With failure of liver or kidney, the excretion of some drugs may be impaired, leading to increased serum concentrations.

Renal failure

• a. Double the dosing interval or halve the dosage in patients with severe renal insufficiency. Use for drugs that are relatively non-toxic.
• b. Increase dosing interval 2-fold when creatinine clearance (Ccr) is 0.5–1.0 ml/min/kg, 3-fold when Ccr is 0.3–0.5 ml/min/kg and 4-fold when Ccr is <0.3 ml/min/kg.
• c. Precise dose modification is required for some toxic drugs that are excreted solely by glomerular filtration, e.g. aminoglycosides. This is determined by using the dose fraction Kfto amend the drug dose or dosing interval according to the following equations:
  • Modified dose reduction = normal dose × Kf
  • Modified dose interval = normal dose interval/Kf
  • where Kf = patient Ccr/normal Ccr

Where Ccr is unavailable, Ccr may be estimated at 88.4/serum creatinine (μmol (micromoles)/l) (where serum creatinine is <350 μmol/l). Kfmay be estimated at 0.33 if urine is isosthenuric or 0.25 if the patient is azotaemic.

a, b, c = refer to section above on dose adjustment; A = avoid in severe renal failure; CI = contraindicated; N = normal dose.

Hepatic insufficiency

Drug clearance by the liver is affected by many factors and thus it is not possible to apply a simple formula to drug dosing. The table below is adapted from information in the human literature.

CI = contraindicated; avoid use if at all possible. DI = a change in dose or dosing interval may be required.