Clarithromycin
Clarithromycin is a semi-synthetic **macrolide antibiotic** closely related to erythromycin. It is structurally modified via the methylation of position 6 in the lactone ring, which confers improved acid stability, better oral bioavailability, and a broader spectrum of activity compared to its parent compound. **Key Clinical Features:** * **Spectrum of Activity:** Similar to erythromycin but highly effective against **atypical mycobacteria** (e.g., *Mycobacterium avium* complex), *Helicobacter* spp., and *Rhodococcus equi*. * **Clinical Utility:** Primarily used in small animals for atypical mycobacterial infections (like feline leprosy or canine leproid granuloma) and *Helicobacter* eradication protocols. In equine medicine, it is a cornerstone treatment for *Rhodococcus equi* pneumonia in foals. * **Tolerability:** Generally better tolerated than erythromycin, with fewer gastrointestinal side effects, as it has less prokinetic (motilin-receptor agonist) activity. > **Clinical Pearl:** Clarithromycin is a potent inhibitor of the cytochrome P450 3A (CYP3A) enzyme system. Concurrent use with other drugs metabolized by this pathway requires careful review to avoid toxicity.
Mechanism: Clarithromycin is typically **bacteriostatic**, though it can be bactericidal at high concentrations against highly susceptible organisms. * **Mechanism:** It penetrates the bacterial cell wall and reversibly binds to the **P site of the 50S ribosomal subunit**. * **Pathway:** Binding โ Inhibition of RNA-dependent protein synthesis (blocks transpeptidation and translocation) โ Suppression of bacterial growth. * **Post-Antibiotic Effect (PAE):** Macrolides generally exhibit a prolonged PAE against Gram-positive pathogens, allowing for sustained efficacy even when plasma levels drop below the MIC.
Dosing by species
- Treatment of feline leprosy ยท 62.5 mg per cat q12h ยท PO ยท q12h ยท Used in a regimen of 2 or 3 drugs including clofazimine and/or rifampin.
- Treatment of Nocardia (N. nova) infections ยท 62.5-125 mg (total dose per cat) PO twice daily ยท PO ยท q12h ยท Combination therapy with amoxicillin and/or doxycycline.
- Treatment of H. pylori infections ยท 7.5 mg/kg PO twice daily ยท PO ยท q12h ยท 14 days ยท Combination therapy with metronidazole and amoxicillin.
- Treatment of M. tuberculosis-bovis variant infections ยท 5-10 mg/kg PO q12h ยท PO ยท q12h ยท At least 2 months, then maintenance for 4 months ยท Used with rifampin and enrofloxacin.
- Susceptible infections ยท 7.5 mg/kg PO q12h ยท PO ยท q12h
- Treatment of Helicobacter mustelae infections ยท 12.5 mg/kg PO q12h ยท PO ยท q12h ยท 14 days ยท With ranitidine bismuth citrate. Same regimen given q8h is also published.
- Treatment of Helicobacter mustelae infections ยท 12.5-50 mg/kg q8-24h ยท PO ยท q8-24h ยท With omeprazole at 0.7 mg/kg PO once daily.
- Treatment of Rhodococcus equi infection in foals ยท 7.5 mg/kg PO q12h ยท PO ยท q12h
- Treatment of Rhodococcus equi infection in foals ยท 7.5 mg/kg PO q12h ยท PO ยท q12h ยท In combination with rifampin at 5 mg/kg PO q12h or 10 mg/kg PO q24h.
Routes of administration
Contraindications
- Known hypersensitivity to clarithromycin or other macrolide antibiotics (e.g., erythromycin, azithromycin)
- Concurrent use with cisapride (due to risk of fatal cardiac arrhythmias)
Adverse effects
- Gastrointestinal disturbances (nausea, vomiting, anorexia, diarrhea)
- Pinnal or generalized erythema (specifically noted in cats)
- Transient, mild BUN elevation
- Prolonged QT interval / torsades de pointes (rare)
- Hepatotoxicity (rare)
- Thrombocytopenia (rare)
- Pseudomembranous colitis secondary to Clostridium difficile (reported in humans)
Drug interactions
- Cisapride ยท Clarithromycin inhibits cisapride metabolism; concurrent use is contraindicated due to risk of severe cardiac arrhythmias.
- Fluconazole ยท May increase clarithromycin serum levels.
- Digoxin ยท Clarithromycin may increase serum levels of digoxin.
- Omeprazole ยท Concurrent use can increase the plasma levels of both drugs.
- Warfarin ยท May potentiate the effects of oral anticoagulant drugs.
- Zidovudine ยท Clarithromycin may decrease serum concentrations of zidovudine.
- CYP3A Substrates (Alfentanil, Bromocriptine, Buspirone, Carbamazepine, Methylprednisolone, Midazolam, Alprazolam, Triazolam, Rifabutin, Tacrolimus, Theophylline) ยท Clarithromycin inhibits CYP3A, potentially increasing plasma concentrations and toxicity of these drugs. Therapeutic monitoring or dose reduction may be required.
- Disopyramide ยท Increased levels and risk of prolonged QT interval.
- Quinidine ยท Increased levels and risk of prolonged QT interval.
Monitoring
- Clinical efficacy (resolution of infection)
- Gastrointestinal adverse effects
- Signs of erythema (especially in cats)
- Potential drug interactions if on concurrent medications
Overdose
Overdoses of clarithromycin are generally not life-threatening and primarily result in **gastrointestinal distress** (vomiting, diarrhea, cramping). * **Treatment:** For recent, large ingestions, administration of activated charcoal with a cathartic may help remove unabsorbed drug. * **Note:** Forced diuresis, peritoneal dialysis, or hemodialysis are **not effective** in enhancing the elimination of clarithromycin from the body.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.