What medications should be avoided in patients with impaired renal function?

Medications to Avoid in Patients with Kidney Disease

Patients with impaired renal function must avoid or use extreme caution with NSAIDs, aminoglycosides, certain opioids, metformin (in advanced CKD), lithium, and tenofovir disoproxil fumarate, as these medications carry significant risk of nephrotoxicity or accumulation of toxic metabolites. 1, 2, 3

High-Priority Medications to Avoid or Adjust

NSAIDs (Nonsteroidal Anti-Inflammatory Drugs)

• Avoid NSAIDs entirely in patients with GFR <30 mL/min/1.73 m² (CKD stages 4-5) 2, 4
• Prolonged NSAID therapy is not recommended for patients with GFR <60 mL/min/1.73 m² (CKD stages 3-5) 1, 2
• NSAIDs inhibit prostaglandin synthesis, which is critical for maintaining renal perfusion in compromised kidneys, and can precipitate acute renal decompensation 4
• Never combine NSAIDs with RAAS blockers (ACE inhibitors or ARBs), as this combination dramatically increases acute kidney injury risk 2, 4
• The triple combination of NSAIDs, diuretics, and ACE inhibitors/ARBs is particularly dangerous 2
• If NSAIDs cannot be avoided in mild CKD, use the lowest effective dose for the shortest duration and monitor renal function within 3-7 days 2, 4

Aminoglycoside Antibiotics

• Aminoglycosides (gentamicin, tobramycin, amikacin) should be avoided in patients with pre-existing renal impairment due to direct nephrotoxicity 1, 3
• The FDA boxed warning states that gentamicin is "potentially nephrotoxic" with greater risk in patients with impaired renal function 3
• If aminoglycosides must be used, monitor peak levels (keep <12 mcg/mL) and trough levels (keep <2 mcg/mL) closely, as excessive concentrations increase risk of renal and eighth cranial nerve toxicity 3
• Avoid concurrent use with other nephrotoxic agents (cisplatin, vancomycin, loop diuretics) 3

Opioid Analgesics with Active Metabolites

• Avoid meperidine, codeine, and morphine in renal insufficiency (GFR <30 mL/min/1.73 m²) and ESRD due to accumulation of active metabolites 1
• Tramadol and tapentadol are not recommended in renal insufficiency (GFR <30 mL/min/1.73 m²) and ESRD 1
• Use hydrocodone, oxycodone, and hydromorphone with caution and adjust dosage in severe renal insufficiency 1
• Preferred opioids for patients with renal insufficiency are those with no active metabolites: fentanyl, sufentanil, and methadone 1

Metformin

• Continue metformin in patients with GFR ≥45 mL/min/1.73 m² (CKD stages 1-3a) 1
• Review metformin use in patients with GFR 30-44 mL/min/1.73 m² (CKD stage 3b) and consider dose reduction 1
• Discontinue metformin in patients with GFR <30 mL/min/1.73 m² (CKD stages 4-5) 1
• Temporarily discontinue metformin during serious intercurrent illness that increases AKI risk (surgery, angiography, acute illness) 1

Lithium

• All patients taking lithium require regular monitoring of GFR, electrolytes, and drug levels due to nephrotoxic potential 1
• Temporarily discontinue lithium in patients with GFR <60 mL/min/1.73 m² who develop serious intercurrent illness 1
• Lithium should be avoided in combination with NSAIDs due to drug interactions 2

Tenofovir Disoproxil Fumarate (TDF)

• TDF should be avoided with concurrent or recent use of nephrotoxic agents (high-dose or multiple NSAIDs) 5
• TDF increases risk of renal tubular toxicity and Fanconi syndrome 6
• Consider safer alternatives like tenofovir alafenamide (TAF) or tenofovir amibufenamide (TMF), which have more favorable renal safety profiles 6

Other Antibiotics to Avoid

• Tetracyclines should be avoided in CKD patients due to nephrotoxicity 1
• Nitrofurantoin should be avoided as it produces toxic metabolites that can cause peripheral neuritis 1

Medications Requiring Temporary Discontinuation During Acute Illness

In patients with GFR <60 mL/min/1.73 m² who develop serious intercurrent illness (infection, dehydration, surgery), temporarily discontinue the following "sick-day medications": 1

• RAAS blockers (ACE inhibitors, ARBs, aldosterone inhibitors, direct renin inhibitors)
• Diuretics
• NSAIDs
• Metformin
• Lithium
• Digoxin

This "sick-day rule" prevents acute kidney injury during periods of hemodynamic stress 1

Antihistamines Requiring Dose Adjustment

In Moderate Renal Impairment (CrCl 10-20 mL/min):

• Avoid acrivastine entirely 1
• Halve the dose of cetirizine, levocetirizine, and hydroxyzine 1

In Severe Renal Impairment (CrCl <10 mL/min):

• Avoid cetirizine, levocetirizine, and alimemazine 1
• Use loratadine and desloratadine with caution 1

Contrast Media Precautions

Iodinated Radiocontrast:

• In patients with GFR <60 mL/min/1.73 m², avoid high osmolar agents, use lowest possible dose, withdraw nephrotoxic agents, provide adequate saline hydration, and measure GFR 48-96 hours post-procedure 1

Gadolinium-Based Contrast:

• Do not use gadolinium-containing contrast media in patients with GFR <15 mL/min/1.73 m² 1
• Use with extreme caution in patients with GFR <30 mL/min/1.73 m² due to risk of nephrogenic systemic fibrosis 1

General Principles for Safe Prescribing

• Always adjust drug dosing based on GFR, not just serum creatinine alone 1
• For drugs with narrow therapeutic windows, consider cystatin C-based estimates or direct GFR measurement 1
• Avoid combining multiple nephrotoxic agents whenever possible 3, 7
• Ensure adequate hydration status, as volume depletion significantly increases nephrotoxicity risk 2, 8
• Monitor renal function closely when initiating potentially nephrotoxic medications 1, 9

Common Pitfalls to Avoid

• Do not rely solely on serum creatinine to assess renal function, especially in elderly patients or those with reduced muscle mass, as it may appear deceptively normal despite reduced GFR 4
• Do not assume small increases in creatinine (10-20%) with ACE inhibitors represent acute kidney injury—this is an expected hemodynamic effect 4
• Do not use over-the-counter medications or herbal remedies without medical consultation, as many have nephrotoxic potential 1
• Avoid forced air warmers over fentanyl patches, as this increases drug absorption 1