Clarithromycin Administration Frequency
Clarithromycin is administered twice daily (every 12 hours) for standard immediate-release formulations, or once daily for extended-release formulations. 1
Standard Dosing Frequency by Formulation
Immediate-Release Formulation (Twice Daily)
- Adults: 500 mg twice daily (total 1 g per day in 2 divided doses) for 7-14 days depending on indication 1, 2
- Children >1 month: 15 mg/kg per day divided into 2 doses (maximum 1 g per day) for 7 days 1, 3
- Infants <1 month: Not recommended due to unknown association with infantile hypertrophic pyloric stenosis (IHPS) 1, 3
Extended-Release Formulation (Once Daily)
- Adults only: 1000 mg (two 500 mg tablets) once daily for 7-14 days 4
- The extended-release formulation must be taken with food to maximize bioavailability (30% reduction when taken fasting) 5
- Extended-release formulation is indicated only for acute bacterial exacerbation of chronic bronchitis, acute maxillary sinusitis, and community-acquired pneumonia in adults 4
Indication-Specific Frequency
Pertussis Treatment
- Adults: 1 g per day in two 500 mg doses for 7 days 1, 2
- Children >1 month: 15 mg/kg per day in 2 divided doses for 7 days 1, 3
Mycobacterium avium Complex (MAC)
- Treatment: 500 mg twice daily with ethambutol 15 mg/kg daily 1, 2
- Prophylaxis in AIDS (CD4 <50): 500 mg twice daily 2
- Pediatric MAC: 7.5 mg/kg twice daily (maximum 500 mg per dose) 1, 3
Community-Acquired Pneumonia
- Immediate-release: 500 mg twice daily for 7-14 days 2
- Extended-release: 1000 mg once daily for 7-14 days 2, 4
Streptococcal Pharyngitis
- 250 mg twice daily for 10 days 2
Critical Dosing Adjustments Affecting Frequency
Renal Impairment
- Severe renal impairment (CrCl <30 mL/min): Reduce dose by 50% while maintaining twice-daily frequency 1, 2, 6
- With ritonavir/lopinavir-ritonavir and CrCl <60 mL/min: Reduce dose by 50% 2, 6
- With ritonavir/lopinavir-ritonavir and CrCl <30 mL/min: Reduce dose by 75% 2, 6
Drug Interactions
- When co-administered with potent CYP3A inhibitors (ritonavir, atazanavir), dose reduction is required but frequency remains twice daily 2, 6, 4
- Clarithromycin efficacy may be reduced by 35-39% with efavirenz or nevirapine; monitor closely for treatment failure but maintain standard frequency 2
Pharmacokinetic Rationale for Frequency
The twice-daily dosing of immediate-release clarithromycin is based on:
- Elimination half-life of 3.3-4.9 hours for the parent compound 7, 8
- Nonlinear pharmacokinetics with saturable metabolism 7, 8
- Active 14-hydroxy metabolite with similar half-life requiring twice-daily dosing to maintain therapeutic concentrations 7, 5
- Goal to maintain unbound drug concentrations above MIC for 40-60% of the dosing interval 7
The once-daily extended-release formulation achieves:
- Equivalent AUC to twice-daily immediate-release when taken with food 5
- Lower peak concentrations (Cmax) and delayed time to peak 5
- Reduced concentration fluctuation throughout the dosing interval 5
Common Pitfalls to Avoid
- Never administer extended-release formulation to children - it is approved only for adults 4
- Never crush or split extended-release tablets - this destroys the controlled-release mechanism 4
- Never administer extended-release formulation on an empty stomach - bioavailability decreases by 30% 5
- Never exceed 1 g per day in children regardless of weight-based calculation 1, 3, 6
- Never use in infants <1 month old due to potential IHPS risk 1, 3, 6
Tolerability Considerations
The extended-release once-daily formulation demonstrates:
- Significantly less severe gastrointestinal adverse events compared to immediate-release twice-daily (P = 0.018) 5
- Lower frequency of premature discontinuation due to GI effects or abnormal taste (P = 0.004) 5
- Similar overall adverse event incidence but better tolerability profile 5
However, doses >1000 mg/day are poorly tolerated in most adults and should be avoided 2