Ampicillin
Ampicillin sodium, Ampicillin trihydrate
Also known as: Polyflex · Principen · Amfipen · Ampicare · aminobenzylpenicillin · ampicillinum anhydricum · anhydrous ampicillin · AY-6108 · BRL-1341 · NSC-528986 · P-50 · Ampicillin sodium · Aminopenicillin
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Audited v13 dosing evidence
Structured calculator evidenceSusceptible infections (extra-label)
Verified clinician required
- q12h
NA
Governing clinical context (3)
- ■ Because penicillins usually have minimal toxicity associated with their use, monitoring for efficacy is usually all that is required unless toxic signs develop. Serum levels and therapeutic drug monitoring are not routinely done with these agents.
- Ampicillin trihydrate (Polyflex®) powder for injection should be stored at or below 25°C (77°F), with excursions permitted up to 30°C (86°F). After reconstitution, it is stable for 3 months when refrigerated.
- Ampicillin sodium powder for injection should be stored at room temperature (15°C-30°C [59°F-86°F]). The drug is relatively unstable after reconstitution and should be used within 1 hour of reconstitution. As the concentration of the drug in solution increases, the stability of the drug decreases. Dextrose may also speed the destruction of the drug by acting as a catalyst in the hydrolysis of ampicillin.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Ampicillin is a broad-spectrum, time-dependent, bactericidal aminopenicillin antibiotic.
Key pharmacological features include:
- Spectrum of Activity: Effective against many gram-positive organisms (including penicillin-sensitive enterococci like E. faecium), anaerobes (e.g., Clostridium spp.), and some gram-negative aerobes (E. coli, Klebsiella, Haemophilus, Proteus mirabilis).
- Resistance: Like natural penicillins, it is highly susceptible to inactivation by beta-lactamase-producing bacteria (e.g., Staphylococcus aureus). It is ineffective against Pseudomonas aeruginosa, Serratia, Enterobacter, and atypical organisms (Mycoplasma, Rickettsia, fungi).
- Clinical Utility: While oral ampicillin has largely been replaced by amoxicillin in small animals due to superior bioavailability, parenteral ampicillin remains a cornerstone therapy.
- Salt Forms:
- Ampicillin Sodium: Highly water-soluble, suitable for IV administration, providing rapid, high peak serum concentrations.
- Ampicillin Trihydrate: A repository form for IM or SC use, providing slower absorption and lower peak serum levels (approximately half that of the sodium salt). It should not be used when high Minimum Inhibitory Concentrations (MICs) are required for systemic infections.
Mechanism of action
Ampicillin is a beta-lactam antibiotic that exerts its bactericidal effect by interfering with bacterial cell wall synthesis.
- Mechanism: Ampicillin covalently binds to specific Penicillin-Binding Proteins (PBPs) (primarily transpeptidases) located inside the bacterial cell wall.
- Pathway: Binding to PBPs → inhibition of the final transpeptidation step of peptidoglycan cross-linking → weakening of the cell wall structure → activation of endogenous autolytic enzymes (autolysins) → osmotic lysis and bacterial cell death.
- Pharmacodynamics: Efficacy is time-dependent, meaning the free drug concentration must remain above the Minimum Inhibitory Concentration (MIC) for a significant portion of the dosing interval (typically >40-50% of the interval).
Safety & warnings
Contraindications
- Patients with a known hypersensitivity to penicillins
- Oral administration in patients with septicemia, shock, or grave illness (due to delayed/diminished GI absorption)
- Oral or parenteral use in small hindgut fermenters (rabbits, guinea pigs, chinchillas, hamsters) due to risk of fatal clostridial enterotoxemia
Adverse effects
- Gastrointestinal upset (anorexia, vomiting, diarrhea)
- Antibiotic-associated diarrhea and superinfections (alteration of gut flora)
- Hypersensitivity reactions (rashes, fever, eosinophilia, anaphylaxis)
- Neurotoxicity (ataxia, seizures) at very high doses or prolonged use
- Elevated liver enzymes (rare)
- Tachypnea, dyspnea, edema, and tachycardia (reported in dogs)
Precautions
Cross-Reactivity: Use cautiously in patients with documented hypersensitivity to other beta-lactam antibiotics (e.g., cephalosporins, carbapenems), as cross-reactivity can occur.
Species Warning: Severe, potentially fatal enteritis and clostridial enterotoxemia can occur if administered to rabbits, guinea pigs, chinchillas, or hamsters.
Laboratory Interference: May cause false-positive urine glucose determinations when using cupric sulfate solutions (e.g., Clinitest). Glucose oxidase tests are unaffected.
Drug interactions
Potential in vitro antagonism; clinical significance is debated but concurrent use is traditionally discouraged.
Ampicillin may decrease the renal excretion of methotrexate, leading to increased levels and potential toxicity.
Competitively blocks the tubular secretion of penicillins, increasing serum levels and prolonging half-life.
In vitro inactivation of aminoglycosides if mixed in the same syringe or fluid bag. May also occur in vivo in patients with severe renal failure.
Antagonism of bactericidal effect due to bacteriostatic action
Antagonism of bactericidal effect due to bacteriostatic action
Antagonism of bactericidal effect due to bacteriostatic action
In vitro inactivation if mixed in the same syringe; however, exhibits synergistic antimicrobial effects when used concurrently in vivo
Monitoring
- Clinical efficacy (resolution of infection signs)
- Adverse effects (GI signs, hypersensitivity reactions)
- Therapeutic drug monitoring is not routinely required due to the wide therapeutic index
Pharmacokinetics
Half-life
Absorption
Relatively stable in gastric acid. Oral absorption is 30-55% in monogastric animals on an empty stomach; food decreases the rate and extent of absorption. Parenteral trihydrate salt achieves serum levels approximately 1/2 those of a comparable dose of the sodium salt.
Distribution
Widely distributed to many tissues (liver, lungs, muscle, bile, ascitic/pleural/synovial fluids). Volume of distribution is ~0.3 L/kg in dogs, 0.167 L/kg in cats, and 0.16-0.5 L/kg in cattle. Crosses inflamed meninges (10-60% of serum levels). Low levels in aqueous humor, tears, sweat, saliva, and milk. Crosses the placenta. Approximately 20% bound to plasma proteins.
Metabolism
Some of the drug is metabolized by hydrolysis to inactive penicilloic acids.
Elimination
Eliminated primarily through renal mechanisms, principally by tubular secretion. Excreted in the urine.
Overdose
Acute oral penicillin overdoses are unlikely to cause significant problems other than gastrointestinal distress (vomiting, diarrhea, anorexia).
In humans, very high dosages of parenteral penicillins, particularly in patients with underlying renal disease, have induced CNS effects (e.g., seizures, ataxia). Treatment is generally supportive and symptomatic.
Available products
Formulations
- Powder for injection (Ampicillin sodium)
- Powder for injection suspension (Ampicillin trihydrate)
- Oral capsules
- Powder for oral suspension
Veterinary
- Ampicillin Trihydrate Injection Powder for Suspension: 10 g and 25 g vials (Polyflex)
Human-labeled
- Ampicillin Sodium Powder for Injection: 250 mg, 500 mg, 1 g, 2 g vials
- Ampicillin Oral Capsules (as trihydrate): 250 mg, 500 mg (Principen)
- Ampicillin Powder for Oral Suspension (as trihydrate): 125 mg/5 mL, 250 mg/5 mL (Principen)
Regulatory status
POM-V classification
POM-V (Prescription Only Medicine - Veterinarian)
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Capsules and powder for oral suspension: Store at room temperature (15-30°C). Reconstituted oral suspension: Stable for 14 days refrigerated (2-8°C) or 7 days at room temperature. Ampicillin trihydrate for injection (Polyflex): Stable for 3 months refrigerated. Ampicillin sodium for injection: Relatively unstable after reconstitution; generally use within 1 hour. Stability decreases as concentration increases. Dextrose speeds destruction. At ≤30 mg/mL in sterile water or 0.9% NaCl, stable up to 48 hours at 4°C.
Client information
- Administration: Unless otherwise instructed by your veterinarian, give this medication orally on an empty stomach (at least 1 hour before feeding or 2 hours after) to ensure proper absorption.
- Storage: Keep the oral liquid suspension in the refrigerator and discard any unused portion after 14 days. If kept at room temperature, discard after 7 days.
- Side Effects: Mild stomach upset (vomiting, diarrhea, or decreased appetite) may occur. If these signs are severe or persist, contact your veterinarian.
- Allergic Reactions: Watch for signs of an allergic reaction, such as facial swelling, hives, rash, or difficulty breathing. Seek immediate veterinary care if these occur.
- Completion of Therapy: Always finish the entire prescription as directed, even if your pet seems to be feeling better, to prevent the development of resistant bacteria.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.