Acarbose

DESCRIPTION Acarbose Tablets, USP are an oral alpha-glucosidase inhibitor for use in the management of type 2 diabetes mellitus. Acarbose is an oligosaccharide which is obtained from fermentation processes of a microorganism, Actinoplanes utahensis, and is chemically known as O -4,6-dideoxy- 4-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexen-1-yl] amino]- α-D-glucopyranosyl-(1 → 4)- O -α -D-glucopyranosyl-(1 → 4)-D-glucose. It is a white to off-white powder with a molecular weight of 645.6. Acarbose is soluble in water and has a pK a of 5.1. Its empirical formula is C 25 H 43 NO 18 and its chemical structure is as follows: Acarbose Tablets, USP are available as 25 mg, 50 mg and 100 mg tablets for oral use. The inactive ingredients are starch (corn starch), microcrystalline cellulose, magnesium stearate, and colloidal silicon dioxide.

INDICATIONS AND USAGE Acarbose tablets, USP are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

CONTRAINDICATIONS Acarbose tablets are contraindicated in patients with known hypersensitivity to the drug. Acarbose tablets are contraindicated in patients with diabetic ketoacidosis or cirrhosis. Acarbose tablets are also contraindicated in patients with inflammatory bowel disease, colonic ulceration, partial intestinal obstruction or in patients predisposed to intestinal obstruction. In addition, acarbose tablets are contraindicated in patients who have chronic intestinal diseases associated with marked disorders of digestion or absorption and in patients who have conditions that may deteriorate as a result of increased gas formation in the intestine.

Drug Interactions Certain drugs tend to produce hyperglycemia and may lead to loss of blood glucose control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel-blocking drugs, and isoniazid. When such drugs are administered to a patient receiving acarbose tablets, the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from patients receiving acarbose tablets in combination with sulfonylureas or insulin, patients should be observed closely for any evidence of hypoglycemia. Patients Receiving Sulfonylureas or Insulin: Sulfonylurea agents or insulin may cause hypoglycemia. Acarbose tablets given in combination with a sulfonylurea or insulin may cause a further lowering of blood glucose and may increase the potential for hypoglycemia. If hypoglycemia occurs, appropriate adjustments in the dosage of these agents should be made. Very rarely, individual cases of hypoglycemic shock have been reported in patients receiving acarbose tablets therapy in combination with sulfonylureas and/or insulin. Intestinal adsorbents (for example, charcoal) and digestive enzyme preparations containing carbohydrate-splitting enzymes (for example, amylase, pancreatin) may reduce the effect of acarbose tablets and should not be taken concomitantly. Acarbose tablets has been shown to change the bioavailability of digoxin when they are co administered, which may require digoxin dose adjustment. (See CLINICAL PHARMACOLOGY, Drug-Drug Interactions ).

Pregnancy Teratogenic Effects: Pregnancy Category B. The safety of acarbose tablets in pregnant women has not been established. Reproduction studies have been performed in rats at doses up to 480 mg/kg (corresponding to 9 times the exposure in humans, based on drug blood levels) and have revealed no evidence of impaired fertility or harm to the fetus due to acarbose. In rabbits, reduced maternal body weight gain, probably the result of the pharmacodynamic activity of high doses of acarbose in the intestines may have been responsible for a slight increase in the number of embryonic losses. However, rabbits given 160 mg/kg acarbose (corresponding to 10 times the dose in man, based on body surface area) showed no evidence of embryotoxicity and there was no evidence of teratogenicity at a dose 32 times the dose in man (based on body surface area). There are, however, no adequate and well-controlled studies of acarbose tablets in pregnant women. Because animal reproduction studies are not always predictive of the human response, this drug should be used during pregnancy only if clearly needed. Because current information strongly suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital anomalies as well as increased neonatal morbidity and mortality, most experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible.

Pediatric Use Safety and effectiveness of acarbose tablets in pediatric patients have not been established.

OVERDOSAGE Unlike sulfonylureas or insulin, an overdose of acarbose tablets will not result in hypoglycemia. An overdose may result in transient increases in flatulence, diarrhea, and abdominal discomfort which shortly subside. In cases of overdosage the patient should not be given drinks or meals containing carbohydrates (polysaccharides, oligosaccharides and disaccharides) for the next 4-6 hours.