Acarbose - Indication, Dosage, and Contraindication

Overview:

Acarbose is an alpha-glucosidase inhibitor used as an adjunct to diet and exercise for managing glycemic control in type 2 diabetes mellitus patients. It is a complex oligosaccharide compound and an inhibitor of enzymes that break the complex structures of carbohydrates in the intestines. It can inhibit pancreatic alpha-amylase and alpha-glucosidase enzyme activities, which further decreases the absorption of carbohydrates and increases glucose and insulin levels in the blood. It can be used, along with exercise and diet, for managing the sugar levels in the blood of type 2 diabetes patients.

What Is Type 2 Diabetes Mellitus?

Diabetes Mellitus is a chronic condition related to elevated blood sugar levels in the body. In type 2 diabetes, the pancreas does not work to produce enough insulin. Insulin is a hormone that regulates the sugar movements taken by the cells. In diabetes, these cells cannot take the insulin, thus leading to less sugar consumption by cells and more sugar levels in the blood.

Symptoms of type 2 diabetes are:

• Increased thirst.

• Frequent urination.

• Increased hunger.

• Weight loss.

• Weakness.

• The slow healing process.

• Frequent infections.

• Numbness in hand and feet.

• Blurred vision.

Diagnosis of Type 2 Diabetes Mellitus:

It is diagnosed by taking a blood test of glycated hemoglobin (A1C) test. The test will present the patient's past two to three months of blood glucose. But if an A1C test is not possible or available, then the patient's random blood sugar test, fasting blood glucose test, or oral glucose test can be performed.

Indications of Acarbose:

• Acarbose is indicated for the treatment of type 2 diabetes patients. It is not recommended for prediabetes as it is not approved by the FDA (The United States Food and Drug Administration).

Mechanism of Action:

• Alpha-glucosidase hydrolase is present in the intestinal mucosa and works for metabolizing complex carbohydrates like sucrose into simpler monosaccharides like glucose; the body can easily absorb that. In addition, alpha-glucosidase works with the pancreatic alpha-amylase (enzymes of the intestinal lumen) to metabolize the complex compound carbohydrates like starches to oligosaccharides.

• Acarbose is like a complex oligosaccharide that works as a competitive and reversible inhibitor of pancreatic alpha-amylase and intestinal alpha-glucoside hydrolase enzymes. Acarbose blocks the metabolism and absorption of dietary carbohydrates, thus decreasing blood glucose and insulin levels.

Dosage:

• Dose Form - Tablets.

• Dose Strength - 25 mg, 50 mg, and 100 mg (milligrams) are available.

• Dose Administration - Orally.

• Dose Recommendation - It is administered orally three times daily with meals. Acarbose is taken with the first bite of the meal.

Contraindications:

• Acarbose is contraindicated in cases with a hypersensitivity reaction, colonic ulceration, diabetic ketoacidosis (a severe diabetic complication where the body makes too much blood acids called ketones), liver cirrhosis (scarring of the healthy liver tissue), bowel disease, and intestinal obstruction patients.

Special Considerations:

• Renal Impairments - Acarbose has increased renal dysfunctions in patients with renal impairments. So, Acarbose is not recommended for renal impairment patients.

• Drug Interactions - Acarbose, if co-administered with Insulins or Sulfonylureas, then a hypoglycemic shock can observe in the patient. So, the administration of Acarbose with these drugs is inhibited.

• Carcinogenesis and Mutagenesis - Acarbose has shown no reports related to DNA changes, and no evidence of carcinogenicity was found in studies performed with Acarbose.

• Impairment of Fertility - The studies have concluded no signs of infertility after using Acarbose.

• Pregnancy - The safe use of Acarbose has not been determined during pregnancy. So, it is ideally not recommended for pregnant women.

• Lactating Mothers - There is some amount of radiolabeled Acarbose in the milk of the lactating mothers. So the use of Acarbose is not recommended in lactating mothers.

• Pediatric Use - The safe use of Acarbose in the pediatric population, has yet to be determined. So, Acarbose is not recommended for child patients.

• Geriatric Use - No specific reports can define the safety and effectiveness of Acarbose in the geriatric population. So, the use of Acarbose in older people is usually not recommended.

Precautions:

• Macrovascular Results - There are no findings for using Acarbose in macrovascular risk reduction.

• Hypoglycemia - If Acarbose is administered alone, it can not cause hypoglycemia (low blood sugar levels). Still, if co-administered with insulins or sulfonylureas, it can cause hypoglycemic shock (a severe complication resulting from decreased blood sugar levels).

• Elevated Serum Transaminase Levels - Studies have reported that Acarbose has presented elevated serum transaminase levels.

• Loss of Control of Blood Glucose Levels - When the patients are involved in fever, infection, or surgery, blood glucose levels can be lost. In these cases needed, temporary insulin therapy is required.

For Patients:

What Is the Use of Acarbose Medicine?

The use of Acarbose medicine is to control blood glucose levels in adults with diabetes mellitus type 2 patients.

Why Is Acarbose Recommended?

Acarbose is recommended to treat type 2 diabetes because it slows the action of some enzymes that metabolize complex sugars to simple sugars. Further, these simple sugars can easily be absorbed by the body and found in the blood. Here Acarbose inhibits and slows food digestion in the body and thus lowers glucose levels in the blood.

How Is Acarbose Used?

Acarbose comes in the form of tablets and is taken through the mouth. The medicine is taken with the first bite of the meals and taken three times with meals. Take the dosage as recommended by the doctor, and do not stop taking it without consulting the doctor.

What Are the Precautions While Taking Acarbose?

Precautions are:

• Precaution is taken if the patient is allergic to Acarbose medicine.

• Precautions are taken if the patient has medical conditions like ketoacidosis, cirrhosis, intestinal diseases, and inflammatory bowel diseases.

• Precautions are required while taking Acarbose with other medicine like Digoxin, estrogen, oral contraceptives, Isoniazid, and Phenytoin.

• Precautions are needed if the patient is a pregnant or lactating mother.

• Precautions are also required if the patient is going through the surgery.

What to Do if the Patient Misses the Dose?

If the dose is missed, the patient should take it as soon as possible. And if the patient is going to have a snack, then take medicine with the snack. But if the timing of the next dose is quite near, they take the next dose and skip the missed dose.

What Are the Side Effects of Acarbose?

The effect of Acarbose is mainly hypoglycemia when the blood glucose level is deficient. But it occurs when Acarbose is co-administered with other medicines like insulin.

The symptoms that appear as side effects of Acarbose are as follows:

• Dizziness.

• Sweating.

• Shakiness.

• Nervousness.

• Changes in mood or behavior suddenly.

• Numbness around the mouth.

• Weakness.

• Headache.

• Hungry.

• Jerky moves.

• Pallor skin.

Adverse effects, if hypoglycemia is not treated, severe symptoms start appearing. Consult the doctor soon on the appearance of any such symptoms listed below:

• Confusion.

• Loss of consciousness.

• Seizures.

• Weakness.

• Extremely hungry and thirsty.

• Frequent urination.

• Blurred vision.

• Dry mouth.

• Difficulty in breathing.

• Fruity breath.

• Vomitings.

• Stomach upset.

How to Store and Dispose of Acarbose Medicine?

Acarbose is available in tablet forms; it is contained in tightly closed containers and stored at room temperature. Therefore, the medicine should be kept away from children and pets.

The unneeded medication is disposed of in a particular way of a take-back program. This program is the best way to dispose of the medicine instead of flushing it in the toilet or throwing it anywhere. It is done to ensure that no pet, child, or any unknown person should not take medicine unnecessarily.

For Doctor:

Acarbose:

Acarbose is an oral alpha-glucosidase inhibitor used to treat type 2 diabetes. It is a complex oligosaccharide that is formed by the fermentation of microorganisms. Its empirical formula is C25H43NO18. It has a white to off-white color. It has a molecular weight of 645.6 and is soluble in water with pKa 5.1. It has inactive ingredients like starch, microcrystalline cellulose, magnesium stearate, and colloidal silicon dioxide.

Mechanism of Action:

• Acarbose is an oligosaccharide that acts on enzymes like pancreatic alpha-amylase and intestinal alpha-glucoside hydrolase for their inhibition. As these enzymes are responsible for the hydrolyzation of complex carbohydrates like sucrose into simple monosaccharides carbohydrates like glucose or fructose, Acarbose here blocks the metabolism and absorption of dietary carbohydrates, thus decreasing blood glucose and insulin levels.

Pharmacokinetics:

• Absorption: The bioavailability of the Acarbose is minimally present; from the administered drug, only 1 to 2 percent is present in the systemic circulation. 35 % of the total radioactive and oral administered dosage is present in the circulation, and the plasma radioactivity peaks at 14 to 24 hours after administration of Acarbose.

• Protein-Binding: 1 to 2% of the orally administered dose is absorbed in circulation. Acarbose does not show any protein binding.

• Metabolism: Acarbose is metabolized in the gastrointestinal tract with the help of intestinal bacteria and digestive enzymes. It has 13 known metabolites like methyl and sulfate. Out of these 13, ⅓ are absorbed in circulation and released by kidneys.

• Elimination: Half of the dosage is excreted in the feces 96 hours after administration. The kidney excretes a few absorbed drugs in the systemic circulation. And if Acarbose is administered intravenously, then 89% is excreted in urine by the kidneys in 48 hours.

Dosage and Administration:

• Dosage Form - Tablets.

• Dosage Strength - 25 mg, 50 mg, or 100 mg.

• Dosage Supplied - It is present in white color to yellow-tinged color.

Administration:

There is no regimen to start with Acarbose for treating diabetes mellitus. It started with a lower dose and gradually increased the dosage to 100 mg. It is taken every three times with meals.

Initial Dosage: Acarbose is started with 25 mg, which is taken orally every three times a day with meals. It is taken with the first bite of the meal. Sometimes, to overcome gastrointestinal changes, it can be started with 25 mg once daily and then gradually increasing it to 25 mg three times daily.

Maintenance Dosage: When the patient is comfortable with 25 mg three times a day, proceeding with increased dosage adjustment in 4 to 8 weeks is done. After that, the dosage is increased to 50 mg three times a day. The maintenance of the dose is from 50 mg to 100 mg. If the patient's weight is more than 60 kg (kilogram), the doctor should recommend a 100 mg increase in dosage because a less than 60 kg patient can develop increased serum transaminases.

The maximum dosage adjustment for a patient who is less than 60 is 50 mg, whereas for patients who have more than 60 is 100 mg.

Drug-Drug Interactions:

Some drugs cause hyperglycemia, like thiazides, diuretics, corticosteroids, phenothiazines, thyroid products, oral contraceptives, Phenytoin, nicotinic acid, sympathomimetics, estrogens, calcium channel-blocking agents, and Isoniazid. When such drugs are co-administered with Acarbose, the patient can have unstable glucose levels in the blood.

When Acarbose is co-administered in insulin or sulfonylureas, the patient can quickly go into hypoglycemic shock.

Acarbose is also not taken along with intestinal adsorbents like charcoal or digestive carbohydrates; metabolizing enzymes like amylase can decrease the effects of Acarbose.

Digoxin should be adjusted before concomitant use with Acarbose, as these change the bioavailability of the Digoxin drug.

Adverse Reactions:

Gastrointestinal Changes: Gastrointestinal has mostly encountered adverse reactions related to Acarbose. It has shown symptoms like diarrhea, abdominal pain, and flatulence.

Overdosage:

Acarbose overdose can result in diarrhea, abdominal pains, and flatulence; these gastrointestinal symptoms will subside soon. But in the cases of overdosage, the patient is recommended to avoid drinks or meals having carbohydrates for at least 4 to 6 hours.

Clinical Trials:

Clinical Trials of Dose-Finding Studies of Type 2 Diabetes Mellitus Patients Who Are on Dietary Treatment Only:

Six controlled studies with fixed-dose from monotherapy study of Acarbose used in treating type 2 diabetes mellitus patients had 769 patients who were treated with Acarbose combined. The use of Acarbose is different from placebo at all doses. And there are no significant differences between the dosing results ranging from 50 to 300 mg given three times a day. Although some benefitted from increasing the dose from 50 to 100 mg, studies provided that 200 to 300 mg is the maximum dosage. But 50 mg in less than 60 kg weight patients and 100 mg in more than 60 kg is the maximum dosage recommendation.

Results: The results showed that the Acarbose differs from the placebo at all the dosages. And the use of 300 mg Acarbose was a superior regimen, but the results of 50 mg to 200 mg used three times a day had no difference reports.

Clinical Trials in Diabetes Mellitus Type 2 Patients Who Are on Monotherapy or Are Using the Combination of Sulfonylureas, Metformin, or Insulin:

It was a one-year study with 316 patients in Canada with primary efficacy. The diet of the patients includes the Sulfonylureas and Metformin groups, and the decreases in HbA1c by adding Acarbose at six months with effects at one year. The patients treated with Acarbose and who were on insulin had a reduction in HbA1c at six months and a more significant reduction at one year.