Acarbose
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Authored by: Rlweber 08:48, 6 April 2007 (PDT)
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Brand/Trade Names of Drug
Precose
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Generic Name of Drug
Acarbose (AY car bose)
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Description
Acarbose was the first member of the alpha-glucosidase inhibitor drug family. It was produced by fermentation of Actinoplanes utahensis.[1]Acarbose received FDA-approval in September of 1995.[2] Alpha-glucosidase ihibitors are safe for use in patients at risk of lactic acidosis and/or hypoglycemia.[2] They are unique in their ability to lower postprandial blood glucose.[2]
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Mechanism of action
Acarbose is an alpha-glucosidase inhibitor. It works to decrease the breakdown of sucrose and complex carbohydrates in the small intestine, allowing for prolonged absorption of carbohydrates and a reduction in the rate of glucose absorption.[2] The end result is a reduction in the postprandial glucose with unchanged fasting glucose levels.[2] Acarbose reversibly inhibits the enzymes required for hydrolysis of complex starches, oligosaccharides, trisaccharides and disaccharides.[3] By inhibiting these enzymes, there is a delay in glucose absorption and a decrease in postprandial glucose.[3] Unlike other antidiabetic medications, acarbose does not enhance insulin secretion, and will not produce hypoglycemia when used as monotherapy.[1]
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Pharmacokinetics
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Absorption
The majority of acarbose is unabsorbed, as less than 2% of an oral dose is absorbed as active drug.[3] Acarbose exhibits low bioavailability of its parent drug. Approximately 51% of the drug is excreted unabsorbed into the feces. It has low systemic bioavailability, and acts locally in the gastrointestinal tract.[3] Radioactive-labeled acarbose showed longer time to peak plasma concentrations when compared to time to peak plasma concentration of the active drug.[3] This delayed absorption is reflective of the absorption of metabolites that may be formed by intestinal enzymatic hydrolysis and/or intestinal bacteria.[3]
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Metabolism
Acarbose is mainly metabolized by digestive enzymes and intestinal bacteria.[3] There have been 13 acarbose-metabolites identified to date.[3]
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Excretion
The majority of acarbose that is absorbed as intact drug is excreted renally.[3] Less than 2% of an oral dose is recovered as active drug in the urine, in comparison to 89% of an intravenous administration of the drug being excreted as active drug in the urine.[3] The plasma half-life of the drug is approximately 2 hours.[3]
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Special Population Pharmacokinetics
- Renal insufficiency: The peak plasma concentrations of acarbose were approximately 5 times higher, and the AUC was 6 times higher in patients with renal dysfunction (CrCl <25 ml/min).[3]
- Hepatic insufficiency: No studies in acarbose pharmacokinetic parameters have been performed with regards to hepatic insufficiency.[3]
- Hemodialysis: No studies in acarbose pharmacokinetic parameters have been performed in patients undergoing hemodialysis.[3]
- Geriatric: The AUC and maximum acarbose concentration was approximately 1.5 times greater in the elderly population when compared to young patients, however this difference was not statistically significant.[3]
- Pediatric: The safety and efficacy of acarbose has not been evaluated in this population.[3]
- Gender: No studies in acarbose pharmacokinetic parameters have been performed with regards to gender.[3]
- Race: Clinical studies showed similar reduction in hemoglobin A1C in Caucasians, African Americans and Latinos, although there was a better response in the Latino population.[3]
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Indications
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FDA Approved Indications
- Diabetes Mellitus Type II
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Dosage
- Diabetes Melitus Type II (in adults weighing > 60 kg)
- Starting Dose: 25 mg orally three times daily with each meal[3]
- Titration Schedule: Can increase to 50 mg orally three times daily after 4-8 weeks.[3] Can increase to 100 mg orally three times daily after three months after starting initial therapy.[3]
- Maintenance Dose: Based on patient response. May increase up to 50-100 orally three times daily.[3]
- Diabetes Mellitus Type II (in adults weighing < = 60 kg)
- Maximum Dosage Limits
- Adults: 300 mg PO/day (adults > 60 kg); 150 mg PO/day (adults < = 60 kg)[3]
- Elderly: 300 mg PO/day (adults > 60 kg); 150 mg PO/day (adults < = 60 kg)[3]
- Adolescents and children >=10 years: Safety and efficacy has not been studied in this population.[3]
- Children < 10 years: Safety and efficacy has not been studied in this population.[3]
- Dosage Adjustment
- Renal insufficiency: The manufacturer recommends against using acarbose in patients with CrCl <=25 ml/min[3]
- Hepatic insufficiency: Contraindicated for use in patients with cirrhosis[3]
- Hemodialysis:
- Geriatric: No dose adjustments needed in this population.[3]
- Pediatric: Safety and efficacy has not been studied in this population.[3]
- Gender: No dose adjustments are needed in this population.[3]
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Administration
- Route: Oral
- Method: Take with full glass of water (8 oz)
- Special considerations: Take with first bite of each meal
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Monitoring Parameters
- Blood glucose
- Hemoglobin A1C
- LFTs
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Contraindications/Precautions
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Contraindications
- Patients with known hypersensitivity to acarbose and/or any of its components[3]
- Patients with cirrhosis[3]
- Patients with diabetic ketoacidosis[3]
- Patients with inflammatory bowel disease[3]
- Patients with partial intestinal obstruction[3]
- Patients with colonic ulceration[3]
- Patients predisposed to intestinal obstruction[3]
- Patients with chronic intestinal diseases/marked disorders of digestion/absorption[3]
- Patients with condition that may deteriorate as a result of increased gas formation in the intestine[3]
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Precautions
- Hypoglycemia- Although acarbose is not known to cause hypoglycemia when used as monotherapy, hypoglycemia may result when acarbose is combined with insulin and/or sulfonylureas.[3]
- Elevated serum transaminase levels: Elevations is ALT and AST with acarbose use are more common in females, and are usually asymptomatic, reversible, and not associated with other signs of liver dysfunction. The increase in serum transaminase levels also appears to be dose related. Long term studies (including doses of acarbose up to 300 mg po TID), showed elevated AST and/or ALT levels in treated patients when compared to placebo patients.[3]
- Patients with renal impairment: CrCl < 25 ml/min or serum creatinine > 2 mg/dl.[3]
- Children: The safety and efficacy of acarbose has not been studied in this population.
- Pregnancy and Breast-Feeding: The safety of acarbose has not been established in pregnant females.[3] The manufacturer recommends against the use of acarbose in breast-feeding females.[3]
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Pregnancy indications
- Pregnancy category: B.
- Teratogenicity: Clinical trials performed in rats at doses up to 9 times the exposure in humans reveal no evidence of fetal harm or impaired fertility.[3] There are no well-controlled studies in human females, and because the safety of acarbose has not been established in pregnant females, acarbose is only recommended for use in pregnant females if clearly needed.[3] Health care professionals recommend insulin as the drug of choice for pregnant females, when therapy for blood glucose control is needed.
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Breast-feeding indications
- Secretion into breast milk: It is unknown if acarbose is excreted into human breast milk.[3] Studies with animals show that a small amount of radioactivity is found in the milk of lactating rats.[3] The manufacturer recommends against the use of acarbose in breast-feeding females.[3]
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Drug-Drug Interactions
Severity Level | Increased Effect/Toxicity | Decreased Effect | |
|---|---|---|---|
| 4 | None Known | None Known | |
| 3 | Digoxin[3] | Amylase/Cellulase/Protease/Lipase[3]
| |
| 2 | Insulins[3] Antidiabetic Medications[3] Beta-blockers/Clonidine[3] Fluoxetine[4] Mecasermin recombinant/Mecasermin rinfabate[5] MAOIs[6] | Corticosteroids[3] Niacin[7] Thiazide Diuretics/Triamterene[8]
| |
| 1 | None Known | Estrogens[3] Isoniazid[9] Thyroid Hormones[3] Phenothiazines[10] Oral Contraceptives[3] Bumetanide/Torsemide/Furosemide[3] Phenytoin[3]
|
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Drug-Food-Herb Interactions
| Severity Level | Increased Effect/Toxicity | Decreased Effect | |
|---|---|---|---|
| 4 | None known | None Known | |
| 3 | Ethanol[11] | None Known | |
| 2 | None Known | None Known | |
| 1 | None Known | None Known |
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Adverse Reactions/Side Effects
The most common side effects from acarbose usually occur during the first few weeks of starting therapy, and subside with time. The common side effects that may occur during the first few weeks of therapy include abdominal discomfort, diarrhea and flatulence.[3] A slightly greater number of patients withdraw from clinical studies in the acarbose group due to adverse events, with are gastrointestinal in nature.[12] The main complaints include flatulence, diarrhea and abdominal discomfort.[12]
| Incidence | Body System | Adverse Reactions |
|---|---|---|
| > 10 % | Gastrointestinal | Flatulence (77%), Abdominal Pain (21%), Diarrhea (33%) |
| Hepatic | Increased Transaminases | |
| < 1% | All | Sleepiness, headache, vertigo, erythema, urticaria, weakness, severe gastrointestinal distress |
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Overdose Measures
Hypoglycemia will not occur as a result of acarbose overdose.[13] An overdose of acarbose will result in an exacerbation of its side effects, such as flatulence, diarrhea and abdominal discomfort. These side effects subside shortly after an overdose.[13] Since acarbose inhibits the absorption of oral disaccharides, an overdose may complicate the treatment of hypoglycemia fro other causes.[13] Dextrose can be used in mild-to-moderate cases of hypoglycemia, and IV glucose should be used for severe hypoglycemia cases.[13] Fluids and food containing carbohydrates (polysaccharides, oligosaccharides and/or disaccharides) should be stopped for 4-6 hours following an overdose of acarbose.[13]
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Product Information and Distribution
| Name | Manufacturer | Dosage Form | Strength | Quantity | NDC | Storage | Markings |
|---|---|---|---|---|---|---|---|
| Precose[3] | Bayer | Oral Tablets | 25 mg | 100 | 00026-2863-51 | 15-30°C (59-86°F) | PRECOSE/25 |
| 50 mg | 100 | 00026-2861-51 | PRECOSE/50 | ||||
| 100 UNIT DOSE BLPK | 00026-2861-48 | ||||||
| 100 mg | 100 | 00026-2862-51 | PRECOSE/100 |
- Manufacturers/Distributors
- Inactive ingredients
colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, starch
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Pharmacogenomic information
Acarbose Pharmacogenomic Information
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Patient Information
- Take acarbose with the first bite of each meal.
- Monitor blood glucose on a regular basis.
- The most common side effects are flatulence, abdominal discomfort and diarrhea.
- These side effects will subside with continued use. (Report to your physician if they become bothersome)
- Report to your physician is you break out in a rash, have trouble breathing, notice yellowing of the eyes and/or skin or experience weight loss.(These are rare, but serious side effects)
- Watch for signs and symptoms of hypoglycemia when acarbose is combined with other diabetic medications.
- Avoid alcohol.
- Follow a diabetic-diet
- Discuss with physician is you are pregnant, plan to become pregnant or are breast-feeding.
- Diet and exercise are non-pharmacological ways to control blood sugar
- Ask your prescriber or pharmacist before you start any new prescription, herbal or over-the counter medication, or before you take any medications for cough, cold or allergies.
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References
- ↑ 1.0 1.1 AHFS Drug Information Handbook 2004
- ↑ 2.0 2.1 2.2 2.3 2.4 Wells, Dipiro, Schwinghammer, et al. Pharmacotherapy Handbook Fifth Edition. Pages 170-183.
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 3.18 3.19 3.20 3.21 3.22 3.23 3.24 3.25 3.26 3.27 3.28 3.29 3.30 3.31 3.32 3.33 3.34 3.35 3.36 3.37 3.38 3.39 3.40 3.41 3.42 3.43 3.44 3.45 3.46 3.47 3.48 3.49 3.50 3.51 3.52 3.53 3.54 3.55 3.56 3.57 3.58 3.59 3.60 3.61 3.62 3.63 3.64 3.65 Precose® (acarbose) package insert. West Haven, CT: Bayer Pharmaceuticals Corporation; 2003 Aug.
- ↑ Pandit MK, Burke J, Gustafson AB, et al. Drug-induced disorders of glucose tolerance. Ann Intern Med 1993;118:529—39. ↑ Jaakkola T, Laitila J, Neuvonen PJ, et al. Pioglitazone is metabolised by CYP2C8 and CYP3A4 in vitro: potential for interactions with CYP2C8 inhibitors. Basic Clin Pharmacol Toxicol 2006;99:44—51.
- ↑ IPLEX™ (mecasermin rinfabate) package insert. Glen Allen, VA: Insmed Incorporated; 2005 Dec.
- ↑ Gilbert RE, Cooper ME, Krum H. Drug Administration in Patients with Diabetes Mellitus, Safety Considerations. Drug Safety 1998;18:441—55.
- ↑ Niaspan® (niacin extended-release tablets) Miami, FL: Kos Pharmaceuticals, Inc; 2003 July.
- ↑ Dyrenium(R) (triamterene) package insert. Neptune, NJ: Wellspring Pharmaceuticals; 2001 Jun.
- ↑ Luntz GRWN, Smith SG. Effect of isoniazid on carbohydrate metabolism in controls and diabetics. BMJ 1953;1:296—9.
- ↑ Lindenmayer JP, Czobor P, Volavka J, et al. Changes in glucose and cholesterol levels in patients with schizophrenia treated with typical or atypical antipsychotics. Am J Psych 2003;160:290—96.
- ↑ Cryer PE, Davis SN, Shamoon H. Hypoglycemia in diabetes. Diabetes Care 2003;26:1902—12.
- ↑ 12.0 12.1 Kelley DE, Bidot P, Freedman Z, et al. Efficacy and safety of acarbose in insulin-treated patients with type 2 diabetes. Diabetes Care 1998;21(12):2056-61
- ↑ 13.0 13.1 13.2 13.3 13.4 13.5 Lexi-Comp (2003). Drug Information Handbook. 11th Edition., APhA.
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PUBMED References
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Efficacy/Safety Trial Articles
- Chiasson JL, Josse RG, Hunt JA, et al. (1994). "The efficacy of acarbose in the treatment of patients with non-insulin-dependent diabetes mellitus. A multicenter controlled clinical trial." Ann Intern Med 121(12):928-35
- Lam KS, Tiu SC, Tsang MW, et al. (1998) "Acarbose in NIDDM patients with poor control on conventional oral agents. A 24-week placebo-controlled study" Diabetes Care 21(7):1154-8
- Coniff RF, Shapiro JA, Robbins D, et al. (1995). "Reduction of glycosylated hemoglobin and postprandial hyperglycemia by acarbose in patients with NIDDM. A placebo-controlled dose-comparison study" Diabetes Care 18(6):817-24
- Coniff RF, Shapiro JA, Seaton TB, et al. (1995). "A double-blind placebo-controlled trial evaluating the safety and efficacy of acarbose for the treatment of patients with insulin-requiring type II diabetes" Diabetes Care 18(7):928-32
- Kelley DE, Bidot P, Freedman Z, et al. (1998). "Efficacy and safety of acarbose in insulin-treated patients with type 2 diabetes." Diabetes Care 21(12):2056-61
- Mertes G. (2001). "Safety and efficacy of acarbose in the treatment of Type 2 diabetes: data from a 5-year surveillance study." Diabetes Res Clin Pract.52(3):193-204
- Scheen AJ. (1998) "Clinical efficacy of acarbose in diabetes mellitus: a critical review of controlled trials." Diabetes Metab. 24(4):311-20
- Hanefeld M, Cagatay M, Petrowitsch T, (2004). "Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies." Eur Heart J. 25(1):10-6 Free Full Text Here
- Martin AE, Montgomery PA. (1996). "Acarbose: an alpha-glucosidase inhibitor." Am J Health Syst Pharm. 53(19):2277-90
- Campbell LK, White JR, Campbell RK. (1996). "Acarbose: its role in the treatment of diabetes mellitus." Ann Pharmacother. 30(11):1255-62
- Acarbose_for_prevention_of_type_2_diabetes_mellitus:_the_STOP-NIDDM_trial
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Therapeutic Class Comparison Trial Articles
- Madar Z. (1989). "The effect of acarbose and miglitol (BAY-M-1099) on postprandial glucose levels following ingestion of various sources of starch by nondiabetic and streptozotocin-induced diabetic rats." J Nutr. 119(12):2023-9
- Joubert PH, Venter HL, Foukaridis GN. (1990). "The effect of miglitol and acarbose after an oral glucose load: a novel hypoglycaemic mechanism?" Br J Clin Pharmacol. 30(3):391-6
- Van de Laar FA, Lucassen PL, Akkermans RP, et al. (2005). "Alpha-glucosidase inhibitors for type 2 diabetes mellitus." Cochrane Database Syst Rev. Apr 18;(2):CD003639
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Pharmacokinetics Articles
- Ahr HJ, Boberg M, Krause HP, et al. (1989). "Pharmacokinetics of acarbose. Part I: Absorption, concentration in plasma, metabolism and excretion after single administration of 14C acarbose to rats, dogs and man." Arzneimittelforschung. 39(10):1254-60
- Ahr HJ, Krause HP, Siefert HM, et al. (1989). "Pharmacokinetics of acarbose. Part II: Distribution to and elimination from tissues and organs following single or repeated administration of 14C acarbose to rats and dogs." Arzneimittelforschung. 39(10):1261-7
- Clissold SP, Edwards C. (1988). "Acarbose. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential." Drugs. 35(3):214-43
- Salvatore T, Giugliano D. (1996). "Pharmacokinetic-pharmacodynamic relationships of Acarbose." Clin Pharmacokinet. 30(2):94-106
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Drug Interaction Articles
- Ben-Ami H, Krivoy N, Nagachandran P, et al. (1999). "An interaction between digoxin and acarbose." Diabetes Care. 22(5):860-1
- AP Morreale and K Janetzky (1997). "Probable interaction of warfarin and acarbose" Am J Health Syst Pharm. 54: 1551-1552
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Images
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External Links
- Manufacturers/Distributors
- Clinical Treatment Guidelines
- Diabetes Mellitus: Institute for Clinical Systems Improvement (ICSI)Guidelines.
- Diabetic Associations
- Patient Information Pages
- Managing your Diabetes;
- Accu-chek Glucose Meter;
- BD Diabetes Glucose Record Sheets
- Glucose Control-Diabetic Diet
- Bayer Diabetes
- Healthcare Professional Information Pages
- Other Resources
- Pill Identifier
