Kanamycin A

484.5

484.50

200-411-7

EQK9Q303C5

DTXSID3023184|DTXSID2041171

C76151

Crystals from ethanol|Crystals from methanol + ethanol

A - Alimentary tract and metabolism|J - Antiinfectives for systemic use|S - Sensory organs

283

-6.3

liquid

1.6±0.1 g/cm3

809.5±65.0 °C at 760 mmHg

443.4±34.3 °C

1.670

9.23e+01 g/L

2-8°C

3.29X10-23 mm Hg at 25 deg C (est)

LD50 i.v. in mice: 583 mg/kg (Wakazawa)

D24 +146° (0.1N H2SO4)

Henry's Law constant = 2.91X10-38 atm-cu m/mol at 25 °C (est)

pKa = 7.2

206.6 Ų [M+H]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]|210.7 Ų [M+Na]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]

White, odorless, crystalline powder. Decompses over a wide range above 250 °C, soluble in water, practically insoluble in methanol and ethanol. /Kanamycin sulfate/|Insoluble in acetone, ethyl acetate, benzene /Kanamycin sulfate/|Irregular prisms, decomposes over a wide range above 250 °C. Freely soluble in water. Practically insoluble in the common alcohols and nonpolar solvents. /Kanamycin A sulfate/

2

Kanamycin sulfate is stable for 24 hours at room temperature in most iv infusion fluids including 0.9% sodium chloride or 5% dextrose injection.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including kanamycin sulfate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Kanamycin sulfate/|The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Kanamycin sulfate is included on this list. /Kanamycin sulfate/|Implantation or injectable dosage form new animal drugs. Kanamycin. ... Indications for use. For the treatment of bacterial infections due to kanamycin sensitive organisms in dogs and cats. ... Limitations. Federal law restricts this drug to use by or on the order of a licensed veterinarian.|Ophthalmic and topical dosage form new animal drugs. Kanamycin ophthalmic ointment. ... Indications for use. For the treatment of various eye infections (conjunctivitis, blepharitis, dacryocystitis, keratitis, and corneal ulcerations) due to bacteria sensitive to kanamycin. For prophylaxis in traumatic conditions, removal of foreign bodies, and intraocular surgery. ... Limitations. Federal law restricts this drug to use by or on the order of a licensed veterinarian.|Ophthalmic and topical dosage form new animal drugs. Kanamycin ophthalmic solution. ... Indications for use. For the treatment of various eye infections (conjunctivitis, blepharitis, dacryocystitis, keratitis, and corneal ulcerations) due to bacteria sensitive to kanamycin. For prophylaxis in traumatic conditions, removal of foreign bodies, and intraocular surgery. ... Limitations. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

|Danger|H360 (100%): May damage fertility or the unborn child [Danger Reproductive toxicity]|P201, P202, P281, P308+P313, P405, and P501|Aggregated GHS information provided by 39 companies from 1 notifications to the ECHA C&L Inventory.

Mild and reversible nephrotoxicity may be observed in 5 - 25% of patients. Amikacin accumulates in proximal renal tubular cells. Tubular cell regeneration occurs despite continued drug exposure. Toxicity usually occurs several days following initiation of therapy. May cause irreversible ototoxicity. Otoxocity appears to be correlated to cumulative lifetime exposure. Drug accumulation in the endolymph and perilymph of the inner ear causes irreversible damage to hair cells of the cochlea or summit of ampullar cristae in the vestibular complex. High frequency hearing is lost first with progression leading to loss of low frequency hearing. Further toxicity may lead to retrograde degeneration of the 8th cranial (vestibulocochlear) nerve. Vestibular toxicity may cause vertigo, nausea, vomiting, dizziness and loss of balance. Oral LD50 is 17500 mg/kg in mice, over 4 g/kg in rats, and over 3 g/kg in rabbits.|IDENTIFICATION AND USE: Kanamycin A is aminoglycoside anti-bacterial agent. Kanamycin injection is indicated in the short-term treatment of serious infections caused by susceptible strains of the designated microorganisms. Kanamycin may be considered as initial therapy in the treatment of infections where one or more of the following are the known or suspected pathogens: E. coli, Proteus species (both indole-positive and indole-negative), Enterobacter aerogenes, Klebsiella pneumoniae, Serratia marcescens, Acinetobacter species. HUMAN EXPOSURE AND TOXICITY: 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. Serious sensitivity reactions, such as anaphylaxis and dermatologic reactions including exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, angioedema, and Stevens-Johnson syndrome, have been reported rarely in patients receiving aminoglycosides; fatalities have occurred rarely. Cross-sensitivity occurs among the aminoglycosides. ANIMAL STUDIES: Intravitreal injection in rabbits and owl monkeys was tolerated at a dose of 0.5 mg, but 1.5 to 6.0 mg produced cataracts in rabbits. Dosages of 200 mg/kg/day in pregnant rats and pregnant guinea pigs led to hearing impairment in the offspring.

Concomitant and/or sequential use of an aminoglycoside and other systemic, oral, or topical drugs that have neurotoxic, ototoxic, or nephrotoxic effects (e.g., other aminoglycosides, acyclovir, amphotericin B, bacitracin, capreomycin, certain cephalosporins, colistin, cisplatin, methoxyflurane, polymyxin B, vancomycin) may result in additive toxicity and should be avoided, if possible. /Aminoglycosides/|Because of the possibility of an increased risk of ototoxicity due to additive effects or altered serum and tissue aminoglycoside concentrations, aminoglycosides should not be given concomitantly with potent diuretics such as ethacrynic acid, furosemide, urea, or mannitol. It has been suggested that concomitant use of certain anti-emetics that suppress nausea and vomiting of vestibular origin and vertigo (e.g., dimenhydrinate, meclizine) may mask symptoms of aminoglycoside-associated vestibular ototoxicity. /Aminoglycosides/|Concurrent use of an aminoglycoside with general anesthetics or neuromuscular blocking agents (e.g., succinylcholine, rocuronium, tubocurarine) may potentiate neuromuscular blockade and cause respiratory paralysis. ... Aminoglycosides should be used with caution in patients receiving anesthetics or neuromuscular blocking agents, and patients should be closely observed for signs of respiratory depression. /Aminoglycosides/|In vitro studies indicate that the antibacterial activity of aminoglycosides and beta-lactam antibiotics may be additive or synergistic against some organisms including Enterobacteriaceae, Pseudomonas aeruginosa, enterococci, and viridans streptococci. The synergistic effect of aminoglycosides and beta-lactams is used to therapeutic advantage, especially in the treatment of infections caused by enterococci or Ps. aeruginosa. Although the exact mechanism of this synergistic effect has not been determined, it appears that by inhibiting bacterial cell-wall synthesis the penicillin allows more effective ingress of the aminoglycoside to the ribosomal binding site. Synergism between aminoglycosides and extended-spectrum penicillins generally is unpredictable and antagonism has been reported rarely in vitro when these penicillins were used in conjunction with amikacin, gentamicin, or tobramycin. Therefore, some clinicians suggest that when concomitant therapy is indicated it may be advisable to use appropriate in vitro studies to demonstrate synergism against the isolated organism. Concomitant administration of an extended-spectrum penicillin and an aminoglycoside has resulted in decreased serum aminoglycoside concentrations and elimination half life, especially in patients with renal impairment. Therefore, serum aminoglycoside concentrations should be monitored in patients receiving concomitant therapy, especially when very high doses of an extended-spectrum penicillin are used or when the patient has impaired renal function. /Aminoglycosides/|For more Interactions (Complete) data for Kanamycin A (10 total), please visit the HSDB record page.

LD50 Rat iv 437 mg/kg|LD50 Rabbit iv 150 mg/kg|LD50 Mouse iv 115 mg/kg|LD50 Mouse sc 1350 mg/kg|For more Non-Human Toxicity Values (Complete) data for Kanamycin A (7 total), please visit the HSDB record page.

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.|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) ... .|The risk of ototoxicity and nephrotoxicity is greatest in patients with past or present histories of renal impairment, dehydration, or previous exposure to ototoxic drugs and in those who receive high dosage or prolonged treatment. In addition, patients with preexisting tinnitus, vertigo, or subclinical high-frequency hearing loss are especially susceptible to ototoxicity and should be carefully observed for signs of eighth cranial nerve damage during aminoglycoside therapy. /Aminoglycosides/|Aminoglycosides should be used with caution in patients with neuromuscular disorder such as myasthenia gravis or parkinsonian syndrome, since the drugs may aggravate muscle weakness as a result of their potential to produce neuromuscular blockade. If signs of respiratory paralysis occur during aminoglycoside therapy, respiration should be assisted and the drug discontinued. /Aminoglycosides/

For treatment of infections where one or more of the following are the known or suspected pathogens: E. coli, Proteus species (both indole-positive and indole-negative), E. aerogenes, K. pneumoniae, S. marcescens, and Acinetobacter species.

Anti-Bacterial Agents; Protein Synthesis Inhibitors|/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Kanamycin A is included in the database.|Kanamycin injection is indicated in the short-term treatment of serious infections caused by susceptible strains of the designated microorganisms: /Escherichia coli, Proteus species (both indole-positive and indole-negative), Enterobacter aerogenes, Klebsiella pneumoniae, Serratia marcescens, Acinetobacter species/. Bacteriological studies to identify the causative organisms and to determine their susceptibility to kanamycin should be performed. Therapy may be instituted prior to obtaining the results of susceptibility testing. /Included in US product label/|Kanamycin may be considered as initial therapy in the treatment of infections where one or more of the following are the known or suspected pathogens: E. coli, Proteus species (both indole-positive and indole-negative), Enterobacter aerogenes, Klebsiella pneumoniae, Serratia marcescens, Acinetobacter species. /Included in US product label/|For more Therapeutic Uses (Complete) data for Kanamycin A (9 total), please visit the HSDB record page.

/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.|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.|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.|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 /kanamycin/ 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.|For more Drug Warnings (Complete) data for Kanamycin A (32 total), please visit the HSDB record page.

Kanamycin is an aminoglycoside antibiotic. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.

Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins. (See all compounds classified as Protein Synthesis Inhibitors.)|Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)

Kanamycin is rapidly absorbed after intramuscular injection and peak serum levels are generally reached within approximately one hour. Poor oral and topical absorption except with severe skin damage.|In one study in premature infants, peak plasma kanamycin concentrations averaging 17.5 ug/mL were attained within 1 hour following IM administration of a single kanamycin dose of 6.3-8.5 mg/kg; plasma concentrations of the drug averaged 5.8 ug/mL at 12 hours. In neonates 1-7 days of age, peak serum concentrations 30 minutes after a 7.5-mg/kg or 10-mg/kg IM dose were 21.8 or 26.8 ug/mL, respectively. When these doses were given by IV infusion over 20 minutes, serum concentrations at 30 minutes were 21.4 or 29.3 ug/mL, respectively.|Kanamycin is poorly absorbed from the GI tract.|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 ug/mL within 15 minutes.|Kanamycin is rapidly absorbed after IM injection. Following IM administration of a single 7.5-mg/kg dose of kanamycin in adults with normal renal function, peak plasma kanamycin concentrations are attained within approximately 1 hour and average 22 ug/mL;1 at 8 hours after the dose, plasma concentrations of the drug average 3.2 ug/mL.1 Similar plasma concentrations of kanamycin are attained when the same dose is administered by IV infusion over 1 hour.|For more Absorption, Distribution and Excretion (Complete) data for Kanamycin A (11 total), please visit the HSDB record page.

Aminoglycosides are not metabolized and are excreted unchanged in the urine primarily by glomerular filtration. /Aminoglycosides/

2.5 hours|The plasma elimination half-life of kanamycin is 2-4 hours in adults with normal renal function, but may be prolonged in geriatric patients. In neonates 1-7 days of age, half-life averaged 4.3-5.1 hours. In premature infants, the elimination half-life of kanamycin reportedly averages 9 hours. In patients with severe burns, plasma half-life and plasma concentrations of the drug may be decreased. Plasma concentrations are higher and the elimination half-life of kanamycin is prolonged in patients with renal impairment. In those with severe renal impairment, the plasma half-life of kanamycin may range from 27-80 hours.

Aminoglycosides like kanamycin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Specifically Kanamycin binds to four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes.|Kanamycin, an aminoglycoside, acts by inhibiting the synthesis of protein in susceptible microorganisms. It is bactericidal in vitro against Gram-negative bacteria and certain Gram-positive bacteria.|Aminoglycosides are usually bactericidal in action. Although the exact mechanism of action has not been fully elucidated, the drugs appear to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits. /Aminoglycosides/|... Aminoglycosides are aminocyclitols that kill bacteria by inhibiting protein synthesis as they bind to the 16S rRNA and by disrupting the integrity of bacterial cell membrane. Aminoglycoside resistance mechanisms include: (a) the deactivation of aminoglycosides by N-acetylation, adenylylation or O-phosphorylation, (b) the reduction of the intracellular concentration of aminoglycosides by changes in outer membrane permeability, decreased inner membrane transport, active efflux, and drug trapping, (c) the alteration of the 30S ribosomal subunit target by mutation, and (d) methylation of the aminoglycoside binding site. ... /Aminoglycosides/

In the event of overdosage or toxic reaction, hemodialysis or peritoneal dialysis will aid in the removal of kanamycin from the blood. In the newborn infant, exchange transfusion may also be considered.|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/SIGNS AND SYMPTOMS/ 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.|/SIGNS AND SYMPTOMS/ Serious sensitivity reactions, such as anaphylaxis and dermatologic reactions including exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, angioedema, and Stevens-Johnson syndrome, have been reported rarely in patients receiving aminoglycosides; fatalities have occurred rarely. Cross-sensitivity occurs among the aminoglycosides. /Aminoglycosides/|/EPIDEMIOLOGY STUDIES/ Amikacin and kanamycin are mainly used for treating multidrug-resistant tuberculosis (MDR-TB), especially in developing countries where the burden of MDR-TB is highest. Their protracted use in MDR-TB treatment is known to cause dose-dependent irreversible hearing loss, requiring hearing aids, cochlear implants or rehabilitation. Therapeutic drug monitoring and regular audiological assessments may help to prevent or detect the onset of hearing loss, but these services are not always available or affordable in many developing countries. We aimed to compare the cumulative incidence of hearing loss among patients treated for MDR-TB with amikacin or kanamycin-based regimens, and to identify the most-at-risk patients, based on the real-life clinical practice experiences in Namibia. We conducted a retrospective cohort study of patients treated with amikacin or kanamycin-based regimens in four public sector MDR-TB treatment sites in Namibia between June 2004 and March 2014. Patients were audiologically assessed as part of clinical care. The study outcome was the occurrence of any hearing loss. Data were manually extracted from patients' treatment records. We compared proportions using the Chi-square test; applied stratified analysis and logistic regression to study the risk of hearing loss and to identify the most-at-risk patients through effect-modification analysis. A P-value<0.05 was statistically significant. All 353 patients had normal baseline hearing, 46% were HIV co-infected. Cumulative incidence of any hearing loss was 58%, which was mostly bilateral (83%), and mild (32%), moderate (23%), moderate-severe (1%), severe (10%), or profound (15%). Patients using amikacin had a greater risk of developing the more severe forms of hearing loss than those using kanamycin (adjusted odds ratio (OR)=4.0, 95 % CI: 1.5-10.8). Patients co-infected with HIV (OR=3.4, 95 % CI: 1.1-10.6), males (OR=4.5, 95 %1.5-13.4) and those with lower baseline body weight (40-59 kg, OR=2.8, 95 % CI: 1.1-6.8), were most-at-risk of developing hearing loss. Amikacin use in the long-term MDR-TB treatment led to a higher risk of occurrence of the more severe forms of hearing loss compared to kanamycin use. Males, patients with low baseline body weight and those co-infected with HIV were most-at-risk. MDR-TB treatment programs should consider replacing amikacin with kanamycin and strengthen the routine renal, serum therapeutic drug levels and audiometric monitoring in the most-at-risk patients treated with aminoglycosides.|/EPIDEMIOLOGY STUDIES/ Quantitative assessments of vestibular hair cells and Scarpa's ganglion cells were performed on 17 temporal bones from 10 individuals who had well-documented clinical evidence of aminoglycoside ototoxicity (streptomycin, kanamycin, and neomycin). Assessment of vestibular hair cells was performed by Nomarski (differential interference contrast) microscopy. Hair cell counts were expressed as densities (number of cells per 0.01 sq mm surface area of the sensory epithelium). The results were compared with age-matched normal data. Streptomycin caused a significant loss of both type I and type II hair cells in all 5 vestibular sense organs. In comparing the ototoxic effect on type I versus type II hair cells, there was greater type I hair cell loss for all 3 cristae, but not for the maculae. The vestibular ototoxic effects of kanamycin appeared to be similar to those of streptomycin, but the small sample size precluded definitive conclusions from being made. Neomycin did not cause loss of vestibular hair cells. Within the limits of this study (maximum postototoxicity survival time of 12 months), there was no significant loss of Scarpa's ganglion cells for any of the 3 drugs. The findings have implications in several clinical areas, including the correlation of vestibular test results to pathological findings, the rehabilitation of patients with vestibular ototoxicity, the use of aminoglycosides to treat Meniere's disease, and the development of a vestibular prosthesis.|/OTHER TOXICITY INFORMATION/ 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. /Aminoglycosides/

Kanamycin

Table: Kanamycin Sulfate Preparations [Table#4442]|Grade: USP. /Kanamycin sulfate/

D-Streptamine, O-3-amino-3-deoxy-.alpha.-D-glucopyranosyl-(1.fwdarw.6)-O-[6-amino-6-deoxy-.alpha.-D-glucopyranosyl-(1.fwdarw.4)]-2-deoxy-: ACTIVE|Kanamycin (8063-07-80) is an antibiotic complex produced by Streptomyces kanamyceticus and consists primarily of kanamycin A and two minor components, one of which is designated kanamycin B.

A method is described for the quantitative determination of kanamycin in blood, urine, cochlear perilymph and kidney. The method is simple, involving only protein precipitation, chromatographic separation and fluorometric determination following reaction with fluorescamine. The method is sensitive, determining as little as 80-100 ng/mL of kanamycin. The method is reliable, recovering better than 90% of the kanamycin added to the fluids and tissues mentioned. It is also less cumbersome and less expensive than other methods currently used.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients|Veterinary Drug -> GROWTH_PROMOTER; -> JECFA Functional Classes

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