been performed with kanamycin to determine its effect in carcinogenesis, mutagenesis, or impairment of fertility.

Pregnancy Category: D

(See WARNINGS section).

Nursing Mothers

Kanamycin is excreted in minute amounts in human milk. Because of the potential for serious adverse reactions from aminoglycosides in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the drug to the mother.

Pediatric Use

Aminoglycosides should be used with caution in prematures and neonates because of the renal immaturity of these patients and the resulting prolongation of serum half-life of these drugs.

References

Adapted from the FDA Package Insert.