Document: spc-doc_PL 20117-0178 change

• spc-doc_PL 20117-0178
• spc-doc_PL 25258-0091

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SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Acarbose 50 mg Tablets.

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 50 mg acarbose.

For the full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Tablet.

White, plane, round tablets, scored on one side.

The scoreline is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Acarbose is recommended for the treatment of type II diabetes mellitus in patients inadequately controlled on diet alone, or on diet and oral hypoglycaemic agents.

4.2 Posology and method of administration

Posology

Adults

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 (see Special warnings and precautions for use, Section 4.4).

Acarbose is intended for continuous long-term treatment.

Elderly

No modification of the normal adult dosage regimen is necessary.

Paediatric population

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.

Renal or hepatic impairment See section 4.3.

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. 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.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Inflammatory bowel disease, colonic ulceration, partial intestinal obstruction or predisposition to intestinal obstruction.

Severe kidney failure (creatinine clearance <25 ml/min)

Severe hepatic impairment (e.g. liver cirrhosis)

4.4 Special warnings and precautions for use

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

Liver enzyme monitoring should be considered during the first 6 to 12 months of treatment (see section 4.8).

The safety and efficacy of acarbose has not been established in patients under 18 years of age.

Acarbose has an antihyperglycaemic effect but does not itself induce hypoglycaemia.

If acarbose is prescribed in addition to other blood glucose lowering drugs (e.g. sulphonylureas, metformin, or insulin) a fall of the blood glucose values into the hypoglycaemic range may require a dose adaption of the respective co-medication. If acute hypoglycaemia develops glucose should be used for rapid correction of hypoglycaemia (see section 4.5).

4.5 Interaction with other medicinal products and other forms of interaction

During treatment with acarbose, sucrose (cane sugar) as well as foods containing sucrose, often cause abdominal discomfort or even diarrhoea as a result of the increased fermentation of carbohydrates in the colon.

Acarbose has an anti-hyperglycaemic effect but, by itself, does not cause hypoglycaemia. In patients treated simultaneously with acarbose and sulphonylurea, metformin or insulin, the glycaemia values may drop to hypoglycaemic levels and so dose adjustment of these medicinal products may be necessary.

Isolated reports of hypoglycaemic shock have been received.

In the event of acute hypoglycaemia, it should be considered that the biotransformation of sucrose into fructose and glucose is slower during treatment; for this reason, sucrose is not suitable for fast relief from hypoglycaemia and glucose should be used instead.In isolated cases Acarbose may affect the bioavailability of digoxin, making dose adjustment necessary. The simultaneous administration of colestyramine, intestinal adsorbents and medicinal products with digestive enzymes should be avoided as they may possibly influence the action of acarbose.

The concomitant administration of acarbose and oral 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 acarbose may be considered.

4.6 Fertility, pregnancy and lactation

Acarbose should not be administered during pregnancy as no information is available from clinical studies on its use in pregnant women.

After the administration of radioactively marked acarbose to nursing rats, a small amount of radioactivity was recovered in the milk. To date there have been no similar findings in humans.

Nevertheless, as the possibility of drug induced effects on nursing infants cannot be excluded, the prescription of acarbose is not recommended during breastfeeding

Effects on ability to drive and use machines

No data are available on alteration of the ability to drive vehicles or use machines while on treatment with acarbose.

4.8 Undesirable effects

The undesirable effects of acarbose found in the placebo controlled clinical trials and classified according to CIOMS III frequency categories (placebo controlled studies in the clinical trial database: acarbose N = 8595; placebo N = 7278; status: 10 February 2006) are described 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) and rare (> 1/10,000 to < 1/1,000).

The ADRs identified only during postmarketing surveillance (status: 31 Dec 2005), and for which a frequency could not be estimated, are listed under “not known”.

In postmarketing, cases of liver disorder, hepatic function abnormal, and liver injury have been reported. Individual cases of fulminant hepatitis with fatal outcome have also been reported, particularly from Japan.

The lack of compliance with the prescribed diet may give rise to intensification of intestinal side effects. In the event that they should appear in spite of complying with the prescribed diabetic diet, the doctor should be consulted and the dose reduced either temporarily or permanently.

In patients treated with the recommended daily dose of 150 mg to 300 mg acarbose a day, clinically relevant abnormal liver function tests (3 times above normal limits) were rarely observed. Abnormal values may be transient during treatment with acarbose (see section 4.4).Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

When Acarbose is taken in conjunction with beverages and/or meals containing carbohydrates (polysaccharides, oligosaccharides or disaccharides) overdose may causemeteorism, flatulence and diarrhoea. However, in the event that acarbose has been ingested in overdose outside meal times, no excessive intestinal symptoms should be expected.

In the event of overdose the intake of beverages or meals containing carbohydrates should be avoided over the next 4-6 hours.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Alpha glucosidase inhibitors, ATC code: A10B F01.

In all species tested, acarbose exerts its activity in the intestinal tract. The action of acarbose is based on the competitive inhibition of intestinal enzymes (a-glucosidases) involved in the degradation of disaccharides, oligosaccharides, and polysaccharides. This leads to a dose-dependent delay in the digestion of these carbohydrates. Glucose derived from these carbohydrates is released and taken up into the blood more slowly. In this way, acarbose reduces the postprandial rise in blood glucose, thus reducing blood glucose fluctuations.

5.2 Pharmacokinetic properties

Following administration, only 1-2% of the active inhibitor is absorbed.

The pharmacokinetics of Acarbose were investigated after oral administration of the ¹⁴C-labelled substance (200 mg) to healthy volunteers. On average, 35 % of the total radioactivity (sum of the inhibitory substance and any degradation products) was excreted by the kidneys within 96 h. The proportion of inhibitory substance excreted in the urine was 1.7 % of the administered dose. 50 % of the activity was eliminated within 96 hours in the faeces. The course of the total radioactivity concentration in plasma was comprised of two peaks. The first peak, with an average acarbose-equivalent concentration of

52.2 ± 15.7 pg/l after 1.1 ± 0.3 h, is in agreement with corresponding data for

the concentration course of the inhibitor substance (49.5 ± 26.9 jjg/l after 2.1 ±

1.6 h). The second peak is on average 586.3 ± 282.7 ng/l and is reached after 20.7 ± 5.2 h. The second, higher peak is due to the absorption of bacterial degradation products from distal parts of the intestine. In contrast to the total radioactivity, the maximum plasma concentrations of the inhibitory substance are lower by a factor of 10-20. The plasma elimination half-lives of the inhibitory substance are 3.7 ± 2.7 h for the distribution phase and 9.6 ± 4.4 h for the elimination phase.

A relative volume of distribution of 0.32 l/kg body-weight has been calculated in healthy volunteers from the concentration course in the plasma.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Microcrystalline cellulose Colloidal anhydrous silica Magnesium stearate Pregelatinised starch

6.2    Incompatibilities

Not applicable.

Shelf life

2 years.

6.4 Special precautions for storage

Do not store above 30° C. Store in the original packaging to protect from light and moisture.

6.5    Nature and contents of container

Transparent and colourless PVC/PCTFE/PVC film/Al foil blisters, packed in outer cartons. is used as container closure system for Acarbose tablets.

Pack sizes: 10, 20, 30, 40, 50, 60, 90, 120 and 270 tablets.

Not all pack sizes may be marketed.

6.6    Special precautions for disposal

No special requirements.

Any unused product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

MORNINGSIDE HEALTHCARE LIMITED 115 NARBOROUGH ROAD LEICESTER LE3 OPA

UNITED KINGDOM

8    MARKETING AUTHORISATION NUMBER(S)

PL 20117/0178

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

18/12/2009

10    DATE OF REVISION OF THE TEXT

21/03/2016