I am a 66‑year‑old man with stage 3 chronic kidney disease (estimated glomerular filtration rate 30–59 mL/min/1.73 m²) taking pregabalin 150 mg daily and experiencing fatigue; could the pregabalin dose be causing my tiredness and what adjustments should be made?

Pregabalin Dose Adjustment Required in Stage 3 CKD

Your pregabalin dose of 150 mg daily is likely excessive for your kidney function and is almost certainly contributing to your fatigue—you need immediate dose reduction to 75 mg daily or less based on your precise eGFR.

Understanding the Problem

Your tiredness is very likely medication-related rather than disease-related. Pregabalin is eliminated almost entirely by the kidneys (not metabolized by the liver), and when kidney function declines, the drug accumulates to toxic levels causing sedation, dizziness, and profound fatigue 1, 2.

• Stage 3 CKD encompasses a wide eGFR range (30-59 mL/min/1.73 m²), and pregabalin dosing must be adjusted based on your specific creatinine clearance 1.
• Pregabalin clearance is directly proportional to creatinine clearance—a 56-58% reduction in kidney function produces a corresponding 56-58% reduction in drug elimination 2.
• This means the drug stays in your system much longer, accumulating to levels that would be appropriate only for someone with normal kidney function 2.

Specific Dose Adjustments Required

The FDA label provides explicit dosing based on creatinine clearance 1:

• If your CLcr is 30-60 mL/min (Stage 3 CKD): Your total daily dose should be 75 mg/day (not 150 mg/day), divided into 2-3 doses 1.
• If your CLcr is 15-30 mL/min (Stage 4 CKD): Your dose should be reduced further to 25-50 mg/day 1.
• If your CLcr is <15 mL/min (Stage 5 CKD): Your dose should be 25 mg/day or less 1.

You are currently taking double the recommended dose for Stage 3 CKD, which explains your fatigue.

Why This Matters for Your Symptoms

• Pregabalin's most common dose-dependent adverse effects are dizziness, somnolence (sleepiness), and fatigue—exactly what you're experiencing 1.
• The effect is dose-related, meaning higher blood levels (from inadequate dose adjustment) produce more severe symptoms 1.
• A 50% dose reduction is recommended for each 50% decrease in creatinine clearance to maintain therapeutic levels without toxicity 2.

Critical Safety Considerations

Do not abruptly stop pregabalin—this can cause withdrawal seizures, even in patients without epilepsy 3:

• A case report documented a tonic-clonic seizure in a CKD patient whose pregabalin was abruptly discontinued during acute illness 3.
• Gradual dose reduction over at least 1 week is essential when adjusting or discontinuing pregabalin 1.

Immediate Action Plan

1. Contact your prescribing physician immediately to discuss dose reduction based on your precise eGFR or calculated creatinine clearance 1.

2. Calculate your creatinine clearance using the Cockcroft-Gault equation (your doctor should do this): CLcr = [(140 - age) × weight in kg] / (72 × serum creatinine in mg/dL) 1.

3. Reduce your dose gradually (do not stop abruptly):

   • If CLcr 30-60 mL/min: Reduce to 75 mg/day total (e.g., 37.5 mg twice daily or 25 mg three times daily) 1.
   • If CLcr 15-30 mL/min: Reduce to 25-50 mg/day 1.
   • Taper over 1 week minimum to avoid withdrawal symptoms 1.

4. Monitor your symptoms after dose adjustment—fatigue should improve within days to weeks as drug levels normalize 2.

Additional CKD Management Considerations

While addressing your pregabalin dosing, ensure your CKD is being optimally managed 4:

• Avoid nephrotoxic medications, particularly NSAIDs (ibuprofen, naproxen), which can worsen kidney function and should be avoided in Stage 3 CKD 5, 4.
• Blood pressure control to ≤130/80 mmHg using ACE inhibitors or ARBs if you have albuminuria 6, 4.
• Monitor for CKD complications including anemia, hyperkalemia, and metabolic acidosis 4.
• Regular eGFR monitoring every 3-6 months to track disease progression 6, 4.

Common Pitfalls to Avoid

• Do not assume all fatigue in CKD is from the disease itself—medication accumulation is a very common and reversible cause 7.
• Do not use standard adult doses of renally-eliminated medications—pregabalin, gabapentin, and many antibiotics require dose adjustment in Stage 3 CKD 7.
• Do not abruptly discontinue pregabalin even if you feel it's causing problems—taper gradually to prevent withdrawal seizures 3.
• Do not delay dose adjustment—continued exposure to excessive pregabalin levels increases risk of falls, cognitive impairment, and other adverse effects 7.

Expert Consensus

Pregabalin and gabapentin were identified by a modified Delphi panel of nephrology, geriatric, and primary care pharmacists as top-priority medications requiring dose adjustment in advanced CKD 7. All panel experts agreed these medications must be adjusted to prevent harm in patients with eGFR <60 mL/min 7.