Drug Monograph
Full clinical overview, indications, dosage references & safety notes.
Available forms4 forms · 8 strengths documentedShow all ↓
Tablet 250 mgTablet 500 mgTablet 600 mgOral packet 1 g single-doseOral packet 2 g Zmax
Suspension 100 mg/5 mLSuspension 200 mg/5 mL
500 mg vial powder for reconstitution
Overview
Azithromycin (Zithromax) is a semisynthetic macrolide antibiotic used in dogs and cats for the treatment of selected bacterial, rickettsial, and protozoal infections. It is available in oral and parenteral formulations and is characterized by excellent tissue penetration and prolonged tissue half-lives.
In small animal practice, azithromycin is valued for its convenient dosing intervals, high intracellular concentrations, and comparatively favorable gastrointestinal tolerability when compared with older macrolides such as erythromycin.
Azithromycin exhibits bacteriostatic activity by inhibiting bacterial protein synthesis through binding to the 50S ribosomal subunit. In addition to its antimicrobial activity, it has been shown to exert anti-inflammatory and immunomodulatory effects; however, the clinical relevance of these properties in dogs and cats remains unclear.
Due to its pharmacokinetic profile, azithromycin persists in tissues long after serum concentrations decline, allowing for extended dosing intervals in some treatment protocols. This characteristic makes it useful for chronic or refractory infections when alternative antimicrobials are not suitable.
Appropriate use of azithromycin should take into account antimicrobial stewardship principles, as it is classified by the World Health Organization as a Critically Important, Highest Priority antimicrobial for human medicine.
Indications
Azithromycin is indicated in dogs and cats for the treatment of selected bacterial, rickettsial, and protozoal infections when culture and sensitivity data, clinical judgment, or patient factors support its use.
- Susceptible bacterial infections: Used for infections caused by susceptible gram-positive and may also used for treatment of gram – negative bacteria ( mycoplasma , Chlamydia ) but not drug of choice .
- Rickettsial and intracellular infections:Effective against certain intracellular pathogens due to high intracellular and tissue concentrations.
- Canine papillomatosis (extra-label): Azithromycin has been used anecdotally in dogs; however, clinical efficacy is unclear, as spontaneous lesion regression may occur without treatment.
- Feline chronic or refractory rhinosinusitis (extra-label): Anecdotally used in cats with recurrent or refractory upper respiratory disease when chlamydiosis is unlikely and other antimicrobials (eg, doxycycline, amoxicillin) are not viable options.
- Protozoal infections (extra-label): Used in dogs and cats as part of combination therapy for selected protozoal diseases, based on its antiprotozoal activity.
- Gastrointestinal promotility (extra-label): Due to prokinetic properties described in humans, azithromycin has been used anecdotally as a GI promotility agent in dogs and cats.
- Ciclosporin-induced gingival hyperplasia (extra-label): Used to reduce gingival overgrowth secondary to ciclosporin when stopping ciclosporin is not possible; 10 mg/kg PO once daily for 4-6 weeks.
Dosage (Reference)
Dog
In dogs, azithromycin dosing is variable and often adjusted based on infection type and duration of therapy. Due to its long tissue half-life, extended dosing intervals may be used after initial daily administration.
| Clinical use | Route | Dose | Frequency | Notes |
|---|---|---|---|---|
| Susceptible infections (general) | PO | 5-10 mg/kg | q24h | Typical duration 3–7 days. After several days, some clinicians switch to every-other-day dosing or higher doses (10–15 mg/kg) twice weekly for longer-term therapy. |
| Babesia gibsoni / B. microti-like piroplasm | PO | Azithromycin 10 mg/kg every 24 h + Atovaquone 13.3 mg/kg every 8 h (with fatty meal); | q24h | Combination therapy for 10 days. Reserve immunosuppressive therapy for cases not responding within 3–5 days. |
| Theileriosis | PO | Azithromycin 10 mg/kg every 24 h + Atovaquone 13.3 mg/kg every 8 h (with fatty meal) | q8h | 10 days. |
| Cryptosporidiosis | PO | 5-10 mg/kg | q12h (twice daily) | 5–7 days. |
| GI promotility (extra-label) | IV / PO | 2 mg/kg | q8h | Anecdotal use. |
| Canine papillomatosis | PO | 10 mg/kg | q24h | 10 days , clinical efficacy is unclear. |
| Ciclosporin-induced gingival hyperplasia | PO | 10 mg/kg | q24h | 4–6 weeks (extra-label). |
- Long tissue half-life allows for extended dosing intervals in selected cases.
- Adjust dose and duration based on clinical response and infection type.
- Give oral doses consistently; GI upset is usually mild and self-limiting.
Cat
In cats, azithromycin is commonly used for selected infections requiring good intracellular and tissue penetration. Dosing intervals may be extended for long-term therapy due to prolonged tissue persistence.
| Clinical use | Route | Dose | Frequency | Notes |
|---|---|---|---|---|
| Susceptible infections (general) | PO | 5-10 mg/kg | q24h | Typical duration 3–7 days. For longer courses, every-48-hour dosing or higher doses (10–15 mg/kg) given twice weekly may be used. |
| Susceptible infections – alternative pulse regimen | PO | 5 mg/kg | q24h ×2 days, then every 3–5 days | Up to 5 doses total. |
| Upper respiratory infections | PO | 5-10 mg/kg | q24h → q72h | Give for 5 days, then every 72 hours long-term. Continue therapy for 6–8 weeks after initial response. |
| Bartonellosis | PO | 10 mg/kg | q24h | 21 days; clinical response is usually rapid. |
| Cryptosporidiosis | PO | 10 mg/kg | q24h | Several weeks; optimal duration not well defined. |
| Cytauxzoonosis | PO | Azithromycin 10 mg/kg every 24 h + Atovaquone 15 mg/kg every 8 h | q8h | 10 days; ensure adequate food intake to maximize absorption. |
| Toxoplasmosis | PO | 10 mg/kg | q24h | Minimum of 4 weeks (efficacy against Toxoplasma is considered questionable ) |
| GI promotility (extra-label) | IV / PO | 2 mg/kg | q8h | Anecdotal use. |
- Extended dosing intervals may be effective due to tissue persistence.
- Azithromycin activity is enhanced in an alkaline pH; administer on an empty stomach
- Monitor for vomiting, diarrhea, or reduced appetite during therapy.
Warnings & Precautions
Azithromycin should be used judiciously in dogs and cats, with consideration given to patient-specific risk factors, concurrent medications, and antimicrobial stewardship principles.
- Hypersensitivity: Contraindicated in animals with known hypersensitivity to azithromycin or other macrolide antibiotics.
- Hepatic and renal dysfunction: Use with caution in dogs and cats with impaired hepatic function, as azithromycin is primarily eliminated via hepatic metabolism and biliary excretion. avoiding azithromycin in renal and hepatic failure in all species.
- Cardiac effects (QT prolongation): Azithromycin may prolong the QT interval and increase the risk of cardiac arrhythmias. Use cautiously in patients with underlying cardiac disease or when administered concurrently with other QT-prolonging drugs.
- Myasthenia gravis: Exacerbation of clinical signs or new-onset neuromuscular weakness has been reported in human patients. The clinical significance in veterinary patients is unknown, but caution is advised in dogs or cats with known or suspected myasthenia gravis.
- Gastrointestinal tolerance: Although generally better tolerated than erythromycin, azithromycin may still cause vomiting, diarrhea, or reduced appetite, particularly at higher doses or with prolonged therapy.
- Antimicrobial stewardship: Azithromycin is classified by the World Health Organization as a critically important antimicrobial for human medicine. Its use should be reserved for cases in which culture and sensitivity data, clinical judgment, or patient factors justify its selection.
- Prescription errors: Medication errors have occurred due to confusion between azithromycin and azathioprine. Use of “tall man” lettering (aZITHROmycin vs azaTHIOprine) is recommended to reduce dispensing and prescribing errors.
- Chronic or long-term therapy: Prolonged courses should be undertaken with caution, and patients should be monitored for adverse effects and treatment efficacy.
- Intravenous administration: Intravenous administration: Do NOT give the IV solution as a rapid bolus or by the IM route. Dilute and infuse slowly over 1-3 hours (a 1 mg/mL solution over 3 hours, or 2 mg/mL over 1 hour).
- Administration & gastric pH: Azithromycin activity is enhanced at alkaline pH dosing on an empty stomach. (Some feline protocols advise giving with food to maximize absorption and reduce GI upset – see Dosage notes.)
Drug Interactions
Azithromycin has the potential to interact with several medications, primarily through effects on cardiac conduction, hepatic metabolism, and drug transport mechanisms. Careful assessment of concurrent therapies and appropriate monitoring are recommended when azithromycin is used in dogs and cats.
- QT-prolonging drugs: Concurrent use with medications known to prolong the QT interval (eg, azole antifungals, cisapride, ondansetron, quinolones, procainamide, quinidine, sotalol) may increase the risk of clinically significant cardiac arrhythmias.
- Cyclosporine: Azithromycin may increase cyclosporine blood concentrations; close monitoring of cyclosporine levels and dose adjustment may be necessary.
- Digoxin: Increased risk of digoxin toxicity has been reported with concurrent administration; monitor for clinical signs of digoxin excess.
- Tacrolimus: Azithromycin may increase tacrolimus serum concentrations; therapeutic drug monitoring is recommended.
- Warfarin: Concurrent use may increase the risk of bleeding; careful monitoring of coagulation status is advised.
- Theophylline: Azithromycin may reduce theophylline metabolism, increasing the risk of theophylline toxicity.
- P-glycoprotein substrates: Azithromycin inhibits P-glycoprotein transport mechanisms and may increase serum concentrations of drugs that rely on this pathway (eg, colchicine, doxorubicin, morphine, vincristine).
- Antacids (oral): Magnesium- or aluminum-containing antacids may reduce the rate of azithromycin absorption; administer azithromycin at least 2 hours apart from these products.
- Methotrexate: Concurrent use may increase methotrexate concentrations and the risk of hepatotoxicity.
- Leflunomide: Combined use may increase the risk of hepatic toxicity; monitor liver enzymes when used together.
- Amiodarone: Increased risk of QT prolongation when combined with azithromycin.
- Estriol: Azithromycin may decrease estriol’s therapeutic effect.
- Methylprednisolone & terfenadine: Azithromycin may increase the serum levels of methylprednisolone and terfenadine.
Side Effects & Overdose
Azithromycin is generally well tolerated in dogs and cats, with adverse effects occurring less frequently and with lower severity than with older macrolide antibiotics such as erythromycin. Most reported adverse effects are gastrointestinal in nature.
Side Effects
- Gastrointestinal effects: Vomiting, reduced appetite, and diarrhea are the most commonly reported adverse effects in dogs and cats, particularly during the initial days of therapy or with higher doses.
- Inappetence: Transient decreases in food intake may occur and usually resolve without intervention.
- Injection site reactions: Local irritation or discomfort has been reported with parenteral administration.
- Hepatic effects: Although uncommon, elevations in liver enzymes may occur, especially in patients with pre-existing hepatic disease or when used concurrently with other hepatotoxic drugs.
- Cardiac effects: QT interval prolongation is possible and may predispose susceptible patients to cardiac arrhythmias, particularly when combined with other QT-prolonging agents.
Overdose
Acute oral overdoses of azithromycin in dogs and cats are unlikely to cause severe toxicity. Clinical signs are typically limited to exaggerated gastrointestinal effects.
- Common signs: Vomiting, diarrhea, abdominal discomfort, and gastrointestinal cramping.
- Severe toxicity: Rare; serious systemic effects are not commonly reported following acute overdose.
- Management: Treatment is supportive and symptomatic. Maintain hydration and monitor for persistent gastrointestinal signs.
- Consultation: For suspected or confirmed overdose, consultation with a 24-hour veterinary poison consultation center is recommended.
Key Notes
Practical clinical points that help optimize the appropriate use of azithromycin in dogs and cats:
- Prolonged tissue persistence: Azithromycin concentrates in tissues and white blood cells, allowing for extended dosing intervals in selected protocols once steady-state tissue levels are achieved.
- Intracellular activity: High intracellular concentrations make azithromycin particularly useful for infections involving intracellular organisms, even when serum concentrations appear low.
- Delayed pharmacodynamic effect: Clinical improvement may continue after completion of therapy due to sustained tissue drug concentrations.
- Variable dosing strategies: Dosing regimens may differ substantially depending on indication, chronicity of disease, and patient response; adherence to indication-specific protocols is essential.
- Limited eradication potential: In some infections, azithromycin may improve clinical signs without fully eliminating the causative organism; relapse may occur after discontinuation.
- Culture and sensitivity: Whenever possible, antimicrobial selection should be guided by culture and susceptibility testing to optimize efficacy and limit resistance.
- Client compliance: Simplified dosing schedules can improve owner adherence, particularly during long-term therapy.
- Pharmacokinetics: Dogs – oral bioavailability ~90-97%, peak serum ~2 h, serum half-life ~30-50 h with tissue half-lives up to 90 h; >50% excreted unchanged in bile; skin concentrations 3.5-12x serum. Cats – ~58%, peak ~0.85 h, plasma half-life ~35 h, tissue half-lives 13-72 h; 66% excreted unchanged in bile.
- Pregnancy & lactation: Safe use during pregnancy has not been fully established; use only when clearly necessary. In humans, low amounts of azithromycin are excreted in breast milk; the clinical significance in veterinary patients is unknown. Use only when maternal benefits outweigh potential risks to offspring.
