Using Creatinine Clearance for Drug Dosing

Creatinine clearance by the Cockcroft-Gault equation estimates glomerular filtration in mL/min for an individual, without indexing to body surface area. It is the basis of most medicine labels and of the dosing studies for oral anticoagulants, so it remains the usual measure for drug dosing.

Equation (creatinine in micromol/L). Men: (140 minus age) × weight in kg × 1.23, divided by creatinine. Women: the same, using 1.04 instead of 1.23.

Equation (creatinine in mg/dL). (140 minus age) × weight in kg, divided by (72 × creatinine), multiplied by 0.85 in women.

Worked example. Man aged 70, 70 kg, creatinine 150 micromol/L: 70 × 70 × 1.23 = 6027, divided by 150 gives 40 mL/min.

Assumptions. Steady state, stable muscle mass and a consistent creatinine assay. Without these, the result is unreliable.

Choice of weight. Use actual weight when body mass is normal or low. In overweight or obese patients use adjusted weight: ideal weight + 0.4 × (actual minus ideal). Ideal weight is 50 kg (men) or 45.5 kg (women) + 0.91 × (height in cm minus 152).

When to prefer this estimate. Narrow therapeutic index drugs, anticoagulants, aminoglycosides, initial vancomycin dosing, enoxaparin, chemotherapy and any patient at extremes of age or body size.

Limitations. The equation overestimates function in older adults, cachexia, oedema, cirrhosis and amputation, because creatinine production is low. It underestimates in muscular patients. Practice varies on whether a floor of about 60 micromol/L is applied to the creatinine of frail older adults, so state the method used.

Special groups.

• Children: the equation is not validated, so use a paediatric formula.

• Pregnancy: not valid.

• Acute kidney injury: not valid.

• East Africa: creatinine assays and reference ranges vary between laboratories, so use the laboratory's own units and check the unit before calculating.

Monitoring. Recalculate at each admission, with any acute illness, and before dose changes. For a patient on an oral anticoagulant, review at intervals in months of about the clearance divided by 10, so a clearance of 40 is reviewed every 4 months.

Stop rules. Withhold or change the anticoagulant when clearance falls under its labelled limit, during dehydrating illness, and before procedures.

Referral and escalation. If the result sits near a dosing cut-off, or if it conflicts with the clinical picture, request a cystatin C estimate or a measured GFR, and involve a pharmacist or nephrologist.

Common errors. Using ideal weight in a thin patient or actual weight in an obese patient, mixing mg/dL and micromol/L, and using the formula during acute kidney injury.