ACARBOSE

Posology Adults 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.

The recommended initial dose is 50 mg 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 50 mg 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 100 mg three times a day. A further increase in dosage to a maximum of 200 mg three times a day may occasionally be necessary.

Patients receiving the maximum dose require careful monitoring. If distressing complaints develop in spite of strict adherence to the diet, the dose should not be increased further, and if necessary should be reduced according to the severity of the side- effects and the clinical judgment of the prescriber.

The average dose is 300 mg Acarbose/day (corresponding to 3 x 2 tablets of 50 mg Acarbose/day, or 3 x 1 tablet of 100 mg Acarbose/day). Acarbose is intended for continuous long-term treatment. Elderly patients No modification of the normal adult dosage regimen is necessary.

4). Paediatric population The safety and efficacy of acarbose in children and adolescents under 18 years of age have not yet been established. Acarbose is not recommended for patients under the age of 18 years. Method of administration Acarbose 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.

The frequencies of adverse drug reactions (ADRs) reported with acarbose, based on placebo- controlled studies (acarbose N = 8,595; placebo N = 7,278), are summarised in the table below. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Frequencies are defined as Very common (≥ 1/10), Common (≥ 1/100 to < 1/10), Uncommon (≥ 1/1,000 to < 1/100) Rare (≥ 1/10,000 to < 1/1,000), and Not known (cannot be estimated from the available data). The ADRs identified only during postmarketing surveillance and for which a frequency could not be estimated, are listed under “Not known”.

System Organ Class (MedDRA) Very common Common Uncommon Rare Not known Blood and lymphatic system disorders Thrombocytopeni a Immune system disorders Drug hypersensitivity and hypersensitivity (rash, erythema, exanthema, urticaria) Vascular disorders Oedema Gastrointestina l disorders Flatulenc e Diarrhoea Gastrointestina l and abdominal pains Nausea Vomiting Dyspepsia Subileus/Ileus Pneumatosis cystoides intestinalis Hepatobiliary disorders Increase in transaminase s Jaundic e Hepatitis Skin and subcutaneous tissue disorders Acute generalised exanthematous pustulosis In postmarketing, cases of liver disorder, abnormal hepatic function and liver injury have been reported.

Individual cases of fulminant hepatitis with a fatal outcome have been reported, particularly in Japan. In patients treated with the recommended daily dose of 150 mg to 300 mg acarbose a day, clinically relevant abnormal liver function tests (three times above upper limit of normal range) were rarely observed.

4). 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.

Hypoglycaemia Acarbose has an antihyperglycaemic effect, but does not itself induce hypoglycaemia. g. sulfonylureas, metformin, or insulin) a fall of the blood glucose values into the hypoglycaemic range may require a dose adaption of the respective co-medication.

5). 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 Cases of fulminant hepatitis have been reported during acarbose therapy. The mechanism is unknown, but acarbose may contribute to a multifactorial pathophysiology of liver injury. 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. 8). If elevations of liver enzymes are observed, a reduction in dosage or withdrawal of therapy may be indicated, particularly if the elevations persist.

In such circumstances, patients should be monitored at weekly intervals until normal values are established. Paediatric population The safety and efficacy of acarbose has not been established in patients under 18 years of age.

1. • Inflammatory bowel disease, colonic ulceration, partial intestinal obstruction or predisposition to intestinal obstruction. g. larger hernias. 73m2) as acarbose has not been studied in patients with severe renal impairment. g. liver cirrhosis).

• Pregnancy and in nursing mothers.