Amoxycillin (with special reference to Hedgehogs, Elephants, Bears, Ferrets and Great Apes)

• Amoxicillin (B263)
• p-hydroxyampicillin (B263)
• BRL 2333 (B263)
• "D-(-)-alpha-amino-p-hydroxybenzyl penicillin trihydrate; [2S-[2alpha,5alpha,6beta(S*)]]-6-[[2-amino-2-(4-hydroxyphenyl) acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; Amoclen; Amopen; Amoxicilline; Amoxil; Amoxycillin; Cemoxin; Clamoxyl; Histocillin; Imacillin; p-Hydroxyampicillin; Larotid; Polymox; Trimox; Sawacillin; Utimox; 4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-(2-amino-2-(p-hydroxyphenyl)acetamido)-3,3-dimethyl-7-oxo, D-; 6-(D-(-)-p-Hydroxy-alpha-aminobenzyl)penicillin; 6-[D(-)-alpha-amino-p-hydroxyphenylacetamido]penicillanic acid; (-)-6-[2-amino-2-(p-hydroxyphenyl)acetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; alpha-amino-p-hydroxybenzyl penicillin; 6-(p-hydroxy-alpha-aminophenylacetamido)penicillanic acid; AMPC; Alfamox; Almodan; Amocilline; Amolin; Amopenixin; Amoxi; Amoxipen; Anemolin; Aspenil; Betamox; Bristamox; Cabermox; Cuxacillin; Delacillin; Efpenix; Grinsil; Ibiamox; Ospamox; Optium; Piramox; Simoxil; Sumox; Clamoxyl (Trihydrate); Trimox (Trihydrate); Sawacillin (Trihydrate); Wymox (Trihydrate); Agram (Trihydrate); Amodex (Trihydrate); Amoxibiotic (Trihydrate); Amoxidal (Trihydrate); Amoxidin (Trihydrate); Amoxillat (Trihydrate); Amoxi-Wolff (Trihydrate); Augmentin; Amoxicillin trihydrate; Alphacin; Alphamox; Cilamox; Fisamox; Moxacin; Amoxil (Trihydrate); 6-(p-Hydroxy-alpha-aminophenylacetamido) pencillanic acid; 6-; Amoxypen (Trihydrate);" (W324)

• Similar to Ampicillin but with an extra hydroxyl group on the phenyl ring. (B263)
• C₁₆H₁₉N₃O₅S (W324)

Amoxycillin trihydrate (commercially available form):

• White crystalline powder. (B263)

• Practically odourless. (B263)

• Sparingly soluble. (B263)
• Polar, hydrophilic. (B201.1.w1)

• Lipid insoluble. (B135.43.w43)
• Low lipophilicity. (B201.1.w1)

• Generally bactericidal. Interfere with cell wall synthesis. (B201.1.w1)
• Bind to various enzymes within the bacterial cytoplasmic membrane and inhibit mucopeptide synthesis in bacterial cell walls. This results in a defective cell wall and osmotically defective spheroplast. (B263)
• More effective against actively growing bacteria. (B263)
• Bactericidal only if active peptidoglycan synthesis is taking place, i.e. in actively growing bacteria. (B135.43.w43)

• Tablets, capsules and powder for oral suspension: store in tight containers at room temperature (15-30°C). (B263)
• Reconstituted oral suspension: preferably refrigerate. Discard after 14 days. (B263)
• Injectable veterinary suspension: stable for three months (room temperature or 12 months (refrigerated). (B263)
• Long-term stability (years) for dry crystalline form at 4°C.  (B135.43.w43)

Associated Techniques

• Active against many Gram-positive and Gram-negative bacteria. (B201.1.w1)
• Greater activity against Gram-negative bacteria than has benzylpenicillin (penicillin G). (B135.43.w43, B201.1.w1)
• Active against Clostridium spp. and many other anaerobic bacteria. (B263)
• May be active against beta-lactamase-producing bacteria such as Escherichia coli, Pasteurella spp., Klebsiella spp. and Proteus spp. if used in combination with a beta-lactamase inhibitor such as potassium clavulanate or sulbactam. (B263)

• Infections with susceptible bacteria. (B263)
• Urinary tract infections. (B135.43.w43)
• Mixed secondary bacterial infections of the respiratory tract (sinusitis, otitis, bronchitis). (B135.43.w43)
• Parenteral and preferably intravenous injection should be used for patients with severe illness such as septicaemia or shock. (B263)
• Useable for bacterial infections of the CNS since increased CNS distribution if the meninges are inflamed. (B135.43.w43, B263)

• Generally inactive against: Pseudomonas aeruginosa, Serratia, Indole-positive Proteus spp., Enterobacter, Citrobacter, Acinetobacter. (B263)
• Poor against Klebsiella, some Proteus spp. and Pseudomonas spp. (B201.1.w1)
• Susceptible to inactivation by beta-lactamase-producing bacteria such as Staphylococcus aureus. (B263); poor activity against beta-lactamase producing Staphylococcus aureus. (B201.1.w1)
• Broken down by beta-lactamases produced by staphylococci and by beta-lactamases produced by Gram-negative organisms such as Escherichia coli and Haemophilus spp. (acquired resistance). (B201.1.w1)
  • Usefulness has been limited by acquired resistance in such bacteria. (B201.1.w1)
• Slightly less active than benzylpenicillin against Gram-positive bacteria and against anaerobic bacteria. (B201.1.w1)
• Not effective against organisms which lack cell walls. (B135.43.w43)
• Not effective against organisms which are metabolically inactive. (B135.43.w43)
• Oral administration is not appropriate in patients with severe illness such as septicaemia or shock as absorption from the gastro-intestinal tract may be significantly diminished or delayed. (B263)

• Relatively good absorption from the gut. (B135.43.w43)
• Better absorption than ampicillin following oral administration (in non-ruminants). (B201.1.w1, B263)
• Absorption not greatly affected by the presence of food in the stomach. (B201.1.w1)

• Widely distributed in body fluids and in tissue. (B135.43.w43)
• Volume of distribution approximately 0.2L/kg in dogs, 0.3L/kg in humans. (B263)
• Tissue levels equal to serum levels in many tissues. (B135.43.w43)
• Good levels in pleural fluid, pericardial fluid, joint fluid.  (B135.43.w43)
• Lower concentration in the eye, CNS, prostate. (B135.43.w43)
• Increased CNS distribution if the meninges are inflamed. (B135.43.w43) May then reach concentrations in the CNS 10-60% of the serum concentration. (B263)
• Low levels in aqueous humour, tears, sweat, saliva. (B263)
• Crosses the placenta. (B263)

• Approximately 13% plasma protein bound in dogs, 17-20% in humans. (B263)

• Kidneys: by glomerular filtration and by tubular secretion. (B135.43.w43)
• Some metabolised to inactive penicilloic acids by hydrolysis prior to excretion in the urine. (B263)
• Excreted in sputum and in milk. (B135.43.w43) . Low levels in milk. (B263)
• Excreted in urine. (B201.1.w1)
• Excreted in bile. (B201.1.w1)

• Elimination half-life: cattle 90 minutes, dogs and cats 45-90 minutes.(B263)
• Clearance: dogs 1.9ml/kg/minute. (B263)

• Penicillins in combination with aminoglycosides or cephalosporins may have synergistic or additive activity against some bacteria.  (B263)
• Not recommended in combination with bacteriostatic antibiotics as penicillins are more effective against actively growing bacteria. (B263)

• There is no evidence that the presence of clavulanic acid affects the pharmacokinetics of amoxycillin. (B263)

• Tablets, capsules, oral suspension, injectable suspension. (B263), also oral paste, mixture. (B201.1.w1)
• Depot preparations with the drug incorporated into an oily vehicle are available. These allow prolonged action from a single injection. (B201.1.w1)
• Premix preparations for addition to feed in pigs. (B201.1.w1)
• Powder preparations for addition to drinking water in pigs, poultry, pigeons, ducks. (B201.1.w1)
• Also available in formulations in combination with clavulanic acid, a beta-lactamase inhibitor. (B201.1.w1, B263)

Use of Drugs (Medication):

• Before administration of any pharmaceutical product the manufacturer's datasheet must be consulted regarding operator safety, relevant withdrawal times etc.
• Many drugs are not registered for use in particular species and additional care should be taken in their use, with proper regard for possible toxic effects. 
• Consideration should be given to relevant legislation regarding the use of drugs.
• In the UK, guidelines regarding the use of drugs are set out in the Royal College of Veterinary Surgeons' Guide to Professional Conduct 2000: (See: LCofC1 - RCVS Guide to Professional Conduct 2000 - Choice of Medicinal Products).

General comments:

• Dosing regimen should maintain the tissue concentration above the minimum inhibitory concentration (MIC) for as long as possible during the inter-dosing interval. (B201.1.w1)
• Dose required may vary with the size of the animal: in general the dosage per unit body weight increases as the size of the animal decreases. (B201.1.w1)
• Dose required may vary with factors such as intercurrent disease and severity of infection. (B201.1.w1)
• In general administration should continue with acute infections for two to three days after clinical cure and with chronic infections for one to two weeks after clinical cure; longer treatment may be required with some conditions. (B201.1.w1)
• Oral medication may be given with food. (B263)

Bears (Ursidae - Bears (Family)):

• In general: "Domestic dog drugs and dosages are used to treat bears." (B336.51.w51)
• For Bacterial Dermatitis in Bears, amoxycillin-clavulanic acid) in two Helarctos malayanus - Sun bear cubs, 50 mg/day was given. (D255.6.w6c, N18.47.w1)
• 22 mg/kg orally twice daily to help prevent the development of secondary bacterial pneumonia in the treatment of Blastomycosis in Bears. (J2.20.w5)
• A 14-day course of oral antibiotics (Amoxycillin/Clavulanic acid 22 mg/kg twice daily was effective in the treatment of two Ursus maritimus - Polar bear with Bordatella bronchiseptica tracheitis. Sensitivity testing confirmed that the isolated organism was sensitive to this antibiotic. (J2.37.w2)
• 2.25 g per bear given to two Ursus maritimus - Polar bears with vomiting and diarrhoea. (J3.145.w4)

Dogs:

• For Gram-positive infections, 10 mg/kg orally, intramuscularly or subcutaneously twice daily, continuing for at least two days after symptoms subside. (B263)
• For Gram-negative infections, 20 mg/kg orally three times daily, or intramuscularly or subcutaneously twice daily, , continuing for at least two days after symptoms subside. (B263)
• For susceptible urinary tract infections, 10-20 mg/kg orally every 12 hours for 5-7 days. (B263)
• For susceptible systemic infections, 22-50 mg/kg orally every eight hours for seven days. (B263)
• For susceptible orthopaedic infections, 22-30 mg/kg intravenously, intramuscularly, subcutaneously or orally every six to eight hours for 7-10 days. (B263)
• For amoxycillin-sensitive infections; 10 mg/kg orally twice daily, or 7 mg/kg by subcutaneous or intramuscular injection daily, or 15 mg/kg by depot subcutaneous or intramuscular injection, repeated after two days. (B373.1.w1)

Amoxycillin-clavulanic acid:

• 13.75 mg/kg twice daily. Do not extend treatment for more than 30 days. (B263)
• Susceptible urinary tract infections, 12.5 mg/kg orally every 12 hours for 5-7 days. (B263)
• Susceptible skin and soft tissue infections, 12.5 mg/kg orally every 12 hours for 5-7 days. Treatment may need to be extended to 21 days but do not extend past 30 days. (B263)
• For susceptible deep pyoderma, 12.5 mg/kg orally every 12 hours for 14-120 days. (B263)
• For systemic bacteraemia, 22 mg/kg orally every 8-12 hours for seven days. (B263)
• Generally treat for at least two days after all signs of infection have ceased. (B263)
• 10-20 mg/kg twice daily orally, or 7 mg/kg once daily by subcutaneous or intramuscular injection. (B373.1.w1)

Erinaceus europaeus - West European Hedgehog:

• 15 mg/kg intramuscularly, twice daily. (B22.27.w3)
• 150 mg/kg once daily subcutaneously for five days (D107)
• 40 mg/kg oral twice daily. (D93, D107)
• Amoxycillin trihydrate 150 mg/kg intramuscularly or subcutaneously every 2-3 days. Long-acting preparation. (D93)
• Amoxycillin LA [] long-acting] 50-150 mg/kg every other day. Broad-spectrum bactericidal. (B284.6.w6)
• Amoxycillin L/A [long-acting] 150 mg/kg every other day. (D107)
• Amoxycillin/clavulanate: 30-50 mg/kg twice daily orally, intramuscularly or subcutaneously. (J15.21.w1)
• Amoxycillin/clavulanate: 12.5 mg/kg oral every 12 hours. Broad spectrum (B267)
• Amoxycillin/clavulanate: 30-50 mg/kg twice daily, intramuscularly, subcutaneously or orally. Broad spectrum antibacterial; useful for respiratory tract infections, for skin and soft tissue infections including abscesses, and for enteritis. (B284.6.w6)
• Amoxycillin/clavulanate: 100 mg/kg intramuscularly once daily or 150 mg/kg orally twice daily. (D93)

Atelerix albiventris - Four-toed hedgehog:

• 15 mg/kg twice daily, orally or intramuscularly. (J204.59.w1)

• 15 mg/kg intramuscularly or orally, every 12 hours. (B150.w1)

Elephants:

Elephas maximus - Asian Elephant

• A female was given 30 g intramuscularly once daily in a case of retained placenta, to prevent secondary metritis. (J2.27.w1)
• A female was given 5 mg/kg intramuscularly once daily for 2 days in a case of dystocia that was treated surgically. (P1.1996.w1)

Loxodonta africana - African Elephant

• An 18-year-old Loxodonta africana - African Elephant weighing approximately 3,000 kg was given 30 g amoxycillin orally once daily for seven days prior to extraction of an infected tusk. (J4.192.w1)

The following information is taken with permission directly from the Elephant Care International website (W580.Aug2005.w4):

Ferrets - Mustela putorius furo - Ferret:

• 10 - 25 mg/kg orally or subcutaneously, once or twice daily. (B626.App.w22)
  • "Useful in combination drug dose, with metronidazole and bismuth subsalicylate, also with enrofloxacin." (B626.App.w22)
• 10 - 35 mg/kg subcutaneously or orally every 12 hours. (B631.21.w21)
• 10 -30 mg/kg orally every 8 - 12 hours. (B602.41.w41)
• 10 - 35 mg/kg orally or subcutaneously, twice daily. Note: can cause reduced appetite in some ferrets. (J213.3.w1)
• With Clavulanic acid: 
  • 12.5 mg/kg (i.e. 1 mL/kg of 12.5 mg/mL clavulanic acid, 50 mg/mL amoxycillin) orally twice daily. (B626.App.w22)
  • 12.5 - 25 mg/kg orally every 8 - 12 hours. (B602.41.w41, B631.21.w21)
  • 10 - 20 mg/kg orally twice or three times daily. (J213.3.w1)

Great Apes

• Adult Pan troglodytes - Chimpanzee: 500 mg/kg intravenously, intramuscularly or orally, three times daily. (W768.Jun2012.w1)
  • With Clavulanic acid:  13.75 mg/kg orally twice daily.  (W768.Jun2012.w1)
• Primates: 7-13 mg/kg subcutaneously, intramuscularly or orally, twice daily. Useful against Gram-positive organisms; used in cases of minor wounds or oral problems. (D425.3.15.w3o)
  • With Clavulanic acid, 10 - 15 mg/kg subcutaneously, intramuscularly or orally, twice daily. Useful against Gram-positive organisms and some Gram-negative organisms; used in cases of infections f the respiratory tract, skin and urinary tract. May cause gastro-intestinal upset or diarrhoea. In serious infections, up to 50 mg/kg three times daily may be used. (D425.3.15.w3o)

• Monitor for efficacy. (B263)

• Withdrawal period varies with species and with preparation used. (B201.1.w1)
• The withdrawal period specified by the manufacturer for a particular product in a particular species, as indicated in the appropriate Data Sheet for that product used in that country, must be consulted.
• Should not be used in birds producing eggs for human consumption. (B201.1.w1)
• Not for use in sheep producing milk for human consumption. (B201.1.w1)
• In cattle milk withholding time may be e.g. one to three days depending on the formulation. (B201.1.w1)
• For slaughter may be as long as 28 days in cattle. (B201.1.w1)

• Contraindicated in patients with a history of sensitivity to penicillins. (B263)
• Must be used with caution in patients with documented hypersensitivity to other beta-lactam antibiotics such as cephalosporins. In humans up to 15% of those hypersensitive to cephalosporins are also hypersensitive to penicillins. (B263)
• In pregnancy use only if potential benefits outweigh the risks, as penicillins cross the placenta and safe use of penicillins during pregnancy has not been firmly established. (B263)
• Contra-indicated for oral administration in horses. (B201.1.w1)
• Contraindicated in cattle once the rumen is functional (including calves with a functional rumen). (B201.1.w1)
• Contraindicated for use in gerbils, guinea-pigs, hamsters, rabbits. (B201.1.w1)

• Oral dosing may result in anorexia, vomiting and diarrhoea. (B263)
• Alterations of gut flora may occur resulting in diarrhoea. (B263)
• Diarrhoea. (B201.1.w1)
• Superinfection of the gut with resistant bacteria may occur in the colon. (B263)
• Neurotoxicity such as ataxia in dogs has been recorded associated with high doses or very prolonged use. (B263)
• Elevated liver enzymes have been reported. (B263)
• Local irritation may occur at injection site. (B201.1.w1)
• Should not be administered to gerbils, guinea pigs, hamsters or rabbits. (B201.1.w1)
• Should not be administered by intrathecal injection as this may result in seizures. (B201.1.w1)
• Hypersensitivity reactions:
  • Unrelated to dose. (B263)
  • May result in rash, fever, eosinophilia, neutropaenia, agranulocytosis, thrombocytopaenia, leucopaenia, anaemias, lymphadenopathy.
  • May cause full-blown anaphylaxis. (B263)

• Before the use of any pharmaceutical product the label instructions for the product should be consulted regarding withdrawal requirements.
• As will all penicillins, may cause hypersensitivity (allergy) following self injection, inhalation, ingestion or skin contact. Should not be handled by operators with known hypersensitivity. Clinical signs of allergic reaction may include: skin rash, swelling of face, lips or eyes, difficulty in breathing. In the event of a reaction seek medical advice. (B201.1.w1)

• May cause gastro-intestinal distress. (B263)
• With very high doses CNS effects may be seen. (B263)

• Neurotoxicity such as ataxia in dogs has been recorded associated with very prolonged use. (B263)

• No documented teratogenic problems associated with the use of penicillins in pregnancy. (B263)

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