Epalrestat is a potent, competitive, and reversible inhibitor of the enzyme aldose reductase, which is the first and rate-limiting enzyme of the polyol pathway. It is specifically indicated for the management of diabetic neuropathy, particularly in patients with poor glycemic control. By inhibiting aldose reductase, it prevents the accumulation of sorbitol and fructose within nerve cells, thereby improving nerve conduction velocity and alleviating symptoms of neuropathy. It is a cornerstone therapy for symptomatic diabetic peripheral neuropathy in the Indian market.
Adult: 150 mg (one tablet) orally, three times a day, taken before meals.
Note: Tablet should be taken whole with water, preferably before meals (breakfast, lunch, and dinner) to ensure consistent drug levels. Do not crush or chew. Adherence to the TDS schedule is crucial for optimal effect.
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. Sorbitol does not diffuse easily across cell membranes and accumulates intracellularly, leading to osmotic stress, depletion of myo-inositol, reduced Na+/K+ ATPase activity, and oxidative stress. This cascade results in nerve damage, reduced nerve conduction velocity (NCV), and the symptoms of diabetic neuropathy. Epalrestat blocks this pathway at its origin.
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. Contraindicated.
Driving: Epalrestat is not known to cause sedation or impair cognitive function. However, if a patient experiences dizziness, they should be cautioned about driving or operating machinery.
| Warfarin | Epalrestat may potentiate anticoagulant effect by displacing warfarin from protein binding sites, increasing INR risk. | Major |
| Other highly protein-bound drugs (e.g., Phenytoin, NSAIDs, Sulfonylureas) | Potential for mutual displacement, altering free concentrations of either drug. | Moderate |
| Strong UGT inducers (e.g., Rifampicin) | May increase metabolism of Epalrestat, reducing its plasma concentration and efficacy. | Moderate |
| Alcohol | Chronic excessive alcohol use may exacerbate hepatic toxicity risk. | Moderate |