Clarithromycin

Clarithromycin is a macrolide with better oral absorption and tolerability than erythromycin. It is used for atypical pneumonia, Helicobacter pylori eradication, Mycobacterium avium complex and leprosy, and is a strong CYP3A4 inhibitor.

Classification. Macrolide.

Mechanism. Binds the 50S ribosomal subunit and blocks protein synthesis.

Spectrum. Streptococci, pneumococci (macrolide resistance common), MSSA, Haemophilus, Moraxella, Legionella, Mycoplasma, Chlamydia, Helicobacter pylori, Mycobacterium avium complex, Mycobacterium leprae and some rapidly growing mycobacteria. Not active against Enterobacterales or Pseudomonas.

Pharmacokinetics. Oral bioavailability about 50%. Half-life 3 to 7 hours (dose-dependent). Converted by CYP3A4 to an active metabolite. Strongly inhibits CYP3A4 and P-glycoprotein. Partly excreted by kidney.

No loading dose. Maximum 1 g daily in most regimens.

Adults. 250 to 500 mg every 12 hours (modified release 500 mg to 1 g once daily with food).

• Community-acquired pneumonia (atypical cover with a beta-lactam): 500 mg every 12 hours for 5 to 7 days.
• Helicobacter pylori triple therapy: clarithromycin 500 mg every 12 hours with amoxicillin 1 g every 12 hours and a proton pump inhibitor twice daily, for 14 days, only where clarithromycin resistance is known to be low.
• Pertussis: 500 mg every 12 hours for 7 days.
• Mycobacterium avium complex disease: 500 mg every 12 hours with ethambutol and a rifamycin, for at least 12 months after culture conversion.
• Leprosy (alternative in multidrug regimens): 500 mg once daily.

Children. 7.5 mg/kg every 12 hours; maximum 500 mg a dose.

Alternatives. Azithromycin (fewer interactions), doxycycline, amoxicillin.

Contraindications. Hypersensitivity to macrolides; QT prolongation or torsades; hypokalaemia; severe liver failure with kidney impairment; co-administration with ergot alkaloids, simvastatin, lovastatin, colchicine in renal or hepatic impairment, ticagrelor, lomitapide and other contraindicated CYP3A4 substrates.

Adverse effects. Taste disturbance (metallic), nausea, diarrhoea, abdominal pain, headache. Serious: QT prolongation and torsades, hepatotoxicity, severe skin reactions, Clostridioides difficile infection, exacerbation of myasthenia gravis. Long-term use in patients with coronary disease was linked to higher cardiovascular mortality.

Interactions. - Simvastatin and lovastatin (contraindicated); atorvastatin (limit to 20 mg daily); pravastatin, fluvastatin and rosuvastatin are preferred. - Colchicine (fatal toxicity), calcium channel blockers (hypotension), ciclosporin, tacrolimus, carbamazepine, digoxin, warfarin (INR rise), theophylline. - Ritonavir raises clarithromycin levels; rifampicin and efavirenz lower them. - QT-prolonging drugs.

Common prescribing errors. Missing statin and colchicine interactions, using it for H. pylori without knowing resistance, and combining it with QT-prolonging drugs.

Special groups. - Pregnancy: avoid unless no alternative. Breastfeeding: compatible with monitoring. - Older adults: increased QT and interaction risk. - Kidney impairment: creatinine clearance under 30 mL/min halve the dose (250 mg every 12 hours); haemodialysis give after the session. - Liver impairment: caution; no adjustment unless renal impairment coexists.

Preparation. Immediate release with or without food; modified release with food. IV is available in some regions (500 mg every 12 hours over 60 minutes at 2 mg/mL).

Baseline and monitoring. - Baseline: medication review, ECG if other QT drugs or cardiac disease, potassium, magnesium, liver tests. - During treatment: liver tests in courses over 2 weeks; ECG in high-risk patients; INR in warfarin users.

Stop rules. Stop for syncope, palpitations, QTc over 500 ms, jaundice, or severe skin reaction.

Referral and escalation. Infectious diseases for mycobacterial infection, and cardiology for torsades.