Epalrestat Uses
Epalrestat is an aldose reductase inhibitor used specifically for the treatment of diabetic peripheral neuropathy, where it improves subjective symptoms (pain, numbness, coldness in extremities), nerve conduction velocity, and vibration perception thresholds. 1, 2, 3
Primary Indication: Diabetic Peripheral Neuropathy
Epalrestat is approved in Japan for improvement of:
- Subjective neuropathy symptoms including spontaneous pain, numbness, hyperesthesia, coldness in extremities, muscular weakness, dizziness, and orthostatic fainting 2, 3
- Abnormality of vibration sense as measured by tuning fork and vibrometry 3, 4
- Abnormal changes in heart beat associated with diabetic peripheral neuropathy 2
Mechanism of Action
Epalrestat works by inhibiting aldose reductase, thereby reducing intracellular sorbitol accumulation in nerves that occurs under hyperglycemic conditions. 2, 3 This addresses the underlying pathophysiology of diabetic neuropathy through the polyol pathway, distinguishing it from symptomatic treatments like antidepressants or anticonvulsants that only provide pain relief without affecting disease progression 2.
Clinical Efficacy Profile
Nerve Function Improvements
- Motor and sensory nerve conduction velocity improves after 12-24 weeks of treatment compared to baseline and placebo 2, 3, 4
- Vibration perception thresholds improve after 24 weeks of treatment 3, 4
- Effects are maintained and may increase with long-term therapy up to 3 years 5
Optimal Patient Selection
Epalrestat is most effective in patients with:
- Good glycemic control (HbA1c ≤ 7.0%), where the odds ratio of efficacy versus control is approximately 4:1 5
- Less severe diabetes mellitus and more recent development of neuropathy 3
- Median motor nerve conduction velocity ≥ 40 m/s 5
- HbA1c ≤ 9.0% 5
Stratified analyses demonstrate significantly better efficacy in patients with good glycemic control and less severe diabetic complications 5.
Symptom-Specific Effectiveness
- Effective for somatic neuropathy (pain, numbness, sensory deficits) 6
- Not effective for autonomic neuropathy 6
Secondary Indication: Diabetic Retinopathy
Epalrestat 300 mg/day for 1-3 years significantly improves electroretinogram parameters and photo stress recovery time in patients with diabetic retinopathy compared to placebo 3. Improvements are also documented by funduscopy and fluorescein angiography 3.
Dosing
Standard dosing is 150 mg/day (50 mg three times daily) for diabetic neuropathy. 1, 2, 4 Higher doses of 300 mg/day have been used for retinopathy 3.
Safety Profile
Epalrestat is well tolerated with predominantly minor adverse events. 2, 3
- Most common adverse effects: liver enzyme elevations and gastrointestinal events (nausea, vomiting) 2
- Liver enzyme elevations generally resolve spontaneously with dose reduction or discontinuation 3
- No adverse effects on glucose or lipid metabolism during long-term treatment 4
Clinical Positioning
Unlike current symptomatic treatments (antidepressants, anticonvulsants, tramadol, capsaicin), epalrestat may affect or delay progression of the underlying disease process rather than merely providing symptomatic relief 2. This represents a disease-modifying approach to diabetic neuropathy management.