Acarbose (acarbose)

No dosing information is available for this tab.

Acarbose is administered orally 3 times daily. The drug should be administered at the beginning (with the first bite) of each main meal. If the prescribed diet designed to minimize adverse GI effects is not observed, adverse GI effects may be intensified. Common adverse GI effects (e.g., flatulence, diarrhea, abdominal discomfort) usually develop during the first few weeks of therapy and generally diminish in frequency and intensity with time, although flatulence usually is only abated rather than returned to pretreatment levels. If adverse GI effects are strongly distressing despite adherence to the prescribed diabetic diet, a clinician should be consulted and the dosage of acarbose temporarily or permanently reduced.

Store acarbose tablets at 20--25degreesC in a tightly closed container protected from moisture.

There is no enhanced messaging for this drug.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Acarbose; Miglitol/Amylase; Pancreatin

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Digestive enzyme preparations such as amylase or pancreatin may break down acarbose(1) and miglitol.(2)

CLINICAL EFFECTS: The concurrent administration digestive enzyme preparations such as amylase or pancreatin may decrease the effectiveness of acarbose(1) and miglitol.(2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of acarbose states that digestive enzymes such as amylase or pancreatin should not be taken concomitantly with acarbose.(1) The manufacturer of miglitol states that digestive enzymes such as amylase or pancreatin should not be taken concomitantly with miglitol.(2)

DISCUSSION: Because digestive enzyme preparations such as amylase or pancreatin may break down acarbose(1) and miglitol(2) and decrease their effectiveness, the manufacturer of acarbose(1) and miglitol(2) state they should not be taken concomitantly with these agents.

Alpha-Glucosidase Inhibitors/Pramlintide

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Pramlintide slows gastric emptying. Alpha-glucosidase inhibitors slow the absorption of nutrients.(1)

CLINICAL EFFECTS: Concurrent use of pramlintide and alpha-glucosidase inhibitors may result in additive or synergistic effects.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of pramlintide states that pramlintide therapy should not be considered in patients taking alpha-glucosidase inhibitors.(1)

DISCUSSION: Patients using alpha-glucosidase inhibitors have not been studied in clinical trials for pramlintide.(1)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Antidiabetic Agents/Gatifloxacin

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The exact mechanism is unknown.

CLINICAL EFFECTS: Concurrent use of gatifloxacin may result in hypoglycemia and/or hyperglycemia.(1-4) Hypoglycemia is more common during the first three days of concurrent therapy. Hyperglycemia is more common after the first three days of concurrent therapy.(2)

PREDISPOSING FACTORS: Elderly patients, especially those with decreased renal function may be predisposed to this interaction.(2)

PATIENT MANAGEMENT: Patients receiving concurrent gatifloxacin should be closely monitored for hypoglycemia during the first three days of concurrent therapy and for hyperglycemia after the first three days of concurrent therapy. Patients should be instructed to discontinue gatifloxacin if hypoglycemia or hyperglycemia occur.(2)

DISCUSSION: Hypoglycemia has been reported with gatifloxacin and glyburide(1,5,6) or glimepiride.(7) In a study in patients with type 2 diabetes mellitus, concurrent gatifloxacin (400 mg daily for 10 days) had no effect on the pharmacokinetics of glyburide (steady state daily regimen); however, pharmacodynamic interactions have been reported.(2) Health Canada has received 19 reports of hypoglycemia in patients taking gatifloxacin. Seventeen of these involved concurrent hypoglycemic agents. Health Canada has received 2 reports of hyperglycemia in patients taking gatifloxacin and hypoglycemic agents. Health Canada has received 2 reports of patients experiencing hypoglycemia and hyperglycemia during concurrent gatifloxacin and hypoglycemic agents.(3) In a study, 13 reports of dysglycemia were reported in patients taking gatifloxacin. Ten of these patients had diabetes mellitus and were on concurrent hypoglycemic agents. Of these ten patients, nine patients experienced hypoglycemia, while one patient experienced hyperglycemia.(8)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Acarbose/Digoxin, Oral

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Acarbose may alter the absorption of digoxin.(1)

CLINICAL EFFECTS: Concurrent use of acarbose with digoxin may result in decreased levels and effectiveness of digoxin.(1-2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Monitor digoxin levels if acarbose is initiated or discontinued. The dosage of digoxin may need to be increased by 20% to 40%.(2)

DISCUSSION: In a randomized cross-over study in healthy subjects, the area-under-curve (AUC) and maximum concentration (Cmax) of a single dose of digoxin (0.5 mg) was significantly lower when digoxin was administered 30 minutes after a single dose of acarbose (200 mg) or 30 minutes after the tenth dose of acarbose (100 mg TID) when compared to the administration of digoxin alone.(1) In a randomized cross-over study in healthy subjects, there were no effects on digoxin AUC when a single dose of digoxin (0.75 mg) was administered 60 minutes after acarbose (50 mg TID for 8 days). Digoxin Cmax increased 28%.(3) There are several case reports of digoxin levels decreasing to subtherapeutic levels following the addition of acarbose to therapy.(4-6)

Antidiabetic Agents/Gymnema

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Gymnema has been shown to increase the number of insulin-secreting beta cells in animals. It has also been shown to increase the activity of enzymes responsible for glucose uptake and utilization and inhibit peripheral utilization of glucose.(1)

CLINICAL EFFECTS: Use of gymnema may result in decreased requirements of antidiabetic agents.(2-4)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Diabetic patients should be carefully monitored if gymnema is initiated or discontinued from concurrent therapy. The dosage of the patient's antidiabetic agent(s) may need to be adjusted.(2)

DISCUSSION: In a study in 22 non-insulin-dependent patients, patients had decreased blood glucose, glycosylated hemoglobin, and glycosylated plasma proteins during gymnema therapy. Patients were able to decrease the dosage of their conventional antidiabetic therapy and five patients were able to discontinue their conventional antidiabetic therapy.(3) In a study in 27 insulin-dependent patients, patients had decreased insulin requirements, fasting blood glucose, glycosylated hemoglobin, and glycosylated plasma protein levels.(4)

Antidiabetics/Epinephrine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Gluconeogenesis, glycogenolysis, and lipolysis are increased by epinephrine. Also, insulin secretion and glucose uptake by peripheral tissues are decreased by epinephrine.

CLINICAL EFFECTS: Increased blood glucose resulting in decreased effectiveness of the antidiabetic agent.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Caution when starting or stopping epinephrine in diabetic patients. Adjust the antidiabetic dose as needed based on blood glucose levels.

DISCUSSION: This interaction is likely to occur based upon well documented properties of the interacting drugs. However, there is individual variability in its occurrence.

Selected Antidiabetic Agents/Chloroquine; Hydroxychloroquine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism is unknown. Chloroquine and hydroxychloroquine may increase insulin sensitivity by inhibiting insulin metabolism and inflammation and increasing cellular uptake of glucose and glycogen synthesis.(1,2) These effects may result in additive hypoglycemia with anti-diabetic agents.

CLINICAL EFFECTS: Concurrent use of chloroquine or hydroxychloroquine and antidiabetic agents may result in severe hypoglycemia.(3) Hypoglycemia can lead to coma.

PREDISPOSING FACTORS: Elderly patients, especially those with decreased renal function may be predisposed to this interaction.

PATIENT MANAGEMENT: Patients maintained on antidiabetic agents who require concurrent therapy with chloroquine or hydroxychloroquine should be closely monitored for hypoglycemia. A decrease in the dose of insulin or other anti-diabetic medications may be required. Patients should be advised of the risk and symptoms of hypoglycemia and to contact their doctor if hypoglycemia occurs.(3) Signs of hypoglycemia may include confusion, dizziness, feeling shaky, unusual hunger, headaches, irritability, pounding heart or very fast pulse, pale skin, sweating, trembling, weakness, or unusual anxiety.

DISCUSSION: Hydroxychloroquine has been shown to cause severe hypoglycemia including loss of consciousness that could be life threatening.(3) Concomitant hypoglycemic agents may increase the risk and/or severity of this effect. A 77 year old man who was stable on twice daily insulin suffered two episodes of hypoglycemic coma 2 weeks after starting prednisone 5 mg daily and hydroxychloroquine 400 mg daily for rheumatoid arthritis. His insulin dosage required a decrease of 37%.(4) Many studies have investigated the glucose-lowering effect of hydroxychloroquine. In a clinical trial of type II diabetics on maximal doses of sulfonylureas, addition of hydroxychloroquine lowered hemoglobin A1C (HbA1C) up to 1% more than placebo.(5) Another clinical trial of type II diabetics on metformin and glimepiride or gliclazide found that hydroxychloroquine 400 mg daily reduced fasting blood glucose (FBG), post-prandial glucose (PPG), and HbA1C to a similar degree as pioglitazone 15 mg daily at 24 weeks.(6) In a prospective observational study, 250 uncontrolled type II diabetics on metformin, glimepiride, pioglitazone, sitagliptin, and a SGLT-2 inhibitor received hydroxychloroquine 400 mg daily for 48 weeks. HbA1C decreased from 8.83% to 6.44%, FBG decreased by 40.78%, and PPG decreased by 58.95%. The doses of metformin were reduced by 50%, glimepiride and sitagliptin by 75%, and SGLT-2 inhibitors were discontinued in most patients.(7)

Selected Antidiabetic Agents/Selected Quinolones

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism is unknown.

CLINICAL EFFECTS: Concurrent use of quinolones and antidiabetic agents may result in severe hypoglycemia.(1-7) Hypoglycemia can lead to coma.

PREDISPOSING FACTORS: Elderly patients, especially those with decreased renal function may be predisposed to this interaction.(5)

PATIENT MANAGEMENT: Patients maintained on antidiabetic agents who require concurrent therapy with a quinolone should be closely monitored for hypoglycemia.(1-4) Patients should be instructed to discontinue quinolone use and contact their doctor if hypoglycemia occurs.(2,4) Signs of hypoglycemia may include confusion, dizziness, feeling shaky, unusual hunger, headaches, irritability, pounding heart or very fast pulse, pale skin, sweating, trembling, weakness, or unusual anxiety.

DISCUSSION: Hypoglycemia has been reported with concurrent ciprofloxacin and glyburide,(1,8,9) levofloxacin and glyburide,(2,10,11) norfloxacin and glyburide,(3) levofloxacin and glipizide (12) as well as levofloxacin and metformin-glibenclamide.(14) There has been one report of fatal hypoglycemia with concurrent levofloxacin and glyburide(9) and one of the above reports of hypoglycemia with concurrent levofloxacin and glyburide resulted in hypoxic brain injury.(11) A review of postmarketing adverse event data for the fluoroquinolones and hypoglycemic coma identified 56 reports in FAERS search from October 1987- April 2017 and 11 additional cases in the medical literature. Most patients had risk factors for hypoglycemia. 41 patients were taking one or more hypoglycemic drugs. 13 deaths occurred (some of these patients had renal insufficiency). 9 patients did not fully recover and had resultant disability.(13)

Selected Antidiabetics/Maois

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism by which MAO inhibitors affect carbohydrate metabolism and subsequent enhancement of the hypoglycemic action of insulin is not clear. The adrenergic response to hypoglycemia may be blocked by insulin release caused by MAOI's. In vitro studies have shown that MAO inhibitors are capable of both potentiating and inhibiting insulin release, depending on their concentrations. Stimulation of glucose-mediated insulin secretion is believed to be related to the MAO inhibitory effects of the drugs.

CLINICAL EFFECTS: The hypoglycemic response to both insulin and glucose lowering agents including alpha glucosidase inhibitors, meglitinides, and sulfonylurea may be increased.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Concurrent MAO inhibitor therapy for depression in a diabetic patient will often require reduction in dosage of the hypoglycemic agent because of enhanced hypoglycemic effects. Since the extent of the reaction is highly unpredictable, any diabetic patients receiving MAO inhibitors should be monitored for possible excessive hypoglycemia.

DISCUSSION: This interaction is likely to occur. The interaction between MAOIs and insulin is well documented. Additional documentation is necessary to confirm the potential interaction of MAOI's with other glucose lowering agents including alpha glucosidase inhibitors, meglitinides, and sulfonylureas but is expected to occur based on pharmacologic similarity. It may take several weeks for the full hypoglycemic effect of the MAOI to occur. Conversely, it may take several weeks for the effect to dissipate after stopping the MAOI. Furazolidone is known to be a monoamine oxidase inhibitor. Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A. Metaxalone is a weak inhibitor of MAO.

Selected Antidiabetics/Safinamide

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism by which MAO inhibitors such as safinamide affect carbohydrate metabolism and subsequent enhancement of the hypoglycemic action of insulin is not clear. The adrenergic response to hypoglycemia may be blocked by insulin release caused by MAOI's. In vitro studies have shown that MAO inhibitors are capable of both potentiating and inhibiting insulin release, depending on their concentrations. Stimulation of glucose-mediated insulin secretion is believed to be related to the MAO inhibitory effects of the drugs.

CLINICAL EFFECTS: The hypoglycemic response to both insulin and glucose lowering agents including alpha glucosidase inhibitors, meglitinides, and sulfonylurea may be increased.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Concurrent MAO inhibitor therapy for depression in a diabetic patient will often require reduction in dosage of the hypoglycemic agent because of enhanced hypoglycemic effects. Since the extent of the reaction is highly unpredictable, any diabetic patients receiving MAO inhibitors should be monitored for possible excessive hypoglycemia.

DISCUSSION: This interaction is likely to occur. The interaction between MAOIs and insulin is well documented. Additional documentation is necessary to confirm the potential interaction of MAOI's with other glucose lowering agents including alpha glucosidase inhibitors, meglitinides, and sulfonylureas but is expected to occur based on pharmacologic similarity. It may take several weeks for the full hypoglycemic effect of the MAOI to occur. Conversely, it may take several weeks for the effect to dissipate after stopping the MAOI.

*Hypersensitivity to acarbose.

*Diabetic ketoacidosis.

*Cirrhosis.

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

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

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

• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Crohn's disease
• Gastrointestinal obstruction
• Hepatic cirrhosis
• Malabsorption states
• Ulcerative colitis

• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Hypoglycemic disorder

• Disease of liver
• Kidney disease with likely reduction in glomerular filtration rate (GFr)

The most common adverse effects of acarbose are GI symptoms, including flatulence, diarrhea, and abdominal pain.

Rare or Very Rare

• Edema
• Hepatitis
• Hypersensitivity drug reaction
• Ileus
• Jaundice
• Pneumatosis cystoides intestinalis
• Thrombocytopenic disorder

More Frequent

• Abdominal pain with cramps
• Diarrhea
• Flatulence

Less Frequent

• Abnormal hepatic function tests
• Weight loss

No enhanced messaging available.

Safety and efficacy of acarbose have not been established in pediatric patients younger than 18 years of age.

There are no adequate and well-controlled studies of acarbose in pregnancy. In animal reproduction studies conducted in rats, acarbose doses up to 480 mg/kg (corresponding to 9 times the exposure in humans based on plasma levels) revealed no evidence of impaired fertility or harm to the fetus. In rabbits, acarbose doses up to 160 mg/kg (corresponding to 10 times the human dose based on body surface area) showed no evidence of embryotoxicity and there was no evidence of teratogenicity at a dose 32 times the human dose (based on body surface area). However, in rabbits, reduced maternal body weight gain, likely the result of the pharmacodynamic activity of high doses of acarbose in the intestines, may have been responsible for a slight increase in embryonic losses.

Abnormal glucose levels during pregnancy are associated with a higher incidence of congenital anomalies as well as increased neonatal morbidity and mortality; acarbose should be used during pregnancy only if clearly needed as safety in pregnant women has not been established.

There is no information regarding the presence of acarbose in human milk. Acarbose is distributed into milk in rats. Acarbose is not recommended for use while breast-feeding.

The manufacturer makes no specific dosage recommendations for geriatric patients.

No overall differences in safety or efficacy of acarbose have been observed between patients >=65 years of age and younger patients. In clinical studies of acarbose, 27% of patients were >=65 years of age and 4% of patients were >=75 years of age. The mean steady-state AUC and maximum concentration of acarbose are approximately 1.5-times higher in geriatric patients compared to younger patients; these differences are not considered significant.