Epalrestat is a potent, competitive, and reversible inhibitor of the enzyme aldose reductase. It is the first and only aldose reductase inhibitor (ARI) approved and widely used in India for the treatment of diabetic peripheral neuropathy (DPN). It acts by inhibiting the polyol pathway, thereby reducing the accumulation of sorbitol in nerve cells, which is a key factor in the pathogenesis of diabetic neuropathy. It is indicated for the improvement of subjective neuropathy symptoms and objective nerve function parameters in patients with diabetic neuropathy.
Adult: 50 mg three times daily (TDS), orally, before meals. Standard total daily dose is 150 mg.
Note: Take capsule/tablet orally with a glass of water, preferably before meals. Do not crush or chew. Adhere strictly to the TDS schedule for consistent enzyme inhibition.
Epalrestat selectively and competitively inhibits the enzyme aldose reductase (AR). Under hyperglycemic conditions, excess intracellular glucose is shunted into the polyol pathway where aldose reductase converts it to sorbitol using NADPH. Sorbitol is then converted to fructose by sorbitol dehydrogenase. This process leads to intracellular accumulation of sorbitol, depletion of myo-inositol, and reduction in Na+/K+ ATPase activity. Epalrestat's inhibition of AR prevents sorbitol accumulation, thereby helping to restore nerve conduction velocity, reduce oxidative stress, and improve microvascular blood flow in nerves.
Pregnancy: Category N (Not classified by US FDA). Animal studies have shown teratogenicity. There are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus. Not recommended.
Driving: Dizziness has been reported rarely. Patients should be cautioned about operating machinery or driving if they experience dizziness.
| Tolbutamide | Epalrestat may potentiate the hypoglycemic effect. Mechanism may involve protein binding displacement. | Moderate |
| Warfarin | Potential increase in anticoagulant effect due to protein binding displacement. Monitor INR closely. | Moderate |
| Strong UGT Inducers (e.g., Rifampicin) | May increase metabolism of Epalrestat, reducing its plasma concentration and efficacy. | Moderate |
| Other Highly Protein-Bound Drugs (e.g., Phenytoin, NSAIDs) | Theoretical potential for mutual displacement. Clinical significance unknown. | Low |