Epalrestat Tablets Alrista
COMPOSITION
Each film coated tablet contains:
Epalrestat 50 mg
DESCRIPTION . . .
Epalrestat occurs as yellow to orange crystal or crystalline powder. It has no odour or taste. It IS practically Insoluble In water.
PHARMACOLOGY
Epalrestat is an aldose reductase inhibitor (ARI).
Pharmacokinetics
Distribution of epalrestat is rapid and peak plasma concentrations are reached within 1 to 2 h after oral dose of 5O-200 mg. Epalrestat is metabolized in tha liver; unchanged drug and metabolites are excreted In the urine. The elimination half-life of epalrestat is about 1 hour.
Pharmacodynamics
Epalrestat (a phenylpropenylidene thiazolidineacetic acid) Is an uncompetitive aldose reductase inhibitor indicated for treatment of diabetic neuropathy and retinopathy. It Is also suggested that there Is a potential usefulness of aldose reductase inhibitor, like epalrestat in preventing the progression of incipient diabetic nephropathy in patients with type 2 diabetes mellitus.
Aldose reductase is the rate-limiting enzyme in the polyol (sorbitol) pathway. This enzyme is activated in the presence of, and converts glucose to sorbitol; the resultant intracellular accumulation of sorbitol leads to increased osmotic pressure and disturbance of cellular function which appears to contribute at least in part to the late complications of diabetes. Reduced sodium/potassium adenosine triphosphatase (Na/K-ATPase) activity also occurs during hyperglycemia and sorbitol accumulation, which alters cellular metabolism and membrane structure. Diabetic animal studies have demonstrated the ability of epalrestat to increase delayed nerve-conduction velocity, and this was accompanied by a reduction in sorbitol levels and improvement of Na/k-ATPase activity. A decrease in sorbitol levels has been observed in ocular tissues, sciatic nerve, and erythrocytes from animal models, and in erythrocytes of diabetic patients. In other diabetic animal models, epalrestat has improved parameters suggestive of retinopathy and renal damage, and reduced the increase in vascular permeability of various tissues (e.g., retina, aorta, optic nerve, caecum).
INDICATIONS AND USAGE
Epalreslat is used in treatment of Improvement of subjective symptoms (numbness and pain), abnormality of vibrational sense, and abnormal change in heartbeat associated with diabetic peripheral neuropathy (when high glycohemoglobin value is noted), and retinopathy.
CONTRAINDICATIONS
Hypersensitivity to any component of the drug, and in severe hepatic insufficiency.
DOSAGE AND ADMINISTRATION
The usual adult dosage for oral use is 50 miligrams of epalrestat three times dally before each meal. The dosage may be adjusted according to the patient's age and symptoms.
DRUG INTERACTIONS
No interactions have been noted with the pharmaceutical base.
WARNING AND PRECAUTIONS
Diabetic neuropathy:. A. re-analysis of available study data revealed that the greatest benefit of epalrestat was in patients with a glycosylated hemoglobin of at least 7.5%. and in those with a relatively short duration of diabetes and diabetic neuropathy; efficacy also appeared greater in patients with mild-to-moderate neuropathy compared to severe neuropathy. These data suggest the need to Initiate therapy at the earliest possible stage of neuropathy.
Liver disease : Elevation of liver enzymes has occurred during therapy, with normalization upon dose reduction or after
Renal impairment: Slight elevation in serum creatinine levels has been observed rarely during therapy. No cases of significant renal impairment have been reported.
Pregnancy
This product should be used in pregnant women or in women who may possibly be pregnant only if the expected therapeutic benefits outweigh the possible risks associated with treatment.
Nursing mothers
Breast-feeding should be avoided during administration of this product.
Pediatric use
The safety of this product in low birth weight infants, neonates, nursing infants, infants or children has not been established.
Geriatric use
Epalrestat, an aldose reductase inhibitor, improved bowel motility and autonomic cardiovascular dysfunction, as evident from heart rate and blood pressure response.
UNDESIRABLE EFFECTS Metabolic effects
Epalrestat does not adversely affect glycemic control (i.e., tasting blood glucose, glycosylated hemoglobin) when given for treatment of late complications of diabetes mellitus. No effect of epalrestat on lipid metabolism was observed, suggesting its safety in patients with coexistent hypercholesterolemia and/or hyperbiglyceridemia
Gastrointestinal effects
Nausea, vomiting, diarrhea, and generalized gastric discomfort have been described by some patients during therapy.
Renal effects
Slight elevation in serum creatinine levels has been observed rarely during therapy (less than 0.5% of patients).
Hepatotoxicity
Elevation of liver enzymes has occured during therapy (less than 2% of patients), With normalization upon dose reduction or after discontinuation.
Dermatologic effects
Cutaneous reactions, including erythema, bullae, and skin blistering, have been described rarely during therapy (less than 1 % of patients). No reactions were considered severe.
OVERDOSAGE
No cases of accidental or intentional overdosage have been recorded in human beings with the appearance of toxic symptoms.
In case of accidental overdosage, normal procedures to eliminate the drug from the digestive tract should be followed: sustain circulation with cardiac drugs, administer, if required, sedatives for the central nervous system (for example, benzodiazepine).
STORAGE
STORE BELOW 25'C IN A DRY PLACE. PROTECT FROM LIGHT.