Acarbose

Tell your doctor about all prescription, non-prescription, illegal, recreational, herbal, nutritional, or dietary drugs you're taking, especially the enzymes listed in the Warning section or any of the following:

• Any medications you take for diabetes and blood-sugar control
• Digoxin (Lanoxin)
• Diuretics (water pills)
• Estrogens
• Isoniazid
• Medicines for high blood pressure or colds
• Medications to treat ADHD (attention deficit hyperactivity disorder)
• Oral contraceptives
• Phenytoin (Dilantin)
• Thyroid medications
• Niacin
• Nicotine patches or gum
• Steroids
• Diet pills
• Vitamins

Acarbose and Alcohol

Alcohol can affect your blood-sugar levels.

Talk to your doctor about consuming alcoholic beverages while taking this medicine.

Acarbose comes as a tablet and is typically taken by mouth three times a day at the beginning of meals.

Take each dose with the first bite of each main meal.

Try to take acarbose at the same time each day to help you remember your doses.

Your dosage will be based on your medical condition, weight, and response to treatment.

Your doctor will probably start you on a lower dose of the drug and gradually increase it.

You will probably monitor your blood-sugar levels after meals and share the information with your doctor to decide on dosage changes.

The aim is to find the lowest effective dose with the fewest side effects.

Only people who weigh more than 132 pounds (60 kilograms) should take more than 50 milligrams (mg) per meal (150 mg per day).

The manufacturer recommends that no one exceed more than 300 milligrams (mg) per day of acarbose.

Follow the directions on your prescription label carefully when taking this medicine. Don't take more of the drug than is prescribed.

Acarbose Overdose

If you suspect an overdose, you should contact a poison-control center or emergency room immediately.

You can reach a poison-control center at (800) 222-1222.

Missed Dose of Acarbose

If you miss a dose of acarbose, take it as soon as you remember.

If you plan on having a snack soon, take your dose with the snack.

If it's almost time for your next dose, skip the missed dose and continue on your regular dosing schedule. Don't double up on doses.

• The preparation for Precose is an oral tablet medication used in conjunction with diet and exercise for reducing blood sugar in patients with type 2 diabetes.
• Precose can be used alone in the treatment type 2 diabetes or can be combined with sulfonylureas such as glyburide (Diabeta) or metformin (Glucophage) or with insulin.

• The recommended initial dose for type 2 diabetes is 25 mg three times daily.
• The dose is then increased every four to eight weeks based on response and tolerance.
• The maximum dose is 50 mg three times daily for patients weighing 60 kg or less and 100 mg three times daily for those weighing more than 60 kg.
• This medication should be taken at the first bite of each meal.
• Smaller doses may be adequate for patients with severe kidney dysfunction or liver disease.
• This medication is not recommended if a patient has cirrhosis.
• Precose therapy is not advised in the presence of certain medical conditions such as inflammatory bowel disease (IBD) or intestinal obstruction and chronic intestinal diseases that interfere with digestion or absorption such as Crohn's disease.
• The doses of this type 2 diabetes medication should be adjusted based upon blood glucose levels taken one hour after a meal and blood HbA1c levels taken about three months after starting or changing the dose. (HbA1c is a chemical in the blood that is a good indicator of blood glucose control.)

Absorption

Bioavailability

Low systemic bioavailability of parent compound; <2% of dose is absorbed as active drug (parent compound and active metabolite).1 Peak plasma concentrations of active drug attained at approximately 1 hour.1 Approximately 34% of dose absorbed as numerous metabolites.1

Onset

Satisfactory control of blood glucose concentrations achieved within a few days after dosage adjustment; however18 23 maximum response may be delayed for up to 2 weeks.18 23

Special Populations

In geriatric patients, mean AUC and peak blood concentrations of the drug were higher compared with younger adults;1 differences not statistically significant.1

In individuals with severe renal impairment (CLcr <25 mL/minute), peak plasma drug concentrations and AUC increased compared with those values in individuals with normal renal function.1

Distribution

Extent

Distributed into milk in rats.1

Elimination

Metabolism

Metabolized exclusively in GI tract, principally by intestinal bacteria but also by digestive enzymes to numerous metabolites, one of which is active.1

Elimination Route

Excreted principally in feces (51% of dose) as unabsorbed drug and in urine as metabolites (34% of dose).1 No accumulation with recommended dosing frequency.1

Half-life

Approximately 2 hours.1

Storage

Oral

≤25°C.1 Protect from moisture.1

• Small inhibitory effect on α-glucosidase enzymes (e.g., glucoamylase, sucrase, maltase, isomaltase) that hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the intestinal brush-border.2 6 14 24 29 30 52 Small inhibitory effect on pancreatic α-amylase, which hydrolyzes starch into maltose, maltotriose, and dextrins in the lumen of the small intestine.2 14 30 33 No inhibitory effect on lactase and would not be expected to produce lactose intolerance.1

• Delays carbohydrate breakdown and glucose absorption and reduces postprandial hyperglycemia in diabetic patients.1 2 6 7 10 14 23 24 30

• Reduces fluctuations in the daily blood glucose concentration-time profile in patients with type 2 diabetes mellitus and in lean or obese nondiabetic individuals.1 2 3 6 7 19 20 21 23 24 35 37 39 47 Fasting blood glucose concentrations either not affected or mildly decreased.1 2 3 6 7 19 20 21 23 24 35 37 39 47

• In contrast to sulfonylurea antidiabetic agents, acarbose does not enhance insulin secretion.1 Does not produce hypoglycemia when given as monotherapy in fasting individuals.1

• When used in combination with sulfonylurea antidiabetic agents are used in combination, acarbose reduces the insulinotropic and weight-increasing effects of sulfonylureas.1 No clinically important loss of calories or weight loss occurs in either diabetic or nondiabetic individuals.2 6 13 14 18 21 23 28 35 37 39

• It is used to lower blood sugar in patients with high blood sugar (diabetes).

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

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

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

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

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

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

No information provided

Acarbose is a complex oligosaccharide that delays the digestion of ingested carbohydrates, thereby resulting in a smaller rise in blood glucose concentration following meals. As a consequence of plasma glucose reduction, PRECOSE reduces levels of glycosylated hemoglobin in patients with type 2 diabetes mellitus. Systemic non-enzymatic protein glycosylation, as reflected by levels of glycosylated hemoglobin, is a function of average blood glucose concentration over time.

Mechanism of Action

In contrast to sulfonylureas, PRECOSE does not enhance insulin secretion. The antihyperglycemic action of acarbose results from a competitive, reversible inhibition of pancreatic alpha-amylase and membrane-bound intestinal alpha-glucoside hydrolase enzymes. Pancreatic alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine, while the membrane-bound intestinal alpha-glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the brush border of the small intestine. In diabetic patients, this enzyme inhibition results in a delayed glucose absorption and a lowering of postprandial hyperglycemia.

Because its mechanism of action is different, the effect of PRECOSE to enhance glycemic control is additive to that of sulfonylureas, insulin or metformin when used in combination. In addition, PRECOSE diminishes the insulinotropic and weight-increasing effects of sulfonylureas.

Acarbose has no inhibitory activity against lactase and consequently would not be expected to induce lactose intolerance.

Pharmacokinetics

In a study of 6 healthy men, less than 2% of an oral dose of acarbose was absorbed as active drug, while approximately 35% of total radioactivity from a 14C-labeled oral dose was absorbed. An average of 51% of an oral dose was excreted in the feces as unabsorbed drug-related radioactivity within 96 hours of ingestion. Because acarbose acts locally within the gastrointestinal tract, this low systemic bioavailability of parent compound is therapeutically desired. Following oral dosing of healthy volunteers with 14C-labeled acarbose, peak plasma concentrations of radioactivity were attained 14–24 hours after dosing, while peak plasma concentrations of active drug were attained at approximately 1 hour. The delayed absorption of acarbose-related radioactivity reflects the absorption of metabolites that may be formed by either intestinal bacteria or intestinal enzymatic hydrolysis.

Acarbose is metabolized exclusively within the gastrointestinal tract, principally by intestinal bacteria, but also by digestive enzymes. A fraction of these metabolites (approximately 34% of the dose) was absorbed and subsequently excreted in the urine. At least 13 metabolites have been separated chromatographically from urine specimens. The major metabolites have been identified as 4-methylpyrogallol derivatives (that is, sulfate, methyl, and glucuronide conjugates). One metabolite (formed by cleavage of a glucose molecule from acarbose) also has alpha-glucosidase inhibitory activity. This metabolite, together with the parent compound, recovered from the urine, accounts for less than 2% of the total administered dose.

The fraction of acarbose that is absorbed as intact drug is almost completely excreted by the kidneys. When acarbose was given intravenously, 89% of the dose was recovered in the urine as active drug within 48 hours. In contrast, less than 2% of an oral dose was recovered in the urine as active (that is, parent compound and active metabolite) drug. This is consistent with the low bioavailability of the parent drug. The plasma elimination half-life of acarbose activity is approximately 2 hours in healthy volunteers. Consequently, drug accumulation does not occur with three times a day (t.i.d.) oral dosing.

Special Populations

The mean steady-state area under the curve (AUC) and maximum concentrations of acarbose were approximately 1.5 times higher in elderly compared to young volunteers; however, these differences were not statistically significant. Patients with severe renal impairment (Clcr < 25 mL/min/1.73m²) attained about 5 times higher peak plasma concentrations of acarbose and 6 times larger AUCs than volunteers with normal renal function. No studies of acarbose pharmacokinetic parameters according to race have been performed. In U.S. controlled clinical studies of PRECOSE in patients with type 2 diabetes mellitus, reductions in glycosylated hemoglobin levels were similar in Caucasians (n=478) and African-Americans (n=167), with a trend toward a better response in Latinos (n=132).

Drug-Drug Interactions

Studies in healthy volunteers have shown that PRECOSE has no effect on either the pharmacokinetics or pharmacodynamics of nifedipine, propranolol, or ranitidine. PRECOSE did not interfere with the absorption or disposition of the sulfonylurea glyburide in diabetic patients. PRECOSE may affect digoxin bioavailability and may require dose adjustment of digoxin by 16% (90% confidence interval: 8-23%), decrease mean Cmax of digoxin by 26% (90% confidence interval: 16–34%) and decreases mean trough concentrations of digoxin by 9% (90% confidence limit: 19% decrease to 2% increase). (See PRECAUTIONS: DRUG INTERACTIONS.)

The amount of metformin absorbed while taking PRECOSE was bioequivalent to the amount absorbed when taking placebo, as indicated by the plasma AUC values. However, the peak plasma level of metformin was reduced by approximately 20% when taking PRECOSE due to a slight delay in the absorption of metformin. There is little if any clinically significant interaction between PRECOSE and metformin.

Clinical Trials

Results from six controlled, fixed-dose, monotherapy studies of PRECOSE in the treatment of type 2 diabetes mellitus, involving 769 PRECOSE-treated patients, were combined and a weighted average of the difference from placebo in the mean change from baseline in glycosylated hemoglobin (HbA1c) was calculated for each dose level as presented below:

Table 1

Although studies utilized a maximum dose of 200 or 300 mg t.i.d., the maximum recommended dose for patients < 60 kg is 50 mg t.i.d.; the maximum recommended dose for patients > 60 kg is 100 mg t.i.d.

Results from these six fixed-dose, monotherapy studies were also combined to derive a weighted average of the difference from placebo in mean change from baseline for one-hour postprandial plasma glucose levels as shown in the following figure:

Figure 1

* PRECOSE was statistically significantly different from placebo at all doses with respect to effect on one-hour postprandial plasma glucose.
**The 300 mg t.i.d. PRECOSE regimen was superior to lower doses, but there were no statistically significant differences from 50 to 200 mg t.i.d.

PRECOSE was studied as monotherapy and as combination therapy to sulfonylurea, metformin, or insulin treatment. The treatment effects on HbA1c levels and one-hour postprandial glucose levels are summarized for four placebo-controlled, double-blind, randomized studies conducted in the United States in Tables 2 and 3, respectively. The placebo-subtracted treatment differences, which are summarized below, were statistically significant for both variables in all of these studies.

Study 1 (n=109) involved patients on background treatment with diet only. The mean effect of the addition of PRECOSE to diet therapy was a change in HbA1c of -0.78%, and an improvement of one-hour postprandial glucose of -74.4 mg/dL.

In Study 2 (n=137), the mean effect of the addition of PRECOSE to maximum sulfonylurea therapy was a change in HbA1c of -0.54%, and an improvement of one-hour postprandial glucose of -33.5 mg/dL.

In Study 3 (n=147), the mean effect of the addition of PRECOSE to maximum metformin therapy was a change in HbA1c of -0.65%, and an improvement of one-hour postprandial glucose of -34.3 mg/dL.

Study 4 (n=145) demonstrated that PRECOSE added to patients on background treatment with insulin resulted in a mean change in HbA1c of -0.69%, and an improvement of one-hour postprandial glucose of -36.0 mg/dL.

A one year study of PRECOSE as monotherapy or in combination with sulfonylurea, metformin or insulin treatment was conducted in Canada in which 316 patients were included in the primary efficacy analysis (Figure 2). In the diet, sulfonylurea and metformin groups, the mean decrease in HbA1c produced by the addition of PRECOSE was statistically significant at six months, and this effect was persistent at one year. In the PRECOSE-treated patients on insulin, there was a statistically significant reduction in HbA1c at six months, and a trend for a reduction at one year.

Table 2: Effect of Precose on HbA1c

Table 3: Effect of Precose on Postprandial Glucose

Figure 2

Figure 2: Effects of PRECOSE (III ) and Placebo ( III ) on mean change in HbA1c levels from baseline throughout a one-year study in patients with type 2 diabetes mellitus when used in combination with: (A) diet alone; (B) sulfonylurea; (C) metformin; or (D) insulin. Treatment differences at 6 and 12 months were tested: * p < 0.01; # p = 0.077.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of acarbose, there are no specific foods that you must exclude from your diet when receiving this medication.

Contraindications

Documented hypersensitivity to acarbose

Diabetic ketoacidosis, cirrhosis, inflammatory bowel disease, colonic ulceration, partial intestinal obstruction or predisposed to intestinal obstruction, known marked absorptive impairment of GI

Conditions that may deteriorate as result of increased gas formation in GI tract

Cautions

No clinical studies exist establishing conclusive evidence of macrovascular risk reduction with acarbose or any other anti-diabetic drug

Concurrent use with sulfonylureas or insulin may result in hypoglycemia; treat hypoglycemia with oral glucose (dextrose), not sucrose (cane sugar)

Monitoring glycemic control with 1,5-AG assay is not recommended; measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking acarbose; use alternate methods to monitor for glycemic control

Patients that are exposed to stress such as fever, trauma, infection, or surgery, may result in temporary loss of control of blood glucose; temporary insulin therapy may be necessary

Significant renal dysfunction (serum creatinine greater than 2 mg/dL): Use is not recommended

Administration advice:
-Take orally at the start of meal (with first bite)

General:
-This drug should be titrated to reduce gastrointestinal side effects; patients should be instructed regarding the importance of following a diabetic diet.
-This drug may be used as monotherapy, or in combination with other antidiabetic agents.
-Patients receiving sulfonylureas or insulin may need a dose adjustment of these agents if hypoglycemia occurs.

Monitoring:
-Glycemic control: During initiation and titration, 1-hour postprandial plasma glucose should be used to monitor therapeutic response; glycosylated hemoglobin levels (HbA1c) should be measured every 3 months to assess long-term glycemic control.
-Hepatic: Serum transaminases should be checked every 3 months for the first year and periodically thereafter.

Patient advice:
-Patients should understand the importance of adhering to a diabetic diet; gastrointestinal side effects are common upon treatment initiation, but should diminish with time.
- Hypoglycemia may occur, more commonly when used in combination with insulin or a sulfonylurea; patients should be instructed to treat hypoglycemia with oral glucose (dextrose) as sucrose (cane sugar) is not expected to correct hypoglycemia due to this drug inhibiting breakdown to glucose and fructose.
-During periods of stress such as fever, trauma, infection, or surgery, management of diabetes may change and patients should be advised to seek medical advice.

Summary of Use during Lactation

Because less than 2% of a dose of acarbose is absorbed from the mother's gastrointestinal tract, it is unlikely that any drug reaches the infant through breastmilk.[1]

Drug Levels

Maternal Levels. Relevant published information was not found as of the revision date.

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

Chlorpropamide, Glyburide, Insulin, Metformin, Tolbutamide

References

1. Everett JA. Use of oral antidiabetic agents during breastfeeding. J Hum Lact. 1997;13:319-21. PMID: 9429368