Gentamicin

1390.71

477.316254

215-765-8

DTXSID5034642

White amorphous powder

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

3004909090

627.17000

-1.89

Solid

1.3±0.1 g/cm3

102-108 °C

669.4±55.0 °C at 760 mmHg

358.6±31.5 °C

1.583

100 mg/mL

Protect from light and store away from heat. Store at controlled room temperature 15 deg - 30 °C (59 deg - 86 °F). /Gentamicin, ophthalmic preparations/|Store at 20 deg to 25 °C (68 deg to 77 °F) /Gentamicin, injectable preparations; Gentamicin, topical preparations/

1.75X10-13 mm Hg at 25 °C (est)

Specific optical rotation: +146 deg at 25 °C/D

Henry's Law constant = 9.78X10-31 atm-cu m/mol at 25 °C (est)

pKb = 9.0 (amine moieties) (est)

MP: 94-100 °C; Specific optical rotation: +158 deg at 25 °C/D /Gentamicin C1/|MP: 107-124 °C; Specific optical rotation: +160 deg at 25 °C/D /Gentamicin C2/|White, hygroscopic powder. MP: 218-237 °C; Specific optical rotation: +102 deg at 25 °C/D. Soluble in ethylene glycol, formamide /Gentamicin C complex sulfate/|Odorless; melts with decomposition between 200 °C and 250 °C /Gentamicin sulfate/|White to buff powder; soluble in water; insoluble in alcohol, acetone, benzene /Gentamicin C complex sulfate/|MP: 194-209 °C; Specific optical rotation: +113 deg at 25 °C?D; freely soluble in water, methanol; slightly soluble in ether; practically insoluble in other organic solvents /Gentamicin hydrochloride/

Stable in light, air, and heat /Gentamycin sulfate/

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 gentamicin sulfate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Gentamicin 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. Gentamicin sulfate is included on this list. /Gentamicin sulfate/|Oral dosage form new animal drugs. Gentamicin sulfate oral solution. ... Indications for use. In weanling swine for control and treatment of colibacillosis caused by strains of Escherichia coli sensitive to gentamicin, and in swine for control and treatment of swine dysentery associated with Treponema hyodysenteriae. ... Limitations. Do not slaughter treated swine for food for at least 3 days following treatment. Federal law restricts this drug to use by or on the order of a licensed veterinarian. /Gentamicin sulfate/|Oral dosage form new animal drugs. Gentamicin sulfate pig pump oral solution. ... Indications for use. In neonatal swine 1 to 3 days of age for control and treatment of colibacillosis caused by strains of Escherichia coli sensitive to gentamicin. ... Limitations. For use in neonatal swine only. Do not slaughter treated swine for food for at least 14 days following treatment. /Gentamicin sulfate/|For more FDA Requirements (Complete) data for Gentamicin (11 total), please visit the HSDB record page.

WHO; Environmental Health Criteria 119: Principles and Methods for the Assessment of Nephrotoxicity Associated with Exposure to Chemicals (1991)

|Danger|H317 (56.47%): May cause an allergic skin reaction [Warning Sensitization, Skin]|P201, P202, P260, P261, P264, P270, P272, P273, P280, P281, P285, P302+P352, P304+P341, P308+P313, P314, P321, P333+P313, P342+P311, P363, P391, P405, and P501|Aggregated GHS information provided by 85 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Mild and reversible nephrotoxicity may be observed in 5 - 25% of patients. Gentamicin accumulates in proximal renal tubular cells and causes cell damage. 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. Mouse, intravenous LD50: 52 mg/kg; rat, intravenous LD50: 96 mg/kg.|IDENTIFICATION AND USE: Gentamicin sulfate is an aminoglycoside antibiotic. Gentamicin is widely used in the treatment of severe infections. It is active against many strains of Gram-negative bacteria and Streptococus aureus. It is inactive against anaerobes and poorly active against Streptococus hemolyticus and Pneumococcus. HUMAN EXPOSURE AND TOXICITY: Main risks and target organs: The main toxic effects are vestibular damage, deafness and renal dysfunction. The damage on the vestibular portion of the eighth cranial nerve appears to be greater than that on the cochlear portion. The main target organs are the eighth cranial nerves and the kidneys. Damage to eighth cranial nerve (both divisions) resulting in tinnitus, deafness, nausea, vomiting, vertigo, dizziness and nystagmus, and nephrotoxicity causing acute tubular necrosis resulting in renal failure. Loss of hearing, dizziness, vertigo, ataxia, nausea, vomiting and renal impairment developing in a patient on gentamicin therapy suggests a diagnosis of gentamicin toxicity. Other toxic features are muscular paralysis and respiratory depression. As gentamicin accumulates in the renal cortex, a critical concentration is reached when the concentrating ability of the kidney becomes impaired. Nephrotoxicity appears to be related to the duration for which the trough serum concentration exceeds 2 ug/ml. The exact mechanism of toxicity is unknown. Ototoxicity and vestibular toxicity seem most highly correlated with elevated peak concentrations (greater than 10 ug/mL) of gentamicin. Gentamicin accumulates in endolymph and perilymph and progressive destruction of ventricular and cochlear cells occurs. Repeated courses of gentamicin may produce progressive destruction of cells leading to deafness. Gentamicin appears to damage the vestibular portion more than the cochlear portion. Neuromuscular blockade with acute muscular paralysis and apnea may occur rarely. Most episodes have occurred in association with anesthesia or administration of other neuromuscular blockers but may also occur after intrapleural or intraperitoneal instillation of large doses of gentamicin or other aminoglycosides. This phenomenon may occur after intravenous or intramuscular administration. ANIMAL STUDIES: Clinical signs of intoxication in rodents included convulsions, prostration, hypoactivity, polydipsia, dyspnoea and ataxia. Dogs exhibited muscle tremors, salivation, and anorexia. Histopathological examination of kidneys from dogs that died up to 13 days after dosing revealed necrosis of the proximal convoluted tubule. Groups of 3 female Rhesus monkeys were injected i.m. with doses of 0, 6 or 30 mg/kg bw/day gentamicin in an aqueous vehicle for 3 weeks. Adverse clinical signs were limited to the 30 mg/kg bw/day group, which included pronounced facial paling and ptosis, markedly disturbed equilibrium from day 20, and depressed food intake and body- weight gain from week 2 onwards. Electron microscopy of renal tubules from the 30 mg/kg bw/day monkeys revealed myeloid bodies present in both tubular cells and lumen, increased phagosomes, disappearance of brush borders and sloughing of epithelial cells from the basement membrane. Groups of beagle dogs (4/sex/group) were administered oral doses of 0, 2, 10, or 60 mg/kg bw/day gentamicin in capsules for 14 weeks. Emesis and diarrhoea were observed occasionally in treated dogs. The only postmortem change was interstitial nephritis observed in 2 animals in the high-dose group. Gentamicin had negative effects on sperm parameters and testis apoptosis in rats. No treatment-related changes in pregnancy rate, litter size and weight, prenatal mortality or fetal abnormalities were reported in 2 generation study in rats. Gentamicin was tested in vitro for its ability to induce forward gene mutation in Chinese hamster ovary cells at concentrations of 128-5000 ug/mL and chromosomal aberrations in these cells at concentrations of 800-5000 ug/mL, both with and without metabolic activation. It was also tested in vivo for its ability to induce nuclear anomalies in mouse bone-marrow cells at intravenous doses of 20-80 mg/kg bw, the highest dose being the maximum tolerated dose. There was no indication of mutagenic activity.

Intravenous and intramuscular therapy with gentamicin has been linked to mild and asymptomatic elevations in serum alkaline phosphatase levels, but rarely affects aminotransferase levels or bilirubin, and changes resolve rapidly once gentamicin is stopped. Only isolated case reports of acute liver injury with jaundice have been associated with aminoglycoside therapy including gentamicin, most of which are not very convincing. The hepatic injury described in these reports is typically mixed but can evolve into a cholestatic hepatitis. The latency to onset is rapid, occurring within 1 to 3 weeks and is typically associated with skin rash, fever and sometimes eosinophilia. Recovery typically occurs within 1 to 2 months and chronic injury has not been described. Aminoglycosides are not listed or mentioned in large case series of drug induced liver disease and acute liver failure; thus, hepatic injury due to gentamicin is rare if it occurs at all.

One in vitro study indicates that cytarabine may antagonize the activity of gentamicin against Klebsiella pneumoniae.|Gentamicin appears to be more readily inactivated by antipseudomonal penicillins (eg, ticarcillin) than amikacin both in vitro and in vivo in patients with renal failure.|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/|For more Interactions (Complete) data for Gentamicin (12 total), please visit the HSDB record page.

LD50 Mouse im 167 mg/kg|LD50 Mouse iv 51 mg/kg|LD50 Mouse sc 274 mg/kg|LD50 Mouse ip 235 mg/kg|For more Non-Human Toxicity Values (Complete) data for Gentamicin (8 total), please visit the HSDB record page.

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/

Low (between 0 and 30%)

Gentamicin is a fermentation product of Micromonospora purpurea or M. echinospora and other variants(1).

Gentamicin's production and administration as a 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 gentamicin is expected to have very high mobility in soil(SRC). The estimated pKb of gentamicin is 9.0(3), indicating that this compound will exist partially 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 of gentamicin from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 9.8X10-31 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Gentamicin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.8X10-13 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 gentamicin is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 9.8X10-31 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from an estimated log Kow of -1.88(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), gentamicin, which has an estimated vapor pressure of 1,8X10-13 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase gentamicin may be removed from the air by wet and dry deposition(SRC). Gentamicin does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

Gentamicin is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Gentamicin does not contain chromophores that absorb at wavelengths >290 nm(1) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for gentamicin(SRC), using an estimated log Kow of -1.88(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 gentamicin can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that gentamicin is expected to have very high mobility in soil. The estimated pKb of gentamicin is 9.0(3), indicating that this compound will exist partially 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). Aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(5,6), suggesting that mobility may be much lower in some soils(SRC).

The Henry's Law constant for gentamicin is estimated as 9.8X10-31 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that gentamicin is expected to be essentially nonvolatile from water and moist soil surfaces(2). Gentamicin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.8X10-13 mm Hg(SRC), determined from a fragment constant method(3).

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

For treatment of serious infections caused by susceptible strains of the following microorganisms: P. aeruginosa, Proteus species (indole-positive and indole-negative), E. coli, Klebsiella-Enterobactor-Serratia species, Citrobacter species and Staphylococcus species (coagulase-positive and coagulase-negative).

Gentamicin is a parenterally administered, broad spectrum aminoglycoside antibiotic typically used for moderate to severe gram negative infections. Despite its wide use, gentamicin has not been definitively linked to instances of clinically apparent liver injury.

Aminoglycosides

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. Gentamycin is included in the database.|Gentamicin Injection is indicated in the treatment of serious infections caused by susceptible strains of the following microorganisms: Pseudomonas aeruginosa, Proteus species (indole-positive and indole-negative), Escherichia coli, Klebsiella-Enterobacter-Serratia species, Citrobacter species, and Staphylococcus species (coagulase-positive and coagulase-negative). /Included in US product label/|Gentamicin has been used effectively in combination with carbenicillin for the treatment of life-threatening infections caused by Pseudomonas aeruginosa. It has also been found effective when used in conjunction with a penicillin-type drug for the treatment of endocarditis caused by group D streptococci. /Included in US product label/|For more Therapeutic Uses (Complete) data for Gentamicin (26 total), please visit the HSDB record page.

/BOXED WARNINGS/ Patients treated with aminoglycosides should be under close clinical observation because of the potential toxicity associated with their use. As with other aminoglycosides, Gentamicin Injection is potentially nephrotoxic. The risk of nephrotoxicity is greater in patients with impaired renal function and in those who receive high dosage or prolonged therapy. Neurotoxicity manifested by ototoxicity, both vestibular and auditory, can occur in patients treated with gentamicin, primarily in those with pre-existing renal damage and in patients with normal renal function treated with higher doses and/or for longer periods than recommended. Aminoglycoside-induced ototoxicity is usually irreversible. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching and convulsions. Renal and eighth cranial nerve function should be closely monitored, especially in patients with known or suspected reduced renal function at onset of therapy, and also in those whose renal function is initially normal but who develop signs of renal dysfunction during therapy. Urine should be examined for decreased specific gravity, increased excretion of protein, and the presence of cells or casts. Blood urea nitrogen (BUN), serum creatinine, or creatinine clearance should be determined periodically. When feasible, it is recommended that serial audiograms be obtained in patients old enough to be tested, particularly high-risk patients. Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears or hearing loss) or nephrotoxicity requires dosage adjustment or discontinuance of the drug. As with the other aminoglycosides, on rare occasions changes in renal and eighth cranial nerve function may not become manifest until soon after completion of therapy. Serum concentrations of aminoglycosides should be monitored when feasible to assure adequate levels and to avoid potentially toxic levels. When monitoring gentamicin peak concentrations, dosage should be adjusted so that prolonged levels above 12 ug/mL are avoided. When monitoring gentamicin trough concentrations, dosage should be adjusted so that levels above 2 ug/mL are avoided. Excessive peak and/or trough serum concentrations of aminoglycosides may increase the risk of renal and eighth cranial nerve toxicity. In the event of overdose or toxic reactions, hemodialysis may aid in the removal of gentamicin from the blood, especially if renal function is, or becomes, compromised. The rate of removal of gentamicin is considerably less by peritoneal dialysis than by hemodialysis. In the newborn infant, exchange transfusions may also be considered. Concurrent and/or sequential systemic or topical use of other potentially neurotoxic and/or nephrotoxic drugs, such as cisplatin, cephaloridine, kanamycin, amikacin, neomycin, polymyxin B, colistin, paromomycin, streptomycin, tobramycin, vancomycin, and viomycin, should be avoided. Other factors which may increase patient risk of toxicity are advanced age and dehydration. The concurrent use of gentamicin with potent diuretics, such as ethacrynic acid or furosemide, should be avoided, since certain diuretics by themselves may cause ototoxicity. In addition, when administered intravenously, diuretics may enhance aminoglycoside toxicity by altering the antibiotic concentration in serum and tissue. Aminoglycosides can cause fetal harm when administered to a pregnant woman.|Hypersensitivity to gentamicin is a contraindication to its use. A history of hypersensitivity or serious toxic reactions to other aminoglycosides may contraindicate use of gentamicin because of the known cross-sensitivity of patients to drugs in this class.|Aminoglycosides can cause fetal harm when administered to a pregnant woman. 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. Serious side effects to mother, fetus, or newborn have not been reported in the treatment of pregnant women with other aminoglycosides. It is not known whether gentamicin sulfate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. If gentamicin is used during pregnancy or if the patient becomes pregnant while taking gentamicin, she should be apprised of the potential hazard to the fetus.|Other reported adverse reactions possibly related to gentamicin include: respiratory depression, lethargy, confusion, depression, visual disturbances, decreased appetite, weight loss, hypotension and hypertension; rash, itching, urticaria, generalized burning, laryngeal edema, anaphylactoid reactions, fever and headache; nausea, vomiting, increased salivation and stomatitis; purpura, pseudotumor cerebri, acute organic brain syndrome, pulmonary fibrosis, alopecia, joint pain, transient hepatomegaly and splenomegaly.|For more Drug Warnings (Complete) data for Gentamicin (38 total), please visit the HSDB record page.

Gentamicin is a broad spectrum 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.

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

Injections lead to peak serum concentrations in 30-60 minutes. Topical gentamicin is readily absorbed from large burned, denuded, or granulating areas but not through intact skin. Absorption of gentamicin is faster and greater with the cream compared to the ointment. Gentamicin is absorbed in small quantities following topical application to the eye. Gentamicin is also absorbed in small amounts following topical application to the ear (especially if the eardrum is perforated or if tissue damage is present). Gentamicin is very poorly absorbed orally.|/MILK/ Gentamicin is distributed into milk following IM administration.|Gentamicin is distributed into cerebrospinal fluid (CSF) in low concentrations following IM or IV administration. CSF concentrations of gentamicin following intrathecal administration depend on the dose administered, the site of injection, the volume in which the dose is diluted, and the presence or absence of obstruction to CSF flow. There may be considerable interpatient variation in concentrations achieved. In one study, intrathecal administration of 4 mg of gentamicin resulted in CSF concentrations of the drug of 19-46 ug/mL for 8 hours and less than 3 ug/mL at 20 hours. Gentamicin crosses the placenta.|Following parenteral administration of usual dosages of gentamicin, the drug can be detected in lymph, subcutaneous tissue, lung, sputum, and bronchial, pleural, pericardial, synovial, ascitic, and peritoneal fluids. Concentrations in bile may be low, suggesting minimal biliary excretion. In patients with ventilator-associated pneumonia receiving IV gentamicin (240 mg once daily), drug concentrations in alveolar lining fluid were 32% of serum concentrations and averaged 4.24 ug/mL 2 hours after a dose. Only minimal concentrations of gentamicin are attained in ocular tissue following IM or IV administration.|Accumulation of gentamicin does not appear to occur in patients with normal renal function receiving 1-mg/kg doses every 8 hours for 7-10 days. However, accumulation may occur with higher doses and/or when the drug is given for prolonged periods, especially in patients with renal impairment.|For more Absorption, Distribution and Excretion (Complete) data for Gentamicin (18 total), please visit the HSDB record page.

Gentamicin is not metabolized. It is excreted by glomerular filtration in an active, unchanged form.

3-3½ hours in infants one week to six months of age; this increases to 5½ hours in full-term and large premature infants less than one week old.|The plasma elimination half-life of gentamicin is usually 2-4 hours in adults with normal renal function and is reported to range from 24-60 hours in adults with severe renal impairment. The serum half-life of gentamicin averages 3-3.5 hours in infants 1 week to 6 months of age and 5.5 hours in full-term infants and large premature infants less than 1 week of age. In small premature infants, the plasma half-life is approximately 5 hours in those weighing over 2 kg, 8 hours in those weighing 1.5-2 kg, and 11.5 hours in those weighing less than 1.5 kg.|... terminal elimination half-lives of greater than 100 hours have been reported in adults with normal renal function following repeated IM or IV administration of the drug.

Aminoglycosides like gentamicin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Specifically gentamicin 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.|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 overdose or toxic reactions, hemodialysis may aid in the removal of gentamicin from the blood, and is especially important if renal function is, or becomes, compromised. The rate of removal of gentamicin is considerably less by peritoneal dialysis than it is by hemodialysis. In the newborn infant, exchange transfusions may also be considered.

/SIGNS AND SYMPTOMS/ Serious adverse effects on both vestibular and auditory branches of the eighth nerve have been reported, primarily in patients with renal impairment (especially if dialysis is required), and in patients on high doses and/or prolonged therapy. Symptoms include dizziness, vertigo, tinnitus, roaring in the ears and hearing loss, which, as with other aminoglycosides, may be irreversible. Hearing loss is usually manifested initially by diminution of high-tone acuity. Other factors which may increase the risk of toxicity include excessive dosage, dehydration and previous exposure to other ototoxic drugs. Peripheral neuropathy or encephalopathy, including numbness, skin tingling, muscle twitching, convulsions and a myasthenia gravis-like syndrome, have been reported.|/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/|/CASE REPORTS/ A 65-year-old man with end-stage renal disease on continuous ambulatory peritoneal dialysis accidentally received an acute massive overdose of gentamicin as a treatment of peritonitis. The patient developed acute vestibular dysfunction and hearing loss following the overdose. His serum gentamicin had reached the extremely toxic level of 220 ug/mL. To remove the gentamicin, the patient received hemodialysis and hemoperfusion immediately. This was followed by two more courses of hemodialysis during the following 2 days. The gentamicin level was brought down to 10 ug/mL after the third hemodialysis. Moderate and persistent high-frequency hearing loss was documented with serial audiograms. The patient made a gradual but incomplete recovery from the vestibular dysfunction. ....|/CASE REPORTS/ A healthy 14-month-old girl received gentamicin 500 mg (56 mg/kg) intravenously as empiric therapy given fever. The overdosage was quickly recognized and the child transferred to a pediatric referral center. Two hours after administration, serum creatinine was 0.3 mg/dL, though serum gentamicin level was 89 mg/L. Hemodialysis was initiated approximately 4 hr after gentamicin was given and stopped 4 hr later, with a serum gentamicin level of 3.4 mg/L. Gentamicin level 4 hr after completion of hemodialysis was 2.3 mg/L. Three months later, the child's serum creatinine was 0.3 mg/dL, urinalysis showed no blood or protein, and audiometry showed normal hearing bilaterally at all frequencies. This child demonstrated the highest gentamicin level recorded in a patient with normal renal function. Her case demonstrates that prompt hemodialysis in this circumstance rapidly clears gentamicin without rebound. If left untreated, long-term adverse sequellae for hearing or renal function were possible; hemodialysis may have altered these outcomes.|For more Human Toxicity Excerpts (Complete) data for Gentamicin (17 total), please visit the HSDB record page.

G Myticin

Table: Gentamicin Sulfate Preparations [Table#4416]|Table: Gentamicin Sulfate in Sodium Chloride Preparations [Table#4417]

Gentamicin or gentamicin sulfate, is a mixture of gentamicin C1 (25876-10-2), gentamicin C2 (25876-11-3), and gentamicin C1a (26098-04-4) isolated from Micromonospora purpurea and related species. Note that compounds obtained from Micromonospora species are given names ending in -micin; those isolated from Streptomyces end in -mycin.|Consists of 3 closely related components, gentamicins C1, C2, C1a, and also gentamicin a which differs from other members of complex but is similar to kanamycin C.

Fluorescence immunoassay and radioassay methods for determining gentamycin in body fluids.|Determination in serum by immunoassay.

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

Veterinary Drug -> ANTIMICROBIAL_AGENT;