Chemicals / Complex Chemical Agents/ Chemical:

Gentamicin (with special reference to Hedgehogs, Elephants, Lagomorphs, Ferrets and Great Apes)

INFORMATION AVAILABLE

GENERAL CHEMICAL INFORMATION THERAPEUTIC INFORMATION [DOSE, FREQUENCY & ROUTE]

NUTRITIONAL INFORMATION

TOXICITY INFORMATION ENVIRONMENTAL INFORMATION
Information in this page has been entered to support the current volumes of Wildpro and further information will be added as new volumes are completed. This page is not intended to substitute for the manufacturer's data sheet and the information is not yet complete for all species, or for all contra-indications etc.

CAUTION: Before any pharmaceutical product is used, the manufacturer's data sheet, containing information on uses, dosage and administration, contra-indications, warnings etc., should always be consulted. It is important to remember that licensing of pharmaceutical products for use in a particular species/condition, as well as mandatory meat and milk withdrawal times for food-producing animals, varies between countries and changes with time. Withdrawal times also may vary between different pharmaceutical formulations and depending on route of administration. In the EU, the prescription cascade must be followed (see LCofC1.2H and W564.Apr05.w1); note that specific restrictions apply for food-producing animals. In the USA, FARAD may be consulted regarding residues and meat and milk withdrawal times.

General Chemical Information

Summary 
Aminoglycoside antibiotic. (B263)

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Names and Formulae
Type Aminoglycoside antibiotic obtained from cultures of Micromonaspora purpurea. Commercially available gentamicin is a mixture of gentamicin sulphate C1, C2 and C3; the three compounds have similar antimicrobial activities to one another. (B263)
Alternative Names Gentamycin. (W324)
Chemical Formula C21H43N5O7. (W324)
Chemical Structure --
Molecular Weight 477.6. (W324)
Related Chemicals --

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Physical Properties / Chemistry
Appearance
  • White to buff powder. (B263)

Melting point --
Boiling point --
Density --
Water solubility
Other solubility
  • Insoluble in alcohol. (B263)
Acid/Base
  • pH 3.0-5.5 (commercially available injections). (B263)

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Pharmacology & General Information
Pharmacology
  • Aminoglycoside antibiotics bind irreversibly to the 50S ribosomal subunit and thus inhibit protein synthesis. (B263)
  • Bactericidal. (B263)
Storage / Stability
  • Gentamicin sulphate for injection: store at room temperature (15-30C), avoiding both freezing and temperatures above 40C. (B263)
  • Gentamicin sulphate oral solution: store at room temperature (15-30C), avoiding both freezing and temperatures above 40C. (B263)
  • Gentamicin sulphate soluble powder: store at 2-30C. (B263)
  • May be destroyed by storage (even for a short time while medicated drinking water is offered to patients) in rusty containers. (B263)
Legal Category (In UK) --

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References

Associated Techniques

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ORGANISATIONS

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ELECTRONIC LIBRARY
(Further Reading)
Click image for full contents list of ELECTRONIC LIBRARY

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Authors Debra Bourne (V.w5); Gracia Vila-Garcia (V.w67)
Referees Suzanne I. Boardman (V.w6); Becki Lawson (V.w26); Susan Mikota (V.w72)

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Therapeutic Information

Uses/Indications
Activity
  • Active against many aerobic Gram-negative organisms. (B263)
Appropriate Use
  • Used most commonly against serious Gram-negative bacterial infections. (B263)
Limitations
  • Due to inherent toxicity, systemic use of aminoglycoside antibiotics is limited to situations in which the organisms causing infection are known not to be susceptible to other, less toxic, antibiotics, or when the clinical situation is such that immediate treatment of a presumed Gram-negative infection is required in advance of culture and sensitivity results. (B263)
  • Many strains of Klebsiella, Escherichia coli, Pseudomonas aeruginosa are resistant to gentamicin. (B263)
Notes --

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Pharmacokinetics and Drug Interactions
Absorption /Bioavailability
  • Minimal absorption following oral administration if the gut is intact. (B263)
  • Minimal absorption following intrauterine administration. (B263)
  • Appreciable absorption may occur from the gut in individuals with haemorrhagic enteritis or necrotic enteritis. (B263)
  • Absorbed following topical irrigation of surgical sites (not including skin, urinary bladder). (B263)
  • Intramuscular injection gives more than 90% bioavailability with peak levels at 30-60 minutes after injection (dogs and cats)
  • Subcutaneous injection gives more than 90% bioavailability with peak levels slightly later than following intramuscular injection and with greater variability. (B263)
Distribution
  • Aminoglycosides are distributed mainly in the extracellular fluid. (B263)
  • Therapeutic levels are reached in bone, heart, gall bladder and lung (following parenteral administration). (B263)
  • Present in ascitic fluid, pleural, pericardial and peritoneal fluids, synovial fluid and abscesses. (B263)
  • High levels in sputum, bronchial secretions, bile. (B263)
  • CSF levels unpredictable: 0 to 50% of serum levels. (B263)
  • Accumulate in the inner ear and in the kidneys. (B263)
  • Cross the placenta: fetal concentrations 15 to50% of maternal serum concentrations. (B263)

Volume of distribution:

  • Adult cats and dogs: 0.15-0.3 L/kg. (B263)
  • Horses: 0.26-0.58 L/kg. (B263)
  • May be higher volume of distribution in neonates and juveniles due to higher extracellular fluid fractions. (B263)
Plasma Protein binding / Storage
  • Plasma protein binding minimal (less than 20%). (B263)
Elimination Route
  • Elimination of aminoglycosides is mainly by glomerular filtration. (B263)
    • Excretion of aminoglycosides is greatly reduced if renal function is impaired. (B135.45.w45)
  • Minimal metabolic breakdown of aminoglycosides by the host. (B135.45.w45)
Elimination half-life / Clearance Rate Elimination half-life: 
  • Horses: 1.82-3.25 hours. (B263)
  • Calves: 2.2-2.7 hours. (B263)
  • Sheep: 2.4 hours. (B263)
  • Cows: 1.8 hours. (B263)
  • Pigs: 1.9 hours. (B263)
  • Dogs and cats: 0.5-1.5 hours. (B263)
  • Rabbits: 1 hour. (B263)
  • Human: half-life of aminoglycosides in serum 2-3 hours. (B135.45.w45)
  • May be significantly prolonged in individuals with decreased renal function. (B263)
Drug Interactions
  • Use with caution in conjunction with other drugs which may be nephrotoxic, ototoxic or neurotoxic, including amphotericin B, other aminoglycosides, acyclovir, bacitracin, cisplatin, methoxyflurane, polymixin B, vancomycin. (B263)
  • Controversy regarding concurrent use with cephalosporins due to potentially additive nephrotoxicity; this has been well documented only with cephalothrin and with the no-longer-marketed cephaloridine. (B263)
  • May get increased nephrotoxicity or ototoxicity if used concurrently with loop diuretics (furosemide, ethacrynic acid) or osmotic diuretics (mannitol, urea). (B263)
  • Neuromuscular blockade could be potentiated if used with general anaesthetics or neuromuscular blocking agents. (B263)
  • Synergism may occur if used concurrently with beta-lactam antibiotics against pseudomonas aeruginosa and enterococci; the effect is unpredictable and its usefulness in clinical situations has been questioned. (B263)
  • Physical incompatibility reported (or compatibility only in certain situations): amphotericin B, ampicillin sodium, carbenicillin disodium, cefamandole naftate, cephalothin sodium, cephapirin sodium, dopamine HCl, furosemide, heparin sodium. (B263)
  • Physical compatibility reported with: all commonly used intravenous solutions, bleomycin sulphate, cefoxitin sodium, cimetidine HCl, clindamycin phosphate, methicillin sodium, metronidazole (with and without sodium bicarbonate), penicillin G sodium, verapamil HCl. (B263)
  • Compatibility is affected by factors including pH, concentration, temperature and diluents used. (B263)
  • In vitro it is well documented that beta-lactam antibiotics inactivate aminoglycosides. (B263)

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Administration
Formulations available
  • Tiacil Ophthalmic Solution, Virbac. Licensed for use in rabbits in the UK. (W713.Oct08.w1)
Doses / Administration Routes / Frequencies
  • In mammals: generally once daily dosing recommended to give high peak levels with resultant greater bactericidal effect. The post-antibiotic effect of aminoglycosides continues to decrease the replication rate of susceptible bacteria once drug levels have fallen below MIC, and may decrease the development of adaptive resistance. (B263)
  • In individuals which are neutropaenic or otherwise immunosuppressed dosing at intervals of eight hours may be beneficial. (B263)
  • An increased dosing interval (longer than one day) may be required in individuals with significantly diminished renal function. (B263)
"Hedgehog" (species not distinguished between Atelerix albiventris - Four-toed hedgehog or Erinaceus europaeus - West European Hedgehog):
  • 2.0 mg/kg subcutaneously or intramuscularly every eight hours. "Rarely indicated." (B267)

In Elephants: 

Elephas maximus - Asian Elephant

  • Two grams of gentamicin, diluted in 0.9% sodium chloride to give a volume of 50 mL, in were administered by regional digital intravenous perfusion (RDIP) to treat a sole abscess in an adult elephant. (J2.34.w2)
  • Sixteen grams of gentamicin sulfate diluted in one litre of lactated Ringers solution was given intravenously once daily, together with 42 x 10 benzathine and penicillin intramuscularly once daily, for 10 days following surgery to amputate a toenail in a 40-year-old 3,300 kg female elephant. (J2.28.w2, P9.1.w7)

The following information is taken with permission directly from the Elephant Care International website (W580.Aug2005.w14):

Elephants:
a) 4.4 mg/kg IV (or IM) once daily. The IV injection can be diluted with 10% saline. Based on trough levels measured at 24 hours, this dose will maintain blood levels at 1.7 1.8 g /ml (recommended trough levels for humans are < 2 g /ml). (Schmidt, 1986).

Elephant References:
a) Schmidt, M.J: Senior Research Veterinarian, Washington Park Zoo, Portland, Oregon, personal communication, 1986. In: Olsen,J.H., 1999. Antibiotic therapy in elephants. In: Fowler,M.E. and Miller R.E. (Editors), Zoo and Wild Animal Medicine: Current Therapy 4. W.B. Saunders, Philadelphia, PA,USA p. 537 [B23.77.w12]

In Bears:

  • In general: "Domestic dog drugs and dosages are used to treat bears." (B336.51.w51)
  • 10 mg gentamicin sulphate was given to a bear, following surgical removal of a mass in the treatment of ocular nodular fasciitis, as well as chloramphenicol ophthalmic ointment applied to the eye and 10 mg methylprednisolone acetate given subconjunctivally. [See: Ocular Disease in Bears](J2.18.w1)

Lagomorphs - Oryctolagus cuniculus domesticus - Domestic rabbit:

  • 4 mg/kg intramuscularly once daily. (B373.Guide.w41)
  • 1.5 - 2.5 mg/kg subcutaneously, intramuscularly or intravenously every eight hours. (B546, B548.w8, B601.15.w15)
    • "Seldom indicated; use with caution." (B548.w8)
  • 2.5 mg/kg subcutaneously, intramuscularly or intravenously every eight to 12 hours. (B548.w8)
  • 4 mg/kg subcutaneously or intramuscularly every 24 hours. (B548.w8, B602.41.w41) "Use with caution or avoid use." (B602.41.w41)
  • 2 mg/kg intramuscularly or intravenously every 6 hours, with fluid therapy to reduce risks of nephrotoxicity. In the management of severe systemic infection. (B603.5.w5)
  • 1 g per 20 g methylmethacrylate. For placing in bone following surgical debridement of jaw abscesses. (B548.w8)
  • Eyedrops
    • Apply three times a day. (B373.Guide.w41)
    • 1 - 2 drops per eye three times daily for 5 - 7 days. In the treatment of conjunctivitis. (B600.4.w4, B601.15.w15)

Ferrets - Mustela putorius furo - Ferret:

  • 5 mg/kg intramuscularly or subcutaneously once daily. (B602.41.w41, B626.App.w22)
    • "Potentially nephrotoxic and ototoxic. Avoid long usage." (B626.App.w22)
    • "Use with caution or avoid use." (B602.41.w41)
  • 4.0 - 8.0 mg/kg total dose divide into two or three doses over the day subcutaneously, intramuscularly or intravenously. Note: this drugs is potentially ototoxic and nephrotoxic; it should only be used in ferrets if there is a specific indication based on bacterial culture and sensitivity testing. (J213.3.w1)

Great Apes

Monitoring parameters
  • Efficacy, as indicated by bacterial culture, clinical signs, white blood cell counts, other signs associated with infection. (B263)
  • Monitoring of serum drug levels are recommended if possible.(B263) Monitoring is particularly important in individuals with renal impairment. The trough level (just before the next dose) should be below 1 g/ml in order to avoid toxicity. (B201)
  • Monitoring for adverse effects is essential, including: gross monitoring of vestibular toxicity or auditory toxicity, renal function tests prior to therapy and urinalyses during therapy (first sign of impending nephrotoxicity is often urinary casts). Daily urinalysis for casts may be useful early in therapy and daily testing for creatinine level once casts are seen or if serum creatinine rises. (B263)
  • In individuals with pre-existing renal disease, monitoring and dosage adjustments are required. (B263)

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Withdrawal period / Withholding time
Notes --

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Toxic Information

Toxic effects of Pharmaceutical Products
Contraindications / Precautions
  • Contraindicated in individuals with known hypersensitivity to aminoglycosides. (B263)
  • Use only with extreme caution in patients with pre-existing renal disease. (B263)
  • Use with caution and with serum monitoring and dosage adjustment in neonatal individuals and in geriatric individuals
  • Use with caution in individuals , fever, sepsis, dehydration. (B263)
  • Use with caution in "working" dogs. such as sheep dogs, "seeing-eye" dogs, hearing dogs for the deaf, due to the risk of irreversible ototoxicity and deafness. (B263)
  • Use with caution in individuals with neuromuscular disorders (such as myasthenia gravis). (B263)
  • Contraindicated in lagomorphs (rabbits/hares) due to adverse effect on the balance of gastrointestinal flora; however dosages are available for rabbits. (B263)
Adverse Effects / Side Effects / Warnings
  • Nephrotoxic: tubular necrosis, probably related to interference in the phospholipid metabolism in proximal tubular cells lysosomes with resultant leakage of proteolytic enzymes into the cytoplasm. (B263)
    • Manifests as increase in blood urea nitrogen (BUN), creatinine and non-protein nitrogen in the serum. In the urine, decreased specific gravity and creatinine clearance, sometimes with proteinuria and presence of cells or casts. (B263)
    • Usually reversible once the drug is withdrawn. (B263)
  • Ototoxic (toxicity to the 8th cranial nerve).
    • May show auditory or vestibular signs. (B263)
    • May be irreversible. (B263)
    • Gentamicin is more likely to cause vestibular than auditory signs. (B263)
    • Cats are very sensitive to vestibular effects from aminoglycosides. (B263)

Other side effects:

  • Neuromuscular blockade. (B263)
  • Facial oedema. (B263)
  • Injection site pain/inflammation. (B263)
  • Peripheral neuropathy. (B263)
  • Hypersensitivity reactions. (B263)
  • Gastrointestinal signs (rare) (B263)
  • Haematological effects (rare). (B263)
  • Hepatic effects (rare). (B263)
  • Rarely may cause 8th cranial nerve toxicity or nephrotoxicity in fetuses. (B263)
Operator Warnings --
Overdose / Acute Toxicity
  • May be treated by:
    • Dialysis (not a viable option in veterinary patients). (B263)
    • Peritoneal dialysis (less efficacious). (B263)
    • Administration of carbenicillin or ticarcillin (in humans 12-20 g/day) to complex with the aminoglycoside. (B263)

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Detailed Toxicological Information
Classification --
Acute Toxicity --
Chronic Toxicity --
Reproductive effects --
Teratogenic effects --
Mutagenic effects --
Carcinogenic effects

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Organ toxicity --
Bird Toxicity --
Aquatic organism activity --
Other organism toxicity --

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Nutrient Information

Nutritional Data
Sources --
Biological Use --
Recommended Daily Allowance / Recommended level in food --
Stability in food (Storage time) --
Interactions --

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External / Environmental Information

External / Environmental Uses
Use --
Formulation --
Application method --
Application Concentration --
Persistence of Effect / Frequency of Application --

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Effects on the Environment
Effects in the aquatic environment

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Effects on land --

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Persistence in the Environment
Breakdown in soil and groundwater

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Breakdown in water --
Breakdown in vegetation --

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