PRECOSE® (acarbose tablets) is 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)-4,5,6­trihydroxy-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 pKa of 5.1. Its empirical formula is C₂₅H₄₃NO₁₈ and its chemical structure is as follows:

PRECOSE is available as 25 mg, 50 mg and 100 mg tablets for oral use. The inactive ingredients are starch, microcrystalline cellulose, magnesium stearate, and colloidal silicon dioxide.

PRECOSE is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

There is no fixed dosage regimen for the management of diabetes mellitus with PRECOSE or any other pharmacologic agent. Dosage of PRECOSE must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended dose of 100 mg t.i.d. PRECOSE should be taken three times daily at the start (with the first bite) of each main meal. PRECOSE should be started at a low dose, with gradual dose escalation as described below, both to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control of the patient.

During treatment initiation and dose titration (see below), one-hour postprandial plasma glucose may be used to determine the therapeutic response to PRECOSE 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 PRECOSE, either as monotherapy or in combination with sulfonylureas, insulin or metformin.

Initial Dosage: The recommended starting dosage of PRECOSE 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 PRECOSE should be adjusted at 4-8 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. PRECOSE 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.

PRECOSE is available as 25 mg, 50 mg or 100 mg round, unscored tablets. Each tablet strength is white to yellow-tinged in color. The 25 mg tablet is coded with the word “PRECOSE” on one side and “25” on the other side. The 50 mg tablet is coded with the word “PRECOSE” and “50” on the same side. The 100 mg tablet is coded with the word “PRECOSE” and “100” on the same side. PRECOSE is available in bottles of 100 and 50 mg strength in unit dose packages of 100.

Do not store above 25°C (77°F). Protect from moisture. For bottles, keep container tightly closed.

Bayer HealthCare Pharmaceuticals Inc., Wayne, NJ 07470. Made in Germany. FDA revision date: 8/23/2008

Digestive Tract: Gastrointestinal symptoms are the most common reactions to PRECOSE. 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 PRECOSE 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 PRECOSE are a manifestation of the mechanism of action of PRECOSE 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 PRECOSE-treated patients than in placebo-treated patients but were not associated with reductions in hemoglobin. Low serum calcium and low plasma vitamin B₆ levels were associated with PRECOSE therapy but are thought to be either spurious or of no clinical significance.

Post Marketing Adverse Event Reports

Additional adverse events reported from worldwide post marketing experience include hypersensitive skin reactions (e.g. rash, erythema, exanthema and uticaria), edema, ileus/subileus, jaundice and/or hepatitis and associated liver damage (see PRECAUTIONS.)

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 PRECOSE, the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from patients receiving PRECOSE 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. PRECOSE 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 PRECOSE therapy in combination with sulfonylureas and/or insulin.

Intestinal adsorbents (e.g., charcoal) and digestive enzyme preparations containing carbohydrate-splitting enzymes (e.g., amylase, pancreatin) may reduce the effect of PRECOSE and should not be taken concomitantly.

PRECOSE has been shown to change the bioavailability of digoxin when they are coadministered, which may require digoxin dose adjustment. (See CLINICAL PHARMACOLOGY, Drug-Drug Interactions).

No information provided.

General

Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with PRECOSE or any other anti-diabetic drug.

Hypoglycemia: Because of its mechanism of action, PRECOSE when administered alone should not cause hypoglycemia in the fasted or postprandial state. Sulfonylurea agents or insulin may cause hypoglycemia. Because PRECOSE 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 PRECOSE was added to metformin therapy. Oral glucose (dextrose), whose absorption is not inhibited by PRECOSE, 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 PRECOSE, 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 PRECOSE 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 PRECOSE-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 PRECOSE 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 PRECOSE-treated patients and placebo-treated patients (p ≥ 0.496).

In approximately 3 million patient-years of international post-marketing experience with PRECOSE, 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 PRECOSE in 55 and were unchanged in two. A few 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.

Laboratory Tests: Therapeutic response to PRECOSE should be monitored by periodic blood glucose tests. Measurement of glycosylated hemoglobin levels is recommended for the monitoring of long-term glycemic control.

PRECOSE, particularly at doses in excess of 50 mg t.i.d., may give rise to elevations of serum transaminases and, in rare instances, hyperbilirubinemia. It is recommended that serum transaminase levels be checked every 3 months during the first year of treatment with PRECOSE and periodically thereafter. If elevated transaminases are observed, a reduction in dosage or withdrawal of therapy may be indicated, particularly if the elevations persist.

Renal Impairment: Plasma concentrations of PRECOSE in renally impaired volunteers were proportionally increased relative to the degree of renal dysfunction. Long-term clinical trials in diabetic patients with significant renal dysfunction (serum creatinine > 2.0 mg/dL) have not been conducted. Therefore, treatment of these patients with PRECOSE is not recommended.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Eight carcinogenicity studies were conducted with acarbose. Six studies were performed in rats (two strains, Sprague-Dawley and Wistar) and two studies were performed in hamsters.

In the first rat study, Sprague-Dawley rats received acarbose in feed at high doses (up to approximately 500 mg/kg body weight) for 104 weeks. Acarbose treatment resulted in a significant increase in the incidence of renal tumors (adenomas and adenocarcinomas) and benign Leydig cell tumors. This study was repeated with a similar outcome. Further studies were performed to separate direct carcinogenic effects of acarbose from indirect effects resulting from the carbohydrate malnutrition induced by the large doses of acarbose employed in the studies. In one study using Sprague-Dawley rats, acarbose was mixed with feed but carbohydrate deprivation was prevented by the addition of glucose to the diet. In a 26-month study of Sprague-Dawley rats, acarbose was administered by daily postprandial gavage so as to avoid the pharmacologic effects of the drug. In both of these studies, the increased incidence of renal tumors found in the original studies did not occur. Acarbose was also given in food and by postprandial gavage in two separate studies in Wistar rats. No increased incidence of renal tumors was found in either of these Wistar rat studies. In two feeding studies of hamsters, with and without glucose supplementation, there was also no evidence of carcinogenicity.

Acarbose did not induce any DNA damage in vitro in the CHO chromosomal aberration assay, bacterial mutagenesis (Ames) assay, or a DNA binding assay. In vivo, no DNA damage was detected in the dominant lethal test in male mice, or the mouse micronucleus test. Fertility studies conducted in rats after oral administration produced no untoward effect on fertility or on the overall capability to reproduce.

Pregnancy

Teratogenic Effects: Pregnancy Category B. The safety of PRECOSE 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 PRECOSE 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.

Nursing Mothers

A small amount of radioactivity has been found in the milk of lactating rats after administration of radiolabeled acarbose. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, PRECOSE should not be administered to a nursing woman.

Pediatric Use

Safety and effectiveness of PRECOSE in pediatric patients have not been established.

Geriatric Use

Of the total number of subjects in clinical studies of PRECOSE in the United States, 27 percent were 65 and over, while 4 percent were 75 and over. No overall differences in safety and effectiveness were observed between these subjects and younger subjects. 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.

Unlike sulfonylureas or insulin, an overdose of PRECOSE 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 disaccharidees) for the next 4-6 hours.

PRECOSE is contraindicated in patients with known hypersensitivity to the drug and in patients with diabetic ketoacidosis or cirrhosis. PRECOSE is also contraindicated in patients with inflammatory bowel disease, colonic ulceration, partial intestinal obstruction or in patients predisposed to intestinal obstruction. In addition, PRECOSE is 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.

Acarbose is a complex oligosaccharide that delays the digestion of ingested carbohydrates, thereby resulting in a smaller rise in blood glucose concentration following meals. As a consequence of plasma glucose reduction, PRECOSE reduces levels of glycosylated hemoglobin in patients with type 2 diabetes mellitus. Systemic non-enzymatic protein glycosylation, as reflected by levels of glycosylated hemoglobin, is a function of average blood glucose concentration over time.

Mechanism of Action

In contrast to sulfonylureas, PRECOSE does not enhance insulin secretion. The antihyperglycemic action of acarbose results from a competitive, reversible inhibition of pancreatic alpha-amylase and membrane-bound intestinal alpha-glucoside hydrolase enzymes. Pancreatic alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine, while the membrane-bound intestinal alpha-glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides 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 PRECOSE to enhance glycemic control is additive to that of sulfonylureas, insulin or metformin when used in combination. In addition, PRECOSE 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 ¹⁴C-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 ¹⁴C-labeled acarbose, peak plasma concentrations of radioactivity were attained 14-24 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 (i.e., 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 (i.e., 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/1.73m²) 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 PRECOSE 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 PRECOSE has no effect on either the pharmacokinetics or pharmacodynamics of nifedipine, propranolol, or ranitidine. PRECOSE did not interfere with the absorption or disposition of the sulfonylurea glyburide in diabetic patients. PRECOSE may affect digoxin bioavailability and may require dose adjustment of digoxin by 16% (90% confidence interval: 8-23%), decrease mean Cmax of digoxin by 26% (90% confidence interval: 16-34%) 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 PRECOSE 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 PRECOSE due to a slight delay in the absorption of metformin. There is little if any clinically significant interaction between PRECOSE and metformin.

Clinical Trials

Clinical Experience from Dose Finding Studies in Type 2 Diabetes Mellitus Patients on Dietary Treatment Only: Results from six controlled, fixed-dose, monotherapy studies of PRECOSE in the treatment of type 2 diabetes mellitus, involving 769 PRECOSE-treated patients, were combined and a weighted average of the difference from placebo in the mean change from baseline in glycosylated hemoglobin (HbA1c) was calculated for each dose level as presented below:

Table 1 Mean Placebo-Subtracted Change in HbA1c in Fixed-Dose Monotherapy Studies

Results from these six fixed-dose, monotherapy studies were also combined to derive a weighted average of the difference from placebo in mean change from baseline for one-hour postprandial plasma glucose levels as shown in the following figure:

Figure 1

* PRECOSE was statistically significantly different from placebo at all doses with respect to effect on one-hour postprandial plasma glucose.
** The 300 mg t.i.d. PRECOSE regimen was superior to lower doses, but there were no statistically significant differences from 50 to 200 mg t.i.d.

Clinical Experience in Type 2 Diabetes Mellitus Patients on Monotherapy, or in Combination with Sulfonylureas, Metformin or Insulin: PRECOSE was studied as monotherapy and as combination therapy to sulfonylurea, metformin, or insulin treatment. The treatment effects on HbA1c levels and one-hour postprandial glucose levels are summarized for four placebo-controlled, double-blind, randomized studies conducted in the United States in Tables 2 and 3, respectively. The placebo-subtracted treatment differences, which are summarized below, were statistically significant for both variables in all of these studies.

Study 1 (n=109) involved patients on background treatment with diet only. The mean effect of the addition of PRECOSE to diet therapy was a change in HbA1c of -0.78%, and an improvement of one- hour postprandial glucose of -74.4 mg/dL.

In Study 2 (n=137), the mean effect of the addition of PRECOSE to maximum sulfonylurea therapy was a change in HbA1c of -0.54%, and an improvement of one-hour postprandial glucose of -33.5 mg/dL.

In Study 3 (n=147), the mean effect of the addition of PRECOSE to maximum metformin therapy was a change in HbA1c of -0.65%, and an improvement of one-hour postprandial glucose of -34.3 mg/dL.

Study 4 (n=145) demonstrated that PRECOSE added to patients on background treatment with insulin resulted in a mean change in HbA1c of -0.69%, and an improvement of one-hour postprandial glucose of ­ 36.0 mg/dL.

A one year study of PRECOSE as monotherapy or in combination with sulfonylurea, metformin or insulin treatment was conducted in Canada in which 316 patients were included in the primary efficacy analysis (Figure 2). In the diet, sulfonylurea and metformin groups, the mean decrease in HbA1c produced by the addition of PRECOSE was statistically significant at six months, and this effect was persistent at one year. In the PRECOSE-treated patients on insulin, there was a statistically significant reduction in HbA1c at six months, and a trend for a reduction at one year.

Table 2: Effect of Precose on HbA1c

Table 3: Effect of Precose on Postprandial Glucose

Figure 2

Figure 2: Effects of PRECOSE (♦) and Placebo (• ) on mean change in HbA1c levels from baseline throughout a one-year study in patients with type 2 diabetes mellitus when used in combination with: (A) diet alone; (B) sulfonylurea; (C) metformin; or (D) insulin. Treatment differences at 6 and 12 months were tested: * p < 0.01; # p = 0.077.

Patients should be told to take PRECOSE 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.

PRECOSE itself does 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 PRECOSE 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 hypoglycemia was observed in patients when PRECOSE was added to metformin therapy. The risk of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be well understood by patients and responsible family members. Because PRECOSE prevents the breakdown of table sugar, patients should have a readily available source of glucose (dextrose, D-glucose) to treat symptoms of low blood sugar when taking PRECOSE in combination with a sulfonylurea or insulin.

If side effects occur with PRECOSE, they usually develop during the first few weeks of therapy. They are most commonly mild-to-moderate gastrointestinal effects, such as flatulence, diarrhea, or abdominal discomfort, and generally diminish in frequency and intensity with time.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

ACARBOSE - ORAL

(AY-kar-bose)

COMMON BRAND NAME(S): Precose

USES: Acarbose is used along with a proper diet and exercise program to control high blood sugar in people with type 2 diabetes (non-insulin-dependent diabetes). Controlling high blood sugar helps prevent heart disease, strokes, kidney disease, blindness, circulation problems, and decreased sexual ability. Acarbose works by slowing the breakdown of starch (carbohydrates) from the food you eat into sugar, so that your blood sugar level does not rise as much after a meal.

Acarbose may be used with other medications (e.g., insulin, metformin, sulfonylureas such as glipizide) to control diabetes because they work in different ways.

HOW TO USE: Take this medication by mouth, usually 3 times a day at the start (with the first bites) of each main meal or as directed by your doctor.

The dosage is based on your medical condition, weight, and response to therapy. Your dose may be gradually increased to determine the most effective dose for you. The manufacturer recommends that you do not take more than 300 milligrams per day.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day.

For best results, continue to eat a proper diet, exercise regularly, and check your urine/blood sugar levels as directed by your doctor.

SIDE EFFECTS: Diarrhea, gas, upset stomach, or stomach pain may occur in the first few weeks of treatment as your body adjusts to this medication but usually improve with time. Follow your prescribed diet to help lessen these side effects. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these rare but very serious side effects occur: unusual tiredness, persistent nausea/vomiting, severe stomach/abdominal pain, yellowing eyes/skin, dark urine.

Acarbose does not cause low blood sugar (hypoglycemia). However, this effect can occur if you also take other anti-diabetic drugs (e.g., sulfonylureas, insulin) and if you do not consume enough calories from food or if you do unusually heavy exercise. Symptoms of low blood sugar include cold sweat, blurred vision, dizziness, drowsiness, shaking, fast heartbeat, headache, fainting, tingling of the hands/feet, and hunger. Do not use table sugar (also called cane sugar or sucrose) to relieve these symptoms because acarbose delays its breakdown. Carry glucose tablets or gel with you to treat low blood sugar. If you are in a situation where you don't have these reliable forms of glucose, eat some honey or drink a glass of orange juice (sources of another sugar, fructose) to quickly raise your blood sugar level. Tell your doctor about the reaction immediately. To help prevent low blood sugar, eat meals on a regular schedule, and do not skip meals. Check with your doctor or pharmacist to find out what you should do if you miss a meal.

Symptoms of high blood sugar (hyperglycemia) include thirst, increased urination, confusion, drowsiness, flushing, rapid breathing, and fruity breath odor. If these symptoms occur, tell your doctor immediately. Your dosage may need to be increased or you may need other drugs.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking acarbose, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: very high blood sugar levels (diabetic ketoacidosis), severe liver disease (cirrhosis), intestine/bowel problems (e.g., inflammatory bowel disease, intestinal blockage/ulcers, digestion/absorption disorders).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease.

You may experience blurred vision, dizziness, or drowsiness due to extremely low or high blood sugar levels. Use caution while driving, using machinery, or taking part in any other activity that requires clear vision and alertness. Limit alcohol because it can increase the risk of developing low blood sugar.

It may be harder to control your blood sugar when your body is stressed (e.g., due to fever, infection, injury, or surgery). Consult your doctor because this may require a change in your treatment plan, medications, or blood sugar testing.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor. Your doctor may substitute insulin for this drug during your pregnancy. Follow all instructions carefully.

It is not known whether this medication passes into breast milk. Breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medications because very serious interactions may occur: activated charcoal, digestive enzyme products (e.g., amylase, pancreatin).

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting acarbose.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: digoxin, certain herbal drugs (fenugreek, ginseng, gymnema), pramlintide, drugs that may decrease your blood sugar levels (e.g., high-dose salicylates, quinolone antibiotics such as gatifloxacin and levofloxacin, MAO inhibitors such as isocarboxazid), drugs that may increase your blood sugar levels (including corticosteroids such as prednisone, diet pills, niacin, "water pills"/diuretics such as hydrochlorothiazide, HIV protease inhibitors such as ritonavir, certain anti-psychotic drugs such as clozapine and olanzapine).

Beta-blocker medications (e.g., metoprolol, propranolol, glaucoma eye drops such as timolol) may prevent the fast/pounding heartbeat you would usually feel when your blood sugar level falls too low (hypoglycemia). Other symptoms of low blood sugar such as dizziness, hunger, and sweating are unaffected by these drugs.

Check all prescription and nonprescription medicine labels carefully since many medications contain aspirin, which in high doses may increase your risk of hypoglycemia. Low-dose aspirin should be continued if prescribed by your doctor for specific medical reasons such as heart attack or stroke prevention (usually at dosages of 81-325 milligrams per day). Consult your doctor or pharmacist about the safe use of aspirin.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents should call the US National Poison Hotline at 1-800-222-1222. Canada residents should call a provincial poison control center.

NOTES: Do not share this medication with others.

You should attend a diabetes education program to learn more about diabetes and all the important aspects of its treatment, including meals/diet, exercise, personal hygiene, medications, and getting regular eye/foot/medical exams.

Keep all medical appointments. Laboratory and/or medical tests (e.g., liver and kidney function tests, fasting and after-meal blood glucose levels, hemoglobin A1c, complete blood counts) should be performed periodically to check for side effects and monitor your response to therapy. Check your blood or urine sugar levels regularly as directed by your doctor or pharmacist.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature below 77 degrees F (25 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.