Clavulanate Renal Excretion
Yes, clavulanate is renally excreted through both glomerular filtration and tubular secretion. According to the FDA drug label, clavulanate undergoes renal clearance and can accumulate in patients with impaired renal function 1.
Pharmacokinetics of Clavulanate
Clavulanate, a beta-lactamase inhibitor commonly combined with amoxicillin (Augmentin), has the following excretion characteristics:
- Primarily eliminated via the kidneys
- Excreted through both glomerular filtration and tubular secretion
- Accumulates in patients with decreased renal function
Impact of Renal Impairment
Research has demonstrated significant changes in clavulanate pharmacokinetics in patients with renal dysfunction:
- The total body clearance of clavulanate decreases with declining renal function 2
- Both renal and non-renal clearance are affected by renal impairment 2
- In patients with severe renal impairment, clavulanate levels can rise significantly
A key study by Horber et al. found that hemodialysis increases the clearance of clavulanate, with an extraction ratio of 0.74, indicating that it is effectively removed during dialysis 3.
Clinical Implications
The altered pharmacokinetics of clavulanate in renal impairment has important clinical implications:
- Dosage adjustment is necessary when creatinine clearance falls below certain thresholds
- High blood levels may occur more readily in patients with impaired renal function 1
- The risk of adverse effects, including crystalluria and interstitial nephritis, increases with accumulation
Comparison with Amoxicillin
When combined with amoxicillin (as in Augmentin), it's important to note:
- The decrease in total body clearance is more pronounced for amoxicillin than for clavulanate 2
- This leads to an increasing ratio of amoxicillin to clavulanate as renal function declines
- For example, in patients with normal renal function (GFR ~75 ml/min), the ratio is approximately 4.9, while in hemodialysis patients, it increases to 14.7 2
Monitoring and Management
For patients with renal impairment receiving clavulanate:
- Monitor renal function regularly
- Consider dosage adjustments based on creatinine clearance
- Ensure adequate fluid intake to reduce the risk of crystalluria 1
- Be aware that hemodialysis can effectively remove clavulanate from circulation 1, 3
In summary, clavulanate is primarily eliminated through renal mechanisms, and its clearance is significantly affected by renal function. This necessitates careful dosing consideration in patients with renal impairment to prevent accumulation and potential toxicity.