What medications are contraindicated in patients with Chronic Kidney Disease (CKD)?

Medications Contraindicated or Requiring Caution in CKD Patients

Patients with CKD must avoid specific nephrotoxic medications entirely, while many commonly prescribed drugs require dose adjustment based on eGFR to prevent further kidney damage, drug accumulation, and life-threatening adverse effects.

Absolute Contraindications (Avoid Completely)

Antidiabetic Agents

• Glyburide (first-generation sulfonylurea) is absolutely contraindicated in any degree of CKD due to accumulation of active metabolites causing severe, prolonged hypoglycemia 1, 2, 3
• Chlorpropamide should be avoided entirely in CKD patients 4
• Metformin must be discontinued when eGFR <30 mL/min/1.73 m² (CKD stages G4-G5) due to lactic acidosis risk 5, 6

Antibiotics

• Aminoglycosides (gentamicin, tobramycin, amikacin, neomycin, streptomycin) are potentially nephrotoxic and should be avoided when possible, requiring close monitoring if absolutely necessary 5, 7
• Tetracyclines should be avoided due to nephrotoxicity 5
• Nitrofurantoin is contraindicated as it produces toxic metabolites causing peripheral neuritis 5, 4

Herbal and Over-the-Counter Products

• All herbal remedies should not be used in people with CKD 5
• Over-the-counter medicines and dietary/herbal supplements require medical or pharmacist review before use 5

Imaging Contrast Agents

• Gadolinium-containing contrast media should not be used when eGFR <15 mL/min/1.73 m² (CKD G5) due to nephrogenic systemic fibrosis risk 5
• For eGFR <30 mL/min/1.73 m² (CKD G4-G5), only macrocyclic chelate preparations (American College of Radiology group II and III agents) should be used if gadolinium is absolutely necessary 5

Medications Requiring Temporary Discontinuation

During Acute Illness or Surgery

The following medications must be temporarily discontinued in patients with eGFR <60 mL/min/1.73 m² (CKD G3a-G5) during serious intercurrent illness, surgery, or conditions increasing AKI risk 5:

• ACE inhibitors and ARBs 5
• Aldosterone inhibitors and direct renin inhibitors 5
• Diuretics 5
• NSAIDs 5
• Metformin 5
• Lithium 5
• Digoxin 5, 8
• SGLT2 inhibitors (during prolonged fasting, surgery, or critical illness due to ketosis risk) 1

Critical pitfall: Failure to restart these medications after the acute event can lead to unintentional harm—a clear restart plan must be communicated and documented 5

Medications Requiring Dose Adjustment by eGFR

NSAIDs (Use with Extreme Caution)

• All NSAIDs (including naproxen, diclofenac, ibuprofen, nimesulide) should be reviewed and limited, as they are the most commonly misprescribed nephrotoxic drugs in CKD 5, 9, 10, 4
• NSAIDs were prescribed to 56.3% of CKD patients in one study, with 35.6% receiving them for >90 days despite being contraindicated 10
• Monitor eGFR, electrolytes closely if NSAIDs cannot be avoided 5

Antidiabetic Agents Requiring Adjustment

• Metformin: Continue if eGFR ≥45 mL/min; review use at eGFR 30-44 mL/min; discontinue at eGFR <30 mL/min 5
• Second-generation sulfonylureas (glipizide, glimepiride, gliclazide): Can be used with caution but require conservative initiation and close glucose monitoring due to hypoglycemia risk 1, 3
• Acarbose: Relatively contraindicated in stage III/IV CKD 4

Cardiovascular Medications

• Digoxin: Requires dose adjustment and therapeutic level monitoring due to narrow therapeutic window 5, 8
• Simultaneous use of ACE inhibitor + ARB + renin inhibitor is potentially harmful and contraindicated 5

Antimicrobials Requiring Adjustment

• Most renally cleared antibiotics require dose adjustment based on eGFR 5
• Vancomycin: Requires regular monitoring of eGFR, electrolytes, and drug levels 5

Other High-Risk Medications

• Baclofen: Must be dose-adjusted in CKD 8
• Lithium: Requires regular monitoring of GFR, electrolytes, and drug levels 5
• Calcineurin inhibitors: Require regular monitoring of GFR, electrolytes, and drug levels 5

Monitoring Requirements for All CKD Patients on Medications

Patients with CKD receiving medications with narrow therapeutic windows, potential adverse effects, or nephrotoxicity require monitoring of 5:

• eGFR and electrolytes (both outpatient and inpatient settings)
• Therapeutic medication levels when indicated
• More frequent monitoring during transitions of care 5

For medications requiring precision in dosing (narrow therapeutic or toxic range), use equations combining creatinine and cystatin C, or measured GFR rather than eGFR alone 5

Clinical Algorithm for Medication Management in CKD

1. Identify CKD stage by calculating eGFR using validated equations 5

2. Perform comprehensive medication review at every visit and transition of care to assess adherence, continued indication, and drug interactions 5

3. Check each medication against eGFR-based dosing requirements using validated references 5

4. Avoid nephrotoxic combinations: Do not use potentially nephrotoxic drugs concurrently (e.g., NSAIDs + ACE inhibitors + diuretics) 5, 7

5. Establish collaborative relationships with pharmacists to enhance drug stewardship and manage complex medication regimens 5

6. Educate patients about expected benefits and risks so they can identify and report adverse events 5

Common Prescribing Pitfalls to Avoid

• 46.6% of CKD stage III/IV patients are prescribed at least one relatively contraindicated drug, demonstrating widespread inappropriate prescribing 4
• CKD diagnosis alone does not reduce nephrotoxic drug prescribing—active intervention is required 10
• Polypharmacy is common as CKD patients are often seen by multiple specialists who do not coordinate treatments 5, 11
• Non-GFR factors (extremes of body weight, non-steady state conditions) require additional consideration for drug dosing 5
• Teratogenicity must be reviewed when prescribing to patients of childbearing potential 5