Clarithromycin

Macrolide antibiotic Antibacterial

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 7.5-15 mg/kg q12h Duration: 5-14 days depending on infection
Notes: For Helicobacter pylori eradication, use 7.5 mg/kg q12h in combination with a proton pump inhibitor and amoxicillin or metronidazole for 14 days.
Cat PO 7.5-15 mg/kg q12h Duration: 5-14 days depending on infection
Notes: For atypical mycobacterial infections, higher doses (up to 15 mg/kg q12h) may be used for prolonged periods.
Horse (foal) PO 7.5-10 mg/kg q12h Duration: 4-12 weeks for Rhodococcus equi pneumonia
Notes: Often used in combination with rifampin (5-10 mg/kg q12h).
Rabbit PO 15 mg/kg q12h Duration: 10-14 days
Notes: Use with caution; gastrointestinal upset is common.
Cattle PO Not established; extra-label use may be 10-15 mg/kg q12h q12h Duration: 5-7 days
Notes: Not approved for food animals; withdrawal times must be observed.
Small Ruminants PO Not established; extra-label use may be 10-15 mg/kg q12h q12h Duration: 5-7 days
Notes: Not approved for food animals; withdrawal times must be observed.

Clinical Indications & Species Uses

General Indications
  • Treatment of infections caused by susceptible gram-positive and atypical bacteria, including Mycoplasma, Chlamydia, and Helicobacter species.
Dog (Canine)
  • Treatment of bacterial infections caused by susceptible organisms, including respiratory tract infections, skin and soft tissue infections, Helicobacter pylori eradication (in combination with other agents), and atypical mycobacterial infections (e.g., Mycobacterium avium complex).
Cat (Feline)
  • Treatment of respiratory tract infections, skin infections, and Helicobacter pylori eradication. Also used for atypical mycobacterial infections and toxoplasmosis (in combination with other drugs).
Horse (Equine)
  • Treatment of respiratory infections, particularly Rhodococcus equi pneumonia in foals (often in combination with rifampin).
Rabbit & Small Mammals
  • Treatment of respiratory infections (e.g., Pasteurella multocida) and other susceptible bacterial infections.
Exotic & Other Species
  • Treatment of bacterial infections in small mammals (e.g., ferrets, rodents) and reptiles, but use is limited and based on susceptibility testing.

Pharmacology & Mechanism of Action

Drug Class: Macrolide antibiotic | Pharmacological Group: Antibacterial

Mechanism of Action: Clarithromycin is a semisynthetic macrolide antibiotic that reversibly binds to the 50S ribosomal subunit of susceptible bacteria, inhibiting protein synthesis by blocking translocation of peptidyl-tRNA. It is bacteriostatic but may be bactericidal at high concentrations. It has activity against a broad range of gram-positive and some gram-negative bacteria, as well as atypical pathogens such as Mycoplasma, Chlamydia, and Helicobacter. Clarithromycin also has immunomodulatory and anti-inflammatory effects, including inhibition of cytokine production and neutrophil function.

Pharmacodynamics: Clarithromycin exhibits time-dependent killing with a post-antibiotic effect (PAE) against susceptible organisms. It is more acid-stable than erythromycin, leading to better oral absorption. Its active metabolite, 14-hydroxyclarithromycin, is two to four times more active against Haemophilus influenzae than the parent compound. The drug concentrates in tissues and phagocytes, achieving high intracellular levels. It is effective against intracellular pathogens and has been used for its anti-inflammatory properties in chronic respiratory diseases.

⚑ Pharmacokinetics Summary

Absorption: Clarithromycin is rapidly absorbed from the gastrointestinal tract after oral administration. Food delays absorption but does not significantly affect total bioavailability. In dogs, oral bioavailability is approximately 70-80%. In horses, oral absorption is variable and may be lower.
Distribution: Clarithromycin is widely distributed into tissues and body fluids, with high concentrations in lung, tonsils, and middle ear fluid. It penetrates intracellularly and accumulates in macrophages and polymorphonuclear leukocytes. Protein binding is approximately 70-80% in dogs and cats. It crosses the placenta and is excreted in milk.
Metabolism: Clarithromycin is extensively metabolized in the liver, primarily by the cytochrome P450 (CYP) 3A4 isoenzyme. The major metabolite is 14-hydroxyclarithromycin, which is pharmacologically active. Metabolism can be saturated at high doses, leading to nonlinear pharmacokinetics.
Excretion: Clarithromycin is excreted primarily in the urine (20-40% as unchanged drug) and in bile. In dogs, approximately 30% of the dose is excreted unchanged in urine. Fecal excretion accounts for a significant portion of the remaining dose. In animals with hepatic or renal impairment, elimination may be prolonged.
Half-Life: Dogs: approximately 2-4 hours; Cats: approximately 3-5 hours; Horses: approximately 1-2 hours; Cattle: approximately 2-3 hours.
Bioavailability: Oral: approximately 70-80% in dogs; 50-60% in cats; variable in horses (30-60%).
Protein Binding: Approximately 70-80% in dogs and cats; 50-70% in horses.

Available Formulations & Strengths

Oral Tablet 250 mg, 500 mg (PO)
Oral Suspension (reconstituted) 25 mg/mL, 50 mg/mL (PO)
Extended-release Tablet 500 mg, 1000 mg (PO)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to clarithromycin, erythromycin, or other macrolide antibiotics.
  • Concurrent use with ergot derivatives (e.g., ergotamine) due to risk of ergotism.
  • Concurrent use with cisapride, pimozide, or terfenadine due to risk of QT prolongation and cardiac arrhythmias.
  • Severe hepatic impairment.
  • Use in animals with known electrolyte disturbances (e.g., hypokalemia, hypomagnesemia) that may predispose to QT prolongation.
Warnings & Clinical Precautions:
  • Use with caution in animals with hepatic or renal impairment; dose adjustment may be necessary.
  • May cause gastrointestinal upset; administer with food to reduce GI irritation.
  • Use with caution in animals with myasthenia gravis; may exacerbate weakness.
  • Prolonged use may result in superinfection with resistant bacteria or fungi.
  • In horses, oral administration may cause diarrhea; monitor for signs of colitis.
  • In rabbits and rodents, clarithromycin may disrupt gastrointestinal flora; use with caution and consider probiotic support.
  • Safety in pregnant or lactating animals has not been fully established; use only when clearly needed.
  • May cause QT prolongation; avoid concurrent use with other drugs that prolong QT interval.

Adverse Effects & Reactions

Common:

  • Gastrointestinal disturbances (vomiting, diarrhea, anorexia, nausea)
  • Abdominal pain
  • Flatulence
  • Dysgeusia (altered taste)

Serious / Severe:

  • Hepatotoxicity (elevated liver enzymes, jaundice)
  • QT prolongation and ventricular arrhythmias
  • Pseudomembranous colitis (due to Clostridium difficile overgrowth)
  • Allergic reactions (angioedema, anaphylaxis)
  • Ototoxicity (especially with high doses or renal impairment)

Rare:

  • Blood dyscrasias (leukopenia, thrombocytopenia)
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
  • Interstitial nephritis
  • Seizures (in patients with renal impairment)

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Cisapride, pimozide, terfenadine Increased risk of QT prolongation and serious cardiac arrhythmias; concurrent use is contraindicated. High
Ergot derivatives (ergotamine, dihydroergotamine) Increased risk of ergotism (peripheral vasospasm, ischemia); concurrent use is contraindicated. High
Theophylline Clarithromycin may increase theophylline levels, leading to toxicity; monitor theophylline concentrations and adjust dose. Moderate
Digoxin Clarithromycin may increase digoxin levels, increasing risk of toxicity; monitor digoxin levels. Moderate
Warfarin Clarithromycin may enhance anticoagulant effect; monitor coagulation parameters. Moderate
Corticosteroids (e.g., methylprednisolone) Clarithromycin may increase corticosteroid levels; monitor for increased effects. Mild
Antacids containing aluminum or magnesium May reduce clarithromycin absorption; separate administration by at least 2 hours. Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Gastrointestinal signs (vomiting, diarrhea, abdominal pain)
  • Hearing loss
  • Severe nausea
  • Confusion
  • QT prolongation and arrhythmias
  • Hepatotoxicity

Emergency Treatment Protocol: There is no specific antidote. Treatment is symptomatic and supportive. Induce emesis if ingestion is recent and the animal is conscious. Administer activated charcoal to reduce absorption. Provide intravenous fluids and electrolyte support. Monitor cardiac function (ECG) and liver enzymes. In severe cases, consider hemodialysis (though clarithromycin is not significantly removed by dialysis).

Food Animal Withdrawal Times

πŸ₯© Meat: 28 daysπŸ₯› Milk: 7 days

Clarithromycin is not approved for use in food animals in many countries. Extra-label use requires extended withdrawal times; consult regulatory guidelines. The values provided are estimates based on pharmacokinetic data; actual withdrawal times may vary.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature (20-25Β°C, excursions permitted to 15-30Β°C).

Handling & Special Conditions: Keep container tightly closed. Protect from moisture. Oral suspension: after reconstitution, store at room temperature for up to 14 days; do not refrigerate.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Clarithromycin is not FDA-approved for veterinary use in dogs, cats, or food animals. It is used extra-label in veterinary medicine.

Extra-Label (Off-Label) Use: In the US, extra-label use in food animals is permitted under AMDUCA with a valid veterinary-client-patient relationship. However, clarithromycin is not approved for food animals, and withdrawal times must be extended. In the EU, extra-label use is also regulated; consult local regulations.

Clinical Pearls & Practice Notes

πŸ’‘ Clinical Insights: Clarithromycin is a valuable macrolide antibiotic in veterinary medicine, particularly for respiratory infections and intracellular pathogens. It is often used in combination with other drugs for Helicobacter pylori eradication and for Rhodococcus equi pneumonia in foals. Its acid stability and good tissue penetration make it a preferred macrolide in some cases. However, its use is extra-label in most veterinary species, and clinicians should be aware of potential drug interactions and adverse effects, especially gastrointestinal upset and QT prolongation. In food animals, withdrawal times must be carefully observed. Always perform culture and susceptibility testing when possible to ensure appropriate antibiotic selection.

References & Literature

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