a-glucosidase inhibitors (alpha- glucosidase inhibitors).

Acarbose

Glucobay 100 Glucobay 50

Tablet for oral administration. White to yellow-tinged oval oblong, convex tablet with 'G score 100' 'G score 50' on one side and a score on the other.

Indications Glucobay is recommended for the treatment of non-insulin dependent (NIDDM) diabetes mellitus in patients inadequately controlled on diet alone, or on diet and oral hypoglycaemic agents. Mode of action Glucobay is a competitive inhibitor of intestinal alpha-glucosidases with maximum specific inhibitory activity against sucrase.

Under the influence of Glucobay, the digestion of starch and sucrose into absorbable monosaccharides in the small intestine is dose-dependently delayed. In diabetic subjects, this results in a lowering of postprandial hyperglycaemia and a smoothing effect on fluctuations in the daily blood glucose profile. In contrast to sulphonylureas Glucobay has no stimulatory action on the pancreas. Treatment with Glucobay also results in a reduction of fasting blood glucose and to modest changes in levels of glycated haemoglobin (HbA1, HbA1c).

The changes may be a reduction or reduced deterioration in HbA1 or HbA1c levels, depending upon the patient's clinical status and disease progression. These parameters are affected in a dose-dependent manner by Glucobay. Following oral administration, only 1-2% of the active inhibitor is absorbed.

Glucobay tablets are taken orally and should be chewed with the first mouthful of food, or swallowed whole with a little liquid directly before the meal. Owing to the great individual variation of glucosidase activity in the intestinal mucosa, there is no fixed dosage regimen, and patients should be treated according to clinical response and tolerance of intestinal side-effects.

Adults

The recommended initial dose is 50mg three times a day. However, some patients may benefit from more gradual initial dose titration to minimise gastrointestinal side-effects. This may be achieved by initiating treatment at 50mg once or twice a day, with subsequent titration to a three times a day regimen.

If after six to eight weeks' treatment patients show an inadequate clinical response, the dosage may be increased to 100mg three times a day. A further increase in dosage to a maximum of 200mg three times a day may occasionally be necessary.

Glucobay is intended for continuous long-term treatment.

Children and adolescents under 18 years

The efficacy and safety of acarbose in children and adolescents have not been established. Acarbose is not recommended for patients under the age of 18 years.

No modification of the normal adult dosage regimen is necessary.

Hypersensitivity to acarbose or any of the excipients, pregnancy and in nursing mothers. Glucobay is also contra-indicated in patients with inflammatory bowel disease, colonic ulceration, partial intestinal obstruction or in patients predisposed to intestinal obstruction. In addition, Glucobay should not be used in patients who have chronic intestinal diseases associated with marked disorders of digestion or absorption and in patients who suffer from states which may deteriorate as a result of increased gas formation in the intestine, e.g. larger hernias.

Glucobay is contra-indicated in patients with hepatic impairment.

As Glucobay has not been studied in patients with severe renal impairment, it should not be used in patients with a creatinine clearance < 25 ml/min/1.73m².

Hypoglycaemia: When administered alone, Glucobay does not cause hypoglycaemia. It may, however, act to potentiate the hypoglycaemic effects of insulin and sulphonylurea drugs, and the dosages of these agents may need to be modified accordingly. In individual cases hypoglycaemic shock may occur (i.e. clinical sequelae of glucose levels < 1 mmol/L such as altered conscious levels, confusion or convulsions).

Episodes of hypoglycaemia occurring during therapy must, where appropriate, be treated by the administration of glucose, not sucrose. This is because acarbose will delay the digestion and absorption of disaccharides, but not monosaccharides.

Transaminases: Patients treated with acarbose may, on rare occasions, experience an idiosyncratic response with either symptomatic or asymptomatic hepatic dysfunction. In the majority of cases this dysfunction is reversible on discontinuation of acarbose therapy. It is recommended that liver enzyme monitoring is considered during the first six to twelve months of treatment. If elevated transaminases are observed, withdrawal of therapy may be warranted, particularly if the elevations persist. In such circumstances, patients should be monitored at weekly intervals until normal values are established.

The administration of antacid preparations containing magnesium and aluminium salts, e.g. hydrotalcite, has been shown not to ameliorate the acute gastrointestinal symptoms of Glucobay in higher dosage and should, therefore, not be recommended to patients for this purpose.

Intestinal adsorbents (e.g. charcoal) and digestive enzyme preparations containing carbohydrate splitting enzymes (e.g. amylase, pancreatin) may reduce the effect of Glucobay and should not therefore be taken concomitantly.

The concomitant administration of neomycin may lead to enhanced reductions of postprandial blood glucose and to an increase in the frequency and severity of gastro-intestinal side-effects. If the symptoms are severe, a temporary dose reduction of Glucobay may be warranted.

The concomitant administration of colestyramine may enhance the effects of Glucobay, particularly with respect to reducing postprandial insulin levels. Simultaneous administration of Glucobay and colestyramine should, therefore, be avoided. In the rare circumstance that both Glucobay and colestyramine therapy are withdrawn simultaneously, care is needed as a rebound phenomenon has been observed with respect to insulin levels in non-diabetic subjects.

In individual cases Glucobay may affect digoxin bioavailability, which may require dose adjustment of digoxin. Monitoring of serum digoxin levels should be considered.

In a pilot study to investigate a possible interaction between Glucobay and nifedipine, no significant or reproducible changes were observed in the plasma nifedipine profiles.

Adverse drug reactions (ADRs) based on placebo-controlled studies with acarbose sorted by CIOMS III categories of frequency (placebo-controlled studies in clinical trial database: acarbose N = 8,595; placebo N = 7,278; status: 10 Feb 2006) are listed below.

ADRs derived from post marketing reports (status: 31 Dec 2005) are printed in bold italic.

Individual cases of fulminant hepatitis with fatal outcome have been reported in Japan. The relationship to acarbose is unclear.

If the prescribed diabetic diet is not observed the intestinal side effects may be intensified.

If strongly distressing symptoms develop in spite of adherence to the diabetic diet prescribed, the doctor must be consulted and the dose temporarily or permanently reduced.

In patients receiving the recommended daily dose of 150 to 300 mg Glucobay, clinically relevant abnormal liver function tests (three times above upper limit of normal range) were rarely observed. Abnormal values may be transient under ongoing Glucobay therapy.

Bayer

(POM)

26 June 2009