A patient with severe renal impairment (eGFR 10 mL/min) is prescribed a drug that is 40% renally excreted as unchanged drug and 60% hepatically metabolised. The approximate dose adjustment required is:

• A No adjustment needed as hepatic metabolism is predominant
• B Reduce dose by 60-70% as renal failure reduces total body clearance proportionally to the fraction of renal clearance at the affected GFR
• C Double the dosing interval with no dose change, regardless of the degree of renal impairment
• D Reduce dose by 40% of normal, as only the renal component is affected ✓

Explanation

Drug clearance (Cl_total) = Cl_renal + Cl_hepatic. If 40% is renally cleared and GFR is severely reduced (near zero), the renal fraction of clearance is effectively eliminated. Total clearance falls to approximately 60% of normal (the hepatic component remains intact). Therefore, dosing should be adjusted to deliver an equivalent AUC by reducing the dose proportionally — the total clearance is 60% of normal, meaning the dose should be reduced by approximately 40% (to maintain target AUC). Alternatively, the same dose can be given at a longer interval. The key principle is that the degree of dose reduction reflects the fraction normally cleared renally multiplied by the fractional reduction in GFR.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.