Amikacin

585.6

585.60

253-538-5

84319SGC3C

DTXSID3022586

C61615

White crystalline powder from methanol-isopropanol

J01GB06|D - Dermatologicals|J - Antiinfectives for systemic use|S - Sensory organs

29419090

332

-7.4

white to off-white

1.6±0.1 g/cm3

203-204 °C

981.8±65.0 °C at 760 mmHg

547.6±34.3 °C

1.664

soluble in water (partly).H2O: 50 mg/mL, clear, colorless

2-8°C

5.79X10-28 mm Hg at 25 deg C (est)

Oral-mouse LD50: >6000 mg/kg; peritoneal-mouse LD50: 750 mg/kg

Flammable; burning produces toxic nitrogen oxide fumes

D23 +99° (c = 1.0 in water)

8.1None

Henry's Law constant = 2.67X10-42 atm-cu m/mol at 25 °C (est)

8.1|pKa1 = 6.7 (primary amine); pKa2 = 8.4 (primary amine); pKa3 = 8.4 (primary amine); pKa4 = 9.7 (primary amine)

235.1 Ų [M+H]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]|233.7 Ų [M+Na]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]

NONH for all modes of transport

2

36/37/38

26-36-24/25

WK1955000

Xi

Warehouse ventilated, low temperature and dry

P201, P202, P260, P261, P264, P270, P271, P272, P280, P281, P302+P352, P304+P312, P304+P340, P305+P351+P338, P308+P313, P310, P312, P314, P321, P333+P313, P363, P405, P501

H317

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 amikacin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.|The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including amikacin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Amikacin 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. Amikacin sulfate is included on this list. /Amikacin sulfate/|Implantation or injectable dosage form new animal drugs. Amikacin. ... Indications for use. For treatment of genitourinary tract infections (cystitis) caused by susceptible strains of Escherichia coli and Proteus spp. and skin and soft tissue infections caused by susceptible strains of Pseudomonas spp. and E. coli. ... Limitations. Do not use in horses intended for human consumption. Federal law restricts this drug to use by or on the order of a licensed veterinarian.|Certain other dosage form new animal drugs. Amikacin. ... Indications for use. For treating genital tract infections (endometritis, metritis, and pyometra) in mares caused by susceptible organisms including Escherichia coli, Pseudomonas spp., and Klebsiella spp. ... Limitations. Do not use in horses intended for human consumption. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

|Danger|H317 (66.67%): May cause an allergic skin reaction [Warning Sensitization, Skin]|P201, P202, P260, P261, P264, P270, P271, P272, P280, P281, P302+P352, P304+P312, P304+P340, P305+P351+P338, P308+P313, P310, P312, P314, P321, P333+P313, P363, P405, and P501|Aggregated GHS information provided by 3 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

moderately toxic

**Oral (LD50):** 6000 mg/kg (Mouse) [MSDS]. No antidote for toxicity is currently available. This drug is only 20% dialyzable; however, this is variable based on the type hemodialysis filter used. **Nephrotoxicity** Mild and reversible nephrotoxicity may be observed in 5 - 25% of patients. Amikacin accumulates in the proximal renal tubular cells. Tubular cell regeneration occurs despite continued drug exposure. Toxicity most commonly occurs several days following initiation of therapy. Amikacin may exacerbate pre-existing renal disease. **Ototoxicity** May cause irreversible ototoxicity. Ototoxicity appears to be correlated to cumulative 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. **Neuromuscular blockade** In addition to the above, amikacin may exacerbate neuromuscular blockade, however, this is less common. **Use in Pregnancy** Category D. Gentamicin and other aminoglycosides are known to cross the placenta. There is evidence of selective uptake of gentamicin by the fetal kidney resulting in damage to immature nephrons. Eighth cranial nerve damage has also been reported after in-utero exposure to some of the aminoglycosides. Because of the chemical similarity, all aminoglycosides should be considered potentially nephrotoxic and ototoxic to the developing fetus. Therapeutic blood amikacin levels in the mother do not equate with safety for the fetus. In reproductive toxicity studies in mice and rats, no effects on fertility or fetal toxicity were observed. **Use in Lactation** It is not known whether amikacin is excreted in breast milk. Since the possible harmful effect on the infant is not known, it is recommended that if nursing mothers must be given amikacin, the infants should not be breastfed during therapy.|IDENTIFICATION AND USE: Amikacin is an aminoglycoside anti-bacterial agent. Amikacin is used for the short-term treatment of serious infections caused by susceptible gram-negative bacteria. HUMAN EXPOSURE AND TOXICITY: Elevation of serum creatinine, albuminuria, presence of red and white cells, casts, azotemia, and oliguria have been reported. Renal function changes are usually reversible when the drug is discontinued. Reports of toxic nephropathy and acute renal failure have been received during postmarketing surveillance. Toxic effects on the eighth cranial nerve can result in hearing loss, loss of balance, or both. Amikacin primarily affects auditory function. Cochlear damage includes high frequency deafness and usually occurs before clinical hearing loss can be detected. Acute muscular paralysis and apnea can occur following treatment with aminoglycoside drugs. Aminoglycosides can cause fetal harm when administered to a pregnant woman. ANIMAL STUDIES: The cochleotoxic effects of aminoglycosides, such as amikacin, are well-established. Reduced cochlear activity compared to the pre-treatment state was described in rabbits treated with i.m. amikacin. Long term studies in animals to evaluate carcinogenic potential have not been performed, and mutagenicity has not been studied. In zebrafish, amikacin induced embryonic toxicity and reduced survival rate. Amikacin administered subcutaneously to rats did not impair male or female fertility.

Intravenous and intramuscular therapy with amikacin has not been linked to serum alkaline phosphatase or aminotransferase elevations, and no convincing cases of symptomatic or icteric hepatotoxicity due to amikacin have been published. Other aminoglycosides have been linked to very rare cases of cholestatic hepatitis, that typically arise within 1 to 3 weeks of starting therapy, often associated with skin rash, fever and sometimes eosinophilia. Recovery typically occurs within 1 to 2 months and chronic injury has not been described. Amikacin as well as other aminoglycosides are not mentioned in large case series of drug induced liver disease and acute liver failure; thus, hepatic injury due to amikacin is very rare if it occurs at all.

A single amikacin dose has potentiated the neuromuscular blocking effects of a single intubating dose of rocuronium.|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/|For more Interactions (Complete) data for Amikacin (12 total), please visit the HSDB record page.

LD50 Mouse oral > 6 g/kg|LD50 Mouse ip 750 mg/kg|LD50 Mouse iv 280 mg/kg|LD50 Mouse subcutaneous 6200 mg/kg

All aminoglycosides have the potential to induce auditory, vestibular, and renal toxicity and neuromuscular blockade. They occur more frequently in patients with present or past history of renal impairment ... . /Aminoglycosides/|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/

The protein binding of amikacin in serum is ≤ 10%.

Amikacin's production and administration as a veterinary and human medication(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that amikacin is expected to have very high mobility in soil(SRC). However, reported pKa values of 6.7, 8.4, 8.4 and 8.9 for the amine moities(3) indicate that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as a cation and cations do not volatilize. Amikacin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.8X10-28 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2017).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that amikacin is not expected to adsorb to suspended solids and sediment(SRC). Reported pKa values of 6.7, 8.4, 8.4 and 8.9(3) indicate amikacin will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 3(SRC), from an estimated log Kow of -8.78(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2017).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), amikacin, which has an estimated vapor pressure of 5.8X10-28 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase. Particulate-phase amikacin may be removed from the air by wet and dry deposition(SRC). Amikacin contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Amikacin is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Amikacin contains chromophores that absorb at wavelengths >290 nm(1) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). Using a municipal wastewater ozonation test, the second order rate constant for the vapor-phase reaction of amikacin with ozone has been estimated as 1.8X10+3 M-1.s-1 at pH 7 at 20 °C(2).

An estimated BCF of 3 was calculated in fish for amikacin(SRC), using an estimated log Kow of -8.78(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of amikacin can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that amikacin is expected to have very high mobility in soil. The pKa values of amikacin are 6.7, 8.4, 8.4 and 8.9(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

The pKa values of 6.7, 8.4, 8.4 and 8.9(1) indicate amikacin will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process. Amikacin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.8X10-28 mm Hg(SRC), determined from a fragment constant method(2).

While data specific to amikacin were not located(SRC, 2017), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are, therefore, discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).

Occupational exposure to amikacin may occur through inhalation and dermal contact with this compound at workplaces where amikacin is produced or used. The general public is not likely to be exposed to amikacin unless by direct medical treatment. (SRC)

The amikacin sulfate injection is indicated in the short-term treatment of serious bacterial infections due to susceptible strains of gram-negative bacteria, including Pseudomonas species, Escherichia coli, species of indole-positive and indole-negative Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, as well as Acinetobacter (Mima-Herellea) species. Clinical studies have shown amikacin sulfate injection to be effective in bacterial septicemia (including neonatal sepsis); in serious infections of the respiratory tract, bones and joints, central nervous system (including meningitis) and skin and soft tissue; intra-abdominal infections (including peritonitis); and in burns and postoperative infections (including post-vascular surgery). Clinical studies have shown amikacin also to be effective in serious, complicated, and recurrent urinary tract infections due to the above organisms. Aminoglycosides, including amikacin, are not indicated in uncomplicated first-time episodes of urinary tract infections unless the causative organisms are not susceptible to antibiotics which are less toxic. In September 2018, a new indication with a new dosage route was approved for this drug. Amikacin liposome inhalation suspension was approved for the treatment of lung disease caused by a group of bacteria, Mycobacterium avium complex (MAC) in a limited population of patients with the disease who do not respond to conventional treatment (refractory disease). This indication is approved under accelerated approval based on achieving sputum culture conversion (defined as 3 consecutive negative monthly sputum cultures) by Month 6 of treatment. Clinical benefit has not yet been established. **Important notes regarding Staphylococcus and Sensitivity testing:** Staphylococcus aureus, including methicillin-resistant strains, is the principal Gram-positive organism sensitive to amikacin. The use of amikacin in the treatment of staphylococcal infections should be restricted only to second-line therapy, and should be limited to only those patients suffering from severe infections caused by susceptible strains of staphylococcus species who have failed to show sensitivity to other available antibiotics. Bacteriologic studies should be performed to identify causative organisms and their susceptibilities to amikacin. Amikacin may be used as initial therapy in suspected gram-negative infections and therapy may be initiated before obtaining the results of susceptibility testing.|FDA Label|Arikayce liposomal is indicated for the treatment of non-tuberculous mycobacterial (NTM) lung infections caused by Mycobacterium avium Complex (MAC) in adults with limited treatment options who do not have cystic fibrosis.

Amikacin is a parenterally administered, broad spectrum aminoglycoside antibiotic typically used for severe gram negative infections. Despite widespread use, amikacin has not been associated with instances of acute liver injury.

Aminoglycosides

Anti-Bacterial Agents|/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. Amikacin is included in the database.|Amikacin is used for the short-term treatment of serious infections caused by susceptible gram-negative bacteria, including Acinetobacter, Escherichia coli, Enterobacter, Klebsiella, Proteus, Providencia, Pseudomonas, or Serratia marcescens. Amikacin may be the preferred aminoglycoside for initial treatment of serious nosocomial gram-negative infections, especially in areas where resistance to gentamicin and tobramycin has been reported. /Included in US product labeling/|Amikacin is used for the treatment of serious intra-abdominal infections (including peritonitis) caused by susceptible gram-negative bacteria, including Acinetobacter, Enterobacter, E. coli, Klebsiella, Proteus, Providencia, Serratia, or Pseudomonas. Amikacin usually is used as an adjunct to other appropriate anti-infectives (e.g., clindamycin, metronidazole, piperacillin and tazobactam, ampicillin and sulbactam). /Included in US product labeling/|For more Therapeutic Uses (Complete) data for Amikacin (15 total), please visit the HSDB record page.

/BOXED WARNING/ WARNINGS: Patients treated with parenteral aminoglycosides should be under close clinical observation because of the potential ototoxicity and nephrotoxicity associated with their use. Safety for treatment periods which are longer than 14 days has not been established. Neurotoxicity, manifested as vestibular and permanent bilateral auditory ototoxicity, can occur in patients with preexisting renal damage and in patients with normal renal function treated at higher doses and/or for periods longer than those recommended. The risk of aminoglycoside-induced ototoxicity is greater in patients with renal damage. High frequency deafness usually occurs first and can be detected only by audiometric testing. 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 due to aminoglycosides increases with the degree of exposure to either high peak or high trough serum concentrations. Patients developing cochlear damage may not have symptoms during therapy to warn them of developing eighth-nerve toxicity, and total or partial irreversible bilateral deafness may occur after the drug has been discontinued. Aminoglycoside-induced ototoxicity is usually irreversible.Aminoglycosides are potentially nephrotoxic. The risk of nephrotoxicity is greater in patients with impaired renal function and in those who receive high doses or prolonged therapy. Neuromuscular blockade and respiratory paralysis have been reported following parenteral injection, topical instillation (as in orthopedic and abdominal irrigation or in local treatment of empyema), and following oral use of aminoglycosides. The possibility of these phenomena 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 reverse these phenomena, but mechanical respiratory assistance may be necessary. Renal and eighth-nerve function should be closely monitored especially in patients with known or suspected renal impairment 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 amikacin should be monitored when feasible to assure adequate levels and to avoid potentially toxic levels and prolonged peak concentrations above 35 micrograms per mL. Urine should be examined for decreased specific gravity, increased excretion of proteins, and the presence of cells or casts. Blood urea nitrogen, serum creatinine, or creatinine clearance should be measured periodically. Serial audiograms should be obtained where 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 discontinuation of the drug or dosage adjustment. Concurrent and/or sequential systemic, oral or topical use of other neurotoxic or nephrotoxic products, particularly bacitracin, cisplatin, amphotericin B, cephaloridine, paromomycin, viomycin, polymyxin B, colistin, vancomycin, or other aminoglycosides should be avoided. Other factors that may increase risk of toxicity are advanced age and dehydration. The concurrent use of amikacin with potent diuretics (ethacrynic acid, or furosemide) should be avoided since diuretics by themselves may cause ototoxicity. In addition, when administered intravenously, diuretics may enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.|Toxic effects on the eighth cranial nerve can result in hearing loss, loss of balance, or both. Amikacin primarily affects auditory function. Cochlear damage includes high frequency deafness and usually occurs before clinical hearing loss can be detected.|A history of hypersensitivity to amikacin is a contraindication for its use. A history of hypersensitivity or serious toxic reactions to aminoglycosides may contraindicate the use of any other aminoglycoside because of the known cross-sensitivities of patients to drugs in this class.|Aminoglycosides should be used with caution in premature and neonatal infants because of the renal immaturity of these patients and the resulting prolongation of serum half-life of these drugs. /Aminoglycosides/|For more Drug Warnings (Complete) data for Amikacin (37 total), please visit the HSDB record page.

Amikacin is an aminoglycoside antibiotic. Aminoglycosides bind to the bacteria, causing misreading of t-RNA, leaving bacteria unable to synthesize proteins vital to their growth. Aminoglycosides are useful mainly in the treatment 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, however, other antibiotics may be more potent and less toxic to humans.

Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)

Rapidly absorbed after intramuscular administration. Rapid absorption occurs from the peritoneum and pleura. Poor oral and topical absorption. Poorly absorbed from bladder irrigations and intrathecal administration. The bioavailability of this drug is expected to vary primarily from individual differences in nebulizer efficiency and airway pathology. Following IM administration of a single dose of amikacin of 7.5 mg/kg in adults with normal renal function, peak plasma amikacin concentrations of 17-25 micrograms/mL are attained within 45 minutes to 2 hours. Following IV infusion of the same dose given over 1 hour peak plasma concentrations of the drug average 38 micrograms/mL immediately following the infusion, 5.5 micrograms/mL at 4 hours, and 1.3 micrograms/mL at 8 hours.|This drug is eliminated by the kidneys. In adults with normal renal function, 94-98% of a single IM or IV dose of amikacin is excreted unchanged by glomerular filtration in the kidney within 24 hours. Amikacin can be completely recovered within approximately 10-20 days in patients with normal, healthy renal function. In patients with impaired renal function, the clearance of amikacin is found to be decreased; the more severe the impairment, the slower the clearance. The interval between doses of amikacin should be adjusted according to the level of renal impairment. Endogenous creatinine clearance rate and serum creatinine which have a high correlation with serum half-life of amikacin, may be used as a guide for dosing.|24 L (28% of body weight healthy adult subjects). Following administration of usual dosages of amikacin, amikacin has been found in bone, heart, gallbladder, and lung tissue. Amikacin is also distributed into bile, sputum, bronchial secretions, and interstitial, pleural, and synovial fluids.|The mean serum clearance rate is about 100 mL/min and the renal clearance rate is 94 mL/min in subjects with normal renal function.|Emergence of a multiply drug resistant Enterobacter cloacae during a seven-week period in 1980 caused amikacin to become the aminoglycoside of choice in the initial management of suspected sepsis in a neonatal intensive care unit. Recommended doses (7.5-10 mg/kg loading; 15 mg/kg in two divided doses IV) were given to 5 infants < or = 1,000 gm and to 13 larger babies. Trough levels 11.5 hours after a dose were 16.6 +/- 11.9 ug/mL in infants < or = 1,000 gm and 6.5 +/- 4.3 ug/mL in the larger infants (P < 0.02). Peak levels one hour postinfusion exceeded 40 ug/mL in 3 of 5 < or = 1,000-gm babies and 4 of 12 > 1,000-gm infants (P = NS). Overall, 7 of 10 peak and/or trough levels in < or = 1,000-gm infants were in the range considered toxic in adults, versus 7 of 24 in larger babies (P = 0.03). These data show that ... excessive blood levels of amikacin are likely in infants < or = 1,000 gm and may also occur in larger infants using currently recommended dosage schedules. These ... findings emphasize the need to monitor drug levels and individualize therapy in very low birthweight infants.|Amikacin is poorly absorbed from the GI tract. Amikacin is rapidly absorbed following IM administration. Following IM administration of a single 7.5-mg/kg dose of amikacin in adults with normal renal function, peak plasma amikacin concentrations are attained within about 0.5-2 hours and average 17-25 ug/mL; plasma concentrations 10 hours after the dose average 2.1 ug/mL.|When a 7.5-mg/kg dose of amikacin is administered by IV infusion over 30 minutes, peak plasma concentrations of the drug average 38 ug/mL immediately following the infusion, 18 ug/mL at 1 hour, and 0.75 ug/mL at 10 hours. In adults receiving 15 mg/kg once daily by IV infusion over 30 minutes, peak serum concentrations (measured 30 minutes after completion of an infusion) were 40.9 ug/mL and trough concentrations (measured immediately before start of an infusion) were 1.8 ug/mL.|Accumulation of amikacin does not appear to occur in adult or pediatric patients with normal renal function receiving usual dosages of the drug twice daily for 4-10 days.|For more Absorption, Distribution and Excretion (Complete) data for Amikacin (15 total), please visit the HSDB record page.

Amikacin's structure has been altered to reduce the possible route of enzymatic deactivation, thus reducing bacterial resistance. Many strains of Gram-negative organisms resistant to gentamicin and tobramycin have shown to be sensitive to amikacin in vitro.|Aminoglycosides are not metabolized and are excreted unchanged in the urine primarily by glomerular filtration. /Aminoglycosides/

The plasma elimination half-life of amikacin is usually 2-3 hours in adults with normal renal function and is reported to range from 30-86 hours in adults with severe renal impairment.|The plasma elimination half-life of amikacin usually is 2-3 hours in adults with normal renal function and is reported to range from 28-86 hours in adults with severe renal impairment. The plasma elimination half-life of amikacin is reported to be 4-5 hours in full-term infants 7 days of age or older and 7-8 hours in low birth-weight infants 1-3 days of age. In preterm neonates, half-life is inversely related to postconceptional age and has ranged from 4.5-15.6 hours. In one study in infants and children 20 days to 6 years of age, mean plasma half-life after a single 7.5-mg/kg IM dose was about 2 hours.

The primary mechanism of action of amikacin is the same as that for all aminoglycosides. It binds to bacterial 30S ribosomal subunits and interferes with mRNA binding and tRNA acceptor sites, interfering with bacterial growth. This leads to disruption of normal protein synthesis and production of non-functional or toxic peptides. Other actions have been postulated for drugs of this class. Amikacin, as well as the rest of the aminoglycosides, are generally bacteriocidal against gram-positive and gram-negative 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/

/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/|In the event of overdosage or toxic reaction, peritoneal dialysis or hemodialysis will aid in the removal of amikacin from the blood. In the newborn infant, exchange transfusion may also be considered.

/SIGNS AND SYMPTOMS/ Elevation of serum creatinine, albuminuria, presence of red and white cells, casts, azotemia, and oliguria have been reported. Renal function changes are usually reversible when the drug is discontinued. As would be expected with any aminoglycoside, reports of toxic nephropathy and acute renal failure have been received during postmarketing surveillance.|/SIGNS AND SYMPTOMS/ Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Amikacin Sulfate Injection USP, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.|/SIGNS AND SYMPTOMS/ Toxic effects on the eighth cranial nerve can result in hearing loss, loss of balance, or both. Amikacin primarily affects auditory function. Cochlear damage includes high frequency deafness and usually occurs before clinical hearing loss can be detected.|/SIGNS AND SYMPTOMS/ Acute muscular paralysis and apnea can occur following treatment with aminoglycoside drugs. /Aminoglycoside/|For more Human Toxicity Excerpts (Complete) data for Amikacin (10 total), please visit the HSDB record page.

A.M.K

Table: Amikacin Sulfate Preparations [Table#4648]

In this paper, a simple, rapid and sensitive method based on liquid chromatography with fluorimetric detection (HPLC-FLD) for the determination of amikacin (AMK) in human plasma is developed. Determination is performed by pre-column derivatization of AMK with ortho-phtalaldehyde (OPA) in presence of N-acetyl-L-cysteine (NAC) at pH 9.5 for 5 min at 80 °C. In our knowledge, this is the first time that NAC has been used in AMK derivatization. Derivatization conditions (pH, AMK/OPA/NAC molar ratios, temperature and reaction time) are optimized to obtain a single and stable, at room temperature, derivative. Separation of the derivative is achieved on a reversed phase LC column (Kromasil C18, 5 um, 150 x 4.6 i.d. mm) with a mobile phase of 0.05 M phosphate buffer:acetonitrile (80:20, v/v) pumped at flow rate of 1.0 mL/min. Detection is performed using 337 and 439 nm for excitation and emission wavelengths, respectively. The method is fitted for the purpose of being a competitive alternative to the currently used method in many hospitals for AMK dosage control: fluorescence polarization immunoassay (FPIA). The method exhibits linearity in the 0.17-10 ug/mL concentration range with a squared correlation coefficient higher than 0.995. Trueness and intermediate precision are estimated using spiked drug free plasma samples, which fulfill current UNE-EN ISO15189:2007 accreditation schemes. Finally, for the first time, statistical comparison against the FPIA method is demonstrated using plasma samples from 31 patients under treatment with AMK.

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