Acarbose 50 mg Tablet, 100-count — NDC 23155-148-01 (Billing 23155-0148-01)

ADVERSE REACTIONS Digestive Tract Gastrointestinal symptoms are the most common reactions to acarbose tablets. In U.S. placebo-controlled trials, the incidences of abdominal pain, diarrhea, and flatulence were 19%, 31%, and 74% respectively in 1255 patients treated with acarbose tablets 50-300 mg t.i.d., whereas the corresponding incidences were 9%, 12%, and 29% in 999 placebo-treated patients. In a one-year safety study, during which patients kept diaries of gastrointestinal symptoms, abdominal pain and diarrhea tended to return to pretreatment levels over time, and the frequency and intensity of flatulence tended to abate with time.

The increased gastrointestinal tract symptoms in patients treated with acarbose tablets are a manifestation of the mechanism of action of acarbose and are related to the presence of undigested carbohydrate in the lower GI tract. If the prescribed diet is not observed, the intestinal side effects may be intensified. If strongly distressing symptoms develop in spite of adherence to the diabetic diet prescribed, the doctor must be consulted and the dose temporarily or permanently reduced.

Elevated Serum Transaminase Levels See PRECAUTIONS . Other Abnormal Laboratory Findings Small reductions in hematocrit occurred more often in acarbose-treated patients than in placebo-treated patients but were not associated with reductions in hemoglobin. Low serum calcium and low plasma vitamin B 6 levels were associated with acarbose tablets therapy but are thought to be either spurious or of no clinical significance.

Postmarketing Adverse Event Reports Additional adverse events reported from worldwide postmarketing experience include fulminant hepatitis with fatal outcome, hypersensitive skin reactions (for example rash, erythema, exanthema and uticaria), edema, ileus/subileus, jaundice and/or hepatitis and associated liver damage, thrombocytopenia, and pneumatosis cystoides intestinalis (see PRECAUTIONS ). Pneumatosis Cystoides Intestinalis There have been rare postmarketing reports of pneumatosis cystoides intestinalis associated with the use of alpha-glucosidase inhibitors, including acarbose tablets.Pneumatosis cystoides intestinalis may present with symptoms of diarrhea, mucus discharge, rectal bleeding, and constipation.Complications may include pneumoperitoneum, volvulus, intestinal obstruction, intussusception, intestinal hemorrhage, and intestinal perforation.

If pneumatosis cystoides intestinalis is suspected, discontinue acarbose tablets and perform the appropriate diagnostic imaging. To report SUSPECTED ADVERSE REACTIONS, contact Avet Pharmaceuticals Inc. at 1-866-901-DRUG (3784) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 ).

PRECAUTIONS General Macrovascular Outcomes There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with acarbose tablets or any other anti-diabetic drug. Hypoglycemia Because of its mechanism of action, acarbose tablets when administered alone should not cause hypoglycemia in the fasted or postprandial state. Sulfonylurea agents or insulin may cause hypoglycemia.

Because acarbose given in combination with a sulfonylurea or insulin will cause a further lowering of blood glucose, it may increase the potential for hypoglycemia. Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use, and no increased incidence of hypoglycemia was observed in patients when acarbose was added to metformin therapy. Oral glucose (dextrose), whose absorption is not inhibited by acarbose tablets, should be used instead of sucrose (cane sugar) in the treatment of mild to moderate hypoglycemia.

Sucrose, whose hydrolysis to glucose and fructose is inhibited by acarbose tablets, is unsuitable for the rapid correction of hypoglycemia. Severe hypoglycemia may require the use of either intravenous glucose infusion or glucagon injection. Elevated Serum Transaminase Levels In long-term studies (up to 12 months, and including acarbose tablets doses up to 300 mg t.i.d.) conducted in the United States, treatment emergent elevations of serum transaminases (AST and/or ALT) above the upper limit of normal (ULN), greater than 1.8 times the ULN, and greater than 3 times the ULN occurred in 14%, 6%, and 3%, respectively, of acarbose-treated patients as compared to 7%, 2%, and 1%, respectively, of placebo-treated patients.

Although these differences between treatments were statistically significant, these elevations were asymptomatic, reversible, more common in females, and, in general, were not associated with other evidence of liver dysfunction. In addition, these serum transaminase elevations appeared to be dose related. In US studies including acarbose doses up to the maximum approved dose of 100 mg t.i.d., treatment-emergent elevations of AST and/or ALT at any level of severity were similar between acarbose-treated patients and placebo-treated patients (p ≥ 0.496).

In approximately 3 million patient-years of international postmarketing experience with acarbose tablets, 62 cases of serum transaminase elevations > 500 IU/L (29 of which were associated with jaundice) have been reported. Forty-one of these 62 patients received treatment with 100 mg t.i.d. or greater and 33 of 45 patients for whom weight was reported weighed < 60 kg. In the 59 cases where follow-up was recorded, hepatic abnormalities improved or resolved upon discontinuation of acarbose tablets in 55 and were unchanged in two.

Cases of fulminant hepatitis with fatal outcome have been reported; the relationship to acarbose is unclear. Loss of Control of Blood Glucose When diabetic patients are exposed to stress such as fever, trauma, infection, or surgery, a temporary loss of control of blood glucose may occur. At such times, temporary insulin therapy may be necessary.

Information for Patients Patients should be told to take acarbose tablets orally three times a day at the start (with the first bite) of each main meal. It is important that patients continue to adhere to dietary instructions, a regular exercise program, and regular testing of urine and/or blood glucose. Acarbose tablets itself do not cause hypoglycemia even when administered to patients in the fasted state.

Sulfonylurea drugs and insulin, however, can lower blood sugar levels enough to cause symptoms or sometimes life-threatening hypoglycemia. Because acarbose tablets given in combination with a sulfonylurea or insulin will cause a further lowering of blood sugar, it may increase the hypoglycemic potential of these agents. Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use, and no increased incidence of hy… [Excerpted — this section continues on DailyMed.]