Generic Name: Acarbose
Class: alpha-Glucosidase Inhibitors
VA Class: HS502
Chemical Name: O - 4,6 - dideoxy - 4 - [[[1S - (1α,4α,5β,6α)] - 4,5,6 - trihydroxy - 3 - (hydroxymethyl) - 2 - cyclohexen - 1 - yl]amino] - α - d -glucopyranosyl-(1→4)-O-α-d-glucopyranosyl-(1→4)-d-glucose
Molecular Formula: C25H43NO18
CAS Number: 56180-94-0

Introduction

Antidiabetic agent; an α-glucosidase inhibitor.1 6 30 52

Uses for Precose

Diabetes Mellitus

Used as monotherapy as an adjunct to diet and exercise for the management of type 2 (noninsulin-dependent) diabetes mellitus (NIDDM) in patients whose hyperglycemia cannot be controlled by diet and exercise alone.1 6 14 47

Also used as adjunct to diet and exercise in combination with metformin, a sulfonylurea, or insulin for management of type 2 diabetes mellitus in patients whose hyperglycemia cannot be controlled with acarbose, metformin, insulin, or sulfonylurea monotherapy, diet, and exercise.1 3 6 14 23 26 44 47

Slideshow: Prediabetes - Am I at Risk?

Metformin generally recommended over other antidiabetic agents for initial oral antidiabetic therapy because of absence of weight gain or hypoglycemia, relatively lower expense and greater efficacy, and generally low adverse effect profile.110

ADA and other clinicians prefer addition of an insulin, a sulfonylurea, or a thiazolidinedione over an α-glucosidase inhibitor (e.g., acarbose), pramlintide, exenatide, or a meglitinide (e.g., repaglinide, nateglinide) as second-line therapy in patients inadequately controlled on metformin monotherapy because of relatively lesser efficacy, limited clinical data, frequent GI adverse effects, and/or greater cost with the latter agents.110

Acarbose should not be used as sole antidiabetic therapy in patients whose diabetes is complicated by ketoacidosis with or without coma (e.g., type 1 [insulin-dependent, IDDM] diabetes mellitus); instead, such patients should receive insulin.1 57

Precose Dosage and Administration

General

  • Individualize treatment and adjust target blood glucose and glycosylated hemoglobin A1c (HbA1c) concentrations based on patient’s understanding and adherence to the treatment regimen, the risk of severe hypoglycemia, and other factors that may increase risk or decrease benefit (e.g., very young or old age, comorbid conditions, other diseases that materially shorten life expectancy).1 62

  • Goal of therapy is to reduce both postprandial blood (or plasma) glucose and hemoglobin values to normal or near normal using lowest effective dosage of acarbose as monotherapy or combined with a sulfonylurea antidiabetic agent, metformin, or insulin.1 (Plasma glucose concentrations generally 10–15% higher than those in whole blood and may vary according to method and laboratory used.)63 During therapy initiation and dosage titration, obtain 1-hour postprandial glucose concentration to determine therapeutic response and minimum effective dosage.1 14 23 52 62 Monitor HbA1c values at approximately every 3 months to evaluate long-term glycemic control.1 14 23 52 62 Monitor glucose concentrations 1–2 hours after the start of a meal in those who have elevated HbA1c despite adequate preprandial glucose concentrations.62

Administration

Oral Administration

Administer orally at the beginning (with the first bite) of each main meal.1 23 If a dose is missed, take the next dose at the next meal.108 Do not take a double dose to make up for the missed dose.108

Dosage

Adults

Diabetes Mellitus
Oral

Initially, 25 mg 3 times daily at the beginning of each main meal.1 23 In patients with adverse GI effects,2 12 23 34 initiate at 25 mg once daily and increase dosage gradually as necessary to 25 mg 3 times daily.1

Once dosage of 25 mg 3 times daily has been reached, increase dosage at intervals of 4–8 weeks as tolerated to achieve the desired 1-hour postprandial glucose concentration (i.e., <180 mg/dL).1 23 34 41 52 62 Maintenance dosage ranges from 50–100 mg 3 times daily.1 6 47

Dosages higher than 100 mg 3 times daily are not recommended since such dosages have been associated with an increased risk of elevated serum aminotransferase concentrations.1 10 18 19 20 22 23 25 27 30 37 43 52 If no further therapeutic benefit occurs at the maximum recommended dosage, consider lowering the dosage.1

Prescribing Limits

Adults

Diabetes Mellitus
Oral

Patients ≤60 kg: maximum 50 mg 3 times daily.1 23 34 41 52

Patients >60 kg: maximum 100 mg 3 times daily.1

Cautions for Precose

Contraindications

  • Known hypersensitivity to the drug.1

  • Diabetic ketoacidosis.1

  • Cirrhosis.1

  • Inflammatory bowel disease, colonic ulceration, existing partial intestinal obstruction or predisposition to this condition.1

  • Chronic intestinal diseases associated with marked disorders of digestion or absorption.1

  • Co-existing conditions that may deteriorate as a result of increased intestinal gas formation.1

Warnings/Precautions

General Precautions

Metabolic Effects

Should not cause hypoglycemia when administered alone in the fasted or postprandial state.1 However, hypoglycemia (rarely hypoglycemic shock) may occur when used concomitantly with a sulfonylurea antidiabetic agent and/or insulin.1 If hypoglycemia occurs, adjust dosage of these agents appropriately.1 Use oral glucose (dextrose) for the treatment of mild to moderate hypoglycemia instead of sucrose (table sugar);1 the absorption of oral glucose is not inhibited by acarbose.1 Severe hypoglycemia may require the use of either IV glucose or parenteral glucagon.1

Insulin may be required for correction of temporary hyperglycemia that is not controlled by dietary regulation or oral antidiabetic agents during periods of severe stress (e.g., acute infection, trauma, surgery, fever).1 57 59

Hepatic Effects

Elevations in serum aminotransferase (i.e., ALT, AST) concentrations and, in rare instances, hyperbilirubinemia may occur, particularly with dosages exceeding 150 mg daily (50 mg 3 times daily).1 23 Jaundice and fatal hepatitis reported during postmarketing experience.1

Determine serum aminotransferase concentrations every 3 months during the first year of therapy and periodically thereafter.1 If elevations in serum aminotransferase concentrations occur, reduce dosage.1 May be necessary to withdraw the drug, particularly if elevated serum aminotransferase concentrations persist.1

Adherence to Prescribed Diet

If prescribed diet not followed closely, adverse GI effects may be intensified.1 108 To minimize adverse GI effects, avoid rich foods, sauces, and certain beverages, including beer and carbonated soft drinks.108 Limit intake of gas-producing foods such as beans, nuts, bran cereals, broccoli, and cabbage.108 Consume low-fat meals and snacks.108 Drink plenty of water, especially in the early morning, midmorning, and afternoon.108 Avoid overeating; food portions should be small to moderate in size.108 Eat food slowly and chew thoroughly.108 Keep food diary to identify problem foods.108

Specific Populations

Pregnancy

Category B.1

Lactation

Distributed into milk in rats.1 Not known whether distributed into human milk.1 Use not recommended in nursing women.1

Pediatric Use

Safety and efficacy in children <18 years of age not established.1 23

Geriatric Use

Safety and efficacy in those ≥65 years of age similar to that in younger adults.1 (See Special Populations under Pharmacokinetics: Absorption.)

Hepatic Impairment

Contraindicated in patients with cirrhosis.1 23 52 Not studied in other conditions associated with hepatic impairment.1 23 52

Renal Impairment

Not recommended for use in diabetic patients with appreciable renal impairment (Scr >2 mg/dL).1 23

Common Adverse Effects

Flatulence, diarrhea, abdominal discomfort/pain.1

Interactions for Precose

Digestive Enzyme Supplements

Possible reduction in the glycemic effects of acarbose.1 Avoid concomitant use.1

Intestinal Adsorbents

Possible reduction in the glycemic effects of acarbose.1 Avoid concomitant use.1

Specific Drugs

Drug

Interaction

Comments

Amylase (digestive enzyme preparation)

Possible reduction in glycemic effects of acarbose1

Avoid concomitant use1

Calcium-channel blocking agents

Potential to exacerbate hyperglycemia, resulting in loss of glycemic control1

No effect of acarbose on the pharmacokinetic or pharmacodynamics of nifedipine1

Monitor for loss of glycemic control1

When calcium-channel blocking agents are withdrawn in patients receiving concurrent sulfonylureas or insulin, monitor for evidence of hypoglycemia1

Charcoal (intestinal adsorbent)

Possible reduction in glycemic effects of acarbose1

Avoid concomitant use1

Corticosteroids

Potential to exacerbate hyperglycemia, resulting in loss of glycemic control1

Monitor for loss of glycemic control1

When corticosteroids are withdrawn in patients receiving concurrent sulfonylureas or insulin, monitor for evidence of hypoglycemia1

Contraceptives, oral

Potential exacerbation of hyperglycemia/loss of glycemic control1

Monitor for loss of glycemic control1

When oral contraceptives are withdrawn in patients receiving concurrent sulfonylureas or insulin, observe for evidence of hypoglycemia1

Digoxin

Decreased blood concentrations of digoxin1

May require increased digoxin dosage1

Diuretics (e.g., thiazides)

Potential exacerbation of hyperglycemia, resulting in loss of glycemic control1

Monitor for loss of glycemic control1

When diuretics are withdrawn in patients receiving concurrent sulfonylureas or insulin, observe for evidence of hypoglycemia1

Estrogens

Potential to exacerbate hyperglycemia, resulting in loss of glycemic control1

Monitor for loss of glycemic control1

When estrogens are withdrawn in patients receiving concurrent sulfonylureas or insulin, observe for evidence of hypoglycemia1

Glyburide

No effect on absorption or disposition of concomitant glyburide1

Pharmacokinetic interaction with glyburide unlikely1

Insulin

Increased risk of hypoglycemia, rarely hypoglycemic shock, with concomitant insulin1

If hypoglycemia occurs, reduce insulin dosage1

Isoniazid

Potential to exacerbate hyperglycemia, resulting in loss of glycemic control1

Monitor for loss of glycemic control1

When isoniazid is withdrawn in patients receiving concurrent sulfonylureas or insulin, monitor for evidence of hypoglycemia1

Metformin

Possible decreased peak plasma concentration of metformin1

Pharmacokinetic interaction not considered clinically important1

Nicotinic acid

Potential to exacerbate diabetes mellitus, resulting in loss of glycemic control1

Monitor for loss of glycemic control1

When nicotinic acid is withdrawn in patients receiving concurrent sulfonylureas or insulin, observe for evidence of hypoglycemia1

Pancreatin (digestive enzyme preparation; no longer commercially available in the US)

Possible reduction in glycemic effects of acarbose1

Avoid concomitant use1

Phenothiazines

Potential to exacerbate hyperglycemia, resulting in loss of glycemic control1

Monitor for loss of glycemic control1

When phenothiazines are withdrawn in patients receiving concurrent sulfonylureas or insulin, monitor for evidence of hypoglycemia1

Phenytoin

Potential to exacerbate hyperglycemia, resulting in loss of glycemic control1

Monitor for loss of glycemic control1

When phenytoin is withdrawn in patients receiving concurrent sulfonylureas or insulin, monitor for evidence of hypoglycemia1

Pramlintide

Delayed gastric emptying caused by α-glucosidase inhibitors may alter effects of pramlintide on GI absorption of nutrients112

Avoid concomitant pramlintide; safety/efficacy of combination therapy not established112

Propranolol

Pharmacokinetic or pharmacodynamic interaction unlikely1

Ranitidine

Pharmacokinetic or pharmacodynamic interaction unlikely1

Rosiglitazone

Reduced extent of absorption and prolonged half-life of rosiglitazone113

Potential for altered glycemic control is uncertain114

Pharmacokinetic interaction not considered clinically important113

Sulfonylureas

Increased risk of hypoglycemia, hypoglycemic shock with sulfonylureas1

If hypoglycemia occurs, reduce sulfonylurea dosage1

Sympathomimetic agents

Potential to exacerbate hyperglycemia, resulting in loss of glycemic control1

Monitor for loss of glycemic control1

When sympathomimetic agents are withdrawn in patients receiving concurrent sulfonylureas or insulin, monitor for evidence of hypoglycemia.1

Thyroid agents

Potential to exacerbate hyperglycemia, resulting in loss of glycemic control1

Monitor for loss of glycemic control1

When thyroid agents are withdrawn in patients receiving concurrent sulfonylureas or insulin, monitor for evidence of hypoglycemia1

Precose Pharmacokinetics

Absorption

Bioavailability

Low systemic bioavailability of parent compound; <2% of dose is absorbed as active drug (parent compound and active metabolite).1 Peak plasma concentrations of active drug attained at approximately 1 hour.1 Approximately 34% of dose absorbed as numerous metabolites.1

Onset

Satisfactory control of blood glucose concentrations achieved within a few days after dosage adjustment; however18 23 maximum response may be delayed for up to 2 weeks.18 23

Special Populations

In geriatric patients, mean AUC and peak blood concentrations of the drug were higher compared with younger adults;1 differences not statistically significant.1

In individuals with severe renal impairment (CLcr <25 mL/minute), peak plasma drug concentrations and AUC increased compared with those values in individuals with normal renal function.1

Distribution

Extent

Distributed into milk in rats.1

Elimination

Metabolism

Metabolized exclusively in GI tract, principally by intestinal bacteria but also by digestive enzymes to numerous metabolites, one of which is active.1

Elimination Route

Excreted principally in feces (51% of dose) as unabsorbed drug and in urine as metabolites (34% of dose).1 No accumulation with recommended dosing frequency.1

Half-life

Approximately 2 hours.1

Stability

Storage

Oral

Tablets

≤25°C.1 Protect from moisture.1

Actions

  • Small inhibitory effect on α-glucosidase enzymes (e.g., glucoamylase, sucrase, maltase, isomaltase) that hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the intestinal brush-border.2 6 14 24 29 30 52 Small inhibitory effect on pancreatic α-amylase, which hydrolyzes starch into maltose, maltotriose, and dextrins in the lumen of the small intestine.2 14 30 33 No inhibitory effect on lactase and would not be expected to produce lactose intolerance.1

  • Delays carbohydrate breakdown and glucose absorption and reduces postprandial hyperglycemia in diabetic patients.1 2 6 7 10 14 23 24 30

  • Reduces fluctuations in the daily blood glucose concentration-time profile in patients with type 2 diabetes mellitus and in lean or obese nondiabetic individuals.1 2 3 6 7 19 20 21 23 24 35 37 39 47 Fasting blood glucose concentrations either not affected or mildly decreased.1 2 3 6 7 19 20 21 23 24 35 37 39 47

  • In contrast to sulfonylurea antidiabetic agents, acarbose does not enhance insulin secretion.1 Does not produce hypoglycemia when given as monotherapy in fasting individuals.1

  • When used in combination with sulfonylurea antidiabetic agents are used in combination, acarbose reduces the insulinotropic and weight-increasing effects of sulfonylureas.1 No clinically important loss of calories or weight loss occurs in either diabetic or nondiabetic individuals.2 6 13 14 18 21 23 28 35 37 39

Advice to Patients

  • Importance of adherence to diet and exercise regimen.1 23 54

  • Importance of adherence to dietary precautions designed to minimize adverse GI effects.1 108 Importance of consulting a clinician for dosage adjustments if adverse GI effects occur despite adherence to such dietary precautions.1 (See Adherence to Prescribed Diet under Cautions.)

  • Importance of regular monitoring of blood glucose concentrations.1 14 23 52 62

  • Importance of avoiding infection.23

  • Provide instruction on the management of hyperglycemia or hypoglycemia.23 62 Advise of the risk of hypoglycemia, its symptoms, and conditions that predispose to the development of hypoglycemia.1 Importance of keeping a readily available source of glucose (dextrose) to treat symptoms of hypoglycemia when used in combination with a sulfonylurea agent or insulin.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Acarbose

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

25 mg

Precose

Bayer

50 mg

Precose

Bayer

100 mg

Precose

Bayer

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Acarbose 100MG Tablets (WATSON LABS): 100/$89.99 or 300/$239.97

Acarbose 25MG Tablets (WATSON LABS): 100/$83.99 or 300/$228.97

Acarbose 50MG Tablets (WATSON LABS): 100/$87.99 or 300/$235.96

Precose 100MG Tablets (BAYER HEALTHCARE PHARMA): 90/$109.99 or 270/$299.97

Precose 25MG Tablets (BAYER PHARMACEUTICAL): 90/$85.51 or 270/$238.56

Precose 50MG Tablets (BAYER HEALTHCARE PHARMA): 30/$36.99 or 90/$92.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions March 23, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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