アミカシン

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.

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.

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.

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).

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.

No antidote for toxicity is available, only 20% dialyzable; however, this is variable based on hemodialysis filter. Avoid potentially toxic prolonged peak concentrations above 35 mcg/mL.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of December 8, 2016: http://actor.epa.gov/dashboard/]

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).

/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.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

amikacin

DILI Negative

Intravenous

DOI:10.1016/j.drudis.2019.09.022

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).

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).

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.

MEDICATION

MEDICATION(VET)

Anti-Bacterial Agents

Use (kg; approx.) in Germany (2009): >25

Amikacin, the 1-L-(-)-4-amino-2-hydroxybutyryl derivative of kanamycin, is obtained by acylation of the C-1 amino group of the 2-deoxystreptamine moiety of kanamycin with L-(-)-4-amino-2-hydroxybutyric acid.

Preparation: H. Kawaguchi, T. Naito, German patent 2234315; H. Kawaguchi et al., United States of America patent 3781268 (both 1973 to Bristol-Myers).