Pregabalin Toxicity in Dialysis Patients: Clinical Manifestations
Pregabalin toxicity in dialysis patients primarily manifests as central nervous system depression, with somnolence, dizziness, confusion, and myoclonus being the hallmark symptoms, and these effects are dose-dependent and significantly more pronounced due to impaired renal clearance. 1, 2, 3
Primary Neurological Symptoms
The most common and clinically significant manifestations include:
- Altered mental status (confusion, agitation, apathy) occurs in up to 29% of poisonings and represents one of the most frequent reasons for emergency presentation 4, 2
- Somnolence and drowsiness affect approximately 62% of patients with pregabalin toxicity and can progress to lethargy 1, 4
- Dizziness is reported in up to 30% of pregabalin-treated patients and occurs more frequently at higher doses 1
- Myoclonic jerks are a particularly concerning sign in dialysis patients and may indicate significant drug accumulation 3
Motor and Coordination Disturbances
Movement-related toxicity manifestations are critical to recognize:
- Falls occur with significantly increased frequency, with hazards elevated by 26-68% depending on dose, making this a major safety concern 2
- Tremor and coordination abnormalities are more frequent in patients with renal impairment 1
- Balance disorders represent a dose-related effect that compounds fall risk 1
Severe Toxicity Presentations
In cases of significant overdose or accumulation:
- Coma can occur, particularly at doses exceeding 20-46 mg/kg, though large interindividual variation exists 4
- Seizures may develop, especially when pregabalin is combined with other CNS depressants 1
- Respiratory depression is a life-threatening complication, particularly when co-administered with opioids or other CNS depressants 1
Dose-Toxicity Relationship in Dialysis Patients
The risk stratification based on dosing is critical for dialysis patients:
- Below 20 mg/kg: 83% of patients experience only mild toxicity 4
- Above 46 mg/kg (median): significant toxicity with PSS moderate-severe is expected 4
- In dialysis patients, even standard doses can accumulate to toxic levels because pregabalin clearance is reduced by 56-58% proportional to creatinine clearance 5
Additional Clinical Features
Other manifestations that may present include:
- Peripheral edema occurs in 6-19% of patients, particularly when combined with thiazolidinediones 1
- Weight gain of 7% or more over baseline in 9% of patients 1
- Withdrawal symptoms upon abrupt discontinuation, including insomnia, nausea, headache, and anxiety 1
Critical Timing Considerations
Symptoms characteristically worsen shortly after dialysis sessions if dosing is not properly timed, as pregabalin is highly cleared by hemodialysis (clearance of 88.8 mL/min achieved) 3. This creates a pattern where:
- Toxicity accumulates between dialysis sessions when doses are not adjusted 5
- Immediate post-dialysis periods may show temporary improvement 3
- Supplemental dosing after dialysis is required to maintain therapeutic levels, but this must be carefully calculated 5
Pharmacokinetic Basis for Toxicity
The mechanism underlying toxicity in dialysis patients involves:
- Elimination half-life increases dramatically with declining renal function, from normal values to potentially 132 hours in anuric patients 6
- AUC increases proportionally as creatinine clearance decreases 5
- Pregabalin is 90% protein-unbound, making it dialyzable but also allowing rapid CNS penetration 3
Common Pitfall to Avoid
The most critical error is failing to reduce the daily dose by 50% for each 50% decrease in creatinine clearance below 60 mL/min 5. Standard dosing in dialysis patients (CrCl <15 mL/min) should not exceed 75 mg daily, divided appropriately, with supplemental doses of 25-100 mg post-dialysis 5.