6-O-methyl erythromycin derivative — improved acid stability and tissue penetration. Strong CYP3A4 inhibitor (via 14-OH metabolite); first-line DDI perpetrator in clinical pharmacology. H. pylori eradication regimens.
Half-Life (t½)
PO: 5h, IV: 5h
Dosing Guidelines
PO: Typical 500 mg (Range: 250–500 mg)
Target Organ Systems
digestive
Interactions
Simvastatin (contraindicated): CYP3A4 inhibition. Jacobson 2004 (PMID:15518608): clarithromycin raised simvastatin AUC ~10× and simvastatin acid 12×. Combination contraindicated; switch to azithromycin or hold the statin during the antibiotic course.
Tacrolimus (major): CYP3A4 inhibition. Kunicki 2005 (PMID:15665756) case report demonstrates tacrolimus rise on clarithromycin co-administration. Mechanism confirmed in vitro (Wen 2024). Avoid; substitute azithromycin if a macrolide is needed.
Midazolam (major): CYP3A4 inhibition (canonical probe). Gorski 1998 (PMID:9728893) n=16 healthy, clarithromycin 500 mg BID × 7d: midazolam systemic CL 28→10 L/h; oral F 0.31→0.75. Combined oral AUC ratio ≈ 6.8. Ki ≈ 3/(6.8−1) = 0.5 µM at Cp_perp ~3 µM. Strong CYP3A inhibitor by FDA criteria.
Triazolam (major): CYP3A4 inhibition. Greenblatt 1998 (PMID:9757151) n=12 healthy, 5-arm: oral CL of triazolam 413 (placebo/azithro) → 95 mL/min with clarithromycin → AUC ratio 4.35. Ki ≈ 3/(4.35−1) = 0.9 µM. PD effects (sedation, psychomotor) also enhanced.
Atorvastatin (warn): CYP3A4 inhibition; SLCO1B1 genotype-modulated. Shin 2011 (PMID:21950641) n=23 healthy, 2-phase crossover, clarithromycin 500 mg BID × 5d + atorvastatin 20 mg single: lactone AUC₀₋∞ ratio ≈ 2.62 (nonexpressors) to 3.59 (SLCO1B1 expressors). Use AUC_R ≈ 3.0 → Ki ≈ 3/(3−1) = 1.5; AUC_R ≈ 3.6 → 1.15; encoded at 1.2. Limit atorvastatin dose with strong CYP3A inhibitors per FDA label.
Colchicine (contraindicated): CYP3A4 + P-gp inhibition. Davis/Wason 2013 (PMID:23462027) by URL Pharma (NDA holder) reports verbatim "Cmax and AUC of colchicine are increased by 277% and 282%" with clarithromycin coadministration → AUC ratio 3.82. Ki ≈ 3/(3.82−1) = 1.06 µM. FDA boxed warning; reported fatalities from severe GI tox + bone marrow suppression + multiorgan failure.