Acarbose dosing

Gastrointestinal In a prospective, randomised, open-label study with diabetic patients (n = 60) treated with human insulin plus acarbose, the most frequent adverse effect was abdominal distension (n = 22,36%). These adverse effects were acarbose-dose-related from acarbose 50 mg once daily to 50 mg three times daily. [18 ]... 

Acarbose (Precose) and miglitol (Glyset) are dosed similarly. Therapy is initiated with a very low dose (25 mg with one meal a day) and increased very gradually (over several months) to a maximum of 50 mg three times daily for patients weighing 60 kg or more, or 100 mg three times daily for patients above 60 kg. The drugs should be taken with the first bite of the meal so that the drug is present to inhibit enzyme activity. 

Dosage of acarbose must be individualized while not exceeding the maximum recommended dose of 100 mg 3 times/day for patients more than 60 kg and 50 mg 3 times/day for patients less than 60 kg. 

During treatment initiation and dose titration, use 1 hour postprandial plasma glucose to determine the therapeutic response to acarbose and identify the minimum effective dose for the patient. Thereafter, measure glycosylated hemoglobin at intervals of about 3 months. 

Metabolism - Acarbose is metabolized exclusively within the Gl tract, principally by intestinal bacteria, but also by digestive enzymes. A fraction of these metabolites (about 34% of the dose) was absorbed and subsequently excreted in the urine. 

Excretion - The fraction of acarbose that is absorbed as intact drug is almost completely excreted by the kidneys. When acarbose was given IV, 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 (ie, parent compound and active metabolite) drug. The plasma elimination half-life of acarbose activity is about 2 hours in healthy volunteers. 

In a post-marketing surveillance study in 27 803 patients with diabetes mellitus (94% type 2), data were reported after 12 weeks. The doses of acarbose were low 4.1% took less than 100 mg/day, 64% 100-250 mg/day, 32% 250-300 mg/day, and 0.1% more than 300 mg/day. Only 2.1% stopped therapy, mainly because of gastrointestinal adverse events. Tolerability appeared to be good and independent of age. Abnormal liver function was reported in 0.01%. The difference between these results and those of many controlled trials may in part be explained by the fact that higher doses have been used in most trials (14). 

In a multicenter, double-blind, placebo-controlled study, 81 patients, in whom treatment with metformin was inadequate, received extra acarbose or placebo during 24 weeks after a 4-week run-in period to establish the optimal dose of acarbose (28). HbAic was reduced by 1.02% and fasting blood glucose by 1.13 mmol/1. Gastrointestinal adverse effects were more common in the acarbose group. 

The author of a review of the use of acarbose concluded that acarbose is safe in both monotherapy and combination therapy (44). The most common adverse effects are mild to moderate gastrointestinal symptoms, such as flatulence, meteorism, diarrhea, soft stools, abdominal discomfort, and pain. As glucose oxidase increases in the small intestine during therapy, it is advisable to start with a low dose so that the gut can adapt to acarbose. 

In a 78-week double-blind single center study 139 patients with type 2 diabetes were randomized to acarbose or placebo in addition to their usual therapy (63). The mean dose of acarbose at the end of the study was 680 mg. Two patients taking 600 mg or more developed raised liver enzymes, to more than three times the upper limit of normal. 

In a 56-week study there was an association between the dose of acarbose in the range 50-300 mg tds and the development of abnormal liver function in 359 patients with type 1 (21%) and type 2 diabetes (38). The patients took the maximum tolerated dose, and 30% took doses of 100 mg or less. Of the patents who were randomized to acarbose (n = 240), 8% developed abnormal liver function tests (alanine transaminase activity more than three times the upper limit of normal) compared with 1% of those who took placebo (n — 119). The dose of acarbose was 200-300 mg tds in those who developed abnormal liver function. Liver function recovered promptly on withdrawal. 

In a randomized, crossover study in healthy men, acarbose 100-200 mg reduced the AUC and Cmax of digoxin and prolonged its tmax, consistent with reduced absorption (73). However, in another study acarbose 50 mg tds for 12 days had no significant effect on the pharmacokinetics of a single oral dose of digoxin 0.75 mg (74). 

Cohen E, Almog S, Staruvin D, Garty M. Do therapeutic doses of acarbose alter the pharmacokinetics of digoxin Isr Med Assoc J 2002 4(10) 772-5. 

The different mechanisms of action of the various classes of hypoglycemic drugs makes combined therapy feasible the sulfonylureas and meglitinides stimulate insulin production by different mechanisms, the biguanides reduce glucose production by the liver and excretion from the liver, acarbose reduces the absorption of glucose from the gut, and the thiazolidinediones reduce insulin resistance in fat. It is not necessary to wait until the maximal dose of... 

ACARBOSE ANTIPLATELET AGENTS -ASPIRIN Risk of hypoglycaemia when high-dose aspirin (3.5-7.5 g/day) given with antidiabetic drugs Additive effect aspirin has a hypoglycaemic effect Avoid high-dose aspirin... 

ACARBOSE MUSCLE RELAXANTS -BACLOFEN 1 hypoglycaemic effect Due to these drugs causing hyperglycaemia, the mechanism being uncertain at present t doses of antidiabetic drugs are often required for adequate glycaemic control... 

Acarhose or Miglitol and Food. Some medications should be administered with food for optimum benefit. Acarbose (Precose) and miglitol (Glyset) are effective in the treatment of diabetes mellitus because they delay the digestion of ingested carbohydrates and reduce the elevation of blood glucose concentrations following meals. Maximum effectiveness is attained when doses are administered at the start (with the first bite) of each main meal. 

However, in a formal study of the pharmacokinetics of a single dose of digoxin 0.75 mg before and after the administration of acarbose 50 mg tds for 12 days in healthy volunteers, apart from a small increase in Cmax, the pharmacokinetics of digoxin were unaffected by acarbose (219). It is not uncommon for anecdotal reports of a possible interaction to be unconfirmed by formal kinetic studies, and it is possible in such cases that there is a subset of patients who are susceptible to the interaction who have not been included in the formal study. In this case, for example, it may be that the interaction occurs in people with diabetes and not in healthy subjects. There may also be a difference in the effect of acarbose on a single dose of digoxin, compared with steady-state therapy. Advice that acarbose and digoxin should be administered 6 hours apart is still reasonable. 

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