1887

Drugs usage in renal and hepatic insufficiency

With failure of liver or kidney, the excretion of some drugs may be impaired, leading to increased serum concentrations. Note: this information is based on mammals and may not be directly applicable to birds, reptiles, amphibians and fish.

  1. Double the dosing interval or halve the dosage in patients with severe renal insufficiency. Use for drugs that are relatively non-toxic.
  2. 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.
  3. 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 K to amend the drug dose or dosing interval according to the following equations:

Modified dose reduction = normal dose × K

Modified dose interval = normal dose interval/K

where K = patient Ccr/normal Ccr

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

Drug Nephrotoxic Dose adjustment in renal failure
Amikacin Yes c
Amoxicillin No a
Amphotericin B Yes c
Ampicillin No a
Cefalexin No b
Chloramphenicol No N, A
Digoxin No c
Gentamicin Yes c
Oxytetracycline Yes CI
Penicillin No a
Streptomycin Yes b
Tobramycin Yes c
Trimethoprim/sulphonamide Yes b, A

a, b, c = Refer to section above on dose adjustment; A = Avoid in severe renal failure; CI = Contraindicated; N = normal dose.

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.

Drug DI CI
Aspirin   X
Azathioprine   X
Cefotaxime X  
Chloramphenicol   X
Clindamycin   X
Cyclophosphamide X  
Diazepam   X
Doxorubicin X  
Doxycycline X  
Furosemide X  
Hydralazine X  
Lidocaine X  
Metronidazole X  
Morphine X  
NSAIDs X  
Oxytetracycline   X
Pentobarbital X  
Phenobarbital X  
Propranolol X  
Theophylline X  
Vincristine X  

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

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