Drug Dosing in Chronic Kidney Disease

Aka: Drug Dosing in Chronic Kidney Disease, Medication Dosing in Chronic Kidney Disease, Renal Dosing, Antibiotic Dose Adjustments in Impaired Renal Function, Antihypertensive Dose Adjustments in Impaired Renal Function, Analgesic Dose Adjustments in Impaired Renal Function, ACE Inhibitor and Angiotensin Receptor Blocker Adjustments in Impaired Renal Function, End Stage Renal Disease Medication Dosing, Drug Dosing in ESRD, Drug Dosing in Renal Failure

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II. 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

III. Precautions: General

  1. Loading doses require no renal dose adjustment
  2. For patients on renal replacement
    1. Dialyzed medications should be taken after Hemodialysis run for the day
    2. Peritoneal Dialysis does not affect the timing of medications
  3. For patients on Phosphate Binders
    1. Take medications (esp. Antibiotics) one hour before or 3 hours after Phosphate Binder dose
  4. 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

IV. 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. Starting dose
      1. Moderate dose in most patients (e.g. Lisinopril 10-20 mg daily)
      2. Lower dose with severe Chronic Kidney Disease, CHF or age over 80 years
    3. Anticipate a 15% increase in Serum Creatinine in week 1
      1. Level usually returns to baseline by 4-6 weeks
    4. Monitoring
      1. Parameters
        1. Blood Pressure
        2. Serum Creatinine
        3. Serum Potassium
      2. Baseline
      3. Week 1-2 after each dose change, then
      4. Week 2-3 after each dose change, then
      5. Every 6-12 months
    5. Abnormal labs requiring medication change
      1. Criteria
        1. Serum Creatinine rises >30% above baseline
        2. Serum Potassium >5.5 mEq/L
      2. Approach
        1. Decrease ACE Inhibitor or ARB to half dose and recheck labs in 1-2 weeks
        2. Decrease Diuretic doses if Serum Creatinine increased
        3. Eliminate Medication Causes of Elevated Serum Potassium
        4. Indications to stop ACE Inhibitor or ARB
          1. Serum Creatinine remains >30% despite changes OR
          2. Serum Potassium >5.5 mEq/L despite changes
    6. References
      1. (2014) Presc Lett 21(6): 31
  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

V. 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

VI. 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

VII. Precautions: Antibiotics

  1. Antibiotics that require NO renal dose adjustment
    1. Azithromycin
    2. Ceftriaxone
    3. Clindamycin
    4. Doxycyline
    5. Linezolid
    6. Moxifloxacin
    7. Nafcillin
    8. Rifampin
  2. Agents to avoid in severe Chronic Kidney Disease
    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)
  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. Cefuroxime
    1. Reduce to 250 to 500 mg every 24 hours if GFR<10 ml/min
  7. Cephalexin
    1. Reduce to every 12-24 hours if GFR<10 ml/min
  8. Ciprofloxacin
    1. Reduce dose to 50-75% if GFR<50 ml/min
    2. Reduce dose to 50% or change to once daily dosing if GFR<10 ml/min
  9. Clarithromycin
    1. Reduce dose to 50-100% if GFR<50 ml/min
    2. Reduce dose to 50% or change to once daily dosing if GFR<10 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 (or 500 mg loading dose, then 250 mg for subsequent doses)
    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. Vancomycin
    1. Adjust dosing intervals based on drug level and Creatinine Clearance

VIII. Precautions: Antivirals

  1. Acyclovir oral
    1. Reduce to 200 mg every 12 hours if GFR<10 ml/min
  2. 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
  3. Ganciclovir
    1. Renal Dosing adjustment is needed for GFR <70 ml/min

IX. Prcautions: Antfungals

  1. Fluconazole
    1. Reduce to 50% if GFR<50 ml/min

X. 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. Hydrocodone
      1. Avoid in ESRD and in Dialysis
    2. 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 in severe CRF (GFR <30 ml/min) that are typically avoided for other risks (listed for historical reasons)
    1. Meperidine (Demerol)
      1. Risk of metabolite accumulation with secondary Seizures
      2. Avoid in ESRD and in Dialysis
    2. Codeine
      1. Reduce dose by 50-75% if GFR<50 ml/min
      2. Avoid in ESRD and in Dialysis
    3. Propoxyphene (Darvon)
  6. 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

XI. 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
  4. Lamotrigine
    1. May require renal dose adjustment
  5. Lithium
    1. Requires renal dose adjustment

XII. Precautions: Gastrointestinal Agents

  1. Avoid phosphate and Magnesium containing Laxatives or enemas
    1. Avoid Magnesium containing Laxatives (e.g. Milk of Magnesia, Magnesium Citrate)
      1. Risk of Hypermagnesemia
    2. Avoid phosphate containing enemas (e.g. Fleets Enema)
      1. Risk of Hyperphosphatemia
  2. 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
  3. 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

XIII. Precautions: Miscellaneous Agents that REQUIRE Renal Dose Adjustment

  1. Allopurinol
  2. Baclofen
  3. Colchicine
  4. Digoxin
  5. Low Molecular Weight Heparin
  6. DOACs

XIV. 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

XV. Resources: University of Penn Antibiotic Manual

  1. http://uphs.upenn.edu/bugdrug/antibiotic_manual/renal

XVI. References

  1. (2020) Presc Lett 27(7): 42
  2. (2002) Am J Kidney Dis 39(2 suppl 1):S1-266 [PubMed]
  3. Kappel (2002) CMAJ 166:473-7 [PubMed]
  4. Mercado (2019) Am Fam Physician 100(11): 687-94 [PubMed]
  5. Munar (2007) Am Fam Physician 75:1487-96 [PubMed]

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