Amoxicillin / Clavulanate Potassium

Antibiotic Aminopenicillin with beta-lactamase inhibitor

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 12.5-25 mg/kg (based on amoxicillin component) q12h Duration: 5-7 days or as directed
Notes: Administer with food to reduce GI upset. For severe infections, higher end of dose range.
Cat PO 12.5-25 mg/kg (based on amoxicillin component) q12h Duration: 5-7 days or as directed
Notes: Administer with food. Use cautiously in cats with renal impairment.
Horse PO 20-25 mg/kg (based on amoxicillin component) q8-12h Duration: 5-7 days or as directed
Notes: Oral absorption may be variable; consider parenteral therapy for severe infections.
Cattle PO 10-20 mg/kg (based on amoxicillin component) q12h Duration: 3-5 days
Notes: Not for use in lactating dairy cattle. Observe withdrawal times.
Small Ruminants (sheep/goats) PO 10-20 mg/kg (based on amoxicillin component) q12h Duration: 3-5 days
Notes: Extra-label use; observe withdrawal times.
Rabbit PO 15-20 mg/kg (based on amoxicillin component) q12h Duration: 5-7 days
Notes: Use with caution; monitor for GI disturbances.
Bird/Poultry PO (in water or oral) 125-250 mg/L drinking water (amoxicillin/clavulanate combination) Continuous administration Duration: 3-5 days
Notes: Ensure fresh solution daily. Withdrawal times apply.
Exotic (Reptiles) PO 10-20 mg/kg (based on amoxicillin component) q24h Duration: 7-14 days
Notes: Dosing based on extrapolation; adjust based on species and temperature.

Clinical Indications & Species Uses

General Indications
  • Treatment of infections caused by susceptible beta-lactamase-producing bacteria
Dog (Canine)
  • Skin and soft tissue infections (e.g., pyoderma, abscesses)
  • Urinary tract infections (UTIs)
  • Respiratory tract infections (e.g., pneumonia, bronchitis)
  • Periodontal infections
  • Gastrointestinal infections (e.g., enteritis)
Cat (Feline)
  • Skin and soft tissue infections
  • Urinary tract infections
  • Respiratory tract infections (e.g., feline upper respiratory infection)
  • Abscesses and wound infections
Horse (Equine)
  • Respiratory tract infections (e.g., strangles)
  • Skin and soft tissue infections
  • Urinary tract infections
  • Septic arthritis (adjunctive therapy)
Cattle (Bovine)
  • Respiratory tract infections (e.g., pneumonia)
  • Metritis
  • Mastitis (not for lactating dairy cattle due to milk withdrawal)
  • Foot rot
  • Skin infections
Small Ruminants (Sheep / Goat)
  • Respiratory infections
  • Skin infections
  • Enteritis
  • Metritis
Rabbit & Small Mammals
  • Respiratory infections (e.g., Pasteurella multocida)
  • Skin abscesses
  • Urinary tract infections
Avian & Poultry
  • Respiratory infections (e.g., colibacillosis)
  • Skin infections
  • Enteritis
Exotic & Other Species
  • Reptiles: respiratory and skin infections
  • Small mammals (e.g., guinea pigs, hamsters): respiratory and skin infections

Pharmacology & Mechanism of Action

Drug Class: Antibiotic | Pharmacological Group: Aminopenicillin with beta-lactamase inhibitor

Mechanism of Action: Amoxicillin is a beta-lactam antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to cell lysis. Clavulanate potassium is a beta-lactamase inhibitor that irreversibly binds to and inactivates beta-lactamase enzymes, thereby protecting amoxicillin from degradation by resistant bacteria. The combination provides broad-spectrum bactericidal activity against many gram-positive and gram-negative aerobes and anaerobes, including beta-lactamase-producing strains.

Pharmacodynamics: Amoxicillin/clavulanate exhibits time-dependent killing; efficacy correlates with the time the drug concentration exceeds the minimum inhibitory concentration (MIC) for the pathogen. The presence of clavulanate extends the spectrum to include beta-lactamase-producing organisms such as Staphylococcus spp., Escherichia coli, and Klebsiella spp. It is effective against many pathogens causing skin, respiratory, urinary, and gastrointestinal infections in animals.

⚑ Pharmacokinetics Summary

Absorption: Amoxicillin and clavulanate are well absorbed from the gastrointestinal tract in most species. Oral bioavailability is approximately 60-80% in dogs and cats, with peak plasma concentrations occurring 1-2 hours after administration. Absorption may be slightly reduced when given with food, but it is often recommended to give with food to reduce gastrointestinal upset.
Distribution: Both components distribute widely into body tissues and fluids, including lung, liver, kidney, muscle, and pleural fluid. They cross the placenta and are excreted in milk. Protein binding is low: amoxicillin is about 17-20% bound, and clavulanate about 25-30% bound in dogs.
Metabolism: Amoxicillin undergoes minimal metabolism; clavulanate is extensively metabolized in the liver to several metabolites, which are excreted in urine and feces.
Excretion: Both amoxicillin and clavulanate are primarily excreted by the kidneys via glomerular filtration and tubular secretion. In dogs, approximately 60-80% of amoxicillin is excreted unchanged in urine within 8 hours. Clavulanate is also excreted in urine, with a small amount in feces.
Half-Life: Dog: 0.75-1 hour; Cat: 0.5-1 hour; Horse: 0.5-1 hour; Cattle: 1-1.5 hours; Rabbit: 0.5-1 hour; Poultry: 0.5-1 hour.
Bioavailability: Oral: 60-80% in dogs and cats; may be lower in large animals.
Protein Binding: Amoxicillin: 17-20% in dogs; Clavulanate: 25-30% in dogs.

Available Formulations & Strengths

Oral Tablet 50 mg amoxicillin/12.5 mg clavulanate; 100 mg/25 mg; 200 mg/50 mg; 250 mg/62.5 mg; 400 mg/100 mg; 500 mg/125 mg (PO)
Oral Suspension (reconstituted) 50 mg/mL amoxicillin/12.5 mg/mL clavulanate (per mL) (PO)
Chewable Tablet 62.5 mg/15.6 mg; 125 mg/31.25 mg; 250 mg/62.5 mg (PO)
Injectable Suspension (for veterinary use in some countries) 100 mg/mL amoxicillin/25 mg/mL clavulanate (IM/SC)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to penicillins or cephalosporins
  • Severe renal impairment (adjust dose)
  • Use in rabbits, guinea pigs, hamsters, and other small herbivores (oral administration may cause fatal enteric dysbiosis)
  • Concurrent use with bacteriostatic antibiotics (e.g., tetracyclines, chloramphenicol) may antagonize bactericidal effect
Warnings & Clinical Precautions:
  • Use with caution in animals with a history of allergic reactions to beta-lactams
  • In herbivores, oral administration may disrupt gastrointestinal flora; monitor for diarrhea
  • Prolonged use may result in overgrowth of non-susceptible organisms (e.g., Candida)
  • In food animals, observe withdrawal times
  • Use in lactating dairy cattle is prohibited (milk withdrawal)
  • In horses, oral administration may be associated with diarrhea; monitor hydration

Adverse Effects & Reactions

Common:

  • Gastrointestinal upset (vomiting, diarrhea, anorexia)
  • Allergic reactions (skin rash, urticaria)

Serious / Severe:

  • Anaphylaxis (rare)
  • Clostridial enterotoxemia in rabbits and rodents
  • Acute interstitial nephritis (rare)
  • Hepatotoxicity (rare)

Rare:

  • Blood dyscrasias (neutropenia, thrombocytopenia)
  • Neurotoxicity (with high doses in renal impairment)

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Probenecid Decreases renal tubular secretion of amoxicillin, increasing plasma levels and duration Moderate
Bacteriostatic antibiotics (e.g., tetracyclines, chloramphenicol, macrolides) May antagonize the bactericidal effect of amoxicillin/clavulanate Moderate
Methotrexate May reduce renal clearance of methotrexate, increasing toxicity Moderate
Oral contraceptives (in humans, but relevant in research) May reduce efficacy of oral contraceptives (not commonly relevant in veterinary medicine) Mild
Allopurinol Increased risk of skin rash Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Gastrointestinal signs (vomiting, diarrhea)
  • Neurological signs (tremors, seizures) in severe cases
  • Allergic reactions

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce vomiting if recent ingestion and animal is stable. Administer activated charcoal to reduce absorption. Provide fluid therapy to maintain hydration and promote renal excretion. Monitor for electrolyte imbalances and neurological signs. In severe cases, consider anticonvulsants. There is no specific antidote.

Food Animal Withdrawal Times

πŸ₯© Meat: 10 daysπŸ₯› Milk: 4 daysπŸ₯š Eggs: 5 days

Withdrawal times vary by country and formulation. For cattle, meat withdrawal is typically 10 days; milk withdrawal is 4 days (but not for lactating dairy cattle). For poultry, meat withdrawal is 5 days, and eggs 5 days. Always follow local regulations.

Storage, Handling & Regulatory Information

Storage Temperature: Store tablets and dry powder at controlled room temperature (20-25Β°C). Reconstituted oral suspension should be refrigerated (2-8Β°C) and discarded after 10 days.

Handling & Special Conditions: Keep container tightly closed. Protect from moisture. Do not freeze reconstituted suspension.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in dogs and cats (e.g., Clavamox). Not approved for food animals in the US, but extra-label use is common.

Extra-Label (Off-Label) Use: In the US, extra-label use in food animals is permitted under AMDUCA with veterinary oversight, but must observe withdrawal times. In the EU, extra-label use is also regulated. Use in lactating dairy cattle is prohibited in many countries.

Clinical Pearls & Practice Notes

πŸ’‘ Clinical Insights: Amoxicillin/clavulanate is a broad-spectrum antibiotic commonly used in small animal practice for skin, respiratory, and urinary infections. It is particularly useful for infections caused by beta-lactamase-producing staphylococci and gram-negative bacteria. In large animals, its use is limited by cost and availability of other antibiotics. In rabbits and other small herbivores, oral administration is contraindicated due to risk of enteric dysbiosis; parenteral amoxicillin (without clavulanate) is also risky. Always culture and sensitivity when possible to ensure appropriate use. Monitor for adverse effects, especially gastrointestinal upset. In food animals, adhere strictly to withdrawal times.

References & Literature

  • πŸ“š Plumb's Veterinary Drug Handbook
  • πŸ“š Papich Veterinary Pharmacology and Therapeutics
  • πŸ“š Compendium of Veterinary Products (CVP)