Drug Dosing in Chronic Kidney Disease

1. See Also
   1. Prevention of Kidney Disease Progression
   2. Chronic Kidney Disease
   3. Intravenous Contrast Related Acute Renal Failure
2. Background
   1. Drug adjustments based on GFR
   2. Glomerular Filtration Rate (GFR) evaluation
      1. 24 Hour Urine Creatinine Clearance (Gold Standard)
      2. Estimates
         1. Cockcroft-Gault Equation (CG)
         2. Modification of Diet in Renal Disease (MDRD)
            1. More accurate than CG when GFR <60 ml/min/1.73 m2
   3. Interpretation of GFR (dosing is based on 3 categories)
      1. Glomerular Filtration Rate <10 ml/min/1.73 m2
      2. Glomerular Filtration Rate <10-50 ml/min/1.73 m2
      3. Glomerular Filtration Rate >50 ml/min/1.73 m2
3. Precautions: General
   1. Loading doses require no renal dose adjustment
   2. Maintenance doses can be adjusted in 2 ways
      1. Reduce each dose, but maintain same dose interval
         1. Risks toxicity due to drug accumulation
      2. Maintain same dose, but lengthen dosing interval
         1. Risks sub-therapeutic dosing
4. Precautions: Antihypertensives
   1. Loop Diuretics (e.g. Lasix) are preferred in CRF
   2. ACE Inhibitors or Angiotensin Receptor Blockers (ARB)
      1. Preferred agents in CRF (renal and cardioprotective)
      2. Anticipate a 15% drop in Serum Creatinine in week 1
         1. Level usually returns to baseline by 4-6 weeks
      3. Indications to stop ACE Inhibitor or ARB
         1. Serum Creatinine rises >30% above baseline
         2. Serum Potassium 5.6 mEq/L or higher
   3. Thiazide Diuretics
      1. Avoid if Serum Creatinine >2.5 mg/dl
      2. Avoid if Creatinine Clearance <30 ml/min/1.73 m2
      3. Loop Diuretics are more effective with reduced GFR
   4. Potassium-Sparing Diuretics or Aldosterone blockers
      1. Avoid in severe Chronic Kidney Disease (Hyperkalemia)
   5. Beta Blockers
      1. Hydrophilic Beta Blockers require renal adjustment
         1. Examples: Atenolol, bisoprolol, Nadolol, acebutolol
      2. Beta Blockers not requiring renal dose adjustment
         1. Metoprolol tartrate (Lopressor), Succinate (Toprol)
         2. Propranolol (Inderal)
         3. Labetolol
      3. Atenolol
         1. Reduce to 50% if GFR<50 ml/min
         2. Reduce to 25% if GFR<10 ml/min
   6. Other agents not requiring renal dose adjustment
      1. Calcium Channel Blockers
      2. Clonidine
      3. Alpha blockers
5. Precautions: AntiHyperlipidemics
   1. Atorvastatin (Lipitor) requires no dosage adjustment
   2. Simvastatin (Zocor) requires minimal dose adjustment
      1. Start at 5 mg if GFR <30 ml/min
   3. Rosuvastatin (Crestor)
      1. Start at 5 mg and do not exceed 10 mg if GFR <30 ml/min
   4. Lescol, Pravachol, Crestor adjusted if GFR <30 ml/min
   5. Lovastatin (Mevacor) avoided if GFR <30 ml/min
6. Precautions: Hypoglycemics (Diabetes Mellitus)
   1. Metformin (Glucophage): Risk of Lactic Acidosis in CRF
      1. Avoid when Serum Creatinine >1.5 mg/dl in men
      2. Avoid when Serum Creatinine >1.4 mg/dl in women
      3. Avoid in age over 80 years or chronic Heart Failure
   2. Sulfonylureas: Risk of Hypoglycemia in CRF
      1. Glipizide is safe to use in CRF
      2. Avoid Glyburide, Chlorpropamide if GFR <60 ml/min
7. Precautions: Antibiotics
   1. Agents to avoid in severe CRF
      1. Penicillin G (Myoclonus, Seizures, coma risk)
      2. Imipenem with cilastin (Seizure risk); Meropenem safe
      3. Tetracycline (exacerbates Uremia); Doxycycline safe
      4. Nitrofurantoin (peripheral neurotoxicity)
      5. Aminoglycosides (or close level monitoring if used)
   2. Acyclovir oral
      1. Reduce to 200 mg every 12 hours if GFR<10 ml/min
   3. Amoxicillin
      1. Reduce to every 24 hours if GFR<10 ml/min
   4. Augmentin
      1. Reduce to every 24 hours if GFR<10 ml/min
      2. Do not use Augmentin 875/125 mg tabs if GFR<30 ml/min
   5. Cefazolin
      1. Reduce to every 12 hours if GFR<50 ml/min
      2. Reduce to 50% every 24-48 hours if GFR<10 ml/min
   6. Cephalexin
      1. Reduce to every 12-24 hours if GFR<10 ml/min
   7. Ciprofloxacin
      1. Reduce to 50-75% if GFR<50 ml/min
      2. Reduce to 50% if GFR<10 ml/min
   8. Clarithromycin
      1. Reduce to 50-100% if GFR<50 ml/min
      2. Reduce to 50% if GFR<10 ml/min
   9. Fluconazole
      1. Reduce to 50% if GFR<50 ml/min
   10. Penicillin
       1. Reduce to 50% if GFR <30 ml/min
   11. Levofloxacin
       1. Reduce to every 24-48 hours if GFR<50 ml/min
       2. Reduce to every 48 hours if GFR<20 ml/min
       3. Avoid if GFR<10 ml/min
   12. Trimethoprim-Sulfamethoxazole (Tmp-Smz, Septra, Bactrim)
       1. Reduce to 50% if GFR <30 ml/min
       2. Avoid if GFR<15 ml/min
   13. Valacyclovir
       1. Reduce to every 12-24 hours if GFR<50 ml/min
       2. Reduce to 500mg every 24 hours if GFR<10 ml/min
   14. Vancomycin
       1. Adjust dosing intervals based on drug level and Creatinine Clearance
8. Precautions: Analgesics
   1. Acetaminophen is safe in CRF
   2. Safest opioid Analgesics (gastrointestinal excretion)
      1. Fentanyl (Duragesic)
         1. GFR 10-50 ml/min: Reduce dose to 75-100%
         2. GFR <10 ml/min: Reduce dose to 50%
      2. Methadone
         1. GFR 10-50 ml/min: No dose adjustment needed
         2. GFR <10 ml/min: Reduce dose to 50-75%
   3. Agents to use with caution
      1. Hydromorphone (Dilaudid)
      2. Oxycodone (Roxicodone)
      3. Tramadol (Ultram)
         1. Do not exceed 50-100 mg twice daily
   4. Agents to avoid in severe CRF (GFR <30 ml/min)
      1. Meperidine (Demerol)
         1. Avoid in ESRD and in Dialysis
      2. Hydrocodone
         1. Avoid in ESRD and in Dialysis
      3. Codeine
         1. Reduce dose by 50-75% if GFR<50 ml/min
         2. Avoid in ESRD and in Dialysis
      4. Propoxyphene (Darvon)
      5. Morphine
         1. Reduce dose by 50-75% if GFR<50 ml/min
         2. In ESRD, limit use to end-stage Hospice patients
   5. Agents to avoid at any level of CRF or risk of CRF
      1. NSAIDS (repeat Serum Creatinine q2 weeks if used)
      2. COX-2 Inhibitors
9. Precautions: Neuropsychiatric agents
   1. Avoid Tricyclic Antidepressants in Chronic Kidney Disease
      1. Risk of arrhythmia
   2. Gabapentin (Neurontin)
      1. If on Dialysis, administer 200-300 mg after each Dialysis session
      2. Dose 200-700 mg twice daily if GFR<60 ml/min
      3. Dose 200-700 mg daily if GFR<30 ml/min
      4. Dose 100-300 mg daily if GFR<15 ml/min
   3. Pregabalin (Lyrica)
      1. Requires decreased dosage at an increased frequency
10. Precautions: Gastrointestinal Agents
    1. Famotidine (Pepcid)
       1. Reduce to 50% if GFR<60 ml/min
       2. Reduce to 25% if GFR<50 ml/min
       3. Reduce to 10% if GFR<10 ml/min
    2. Ranitidine (Zantac)
       1. Reduce to 75% if GFR<60 ml/min
       2. Reduce to 50% if GFR<50 ml/min
       3. Reduce to 25% if GFR<10 ml/min
11. Precautions: Herbals
    1. Avoid nephrotoxic herbals
       1. Heavy metal-laced herbals
       2. Ephedra-like compounds for weight loss
       3. Aristolochic Acid (chinese herbal for weight loss)
    2. Avoid herbals with risk of potassium overload
       1. Alfalfa
       2. Dandelion
       3. Noni juice
12. Resources: University of Penn Antibiotic Manual
    1. http://uphs.upenn.edu/bugdrug/antibiotic_manual/renal
13. References
    1. (2002) Am J Kidney Dis 39(2 suppl 1):S1-266
    2. Kappel (2002) CMAJ 166:473-7
    3. Munar (2007) Am Fam Physician 75:1487-96