Generic Name

Clarithromycin

Mechanism

• Protein synthesis inhibition: Binds reversibly to the 50S ribosomal subunit, blocking the translocation of peptide chains, thereby halting bacterial protein synthesis.
• Bactericidal at high concentrations; bacteriostatic at lower concentrations.
• Broad Gram‑positive and atypical coverage (e.g., *Streptococcus pneumoniae*, *Mycoplasma pneumoniae*, *Chlamydia trachomatis*, *Legionella pneumophila*), with activity against some Gram‑negative organisms via a distinct 600‑kDa macrolide‑binding site.

Pharmacokinetics

• Absorption: Oral bioavailability ~30 % in fasted state; increases ~10 % when taken with food.
• Distribution: Highly protein‑bound (≈90 %); penetrates pulmonary tissues, CNS, and gastrointestinal tract.
• Metabolism: Extensive hepatic CYP3A4-mediated oxidation to active metabolite des‑chloro‑clarithromycin.
• Elimination: Primarily fecal (~70 %), renal (~20 %).
• Half‑life: 3–4 h (free drug); 5–6 h after oral dosing.
• Drug interactions: Potentiates CYP3A4 inhibitors/inducers; caution with QT‑prolonging agents.

Indications

• Respiratory tract: Acute bacterial bronchitis, community‑acquired pneumonia (after β‑lactam allergy), exacerbations of chronic bronchitis.
• Skin & Soft Tissue: Mild‑to‑moderate cutaneous infections, cellulitis, ecthyma, impetigo, abscesses.
• GERD & H. pylori: Used in combination with a proton‑pump inhibitor and amoxicillin for H. pylori eradication.
• Prophylaxis: Post‑traumatic or post‑operative prophylaxis for *Staphylococcus aureus*‑related infections.
• Atypical Mycobacterial infections: (e.g., *Mycobacterium avium* complex) in multi‑drug regimens.

Contraindications

• Contraindications: Severe hepatic impairment; hypersensitivity to macrolides; use with caution in patients on CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin itself).
• Warnings:
• QT prolongation: Avoid in patients with congenital long QT, electrolyte abnormalities, or those on other QT‑prolonging drugs.
• Liver dysfunction: Monitor transaminases; consider dose adjustment or alternative therapy.
• Drug‑drug interactions: High risk of drug‑related arrhythmias and elevated CYP3A4 substrates.

Dosing

• Adjustments: Reduce dose in severe hepatic dysfunction (use 250 mg BID), renal impairment (monitor levels), or pregnancy (Category B).
• Co‑administration: Take with food to improve absorption. Avoid concomitant CYP3A4 inhibitors.

Adverse Effects

• Common (≤10 %): Nausea, vomiting, diarrhea, abdominal pain, metallic taste.
• Serious (>10 %):
• Hepatotoxicity: Elevated AST/ALT, cholestatic jaundice.
• QT prolongation/arrhythmia: Torsades de pointes risk, especially in prolonged therapy.
• Severe rash/angioedema: Possible hypersensitivity reaction.
• Cytomegalovirus reactivation in transplant patients.
• Clostridioides difficile colitis – rare but possible.

Monitoring

• Liver function tests (ALT/AST, bilirubin): Baseline, mid‑treatment, then end‑of‑course.
• EKG/ QT interval: If baseline prolonged or when initiating QT‑prolonging therapy.
• Renal function: Serum creatinine for dosage adjustment in severe impairment.
• Therapeutic drug monitoring: Rarely needed but may be considered in special populations (e.g., transplant, obesity).
• Signs of hypersensitivity or severe GI upset should prompt drug discontinuation.

Clinical Pearls

• “Food‑fasted paradox”: While bioavailability is slightly higher with food, the risk of GI upset is higher; thus, medicate a light meal to balance efficacy and tolerability.
• CYP3A4 “double‑hit”: Clarithromycin is both a substrate and inhibitor; this can compound drug levels of statins, benzodiazepines, or clopidogrel—monitor closely or switch.
• Macrolide synergy: In H. pylori eradication, clarify the triples regimen (PPI + amoxicillin + clarithromycin) outperforms PPI + bismuth + tetracycline in compliance, especially in patients with penicillin allergy.
• Avoid in QT‑long: In patients with congenital Long QT or on amiodarone/fluoxetine, consider azithromycin instead (less QT risk).
• Rapid metabolism: Rapid hepatically‑mediated conversion to des‑chloro‑clarithromycin yields similar antimicrobial potency but also shares similar interaction profile—dosing intervals remain BID for typical therapy.
• Children <12 mo: Use the pooled paediatric dose (25 mg/kg BID) based on safety data; but if hepatic disease present, lower to 12.5 mg/kg.

Key Takeaway: Clarithromycin, a macrolide with substantial tissue penetration and favorable oral bioavailability, remains a first‑line or second‑line agent for a spectrum of infections, provided clinicians vigilantly monitor hepatic function, QT intervals, and potential drug interactions.