Acarbose

Acarbose: Drug information
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(For additional information see “Acarbose: Patient drug information” and see “Acarbose: Pediatric drug information”)

Brand Names: U.S. Precose®
Brand Names: Canada Glucobay™
Pharmacologic Category Antidiabetic Agent, Alpha-Glucosidase Inhibitor
Dosing: Adult 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: Geriatric 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: U.S. Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral: 25 mg, 50 mg, 100 mg

Precose®: 25 mg, 50 mg, 100 mg

Generic Equivalent Available: U.S. 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)
Medication Safety Issues
Sound-alike/look-alike issues:
Precose® may be confused with PreCare®

International issues:
Precose® [U.S., Malaysia] may be confused with Precosa brand name for Saccharomyces boulardii [Finland, Sweden]

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, pneumatosis cystoides intestinalis, rash, thrombocytopenia, 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.

Drug Interactions
(For additional information: Launch Lexi-Interact™ Drug Interactions Program )
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

Neomycin: May enhance the adverse/toxic effect of Acarbose. Neomycin may enhance the therapeutic effect of Acarbose. Neomycin may decrease the metabolism of Acarbose. 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: U.S. (www.drugstore.com)
Tablets (Acarbose)

25 mg (100): $81.99

50 mg (100): $87.99

100 mg (100): $89.99

Tablets (Precose)

25 mg (90): $85.51

50 mg (90): $88.49

100 mg (90): $109.99

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

International Brand Names Accarb (NZ); Acrose (IL); Decarbay (TW); Deglu (TW); Dibose (MY); Eclid (ID); Garbose (MY); Glibos (TW); Glicobase (IT); 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, EC, EG, ES, ET, FI, GB, GH, GM, GN, GT, GY, HK, HN, HR, HU, IE, 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, PK, PL, PT, PY, QA, RU, SA, SC, SD, SE, SG, SL, SN, SR, SV, SY, TH, TN, TR, TT, TZ, UG, UY, VE, YE, ZA, ZM, ZW); Gluconase (PH); Glucor (FR); Glucorid (MY); Glumida (ES); Incardel (MX); Kertonbose (TW); Prandase (IL); Precose (MY); Rebose (IN); Sincrosa (MX); Tardensone (TW)
Mechanism of Action Competitive inhibitor of pancreatic α-amylase and intestinal brush border α-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)

 

REFERENCES
American Diabetes Association, “Standards of Medical Care in Diabetes Mellitus — 2011,” Diabetes Care, 2011, 34(Suppl 1):11-61. [PubMed 21193625]
Balfour JA and McTavish D, “Acarbose: A Reappraisal,” Drugs, 1993, 46(6):1025-54. [PubMed 7510610]
Bischoff H, “Pharmacology of α-Glucosidase Inhibition,” Eur J Clin Invest, 1994, 24(Suppl 3):3-10.
Handelsman Y, Mechanick JI, Blonde L, et al, “American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for Developing a Diabetes Mellitus Comprehensive Care Plan,” Endocr Pract, 2011, 17(Suppl 2):1-53. [PubMed 21474420]
Rodbard HW, Jellinger PS, Davidson JA, et al, “Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology Consensus Panel on Type 2 Diabetes Mellitus: An Algorithm for Glycemic Control,” Endocr Pract, 2009, 15(6):540-59. [PubMed 19858063]
Scheen AJ, de Magalhaes AC, Salvatore T, et al, “Reduction of the Acute Bioavailability of Metformin by the α-Glucosidase Inhibitor Acarbose in Normal Man,” Eur J Clin Invest, 1994, 24(Suppl 3):50-4.