may be used to determine the therapeutic response to acarbose and identify the minimum effective dose for the patient. thereafter, glycosylated hemoglobin should be measured at intervals of approximately three months. the therapeutic goal should be to decrease both postprandial plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of acarbose, either as monotherapy or in combination with sulfonylureas, insulin or metformin. initial dosage the recommended starting dosage of acarbose is 25 mg given orally three times daily at the start (with the first bite) of each main meal. however, some patients may benefit from more gradual dose titration to minimize gastrointestinal side effects. this may be achieved by initiating treatment at 25 mg once per day and subsequently increasing the frequency of administration to achieve 25 mg t.i.d. maintenance dosage once a 25 mg t.i.d. dosage regimen is reached, dosage of acarbose should be adjusted at 4 to 8 week intervals based on one-hour postprandial glucose or glycosylated hemoglobin levels, and on tolerance. the dosage can be increased from 25 mg t.i.d. to 50 mg t.i.d. some patients may benefit from further increasing the dosage to 100 mg t.i.d. the maintenance dose ranges from 50 mg t.i.d. to 100 mg t.i.d. however, since patients with low body weight may be at increased risk for elevated serum transaminases, only patients with body weight > 60 kg should be considered for dose titration above 50 mg t.i.d. (see precautions ). if no further reduction in postprandial glucose or glycosylated hemoglobin levels is observed with titration to 100 mg t.i.d., consideration should be given to lowering the dose. once an effective and tolerated dosage is established, it should be maintained. maximum dosage the maximum recommended dose for patients ≤ 60 kg is 50 mg t.i.d. the maximum recommended dose for patients > 60 kg is 100 mg t.i.d. patients receiving sulfonylureas or insulin sulfonylurea agents or insulin may cause hypoglycemia. acarbose given in combination with a sulfonylurea or insulin will 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.

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 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 urticaria), 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. 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 and perform the appropriate diagnostic imaging.

des to glucose and other monosaccharides in the brush border of the small intestine. in diabetic patients, this enzyme inhibition results in a delayed glucose absorption and a lowering of postprandial hyperglycemia. because its mechanism of action is different, the effect of acarbose to enhance glycemic control is additive to that of sulfonylureas, insulin or metformin when used in combination. in addition, acarbose diminishes the insulinotropic and weight-increasing effects of sulfonylureas. acarbose has no inhibitory activity against lactase and consequently would not be expected to induce lactose intolerance. pharmacokinetics absorption in a study of 6 healthy men, less than 2% of an oral dose of acarbose was absorbed as active drug, while approximately 35% of total radioactivity from a 14 c-labeled oral dose was absorbed. an average of 51% of an oral dose was excreted in the feces as unabsorbed drug-related radioactivity within 96 hours of ingestion. because acarbose acts locally within the gastrointestinal tract, this low systemic bioavailability of parent compound is therapeutically desired. following oral dosing of healthy volunteers with 14 c-labeled acarbose, peak plasma concentrations of radioactivity were attained 14 to 24 hours after dosing, while peak plasma concentrations of active drug were attained at approximately 1 hour. the delayed absorption of acarbose-related radioactivity reflects the absorption of metabolites that may be formed by either intestinal bacteria or intestinal enzymatic hydrolysis. metabolism acarbose is metabolized exclusively within the gastrointestinal tract, principally by intestinal bacteria, but also by digestive enzymes. a fraction of these metabolites (approximately 34% of the dose) was absorbed and subsequently excreted in the urine. at least 13 metabolites have been separated chromatographically from urine specimens. the major metabolites have been identified as 4-methylpyrogallol derivatives (that is, sulfate, methyl, and glucuronide conjugates). one metabolite (formed by cleavage of a glucose molecule from acarbose) also has alpha-glucosidase inhibitory activity. this metabolite, together with the parent compound, recovered from the urine, accounts for less than 2% of the total administered dose. excretion the fraction of acarbose that is absorbed as intact drug is almost completely excreted by the kidneys. when acarbose was given intravenously, 89% of the dose was recovered in the urine as active drug within 48 hours. in contrast, less than 2% of an oral dose was recovered in the urine as active (that is, parent compound and active metabolite) drug. this is consistent with the low bioavailability of the parent drug. the plasma elimination half-life of acarbose activity is approximately 2 hours in healthy volunteers. consequently, drug accumulation does not occur with three times a day (t.i.d.) oral dosing. special populations the mean steady-state area under the curve (auc) and maximum concentrations of acarbose were approximately 1.5 times higher in elderly compared to young volunteers; however; these differences were not statistically significant. patients with severe renal impairment (clcr < 25 ml/min/1.73 m 2 ) attained about 5 times higher peak plasma concentrations of acarbose and 6 times larger aucs than volunteers with normal renal function. no studies of acarbose pharmacokinetic parameters according to race have been performed. in u.s. controlled clinical studies of acarbose in patients with type 2 diabetes mellitus, reductions in glycosylated hemoglobin levels were similar in caucasians (n=478) and african-americans (n=167), with a trend toward a better response in latinos (n=132). drug-drug interactions studies in healthy volunteers have shown that acarbose has no effect on either the pharmacokinetics or pharmacodynamics of nifedipine, propranolol, or ranitidine. acarbose did not interfere with the absorption or disposition of the sulfonylurea glyburide in diabetic patients. acarbose may affect digoxin bioavailability and may require dose adjustment of digoxin by 16% (90% confidence interval: 8 to 23%), decrease mean c max of digoxin by 26% (90% confidence interval: 16 to 34%) and decreases mean trough concentrations of digoxin by 9% (90% confidence limit: 19% decrease to 2% increase). (see precautions : drug interactions ). the amount of metformin absorbed while taking acarbose was bioequivalent to the amount absorbed when taking placebo, as indicated by the plasma auc values. however, the peak plasma level of metformin was reduced by approximately 20% when taking acarbose due to a slight delay in the absorption of metformin. there is little if any clinically significant interaction between acarbose and metformin.