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ACARBOSE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Acarbose is an alpha-glucosidase inhibitor used for the management of type 2 diabetes mellitus.

Specific Substances

    1) Acarbose BAN
    2) DCF
    3) USAN
    4) BAY g 5421
    5) CAS 56180-94-0

Available Forms Sources

    A) FORMS
    1) Acarbose is available as 25 mg, 50 mg, and 100 mg round, unscored tablets (Prod Info PRECOSE(R) oral tablets, 2011a).
    B) USES
    1) Acarbose is used as adjunctive therapy to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus (Prod Info PRECOSE(R) oral tablets, 2011a).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Acarbose is an alpha-glucosidase inhibitor used as adjunctive therapy to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.
    B) PHARMACOLOGY: Acarbose lowers postprandial blood glucose concentrations in patients with diabetes by competitive, reversible inhibition of pancreatic alpha-amylase and membrane-bound intestinal alpha-glucoside hydrolases. These enzymes hydrolyze complex starches to oligosaccharides in the lumen of the small intestine and hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the brush border of the small intestine. Acarbose does not enhance insulin secretion and, when used as monotherapy, should not cause hypoglycemia.
    C) TOXICOLOGY: Acarbose does not enhance insulin secretion and, when taken alone, should not cause hypoglycemia.
    D) EPIDEMIOLOGY: Overdose is rare.
    E) WITH THERAPEUTIC USE
    1) COMMON: Gastrointestinal symptoms (ie, flatulence, diarrhea, abdominal pain) are the most common adverse effects that occur following therapeutic administration.
    2) RARE: Less frequent adverse effects that have occurred include elevated hepatic enzyme concentrations, anemia, ileus, and acute allergic reactions. Acarbose has been associated with hypoglycemia when given with sulfonylureas or insulin. When administered alone, acarbose should not cause hypoglycemia in the fasting or postprandial state.
    F) WITH POISONING/EXPOSURE
    1) Toxicity following overdose is rare. Overdose effects are anticipated to be an extension of adverse effects following therapeutic use and may include flatulence, diarrhea, and abdominal pain. Acarbose does not enhance insulin secretion; hypoglycemia should NOT occur following overdose with acarbose as the sole ingestant.
    0.2.20) REPRODUCTIVE
    A) Acarbose is classified as FDA pregnancy category B. The safety of acarbose in pregnant women has not been established. Reproductive studies in rats revealed no evidence of impaired fertility or harm to the fetus. Rabbit studies showed no evidence of embryotoxicity or teratogenicity, but a reduction in maternal body weight gain may have contributed to a slight increase in embryonic losses. It is not known whether acarbose is excreted in human milk; however, acarbose or its metabolites were secreted in the milk of lactating rats. The manufacturer does not recommend acarbose for lactating women.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, the manufacturer does not report any carcinogenic potential for acarbose in humans.

Laboratory Monitoring

    A) Hypoglycemia is not expected if acarbose is ingested alone. If a sulfonylurea or insulin is also involved, monitor blood glucose; hypoglycemic effects may be enhanced in patients with concurrent administration of sulfonylureas or insulin.
    B) Monitor electrolytes and fluid status in patients with severe diarrhea.
    C) Although a rare event, hepatotoxicity has been reported with therapeutic use. A baseline serum aminotransferase (AST) and an alanine aminotransferase (ALT) may be indicated in patients following significant overdose.
    D) Plasma concentrations are not readily available or clinically useful in the management of overdose.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with severe diarrhea.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Significant toxicity is not expected after overdose with acarbose as the sole ingestant. If overdose ingestion is combined with another hypoglycemic agent, refer to the appropriate management (eg sulfonylurea, insulin) for treatment recommendations.
    C) DECONTAMINATION
    1) PREHOSPITAL: Acarbose is only minimally absorbed following oral ingestions; prehospital gastrointestinal decontamination is generally not required.
    2) HOSPITAL: Severe toxicity is not expected after overdose of acarbose. Gastrointestinal decontamination is generally not necessary. Consider activated charcoal only if coingestants with significant toxicity are involved.
    D) AIRWAY MANAGEMENT
    1) Airway management is very unlikely to be necessary unless other toxic agents have been administered concurrently.
    E) ANTIDOTE
    1) None
    F) ENHANCED ELIMINATION
    1) Hemodialysis is not recommended given the low toxicity of this drug.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: A patient with an inadvertent exposure and remains asymptomatic can be managed at home.
    2) OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic, need to be monitored for several hours to assess electrolyte and fluid balance, and blood glucose concentration. Patients that remain asymptomatic can be discharged.
    3) ADMISSION CRITERIA: Patients should be admitted for profuse diarrhea, severe abdominal pain, dehydration, electrolyte abnormalities, and symptoms of hypoglycemia.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    H) PITFALLS
    1) When managing a suspected acarbose overdose, the possibility of multidrug involvement should be considered.
    I) PHARMACOKINETICS
    1) Acarbose acts locally within the gastrointestinal tract. In a small study (n=6), less than 2% of an oral dose was absorbed as active drug. Metabolized exclusively within the gastrointestinal tract, principally by intestinal bacteria, but also by digestive enzymes. Of the small amount of acarbose that is absorbed as intact drug, it is almost completely excreted by the kidneys. The plasma elimination half-life of acarbose activity is approximately 2 hours.
    J) DIFFERENTIAL DIAGNOSIS
    1) Exposure to hypoglycemic agents such as sulfonylureas or insulin.

Range Of Toxicity

    A) TOXICITY: A specific toxic dose has not been established. Doses of 300 mg three times daily have been well tolerated in clinical studies.
    B) THERAPEUTIC DOSE: ADULT: The recommended initial dose is 25 mg orally three times daily. The dose may be titrated up to a maximum of 50 mg three times daily for patients weighing 60 kg or less, or 100 mg three times daily for patients weighing more than 60 kg. PEDIATRIC: Safety and efficacy have not been established in pediatric patients.

Clinical Effects

Summary Of Exposure

    A) USES: Acarbose is an alpha-glucosidase inhibitor used as adjunctive therapy to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.
    B) PHARMACOLOGY: Acarbose lowers postprandial blood glucose concentrations in patients with diabetes by competitive, reversible inhibition of pancreatic alpha-amylase and membrane-bound intestinal alpha-glucoside hydrolases. These enzymes hydrolyze complex starches to oligosaccharides in the lumen of the small intestine and hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the brush border of the small intestine. Acarbose does not enhance insulin secretion and, when used as monotherapy, should not cause hypoglycemia.
    C) TOXICOLOGY: Acarbose does not enhance insulin secretion and, when taken alone, should not cause hypoglycemia.
    D) EPIDEMIOLOGY: Overdose is rare.
    E) WITH THERAPEUTIC USE
    1) COMMON: Gastrointestinal symptoms (ie, flatulence, diarrhea, abdominal pain) are the most common adverse effects that occur following therapeutic administration.
    2) RARE: Less frequent adverse effects that have occurred include elevated hepatic enzyme concentrations, anemia, ileus, and acute allergic reactions. Acarbose has been associated with hypoglycemia when given with sulfonylureas or insulin. When administered alone, acarbose should not cause hypoglycemia in the fasting or postprandial state.
    F) WITH POISONING/EXPOSURE
    1) Toxicity following overdose is rare. Overdose effects are anticipated to be an extension of adverse effects following therapeutic use and may include flatulence, diarrhea, and abdominal pain. Acarbose does not enhance insulin secretion; hypoglycemia should NOT occur following overdose with acarbose as the sole ingestant.

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) DIARRHEA
    1) WITH THERAPEUTIC USE
    a) In placebo-controlled trials, the incidence of diarrhea was 31% in patients treated with acarbose at doses of 50 to 300 mg 3 times daily (n=1255), compared with 12% in patients treated with placebo (n=999) (Prod Info PRECOSE(R) oral tablets, 2011).
    b) Patients that kept a diary of gastrointestinal symptoms over the course of a 1-year safety study noted that the incidence of diarrhea tended to return to pretreatment levels over time(Prod Info PRECOSE(R) oral tablets, 2011).
    c) Of 10,462 patients evaluated in postmarketing surveillance, 3.2% reported diarrhea(Spengler & Cagatay, 1995).
    B) ABDOMINAL PAIN
    1) WITH THERAPEUTIC USE
    a) In placebo-controlled trials, the incidence of abdominal pain was 19% in patients treated with acarbose at doses of 50 to 300 mg 3 times daily (n=1255), compared with 9% in patients treated with placebo (n=999) (Prod Info PRECOSE(R) oral tablets, 2011).
    b) Patients that kept a diary of gastrointestinal symptoms over the course of a one-year safety study noted that the incidence of abdominal pain tended to return to pretreatment levels over time(Prod Info PRECOSE(R) oral tablets, 2011).
    c) Incidence of adverse events affecting the digestive system (abdominal pain, diarrhea and flatulence) have been reported in 50% to 91% of patients in clinical trials and appear to be dose-related and decrease with time (Chiasson et al, 1994; Coniff et al, 1995; Folsch, 1995; Hollander, 1992).
    d) Of 10,462 patients evaluated in post-marketing surveillance, 19% reported meteorism/flatulence and 3.2% diarrhea (Spengler & Cagatay, 1995a).
    C) FLATULENCE/WIND
    1) WITH THERAPEUTIC USE
    a) In placebo-controlled trials, the incidence of flatulence was 74% in patients treated with acarbose at doses of 50 to 300 mg 3 times daily (n=1255), compared with 29% in patients treated with placebo (n=999) (Prod Info PRECOSE(R) oral tablets, 2011).
    b) Patients that kept a diary of gastrointestinal symptoms over the course of a 1-year safety study noted that their flatulence was transient, with both intensity and frequency declining over time(Prod Info PRECOSE(R) oral tablets, 2011).
    c) Of 10,462 patients evaluated in post-marketing surveillance, 19% reported flatulence(Spengler & Cagatay, 1995).
    D) INTESTINAL ABSORPTION
    1) Acarbose does NOT appear to affect serum concentrations of vitamins or minerals with the possible exception of iron (Chiasson et al, 1994; Josse, 1995).
    E) DRUG-INDUCED ILEUS
    1) WITH THERAPEUTIC USE
    a) Although a rare event, ileus, sometimes with serious consequences, has been reported in association with acarbose therapy. In 3 reported cases surgery was required, and in 1 case a patient died (Odawara et al, 1997; Nishii et al, 1996).
    b) Ileus and subileus have been reported during postmarketing surveillance of patients treated with acarbose (Prod Info PRECOSE(R) oral tablets, 2011).
    c) CASE REPORT: An ileus developed in a 39-year-old woman treated with acarbose for less than 1 year. There was not a history of previous gastrointestinal complaints or diseases, which might be predisposing factors for development of this adverse effect, and diabetic neuropathy was not present. Presenting symptoms included a diffusely tender, distended abdomen and mechanical bowel sounds. An abdominal radiograph revealed an abnormal gas pattern in the intestines. Treatment consisted of stopping acarbose and oral intake and administering fluids. The ileus resolved in 2 days. The authors mention 6 other cases of ileus associated with acarbose treatment; three required surgery, and 1 patient died. Acarbose should be used cautiously, if at all, in patients with previous abdominal surgery or other predisposing factors for ileus (Nishii et al, 1996).
    F) LYMPHOCYTIC-PLASMACYTIC COLITIS
    1) WITH THERAPEUTIC USE
    a) Acarbose-induced lymphocytic colitis has been reported in one case report. A 52-year-old man was started on acarbose 50 mg twice daily for carbohydrate intolerance. Two weeks after initiation of therapy he experienced 6 to 8 episodes of watery diarrhea daily resulting in a 3 kg weight loss in 1 month. Physical examination, lab tests, and fecal culture were normal; however, colon biopsy revealed typical features of lymphocytic colitis. Upon discontinuation of acarbose, diarrhea disappeared within 4 days and no relapse occurred. When acarbose was reintroduced at a later date, diarrhea reappeared within 3 days and biopsy again confirmed lymphocytic colitis; symptoms resolved upon drug discontinuation (Piche et al, 2000).
    G) PNEUMATOSIS CYSTOIDES INTESTINALIS
    1) WITH THERAPEUTIC USE
    a) Pneumatosis cystoides intestinalis has been reported during postmarketing surveillance of patients treated with acarbose. Presenting symptoms may include diarrhea, mucus discharge, rectal bleeding, and constipation, with possible complications of pneumoperitoneum, volvulus, intestinal obstruction, intussusception, intestinal hemorrhage, and intestinal perforation (Prod Info PRECOSE(R) oral tablets, 2011).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) WITH THERAPEUTIC USE
    a) SUMMARY: Elevated liver enzymes have been infrequently reported following therapeutic use of acarbose (Carrascosa et al, 1997; Diaz-Gutierrez et al, 1998; Andrade et al, 1998). In most cases, liver enzymes improved with drug cessation.
    b) In studies up to 12 months duration (with doses up to 300 mg 3 times daily) treatment-emergent elevations of serum transaminases (AST and/or ALT) occurred in 14% of acarbose treated patients, compared with 7% in the placebo group. The observed incidence of serum transaminase elevations greater than 3 times the upper limit of normal was 3% in acarbose-treated patients, compared with 1% of placebo-treated patients. Liver enzyme elevations were asymptomatic, reversible, more common in females and typically were not associated with liver dysfunction. The elevations appear to be dose-related, as patients receiving acarbose had similar incidence to patients receiving placebo, up to a daily dose of 100 mg 3 times daily. Of approximately 3 million patient-years of international post-marketing experience with acarbose, 62 cases of serum transaminase elevations greater than 500 international units/L (29 of which were associated with jaundice) have been reported. Hepatic abnormalities improved or resolved in 55 of 59 cases upon discontinuation of acarbose (Prod Info PRECOSE(R) oral tablets, 2011).
    c) CASE REPORTS
    1) Severe liver injury with hepatomegaly, jaundice and elevated liver enzymes occurred in a 40-year-old woman with non-insulin dependent diabetes mellitus (NIDDM) after receiving acarbose (100 mg every 8 hours) for approximately 2 months. Liver function returned to normal with drug cessation. Hepatotoxicity recurred with rechallenge at a lower dose (Carrascosa et al, 1997).
    2) Andrade et al (1998) described two patients who developed hepatotoxicity associated with acarbose therapy. One patient's had symptoms consistent with acute hepatocellular injury while the other appeared to have chronic injury. Liver function returned to normal in both patients when drug therapy was stopped (Andrade et al, 1998).
    3) Fujimoto et al (1998) have suggested that an idiosyncratic effect may be responsible for the liver injury observed in two patients receiving acarbose therapy. Elevated liver enzymes developed at 2.5 and 8 months, respectively after the start of treatment (Fujimoto et al, 1998).
    4) Acute liver toxicity with hepatomegaly, scleral jaundice, and elevated liver enzymes occurred in a 57-year-old woman with NIDDM 2 months after starting acarbose (50 mg 3 times daily). Liver function returned to normal with drug cessation. The authors suggested that an idiosyncratic effect may be responsible for this liver toxicity (Diaz-Gutierrez et al, 1998).
    B) INFLAMMATORY DISEASE OF LIVER
    1) WITH THERAPEUTIC USE
    a) Several cases of fulminant hepatitis that resulted in death have been reported, although the relationship to acarbose is unclear. Jaundice and/or hepatitis with associated liver damage has been reported during postmarketing surveillance of patients treated with acarbose (Prod Info PRECOSE(R) oral tablets, 2011)

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) ANEMIA
    1) WITH THERAPEUTIC USE
    a) In some phase III trials, a significantly higher incidence of anemia was observed in acarbose treated patients (7 of 618) compared to placebo (1 of 627). There is some evidence that acarbose may interfere with the absorption of iron from the gastrointestinal tract. However, an increased incidence of anemia was not observed in other studies (Hollander, 1992a).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) HYPERSENSITIVITY REACTION
    1) WITH THERAPEUTIC USE
    a) Hypersensitivity reactions such as exanthema, rash, erythema, and urticaria have been reported during postmarketing surveillance of acarbose use (Prod Info PRECOSE(R) oral tablets, 2011).
    B) ERYTHEMA MULTIFORME
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Thirteen days after beginning acarbose 300 mg daily, generalized erythema multiforme (GEM) developed in a 58-year-old man. Due to erythematous plaques with vesicles over his entire body, he was admitted to the hospital for treatment that consisted of stopping acarbose and beginning prednisolone 20 mg daily for 6 days. Biopsy of the dermis revealed lymphocyte and eosinophil infiltration. Three weeks after stopping acarbose, the patient was rechallenged with a single-dose of acarbose 50 mg. Within 12 hours, an erythematous rash developed on the trunk and extremities. Skin biopsy was consistent with GEM. Laboratory tests and radiologic examination did not reveal other causes of GEM (Kono et al, 1999).

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) HYPOGLYCEMIA
    1) WITH THERAPEUTIC USE
    a) Based on its mechanism of action acarbose should NOT cause hypoglycemia when administered alone in the fasting or postprandial state. Acarbose when given in combination with sulfonylurea agents or insulin may cause a further lowering of blood glucose and increase the hypoglycemic potential of these medications (Prod Info PRECOSE(R) oral tablets, 2011a).
    b) Earlier studies with acarbose have reported that 2% of patients treated with acarbose alone or in combination with sulfonylureas or insulin developed hypoglycemia (Hollander, 1992).
    1) Chiasson et al (1994) reported only one patient (N = 316) treated with acarbose and insulin developed severe hypoglycemia which required correction (Chiasson et al, 1994).
    2) In a prospective post-marketing surveillance study of 10,462 patients, hypoglycemia was found in 0.8% of Type I and 0.6% of Type II patients who received concurrent insulin (N=8) or glibenclamide (N=1) treatment (Spengler & Cagatay, 1995a).
    c) Several other studies reported NO significant episodes of hypoglycemia with acarbose use as a monotherapy or in combination with insulin therapy (Folsch, 1995; Coniff et al, 1995a).
    d) Hypoglycemic events, appear to be related to an additive effect of the drug when used in combination with an oral hypoglycemic agent or insulin. Prolonged severe hypoglycemia as reported with sulfonylureas has not been observed during acarbose therapy (Hollander, 1992).

Reproductive

    3.20.1) SUMMARY
    A) Acarbose is classified as FDA pregnancy category B. The safety of acarbose in pregnant women has not been established. Reproductive studies in rats revealed no evidence of impaired fertility or harm to the fetus. Rabbit studies showed no evidence of embryotoxicity or teratogenicity, but a reduction in maternal body weight gain may have contributed to a slight increase in embryonic losses. It is not known whether acarbose is excreted in human milk; however, acarbose or its metabolites were secreted in the milk of lactating rats. The manufacturer does not recommend acarbose for lactating women.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) The safety of acarbose in pregnant women has not been established (Prod Info acarbose oral tablets, 2015).
    B) ANIMAL STUDIES
    1) Reproductive studies with acarbose in rats at doses up to 480 mg/kg (9 times the exposure in humans based on blood levels) revealed no evidence of harm to the fetus (Prod Info acarbose oral tablets, 2015). Rabbits given 160 mg/kg acarbose (10 times the dose in humans based on body surface area) showed no evidence of embryotoxicity. There was no evidence of teratogenicity in rabbits given 32 times the human dose based on body surface area (Prod Info acarbose oral tablets, 2015).
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) The safety of acarbose in pregnant women has not been established (Prod Info acarbose oral tablets, 2015).
    B) PREGNANCY CATEGORY
    1) The manufacturer has classified acarbose as FDA pregnancy category B (Prod Info acarbose oral tablets, 2015).
    C) ANIMAL STUDIES
    1) Acarbose administration to rabbits caused a reduction in maternal body weight gain, which may have been related to a slight increase in the number of embryonic losses (Prod Info acarbose oral tablets, 2015).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) It is not known whether acarbose is excreted in human milk, but the drug is not recommended for nursing women (Prod Info acarbose oral tablets, 2015).
    B) ANIMAL STUDIES
    1) BREAST MILK
    a) The milk of lactating rats had small amounts of radioactivity after administration of radiolabeled acarbose (Prod Info acarbose oral tablets, 2015).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) Fertility studies in rats after oral administration produced no untoward effects (Prod Info acarbose oral tablets, 2015).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, the manufacturer does not report any carcinogenic potential for acarbose in humans.
    3.21.4) ANIMAL STUDIES
    A) RENAL CARCINOMA
    1) Sprague-Dawley rats that were given acarbose in doses up to approximately 500 mg/kg body weight for 104 weeks had significant increases in the incidence of renal adenomas, renal adenocarcinomas, and benign Leydig cell tumors. A repeat of the study yielded a similar outcome (Prod Info PRECOSE(R) oral tablets, 2008).
    B) LACK OF EFFECT
    1) RATS: No renal tumors occurred in Sprague-Dawley rats when carbohydrate deprivation was prevented during the administration of acarbose. Acarbose was mixed with food or given by daily postprandial gavage, and glucose supplements were added to the diet. Wistar rats given acarbose in food or by postprandial gavage also did not have an increased incidence of renal tumors (Prod Info PRECOSE(R) oral tablets, 2008).
    2) HAMSTERS: No evidence of carcinogenicity was found when acarbose was added to food and given with or without glucose supplements to hamsters (Prod Info PRECOSE(R) oral tablets, 2008).

Genotoxicity

    A) No DNA damage or mutagenic activity were associated with acarbose using the following in vitro tests: Chinese hamster ovary (CHO) chromosomal aberration assay, bacterial mutagenesis (Ames) assay, or DNA binding assay. The in vivo dominant lethal test in male mice and the mouse micronucleus test indicated no DNA damage (Prod Info PRECOSE(R) oral tablets, 2008).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Hypoglycemia is not expected if acarbose is ingested alone. If a sulfonylurea or insulin is also involved, monitor blood glucose; hypoglycemic effects may be enhanced in patients with concurrent administration of sulfonylureas or insulin.
    B) Monitor electrolytes and fluid status in patients with severe diarrhea.
    C) Although a rare event, hepatotoxicity has been reported with therapeutic use. A baseline serum aminotransferase (AST) and an alanine aminotransferase (ALT) may be indicated in patients following significant overdose.
    D) Plasma concentrations are not readily available or clinically useful in the management of overdose.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients should be admitted for profuse diarrhea, severe abdominal pain, dehydration, electrolyte abnormalities, and symptoms of hypoglycemia.
    6.3.1.2) HOME CRITERIA/ORAL
    A) A patient with an inadvertent exposure and remains asymptomatic can be managed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a deliberate overdose, and those who are symptomatic, need to be monitored for several hours to assess electrolyte and fluid balance, and blood glucose concentration. Patients that remain asymptomatic can be discharged.

Monitoring

    A) Hypoglycemia is not expected if acarbose is ingested alone. If a sulfonylurea or insulin is also involved, monitor blood glucose; hypoglycemic effects may be enhanced in patients with concurrent administration of sulfonylureas or insulin.
    B) Monitor electrolytes and fluid status in patients with severe diarrhea.
    C) Although a rare event, hepatotoxicity has been reported with therapeutic use. A baseline serum aminotransferase (AST) and an alanine aminotransferase (ALT) may be indicated in patients following significant overdose.
    D) Plasma concentrations are not readily available or clinically useful in the management of overdose.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Gastrointestinal decontamination is generally not necessary, but should be considered when taken with coingestants, particularly other oral hypoglycemic agents.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Acarbose acts locally within the gastrointestinal tract, competitively inhibiting enzymes that break down carbohydrates. Its bioavailability is low (2% for parent drug and about 35% for metabolites). Gastrointestinal decontamination is generally not necessary, but should be considered when taken with coingestants, particularly other oral hypoglycemic agents.
    2) ACTIVATED CHARCOAL
    a) CHARCOAL ADMINISTRATION
    1) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    b) CHARCOAL DOSE
    1) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    a) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    2) ADVERSE EFFECTS/CONTRAINDICATIONS
    a) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    b) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    3) Do not administer cathartic. Acarbose causes diarrhea and sweetening agents in cathartics could worsen symptoms of undigested carbohydrates.
    6.5.3) TREATMENT
    A) SUPPORT
    1) Management of electrolyte imbalance may be necessary. Overdose treatment is symptomatic and supportive. Avoid carbohydrates for 4 to 6 hours, as they may induce flatulence, diarrhea and abdominal pain(Prod Info PRECOSE(R) oral tablets, 2011a).
    B) MONITORING OF PATIENT
    1) Hypoglycemia is not expected if acarbose is ingested alone. If a sulfonylurea or insulin is also involved, monitor blood glucose; hypoglycemic effects may be enhanced in patients with concurrent administration of sulfonylureas or insulin.
    2) Monitor electrolytes and fluid status in patients with severe diarrhea.
    3) Although a potentially rare event, hepatotoxicity has been reported with therapeutic use. A baseline serum aminotransferase (AST) and an alanine aminotransferase (ALT) may be indicated in patients following significant exposure.
    4) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    C) HYPOGLYCEMIA
    1) Acarbose itself does NOT cause hypoglycemia (even in the fasted state), however, when combined with sulfonylurea agents or insulin, it may cause hypoglycemic symptoms which can be life threatening (Prod Info PRECOSE(R) oral tablets, 2011a).
    2) Acarbose inhibits the hydrolysis of sucrose to glucose and fructose. Oral glucose (dextrose or d-glucose; NOT sucrose), whose absorption is not inhibited by acarbose, should be used in mild to moderate hypoglycemia. Intravenous glucose infusion or glucagon injection may be necessary in severe hypoglycemia (Prod Info PRECOSE(R) oral tablets, 2011a). If overdose ingestion is combined with another hypoglycemic agent, refer to the appropriate management (eg sulfonylurea, insulin) for treatment recommendations.

Enhanced Elimination

    A) HEMODIALYSIS
    1) Hemodialysis is not recommended given the limited bioavailability and low toxicity of this drug.

Range Of Toxicity

Summary

    A) TOXICITY: A specific toxic dose has not been established. Doses of 300 mg three times daily have been well tolerated in clinical studies.
    B) THERAPEUTIC DOSE: ADULT: The recommended initial dose is 25 mg orally three times daily. The dose may be titrated up to a maximum of 50 mg three times daily for patients weighing 60 kg or less, or 100 mg three times daily for patients weighing more than 60 kg. PEDIATRIC: Safety and efficacy have not been established in pediatric patients.

Therapeutic Dose

    7.2.1) ADULT
    A) Initially, 25 mg orally 3 times a day with the first bite of each main meal; may initiate at 25 mg orally once daily with gradual dose titration to 25 mg orally 3 times a day in some patients to minimize gastrointestinal side effects (Prod Info PRECOSE(R) oral tablets, 2011).
    B) The maintenance dose is 50 to 100 mg orally 3 times a day with the first bite of each main meal. MAX 50 mg 3 times daily for patients weighing 60 kg or less; MAX 100 mg 3 times daily for those weighing more than 60 kg (Prod Info PRECOSE(R) oral tablets, 2011).
    7.2.2) PEDIATRIC
    A) Safety and effectiveness in pediatric patients have not been established (Prod Info PRECOSE(R) oral tablets, 2011).

Maximum Tolerated Exposure

    A) A dose of 300 mg three times daily was well tolerated by diabetic patients in clinical studies (Prod Info PRECOSE(R) oral tablets, 2011a).

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Acarbose lowers postprandial blood glucose concentrations in patients with diabetes by competitive, reversible inhibition of pancreatic alpha-amylase and membrane-bound intestinal alpha-glucoside hydrolases. These enzymes inhibit hydrolysis of complex starches to oligosaccharides in the lumen of the small intestine and hydrolysis of oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the brush border of the small intestine. Acarbose does not enhance insulin secretion and, when used as monotherapy, should not cause hypoglycemia (Prod Info PRECOSE(R) oral tablets, 2011a).

References

General Bibliography

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