Clarithromycin Dosing for Adults with Normal Renal Function
For an adult patient with normal renal function and no underlying medical conditions, the standard dose of clarithromycin is 500 mg orally twice daily (every 12 hours) for most indications, or 1000 mg once daily using the extended-release formulation. 1
Standard Dosing by Indication
The specific dose and duration depend on the infection being treated:
Community-acquired pneumonia: 500 mg twice daily for 7-14 days (immediate-release) or 1000 mg once daily for 7 days (extended-release) 2, 1
Acute bacterial exacerbation of chronic bronchitis: 500 mg twice daily for 7-14 days (immediate-release) or 1000 mg once daily for 7 days (extended-release) 1
Acute maxillary sinusitis: 500 mg twice daily for 10-14 days (immediate-release) or 1000 mg once daily for 14 days (extended-release) 2, 1
Pharyngitis (Group A Streptococcus): 250 mg twice daily for 10 days 2
Mycobacterium avium complex (MAC) treatment: 500 mg twice daily in combination with ethambutol, or 1000 mg three times weekly for nodular/bronchiectatic disease 3, 2
MAC prophylaxis in AIDS: 1000 mg daily 2
Pertussis: 1000 mg per day divided into two 500 mg doses for 7 days 2
Critical Administration Instructions
Extended-release tablets must be taken with food and swallowed whole—never chewed, broken, or crushed. 1 This is essential because bioavailability decreases by 30% when taken on an empty stomach 4. The immediate-release formulation can be taken with or without food 5.
Important Dosing Considerations
Maximum Tolerated Dose
Doses exceeding 1000 mg per day are poorly tolerated in most adults and should be avoided. 2 The Centers for Disease Control and Prevention specifically advises against higher doses due to increased gastrointestinal side effects including metallic taste, nausea, vomiting, and diarrhea, which are dose-dependent 2, 6.
Special Populations Requiring Lower Doses
Even with normal renal function, certain patients may benefit from dose reduction:
Elderly patients (>70 years) or those weighing <50 kg: Consider reducing to 250-500 mg daily due to increased risk of gastrointestinal intolerance 2
Patients with hepatic impairment: While no formal dose adjustment is required for hepatic impairment alone, be cautious as 14-hydroxylation of clarithromycin is reduced, potentially affecting efficacy for certain pathogens 7
Common Pitfalls to Avoid
Drug Interactions
Clarithromycin is a potent CYP3A4 inhibitor, which creates multiple clinically significant drug interactions 5:
Absolutely contraindicated combinations: Cisapride, pimozide, ergot alkaloids, lomitapide, lovastatin, simvastatin, and lurasidone 1
Requires dose adjustment: When used with ritonavir or atazanavir in patients with normal renal function, no adjustment is needed, but monitor closely 8
Monitor carefully: Statins (other than lovastatin/simvastatin), calcium channel blockers, warfarin, digoxin, theophylline, and carbamazepine 6, 5
Cardiovascular Risk
Avoid clarithromycin in patients with known QT prolongation, ventricular arrhythmias, hypokalemia, hypomagnesemia, significant bradycardia, or those taking Class IA or III antiarrhythmics. 1 There is also an increased risk of all-cause mortality one year or more after treatment in patients with coronary artery disease, so balance this risk against treatment benefits 1.
Resistance Considerations
Macrolide resistance in Streptococcus pneumoniae and Staphylococcus aureus is well-documented and varies geographically. 2 Susceptibility testing should be performed when clinically indicated, particularly for serious infections 1.
Pregnancy
Clarithromycin is FDA Pregnancy Category C and should only be used during pregnancy when no alternatives exist due to embryo-fetal toxicity demonstrated in animal studies. 6, 1
Pharmacokinetic Rationale
The twice-daily dosing is based on clarithromycin's elimination half-life of 3.3-4.9 hours and the pharmacodynamic goal of maintaining unbound drug concentrations above the minimum inhibitory concentration for 40-60% of the dosing interval. 5 Peak concentrations after 250 mg dosing reach approximately 1.0-1.5 mg/L, while 500 mg dosing achieves 2.4-2.9 mg/L 5. The drug achieves excellent tissue penetration, with lung concentrations approximately five-fold higher than serum 9.