Clarithromycin Dosing in Renal Impairment
In patients with severe renal impairment (creatinine clearance <30 mL/min), reduce the clarithromycin dose by 50%; in patients with moderate renal impairment (CrCl 30-60 mL/min) taking concomitant ritonavir or atazanavir, reduce the dose by 50%; and in patients with severe renal impairment taking these antiretrovirals, reduce the dose by 75%. 1
Dosing Algorithm by Renal Function
Severe Renal Impairment (CrCl <30 mL/min)
- Without concomitant ritonavir or atazanavir: Reduce clarithromycin dose by 50% 1
- With concomitant ritonavir or atazanavir: Reduce clarithromycin dose by 75% 1
Moderate Renal Impairment (CrCl 30-60 mL/min)
- Without concomitant ritonavir or atazanavir: No dose adjustment required 1
- With concomitant ritonavir or atazanavir: Reduce clarithromycin dose by 50% 2, 1
Normal or Mild Renal Impairment (CrCl >60 mL/min)
- No dose adjustment required regardless of concomitant medications 1
Pharmacokinetic Rationale
The need for dose reduction in renal impairment is based on clarithromycin's elimination profile. Approximately 22% of an oral dose is recovered as parent compound (18% in urine, 4% in feces), and renal clearance accounts for 6.7-12.8 L/h of the total body clearance of 29.2-58.1 L/h 3, 4. In patients with severe renal impairment, both clarithromycin and its active 14-hydroxyclarithromycin metabolite accumulate, resulting in increased plasma concentrations and prolonged elimination half-life 3, 5, 4.
Drug Interaction Considerations
Critical caveat: When clarithromycin is co-administered with ritonavir or lopinavir-ritonavir, drug levels increase by 77% due to inhibition of CYP3A metabolism 2. This interaction necessitates dose adjustment only when renal dysfunction is present, creating the specific dosing thresholds outlined above 2.
Contraindications in Renal Impairment
Absolute contraindication: Do not co-administer clarithromycin with colchicine in patients with any degree of renal or hepatic impairment due to risk of fatal colchicine toxicity 1.
Extended-Release Formulation Specifics
For clarithromycin extended-release tablets (the formulation addressed in the FDA labeling), the standard adult dose is 1 gram every 24 hours 1. Apply the same percentage reductions outlined above to this base dose when renal impairment is present 1.
Monitoring Recommendations
While not explicitly stated in dosing guidelines, be aware that clarithromycin can prolong the QT interval, and this risk may be amplified in renal impairment due to drug accumulation 1. Avoid clarithromycin in patients with known QT prolongation, hypokalemia, hypomagnesemia, or those receiving Class IA or III antiarrhythmics 1.
Common Pitfall to Avoid
Do not reduce the dose in moderate renal impairment (CrCl 30-60 mL/min) unless the patient is taking ritonavir or atazanavir. The FDA labeling is explicit that dose reduction at this level of renal function is only necessary when these specific drug interactions are present 1. This differs from some other renally cleared antibiotics where dose adjustment begins at higher creatinine clearance thresholds.