Acarbose:

EDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Precose® may be confused with PreCare®

International issues:
Precose® may be confused with Precosa® which is a brand name for Saccharomyces boulardii in Denmark, Finland, Norway, and Sweden

U.S. BRAND NAMES — Precose®

PHARMACOLOGIC CATEGORY
Antidiabetic Agent, Alpha-Glucosidase Inhibitor

DOSING: ADULTS — Type 2 diabetes: Oral:

Initial: 25 mg 3 times/day with the first bite of each main meal; to reduce GI effects, some patients may benefit from initiating at 25 mg once daily with gradual titration to 25 mg 3 times/day as tolerated

Maintenance dose: Should be adjusted at 4- to 8-week intervals based on 1-hour postprandial glucose levels and tolerance until maintenance dose is reached; maintenance dose: 50-100 mg 3 times/day. Dosage must be individualized on the basis of effectiveness and tolerance while not exceeding the maximum recommended dose.

Maximum:
≤ 60 kg: 50 mg 3 times/day
>60 kg: 100 mg 3 times/day

Patients receiving sulfonylureas or insulin: Acarbose given in combination with a sulfonylurea or insulin will cause a further lowering of blood glucose and may increase the hypoglycemic potential of the sulfonylurea or insulin. If hypoglycemia occurs, appropriate adjustments in the dosage of these agents should be made.

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT
Clcr <25 mL/minute: Peak plasma concentrations were 5 times higher and AUCs were 6 times larger than in volunteers with normal renal function.

Significant renal dysfunction (Scr >2 mg/dL): Use is not recommended.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet: 25 mg, 50 mg, 100 mg
Precose®: 25 mg, 50 mg, 100 mg

DOSAGE FORMS: CONCISE
Tablet: 25 mg, 50 mg, 100 mg
Precose®: 25 mg, 50 mg, 100 mg

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION — Should be administered with the first bite of each main meal.

USE — Adjunct to diet and exercise to lower blood glucose in patients with type 2 diabetes mellitus (noninsulin dependent, NIDDM)

ADVERSE REACTIONS SIGNIFICANT
>10%:
Gastrointestinal: Diarrhea (31%) and abdominal pain (19%) tend to return to pretreatment levels over time; frequency and intensity of flatulence (74%) tend to abate with time
Hepatic: Transaminases increased (≤ 4%)

Postmarketing and/or case reports: Edema, erythema, exanthema, hepatitis, ileus/subileus, jaundice, liver damage, rash, urticaria

CONTRAINDICATIONS — Hypersensitivity to acarbose or any component of the formulation; patients with diabetic ketoacidosis or cirrhosis; patients with inflammatory bowel disease, colonic ulceration, partial intestinal obstruction, or in patients predisposed to intestinal obstruction; 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

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Elevated serum transaminases: Treatment-emergent elevations of serum transaminases (AST and/or ALT) occurred in up to 14% of acarbose-treated patients in long-term studies. These serum transaminase elevations appear to be dose related. At doses >100 mg 3 times/day, the incidence of serum transaminase elevations greater than 3 times the upper limit of normal was 2-3 times higher in the acarbose group than in the placebo group. These elevations were asymptomatic, reversible, more common in females, and, in general, were not associated with other evidence of liver dysfunction. Fulminant hepatitis has been reported rarely.

Disease-related concerns: Renal impairment: Use not recommended in patients with significant impairment (Scr >2 mg/dL); use with caution in other patients with renal impairment. Stress-related states: It may be necessary to discontinue acarbose and administer insulin if the patient is exposed to stress (ie, fever, trauma, infection, surgery).

Concurrent drug therapy issues: Sulfonylureas/insulin: In combination with a sulfonylurea or insulin will cause a further lowering of blood glucose and may increase the hypoglycemic potential of the sulfonylurea or insulin.

Special populations: Pediatrics: Safety and efficacy have not been established in children.

DRUG INTERACTIONS
Corticosteroids (Orally Inhaled): May diminish the hypoglycemic effect of Antidiabetic Agents. In some instances, corticosteroid-mediated HPA axis suppression has led to episodes of acute adrenal crisis, which may manifest as enhanced hypoglycemia, particularly in the setting of insulin or other antidiabetic agent use. Risk C: Monitor therapy

Corticosteroids (Systemic): May diminish the hypoglycemic effect of Antidiabetic Agents. In some instances, corticosteroid-mediated HPA axis suppression has led to episodes of acute adrenal crisis, which may manifest as enhanced hypoglycemia, particularly in the setting of insulin or other antidiabetic agent use. Risk C: Monitor therapy

Digoxin: Acarbose may decrease the serum concentration of Digoxin. Risk C: Monitor therapy

Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemic Agents. Risk C: Monitor therapy

Hypoglycemic Agents: May enhance the adverse/toxic effect of other Hypoglycemic Agents. Risk C: Monitor therapy

Luteinizing Hormone-Releasing Hormone Analogs: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Somatropin: May diminish the hypoglycemic effect of Antidiabetic Agents. Risk D: Consider therapy modification

Thiazide Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Limit ethanol.

PREGNANCY RISK FACTOR — B (show table)

PREGNANCY IMPLICATIONS — Adverse events have not been reported in animal reproduction studies; therefore, acarbose is classified as pregnancy category B. Low amounts of acarbose are absorbed systemically which should limit fetal exposure. Maternal hyperglycemia can be associated with adverse effects in the fetus, including macrosomia, neonatal hyperglycemia, and hyperbilirubinemia; the risk of congenital malformations is increased when the Hb A1c is above the normal range. Diabetes can also be associated with adverse effects in the mother. Poorly-treated diabetes may cause end-organ damage that may in turn negatively affect obstetric outcomes. Physiologic glucose levels should be maintained prior to and during pregnancy to decrease the risk of adverse events in the mother and the fetus. Acarbose has been studied for its potential role in treating GDM; however, only limited information is available describing pregnancy outcomes. Until additional safety and efficacy data are obtained, the use of oral agents is generally not recommended as routine management of GDM or type 2 diabetes mellitus during pregnancy. Insulin is the drug of choice for the control of diabetes mellitus during pregnancy.

LACTATION — Excretion in breast milk unknown/not recommended

BREAST-FEEDING CONSIDERATIONS — It is not known if acarbose is found in breast milk; however, low amounts of acarbose are absorbed systemically in adults, which may limit the amount that could distribute into breast milk. Breast-feeding is not recommended by the manufacturer.

DIETARY CONSIDERATIONS — Take with food (first bite of meal).

PRICING — (data from drugstore.com)
Tablets (Acarbose)
25 mg (100): $81.99
50 mg (100): $87.99
100 mg (100): $89.99

Tablets (Precose)
25 mg (90): $85.52
50 mg (90): $88.49
100 mg (90): $102.58

MONITORING PARAMETERS — Postprandial glucose, glycosylated hemoglobin levels, serum transaminase levels should be checked every 3 months during the first year of treatment and periodically thereafter, renal function (serum creatinine); blood pressure

REFERENCE RANGE — Recommendations for glycemic control in adults with diabetes:

Hb A1c: <7%

Preprandial capillary plasma glucose: 70-130 mg/dL

Peak postprandial capillary blood glucose: <180 mg/dL

CANADIAN BRAND NAMES — Glucobay™

INTERNATIONAL BRAND NAMES — Decarbay (TW); Deglu (TW); Dibose (MY); Glibose (TW); Glicobase (IT); Glucar (MY); Glucobay (AE, AR, AT, AU, BB, BD, BE, BF, BG, BH, BJ, BM, BR, BS, BZ, CH, CI, CL, CN, CO, CR, CY, CZ, DE, DK, DO, EG, ES, ET, FI, GB, GH, GM, GN, GT, GY, HK, HN, HR, HU, ID, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, NO, OM, PA, PE, PH, PK, PL, PT, PY, QA, SA, SC, SD, SE, SG, SL, SN, SR, SV, SY, TH, TN, TT, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW); Gluconase (PH); Glucor (FR); Glumida (ES); Incardel (MX); Prandase (IL); Precose (MY); Rebose (IN); Sincrosa (MX)

MECHANISM OF ACTION — Competitive inhibitor of pancreatic alpha-amylase and intestinal brush border alpha-glucosidases, resulting in delayed hydrolysis of ingested complex carbohydrates and disaccharides and absorption of glucose; dose-dependent reduction in postprandial serum insulin and glucose peaks; inhibits the metabolism of sucrose to glucose and fructose

PHARMACODYNAMICS / KINETICS
Absorption: <2% as active drug; ~35% as metabolites

Metabolism: Exclusively via GI tract, principally by intestinal bacteria and digestive enzymes; 13 metabolites identified (major metabolites are sulfate, methyl, and glucuronide conjugates)

Bioavailability: Low systemic bioavailability of parent compound; acts locally in GI tract

Half-life elimination: ~2 hours

Time to peak: Active drug: ~1 hour

Excretion: Urine (~34% as inactive metabolites, <2% parent drug and active metabolite); feces (~51% as unabsorbed drug)

PATIENT INFORMATION — Take this medication exactly as directed, with the first bite of each main meal. It is important to continue to adhere to dietary instructions, a regular exercise program, and regular testing of urine and/or blood glucose. 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. A source of glucose (dextrose) should be readily available to treat symptoms of low blood glucose when taking acarbose in combination with a sulfonylurea or insulin. If side effects occur, they usually develop during the first few weeks of therapy and are most often mild-to-moderate gastrointestinal effects, such as flatulence, diarrhea, or abdominal discomfort and generally diminish in frequency and intensity with time.

(For additional information see "Acarbose: Patient drug information")