Azithromycin

Macrolide antibiotic Azalide antibiotic

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 5-10 mg/kg q24h Duration: 5-7 days; for rickettsial infections, 7-14 days
Notes: Administer on an empty stomach to enhance absorption, but if GI upset occurs, give with food. For Bartonella, use 10 mg/kg q24h for 7 days.
Cat PO 5-10 mg/kg q24h Duration: 5-7 days; for Mycoplasma haemofelis, 7-14 days
Notes: Administer with food to reduce vomiting. For Chlamydia felis, use 10 mg/kg q24h for 7 days.
Horse (foal) PO 10 mg/kg q24h Duration: For Rhodococcus equi: 30-60 days or longer; often combined with rifampin
Notes: Administer via nasogastric tube or oral syringe. Monitor for diarrhea.
Horse (adult) PO 10 mg/kg q24h Duration: 5-10 days
Notes: Use with caution; may cause GI disturbances.
Cattle SC 10-20 mg/kg q48h Duration: 3-5 doses
Notes: Extra-label use; not FDA-approved for cattle. Use with veterinary supervision. Observe withdrawal times.
Sheep/Goat PO 10 mg/kg q24h Duration: 5-7 days
Notes: Extra-label use; monitor for GI upset.
Rabbit PO 15 mg/kg q24h Duration: 5-7 days
Notes: Extra-label; may cause GI stasis, use with caution.
Bird (Psittacines) PO 40-80 mg/kg q24h Duration: 5-7 days
Notes: Extra-label; for chlamydiosis, treat for 45 days.
Poultry PO (drinking water) 20-40 mg/kg q24h Duration: 3-5 days
Notes: Extra-label; ensure adequate water intake.

Clinical Indications & Species Uses

General Indications
  • Treatment of infections caused by susceptible Gram-positive and Gram-negative bacteria, mycoplasmas, and intracellular pathogens.
  • Alternative to erythromycin or clarithromycin for patients with gastrointestinal intolerance.
  • Used for its immunomodulatory effects in chronic respiratory diseases (e.g., canine chronic bronchitis).
Dog (Canine)
  • Treatment of bacterial infections caused by susceptible organisms, including respiratory tract infections (e.g., Bordetella bronchiseptica, Streptococcus, Pasteurella), skin and soft tissue infections, urinary tract infections, and otitis externa.
  • Treatment of rickettsial infections (e.g., Ehrlichia, Anaplasma) as an alternative to doxycycline.
  • Treatment of Bartonella infections (e.g., Bartonella henselae).
  • Treatment of Mycoplasma infections (e.g., Mycoplasma haemofelis).
  • Treatment of cryptosporidiosis (in combination with other drugs).
Cat (Feline)
  • Treatment of upper respiratory tract infections (e.g., Bordetella bronchiseptica, Chlamydia felis, Mycoplasma).
  • Treatment of Bartonella infections (e.g., Bartonella henselae).
  • Treatment of Mycoplasma haemofelis (feline infectious anemia).
  • Treatment of toxoplasmosis (in combination with other agents).
  • Treatment of cryptosporidiosis.
Horse (Equine)
  • Treatment of respiratory tract infections, including Rhodococcus equi pneumonia in foals (often in combination with rifampin).
  • Treatment of bacterial pneumonia caused by susceptible organisms (e.g., Streptococcus zooepidemicus).
  • Treatment of nocardioform placentitis (in combination with other antibiotics).
Cattle (Bovine)
  • Treatment of bovine respiratory disease (BRD) complex caused by Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni (though not FDA-approved for cattle, extra-label use may occur).
  • Treatment of infectious keratoconjunctivitis (pinkeye) caused by Moraxella bovis (extra-label).
  • Treatment of foot rot (interdigital necrobacillosis) (extra-label).
Small Ruminants (Sheep / Goat)
  • Treatment of respiratory infections (e.g., Pasteurella, Mycoplasma) in sheep and goats (extra-label).
  • Treatment of contagious ecthyma (orf) complicated by secondary bacterial infection (extra-label).
  • Treatment of caseous lymphadenitis (Corynebacterium pseudotuberculosis) (extra-label).
Rabbit & Small Mammals
  • Treatment of respiratory infections (e.g., Pasteurella multocida, Bordetella bronchiseptica) (extra-label).
  • Treatment of bacterial enteritis (e.g., Clostridium, E. coli) (extra-label).
Avian & Poultry
  • Treatment of respiratory infections (e.g., Mycoplasma gallisepticum, Ornithobacterium rhinotracheale) in poultry (extra-label).
  • Treatment of chlamydiosis (psittacosis) in psittacines (extra-label).
  • Treatment of bacterial infections in companion birds (e.g., macaws, cockatiels) (extra-label).
Exotic & Other Species
  • Treatment of bacterial infections in reptiles (e.g., Mycoplasma, Chlamydia) (extra-label).
  • Treatment of bacterial infections in ferrets (e.g., Helicobacter mustelae) (extra-label).
  • Treatment of bacterial infections in small mammals (e.g., guinea pigs, hamsters) (extra-label).

Pharmacology & Mechanism of Action

Drug Class: Macrolide antibiotic | Pharmacological Group: Azalide antibiotic

Mechanism of Action: Azithromycin binds to the 50S ribosomal subunit of susceptible bacteria, specifically to the 23S rRNA of the 50S subunit, thereby inhibiting bacterial protein synthesis. It acts by interfering with the translocation step of protein synthesis, preventing the elongation of the peptide chain. This action is generally bacteriostatic, but at higher concentrations it may be bactericidal against certain organisms. Azithromycin is a derivative of erythromycin with an expanded ring structure (azalide) that enhances its acid stability, tissue penetration, and spectrum of activity against Gram-negative organisms.

Pharmacodynamics: Azithromycin exhibits time-dependent killing with a prolonged post-antibiotic effect (PAE). It is effective against a range of Gram-positive and Gram-negative bacteria, including Staphylococcus, Streptococcus, Moraxella, Pasteurella, Bordetella, and some mycoplasmas. It also has activity against intracellular pathogens such as Chlamydia, Rickettsia, and Bartonella. The drug concentrates in tissues and phagocytic cells, achieving high intracellular levels, which is beneficial for treating intracellular infections. Its anti-inflammatory and immunomodulatory properties have been noted, which may contribute to its efficacy in chronic respiratory conditions.

⚡ Pharmacokinetics Summary

Absorption: Azithromycin is rapidly absorbed after oral administration, but its bioavailability is variable (approximately 37% in dogs, 30% in cats, and 25% in horses). Food can decrease absorption, but it is often administered with food to reduce gastrointestinal upset. In ruminants, oral absorption is poor due to ruminal degradation; therefore, parenteral administration is preferred.
Distribution: Azithromycin has a large volume of distribution, indicating extensive tissue penetration. It concentrates in tissues, particularly in the lungs, tonsils, prostate, and phagocytic cells. Tissue concentrations can be 10-100 times higher than plasma concentrations. It crosses the blood-brain barrier poorly, but it does cross the placenta and is excreted in milk.
Metabolism: Azithromycin undergoes minimal hepatic metabolism. It is primarily eliminated unchanged in the bile and feces. Some metabolism occurs via demethylation, but the majority of the drug is excreted as the parent compound.
Excretion: The primary route of excretion is biliary, with significant fecal elimination. Renal excretion accounts for only about 6-12% of the dose. The elimination half-life is prolonged due to extensive tissue binding and enterohepatic recirculation.
Half-Life: Dogs: 24-48 hours; Cats: 24-36 hours; Horses: 10-20 hours; Cattle: 24-48 hours (after IV/SC); Rabbits: 4-8 hours (variable)
Bioavailability: Oral: Dogs ~37%, Cats ~30%, Horses ~25%; IM/SC: nearly 100% in cattle and swine (if available)
Protein Binding: Azithromycin is approximately 50% protein-bound in plasma, but binding is concentration-dependent and lower in tissues.

Available Formulations & Strengths

Oral Tablet 250 mg, 500 mg, 600 mg (PO)
Oral Suspension 200 mg/5 mL, 100 mg/5 mL (PO)
Powder for Oral Suspension 1 g packet (for reconstitution) (PO)
Injectable Solution (for veterinary use in some countries) 100 mg/mL (IV, IM, SC)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to azithromycin, erythromycin, or any macrolide antibiotic.
  • Severe hepatic impairment.
  • Concurrent use with ergot derivatives (e.g., ergotamine) due to risk of ergotism.
  • Use in animals with known QT prolongation or those receiving drugs that prolong QT interval (e.g., cisapride, pimozide) due to risk of cardiac arrhythmias.
  • In horses, avoid oral administration in animals with colic or severe GI stasis.
Warnings & Clinical Precautions:
  • Use with caution in animals with hepatic disease, as azithromycin is metabolized by the liver.
  • Use with caution in animals with renal impairment; dose adjustment may be necessary.
  • May cause gastrointestinal upset (vomiting, diarrhea, anorexia); administer with food to reduce GI signs.
  • In herbivores (horses, rabbits, ruminants), oral administration may disrupt normal gut flora and predispose to enteritis or colitis; monitor closely.
  • Prolonged use may result in overgrowth of non-susceptible organisms, including Clostridium difficile, leading to pseudomembranous colitis.
  • In food animals, observe withdrawal times; extra-label use requires veterinary oversight and extended withdrawal periods.
  • Use in pregnant or lactating animals only if clearly needed; safety not fully established.
  • In birds, avoid use in species with known sensitivity to macrolides (e.g., some passerines).

Adverse Effects & Reactions

Common:

  • Gastrointestinal disturbances: vomiting, diarrhea, anorexia, nausea
  • Soft stools or diarrhea in horses and rabbits
  • Injection site reactions (if injectable form used): pain, swelling, inflammation

Serious / Severe:

  • Hepatotoxicity (elevated liver enzymes, jaundice)
  • QT prolongation and cardiac arrhythmias (especially in animals with underlying heart disease or concurrent QT-prolonging drugs)
  • Clostridium difficile-associated diarrhea (potentially fatal)
  • Anaphylaxis (rare but possible)
  • Ototoxicity (rare, especially with high doses)

Rare:

  • Allergic skin reactions (urticaria, angioedema)
  • Blood dyscrasias (leukopenia, thrombocytopenia)
  • Seizures (in overdose or with renal impairment)
  • Acute pancreatitis
  • Hearing loss (reversible)

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Antacids (aluminum/magnesium) Decreased absorption of azithromycin; separate administration by at least 2 hours. Moderate
Warfarin and other anticoagulants May enhance anticoagulant effect; monitor prothrombin time. Moderate
Digoxin May increase digoxin levels; monitor for toxicity. Moderate
Cisapride, pimozide, and other QT-prolonging drugs Increased risk of ventricular arrhythmias; avoid concurrent use. High
Cyclosporine May increase cyclosporine levels; monitor renal function and drug levels. Moderate
Ergot alkaloids (ergotamine, dihydroergotamine) Risk of ergotism (peripheral vasospasm, ischemia); avoid concurrent use. High
Theophylline May increase theophylline levels; monitor for toxicity. Mild
Rifampin May reduce azithromycin levels; used together in Rhodococcus equi therapy but monitor efficacy. Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Severe vomiting and diarrhea
  • Lethargy
  • Ataxia
  • Tremors
  • Seizures (in severe cases)
  • Hepatotoxicity (elevated liver enzymes, jaundice)
  • QT prolongation and cardiac arrhythmias

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce emesis if ingestion is recent (within 1-2 hours) and the animal is conscious. Administer activated charcoal to reduce absorption. Provide intravenous fluids to maintain hydration and electrolyte balance. Monitor liver enzymes, renal function, and cardiac parameters (ECG). In cases of severe arrhythmias, administer antiarrhythmic agents as needed. There is no specific antidote; hemodialysis is not effective.

Food Animal Withdrawal Times

🥩 Meat: 30 days🥛 Milk: 7 days

Withdrawal times are not established for azithromycin in food animals in the US. Extra-label use requires a prolonged withdrawal period; consult FARAD (Food Animal Residue Avoidance Databank) for specific recommendations. In cattle, a meat withdrawal of at least 30 days and milk withdrawal of at least 7 days is often recommended, but these are estimates and should be adjusted based on the formulation and route of administration.

Storage, Handling & Regulatory Information

Storage Temperature: Store at room temperature (20-25°C, 68-77°F) in a tightly closed container. Protect from moisture.

Handling & Special Conditions: Store oral suspension in the refrigerator after reconstitution (2-8°C, 35-46°F) and discard after 10 days. Keep away from direct sunlight.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use. Some veterinary products may be available in other countries.

Extra-Label (Off-Label) Use: Azithromycin is not FDA-approved for veterinary use in the US, but it can be used legally under the Animal Medicinal Drug Use Clarification Act (AMDUCA) by or on the order of a licensed veterinarian within a valid veterinarian-client-patient relationship. Extra-label use in food animals requires an extended withdrawal period and must not result in violative residues. In the EU, similar regulations apply under the Cascade.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Azithromycin is a valuable antibiotic in veterinary medicine due to its broad spectrum, excellent tissue penetration, and long half-life, allowing once-daily dosing. It is particularly useful for treating intracellular pathogens and respiratory infections. However, its use in herbivores is limited by the risk of GI disturbances and enteritis. In horses, it is a cornerstone for treating Rhodococcus equi pneumonia in foals, often combined with rifampin. In small animals, it is commonly used for respiratory infections, Bartonella, and Mycoplasma. Always consider culture and susceptibility testing when possible. Monitor for adverse effects, especially gastrointestinal and hepatic. In food animals, adhere to withdrawal times and use extra-label judiciously.

References & Literature

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