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Acarbose


General


Pronunciation

(AY car bose)


Brand Names: U.S.

  • Precose

Indications


Use: Labeled Indications

Diabetes mellitus, type 2: Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (noninsulin dependent, NIDDM)


Contraindications


Hypersensitivity to acarbose or any component of the formulation; diabetic ketoacidosis; cirrhosis; inflammatory bowel disease, colonic ulceration, partial intestinal obstruction, patients predisposed to intestinal obstruction; chronic intestinal diseases associated with marked disorders of digestion or absorption conditions that may deteriorate as a result of increased gas formation in the intestine


Dosing and Administration


Dosing: Adult

Diabetes mellitus, type 2: Oral: Note: Dosage must be individualized on the basis of effectiveness and tolerance.

US labeling: Initial dose: 25 mg 3 times daily with the first bite of each main meal (may also initiate at 25 mg once daily with gradual titration to 25 mg 3 times daily as tolerated); increase dose at 4- to 8-week intervals based on 1-hour postprandial glucose or glycosylated hemoglobin levels and tolerance until maintenance dose of 50 to 100 mg 3 times daily is reached (maximum dose: ≤60 kg: 50 mg 3 times daily; >60 kg: 100 mg 3 times daily)

Canadian labeling: Initial dose: 50 mg once daily with the first bite of a main meal; increase dosage to 50 mg twice daily after 1 to 2 weeks, with a subsequent increase to 50 mg 3 times daily after an additional 1 to 2 weeks. Adjust dose at 4- to 8-week intervals based on 2-hour postprandial glucose and tolerance; maintenance dose: 50 to 100 mg 3 times daily (maximum dose: 100 mg 3 times daily)


Dosing: Geriatric

Refer to adult dosing.


Dosing: Renal Impairment

US labeling:

Serum creatinine ≤2 mg/dL: There are no dosage adjustments provided in the manufacturer 's labeling.

Serum creatinine >2 mg/dL: Use not recommended (has not been studied).

Canadian labeling:

CrCl ≥25 mL/minute: There are no dosage adjustments provided in the manufacturer 's labeling.

CrCl <25 mL/minute: Use is not recommended.


Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturers labeling; contraindicated in patients with cirrhosis.


Administration

Oral: Administer with the first bite of each main meal.


Dietary Considerations

Take with food (first bite of meal).


Storage

Store at <25 ‚ °C (77 ‚ °F). Protect from moisture.

Canadian labeling: Additional information (not in US labeling): Store tablets in foil pack until ready to use. At storage conditions up to 25 ‚ °C and below 60% relative humidity, the unpacked tablets can be stored for up to two weeks (discoloration may occur at higher temperatures and/or humidity).


Dosage Forms/Strengths


Dosage Forms

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

Tablet, Oral:

Precose: 25 mg, 50 mg, 100 mg

Generic: 25 mg, 50 mg, 100 mg


Drug Interactions

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy

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

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

MAO Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Neomycin: May enhance the adverse/toxic effect of Acarbose. Neomycin may decrease the metabolism of Acarbose. Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Quinolone Antibiotics: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy


Monitoring Parameters

Postprandial glucose, hemoglobin A1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2016a]), serum creatinine; serum transaminase levels every 3 months during the first year of treatment and periodically thereafter.


Adverse Reactions


>10%: Gastrointestinal: Frequency and intensity of flatulence (74%) tend to abate with time; diarrhea (31%) and abdominal pain (19%) tend to return to pretreatment levels over time

1% to 10%: Hepatic: Increased serum transaminases ( ≤4%)

<1% (Limited to important or life-threatening): Edema, erythema, hepatic injury, hepatitis, intestinal obstruction, jaundice, pneumatosis cystoides intestinalis, skin rash, subileus, thrombocytopenia, urticaria


Warnings/Precautions


Special Populations: Renal Function Impairment

In patients with CrCl <25 mL/minute/1.73 m2, the Cmax was ~5 times higher, and the AUC was 6 times larger.


Special Populations: Elderly

AUC and Cmax are approximately 1.5 times higher in the elderly.


Warnings/Precautions

Concerns related to adverse effects:

- Elevated serum transaminases: Treatment-emergent elevations of serum transaminases (AST and/or ALT) and hyperbilirubinemia may occur (dose-related). These elevations were asymptomatic, reversible, more common in females, and, in general, were not associated with other evidence of liver dysfunction. Fulminant hepatitis (may be fatal) has been reported. If elevations are observed, a reduction in dosage or withdrawal of therapy may be indicated, particularly if the elevations persist.

- Hypoglycemia: Hypoglycemia is unlikely to occur with acarbose monotherapy but may occur with combination therapy (eg, sulfonylureas, insulin, metformin). In patients taking acarbose, oral glucose (dextrose) should be used instead of sucrose (cane sugar) in the treatment of mild-to-moderate hypoglycemia since the hydrolysis of sucrose to glucose and fructose is inhibited by acarbose.

Disease-related concerns:

- Hepatic impairment: Use with caution in patients with hepatic impairment.

- Renal impairment: Not recommended in patients with significant impairment (US labeling: serum creatinine >2 mg/dL; Canadian labeling: CrCl <25 mL/minute).

- 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:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

- Appropriate use: Diet: Increased intake of sucrose (cane sugar) and food that contains sucrose during treatment can lead to GI symptoms (eg, flatulence and bloating), loose stools, and occasionally diarrhea. If a diabetic diet is not followed, the GI side effects may be intensified. If severe symptoms develop in spite of adherence to a diabetic diet, temporarily or permanently reduce dose.

- Patient education: Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.


Pregnancy Risk Factor

B


Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Low amounts of acarbose are absorbed systemically which should limit fetal exposure.

In women with diabetes, maternal hyperglycemia can be associated with congenital malformations as well as adverse effects in the fetus, neonate, and the mother (ACOG 2005; ADA 2015; Kitzmiller 2008; Metzger 2007). To prevent adverse outcomes, prior to conception and throughout pregnancy maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ACOG 2013; ADA 2015; Blumer 2013; Kitzmiller 2008). Prior to pregnancy, effective contraception should be used until glycemic control is achieved (Kitzmiller 2008). Other agents are currently recommended to treat diabetes in pregnant women (ACOG 2013; Blumer 2013).


Actions


Pharmacology

Competitive inhibitor of pancreaticα-amylase and intestinal brush borderα-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


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)


Excretion

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


Time to Peak

Active drug: ~1 hour


Half-Life Elimination

~2 hours


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience abdominal pain, flatulence, diarrhea, or bloating. Have patient report immediately to prescriber signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, tachycardia, confusion, increased hunger, or sweating), or signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice) (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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