Glucobay is recommended for the treatment of noninsulin dependent (NIDDM) diabetes mellitus in patients inadequately controlled on diet alone, or on diet and oral  hypoglycemic agents.

Posology

The dosage must be adjusted in each individual case by the treating physician, because there are individual differences in efficacy and tolerability. Treatment can be commenced with:

1 Glucobay 50 mg tablet, 3 x daily
or       ½ Glucobay 100 mg tablet, 3 x daily
          (equivalent to 150 mg acarbose/day).

To reduce gastrointestinal undesirable effects, it has proven beneficial in some patients to start treatment with Glucobay gradually, with:

1 Glucobay 50 mg tablet, 1 to 2 x daily
(equivalent to 50‑100 mg acarbose/day).

Depending on blood sugar levels, the dose can then be increased gradually and also, if therapeutic efficacy is insufficient, during the subsequent course of treatment, up to:

1 Glucobay 100 mg tablet, 3 x daily
(equivalent to 300 mg acarbose/day).

The average dosage is 150 to 300 mg acarbose per day, depending on the individual requirements.

A further dose increase to:

2 Glucobay 100 mg tablets, 3 x daily
(equivalent to 600 mg acarbose/day)

may be required in exceptional cases (see also section 4.8).

If, despite strict adherence to diet, troublesome symptoms occur, the dose should be increased no further; if necessary, it should be slightly reduced.

The dosage increase can take place at intervals of 4 to 8 weeks and at the inadequate response of the patients in the later course of treatment.

Elderly patients:

No modification of the normal adult dosage regimen is necessary.

Children and adolescents under 18 years:

The efficacy and safety of Glucobay in children and adolescents have not been established.

Glucobay is not recommended for patients under the age of 18 years.

Method of administration

The optimal effect of Glucobay tablets is achieved when taken whole with some liquid immediately before a meal, or with the first mouthful of a meal.

▫ Hypersensitivity to the active substance or to any of the excipients stated in section 6.1. ▫ Chronic inflammatory bowel disease associated with pronounced digestive and absorption disorders. ▫ Colonic ulceration (ulcers of the large intestine), with partial bowel obstruction or in patients predisposed to bowel obstruction. ▫ Conditions that can deteriorate due to increased gas formation in the intestine (e.g. Roemheld syndrome, larger hernias, strictures and ulcers of the bowel). ▫ Glucobay must not be used in cases of severe renal insufficiency with a creatinine clearance of less than 25 mL/min. ▫ Severe hepatic dysfunction (e.g. liver cirrhosis).

Cases of fulminant hepatitis have been reported in patients treated with Glucobay. Although the mechanism is not known, it is assumed that Glucobay contributes to a multifactorial pathophysiology of liver injury. If liver enzyme elevations are observed, it may be necessary to reduce the dosage or discontinue therapy, particularly if the elevations persist.

Therefore, regular monitoring of liver enzyme levels should be considered in the first 6 to 12 months of treatment (see section 4.8).

Other precautions

▫       Of course, strict adherence to a diabetic diet is essential even whilst taking Glucobay.

▫       Regular ingestion of Glucobay should not be discontinued without the knowledge of the physician, as a rise in blood sugar may occur.

▫       Glucobay has a blood glucose-lowering effect, but does not cause hypoglycaemia in patients treated only with diet.

▫       If Glucobay is prescribed concomitantly with other blood glucose-lowering agents (e.g. sulfonylureas, metformin or insulin), the dose of the concomitant medication has to be adjusted if blood glucose levels fall within the hypoglycaemic range.

▫       If hypoglycaemic manifestations should occur during Glucobay treatment, due to the lower insulin requirement in patients treated with insulin or sulphonylurea/metformin, glucose (not table sugar [sucrose]) must be taken (see also section 4.5 ).

▫       Treatment with Glucobay should be recorded on diabetes ID cards.

Table sugar (sucrose) and foodstuffs containing sucrose

Table sugar (sucrose) and foodstuffs containing sucrose can readily lead to intestinal complaints and diarrhoea as a result of increased carbohydrate fermentation in the colon during Glucobay treatment (see section 4.8 ).

Sulphonylurea/metformin preparations or insulin

Glucobay has an antihyperglycaemic effect and causes no hypoglycaemia per se. If Glucobay is prescribed in addition to sulphonylurea/metformin preparations or insulin, the dose of sulphonylurea/metformin or insulin must be reduced accordingly if blood sugar levels fall within the hypoglycaemic range. In individual cases, hypoglycaemic shock may occur. If acute hypoglycaemic episodes occur, it should be remembered that table sugar (sucrose) is cleaved into fructose and glucose more slowly during Glucobay treatment; it is therefore unsuitable for rapid correction of hypoglycaemia. Instead of table sugar (sucrose), glucose should therefore be used.

Digoxin

In individual cases, acarbose may affect the bioavailability of digoxin, so that a digoxin dose adjustment may be required.

Cholestyramine, intestinal adsorbents and digestive enzyme preparations

Due to possible attenuation of the acarbose effect, concomitant use of these preparations with Glucobay should be avoided.

Neomycin

Concomitant oral administration of neomycin and Glucobay may lead to a marked reduction of postprandial blood sugar and an increase in the frequency and severity of gastrointestinal undesirable effects. If the symptoms are very severe, a temporary reduction in the Glucobay dose may be considered.

Pregnancy

There are no available data on the use of Glucobay during pregnancy.

For this reason, Glucobay should not be used during pregnancy.

 

Lactation

Small amounts of acarbose pass into the milk of lactating rats. There are no available data for humans. As a pharmacological effect of acarbose in human milk cannot be excluded in the infant, it is recommended, not to use acarbose during the breast-feeding period.

 

Fertility

Animal studies have shown no direct or indirect harmful effects with respect to reproductive toxicity (see section 5.5). No fertility disorders have been observed in animals.

Monotherapy with Glucobay does not lead to hypoglycaemia and therefore has no or negligible influence on the ability to drive and use machines. However, patients should be informed that there is a risk of hypoglycaemia on combination of acarbose and antidiabetic agents (metformin, sulfonylureas, insulin).

The following categories are used for expressing the frequency of undesirable effects:

Very common (≥ 1/10)

Common (≥ 1/100, < 1/10)

Uncommon (≥ 1/1,000, < 1/100)

Rare (≥ 1/10,000, < 1/1,000)

Very rare (< 1/10,000)

Not known (cannot be estimated from the available data)

Within each frequency group, undesirable effects are listed in order of decreasing seriousness.

The following table lists the undesirable effects from placebo-controlled clinical studies with acarbose. The undesirable effects are categorised according to CIOMS III frequency classes (patient numbers in placebo-controlled studies in the clinical trial database: acarbose: n=8,595, placebo: n=7,228; as of 10^th February 2006).

The undesirable effects from post-marketing surveillance reports (as of 31^st December 2005) for which no frequency could be estimated are listed under “Not known”.

 

System organ class	Very common	Common	Uncommon	Rare	Not known
Blood and lymphatic system disorders					Thrombocytopenia
Immune system disorders					Hypersensitivity reactions (rash, erythema, exanthem, urticaria)
Vascular disorders				Oedema
Gastrointestinal disorders	Flatulence	Diarrhoea Gastrointestinal and abdominal pain	Nausea Vomiting Indigestion		Subileus/ileus Pneumatosis cystoides intestinalis
Hepatobiliary disorders			Liver enzyme elevations	Jaundice	Hepatitis
Skin and subcutaneous tissue disorders					Acute generalised exanthematous pustulosis

 

There have been post-marketing reports of hepatic disease, abnormal liver function and liver injury.

Especially in Japan, individual cases of fulminant hepatitis with a fatal outcome have been observed.

Particularly in the case of non-compliance with the prescribed diabetic diet, intestinal undesirable effects may be enhanced. If painful symptoms develop despite strict compliance with the prescribed diet, the physician must be consulted and the dose reduced temporarily or permanently.

The gastrointestinal symptoms may be serious and pronounced. In these cases, a decision must be made whether to continue therapy with Glucobay 50 mg/100 mg.

In patients receiving the recommended dose of 150 to 300 mg acarbose daily, abnormal clinically relevant liver function tests (3 times above the upper limit of normal) have been observed in rare cases. The abnormal values may also be of a temporary nature during prolonged acarbose therapy (see section 4.4 ).

 

Reporting of suspected undesirable effects

Reporting suspected undesirable effects after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

 

To report any side effect(s):

National Pharmacovigilance and Drug Safety Center (NPC).

Fax: + 966 - 11 - 205 - 7662.

Call NPC at +966 - 11 - 2038222,

Ext.: 2317 - 2356 - 2353 - 2354 - 2334 - 2340.

Toll - free: 8002490000.

E - mail: npc.drug@sfda.gov.sa.

Website: www.sfda.gov.sa/npc

As a result of an overdose, meteorism, flatulence and diarrhoea may occur in cases where Glucobay is taken with beverages and/or meals containing carbohydrates (poly-, oligo-, disaccharides). In the event that an overdose of Glucobay is taken without any food ingestion, excessive intestinal symptoms are not to be expected.

In the event of an overdose, ingestion of beverages and/or meals containing carbohydrates (poly-, oligo-, disaccharides) should be avoided for the next 4‑6 hours

Pharmacotherapeutic group: Oral antidiabetic agent from the class of alpha-glucosidase inhibitors, ATC code: A10BF01.

In all of the species studied, acarbose exerts its effect in the intestinal tract. The effect of acarbose is due to inhibition of those intestinal enzymes (α-glucosidase) that are involved in the degradation of di-, oligo- and polysaccharides. This leads to a dose-dependent delay in the digestion of these carbohydrates. As a result, glucose derived from carbohydrates in particular is released more slowly and absorbed more slowly into the blood. In this way, acarbose reduces the blood sugar level after meals. This relieves stress on beta cells; compensatory postprandial hyperinsulinaemia is avoided.

For acarbose, the degree of efficacy is determined by the time of ingestion: the peak effect is reached when ingested with the first mouthful of a main meal; the effect of acarbose is already significantly reduced when taken approximately 30 minutes before the start of the meal. However, there is barely any interference with the effect of acarbose when taken 15 minutes after the start of the meal.

Even with long-term use, the effect of acarbose does not diminish: the enzymes in the small intestine lose none of their activity; the ability to be inhibited by acarbose is maintained.

Acarbose treatment does not lead to an increase in body weight. Improved insulin sensitivity has been observed in patients with manifest diabetes. During treatment with acarbose, the fasting blood glucose and glycosylated haemoglobin (HbA1c) values significantly decrease.

In a meta-analysis of 7 double-blind, placebo-controlled studies with 2,180 type 2 diabetics and a study duration of at least 52 weeks, there was a significant decrease in the risk of cardiovascular events, especially myocardial infarction, on acarbose.

The pharmacokinetics of Glucobay was investigated after oral administration of the labelled substance (200 mg) in trial subjects.

Absorption

As, on average, 35% of total radioactivity (sum of inhibitory active substance and possible degradation products) was excreted renally within 96 hours, an activity absorption rate can at least within this range be assumed.

The concentration profile of total radioactivity in plasma was comprised of two peaks. The first peak, with a mean acarbose-equivalent concentration of 52.2 ± 15.7 µg/L after 1.1 ± 0.3 h, correlates with the corresponding data for the concentration profile of the inhibitory active substance (49.5 ± 26.9 µg/L after 2.1 ± 1.6 h). The second peak averages 586.3 ± 282.7 µg/L and is reached after 20.7 ± 5.2 h. In contrast to the total radioactivity, peak plasma concentrations of the inhibitory active substance are lower by a factor of 10‑20. The second, higher peak, after about 14 to 24 hours, is probably due to the absorption of bacterial degradation products from deeper sections of the intestine.

Distribution

From the concentration profile in plasma, it was possible to calculate a relative volume of distribution of 0.32 L/kg BW in healthy subjects (intravenous administration, 0.4 mg/kg BW).

Elimination

Elimination half-lives of the inhibitory active substance from plasma are 3.7 ± 2.7 h for the distribution phase and 9.6 ± 4.4 h for the elimination phase.

The proportion of active inhibitory substance excreted with the urine was 1.7% of the administered dose. 51% of the activity was eliminated within 96 hours with the faeces.

Bioavailability

Bioavailability is 1‑2%. This extremely small, systemically available proportion of inhibitory active substance is desirable and without relevance for the therapeutic effect.

Based on conventional studies on safety pharmacology, repeated dose toxicity, genotoxicity, reproductive and development toxicity as well as on the carcinogenic potential, the preclinical data do not indicate any special risks for humans that are not in agreement with those already described in other sections of this Summary of Product Characteristics.

A clearly reduced weight gain in rats and dogs after repeated administration of acarbose has been regarded as pharmacodynamic effect (carbohydrate loss) and could be counteracted by an increased food intake and glucose supplementation.

Studies on carcinogenicity have been performed in Sprague-Dawley rats, Wistar rats and hamsters. An increased tumour incidence in certain tissues (kidney, testis) was observed, if the malnutrition caused by acarbose was not corrected. No increase in tumour rate was observed if the weight gain was kept normal by food or glucose supplementation.

Microcrystalline cellulose, magnesium stearate (Ph. Eur), corn starch, colloidal anhydrous silica.

Not applicable.

3 years

Store below 30°C.

At higher temperatures and/or higher relative ambient humidity, discoloration may occur in tablets outside the pack. Tablets should therefore not be removed from the blister pack until immediately prior to use.

Carton with polypropylene (colourless) and aluminium blisters.

Glucobay 50 mg:

30 tablets;

105 tablets;
Hospital packs for hospital supply: 240 tablets

Glucobay 100 mg:

30 tablets;

105 tablets
Hospital packs for hospital supply: 200 tablets

No special requirements.