Acarbose 100mg tablets

United Kingdom - English - MHRA (Medicines & Healthcare Products Regulatory Agency)

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Active ingredient:
Acarbose
Available from:
Mylan
ATC code:
A10BF01
INN (International Name):
Acarbose
Dosage:
100mg
Pharmaceutical form:
Tablet
Administration route:
Oral
Class:
No Controlled Drug Status
Prescription type:
Valid as a prescribable product
Product summary:
BNF: 06010203; GTIN: 5016695000053
Authorization number:
PL 04569/1620

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v1/May 2015

20 May 2016

11:12

Acarbose 50/100mg 90

Leaflet

898213

671958

898213

04569/1619,04569/1620

50061535

4851

281544

Black

Myriad Pro

170 x 360mm

9 pt

8 pt

50061535

Package leaflet: Information for the patient

Acarbose 50 mg Tablets

Acarbose 100 mg Tablets

(acarbose)

Read all of this leaflet carefully before you

start taking this medicine because it contains

important information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor

or pharmacist.

This medicine has been prescribed for you only.

Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

If you get any side effects, talk to your doctor or

pharmacist. This includes any possible side effects

not listed in this leaflet. See section 4.

What is in this leaflet

What Acarbose is and what it is used for

What you need to know before you take Acarbose

How to take Acarbose

Possible side effects

How to store Acarbose

Contents of the pack and other information

1. What Acarbose is and what it is

used for

Acarbose contains the active substance acarbose,

which belongs to a group of medicines called

glucosidase inhibitors.

Acarbose is used in the treatment of non-insulin

dependent (type II) diabetes mellitus in patients

inadequately controlled on diet alone, or on diet

and oral hypoglycaemic agents. Acarbose is for

adults aged over 18 years. This medicine has

been prescribed for you by your doctor to treat

your diabetes.

Acarbose will help to control your blood sugar levels.

This is because acarbose works by slowing down

the digestion of carbohydrates (complex sugars)

from your diet, and this reduces the abnormally high

blood sugar levels that occur after each meal.

2. What you need to know before you

take Acarbose

Do not take Acarbose:

if you are allergic to acarbose or any of the other

ingredients of this medicine (listed in section 6)

if you are pregnant or breast-feeding

if you suffer from inflammation or ulceration of

the bowel, for example ulcerative colitis or

Crohn’s disease

if you have an obstruction in your intestines, or are

likely to get this

if you have a large hernia, or any other condition

where increased gas in your intestine may make

it worse

if you have an intestinal disease where you do not

digest or absorb food properly

if you have severe kidney problems

if you have a severe liver disorder.

If you have a kidney or liver disorder, do not take

Acarbose without consulting your doctor first. If you

are unsure whether you might have any of these

conditions, please ask your doctor.

Warnings and precautions

Treating hypoglycaemic episodes (‘hypos’)

As a diabetic you may also be receiving other

treatments for your diabetes.

If you are taking insulin, metformin or sulfonylureas

(e.g. glimepiride, glipizide) to control your blood

sugar, you will probably be used to avoiding

hypoglycaemic episodes by taking sugar when you

feel that your blood sugar level is too low.

When taking acarbose DO NOT treat a

hypoglycaemic episode with ordinary sugar

(sucrose) instead take some glucose (also known as

dextrose) tablets, syrup, or sweets which should be

available from your pharmacist.

Talk to your doctor or pharmacist before taking

acarbose if you have any questions on the above.

This medicine may affect the level of certain proteins

called enzymes in your blood which show how your

liver is working. Your doctor may wish to see you

more frequently in order to monitor the levels of

these enzymes. Your doctor may decide to reduce

the dose or stop treatment with Acarbose.

Other medicines and Acarbose

Tell your doctor or pharmacist if you are taking,

have recently taken or might take any other

medicines. Acarbose may alter the effect of other

drugs, or alternatively, some drugs may alter the

effect of acarbose:

In particular tell your doctor or pharmacist if

you are taking:

medicines called intestinal absorbants,

such as charcoal

medicines containing digestive enzymes that help

digestion, such as amylase and pancreatin

neomycin, an antibiotic

colestyramine, to treat high cholesterol

digoxin, to treat heart problems

other blood glucose lowering drugs

(e.g. sulfonylureas, metformin, or insulin).

Acarbose with food and drink

Keep to the diet prescribed by your doctor. If

distressing stomach or digestive complaints develop

in spite of strict adherence to your diet (see section

4), contact your doctor as your dose of acarbose may

need to be reduced.

Household sugar (cane sugar) and foods containing

it can cause abdominal discomfort or even diarrhoea

due to carbohydrate-fermentation in the colon

during treatment with acarbose.

You may notice side effects such as severe wind

(flatulence) and diarrhoea if you have taken acarbose

together with carbohydrate containing drinks or

food. In this case, do not eat or drink carbohydrate

containing drinks or food for 4 to 6 hours.

Pregnancy and breast-feeding

Do not take acarbose if you are pregnant or

breastfeeding. If you think you might be pregnant or

are planning to have a baby, tell your doctor before

taking this medicine.

Driving and using machines

Acarbose is unlikely to affect your ability to drive or

use machines.

3. How to take Acarbose

Always take this medicine exactly as your doctor or

pharmacist has told you. Check with your doctor or

pharmacist if you are not sure.

Adults (including over 65s):

The recommended initial dose is 50 mg, three times a

day. To start treatment your doctor may recommend

taking 50 mg only once or twice a day to help

minimise side effects. Your doctor will then increase

your dose to 50 mg, three times a day.

If after six to eight weeks treatment your medicine

is not working as well as it should your doctor may

increase your dose up to 100 mg, three times a day.

The maximum dose is 200 mg, three times a day.

Use in children and adolescents:

Acarbose is not recommended in patients under

18 years of age.

Method of administration

Tablets are swallowed whole with a glass of water

immediately before the meal or chewed with the first

mouthful of food.

The score line on the 100 mg tablet is not intended

for breaking the tablet.

This medicine is for long-term use. Take the tablets

for as long as your doctor has told you to.

If you take more Acarbose than you should

Go to your doctor or nearest hospital immediately.

Take the container and any remaining tablets with

you. If you have taken more tablets than you should

do not take food or drinks containing carbohydrates

for the next 4 to 6 hours. Symptoms of overdose may

include: severe flatulence and diarrhoea.

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Barcode Info

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TrackWise PR No.

MA No.

Packing Site/Printer

Supplier Code

Sign-offs

v1/May 2015

20 May 2016

11:12

Acarbose 50/100mg 90

Leaflet

898213

671958

898213

04569/1619,04569/1620

50061535

4851

281544

Black

Myriad Pro

170 x 360mm

9 pt

8 pt

898213

50061535

If you forget to take Acarbose

Do not take a double dose to make up for a forgotten

dose. Take the next dose with your next meal. Do not

take the tablets between meals.

If you stop taking Acarbose

If you suddenly stop taking Acarbose your blood

glucose level may rise. Speak to your doctor before

stopping this medicine.

If you have any further questions on the use of this

medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side

effects, although not everybody gets them.

Side effects which may occur in the first two or

three days of treatment:

increased wind (flatulence)

rumbling in your stomach

feeling of fullness or abdominal cramps.

Contact your doctor if these effects continue

for more than 2 or 3 days, if they are severe, or

particularly if you have diarrhoea. Do not take

indigestion preparations (antacids) as they are

unlikely to help.

If you think you may have any of the following

side effects, stop taking this medicine and

contact your doctor or go to your nearest

hospital emergency department immediately:

Rare (may affect up to 1 in 1,000 people):

yellowing of the whites of the eyes or

skin (jaundice)

Not known (frequency cannot be estimated from the

available data):

inflammation of the liver (hepatitis). You may feel

sick, notice yellowing of the skin and eyes, and

have abdominal pain and swelling. Some cases

of hepatitis with a fatal outcome have been

reported, but it is not clear if this occurs as a result

of taking acarbose.

allergic reaction, such as rash, redness of the skin,

skin eruptions, itching

gas pockets in the bowel (Pneumatosis cystoides

intestinalis). This will show up in a radiograph

(e.g. CT scan, MRI).

a decrease in bowel activity

(e.g. severe constipation)

Other possible side effects

Very common (may affect more than 1 in

10 people):

wind (flatulence).

Common (may affect up to 1 in 10 people):

diarrhoea

stomach or abdominal pain.

These side effects are likely to occur after a meal

containing sugar (sucrose). Symptoms may be

reduced by avoiding foods and drinks that contain

sugar (sucrose, cane sugar). If your diarrhoea does

not go away your doctor will need to reduce your

dose or in some cases stop treatment. Do not take

indigestion remedies to treat the above side effects

as this can make the symptoms worse.

Uncommon (may affect up to 1 in 100 people):

feeling sick (nausea)

being sick (vomiting)

indigestion (dyspepsia)

increase in liver enzymes (transaminases) in the

blood. This would show in blood tests.

Rare (may affect up to 1 in 1,000 people):

swelling (oedema).

Not known (frequency cannot be estimated from

the available data):

a decrease in the number of blood cells necessary

for clotting (thrombocytopenia)

rash with pus filled pimples/blisters (acute

generalised exanthematous pustulosis)

In addition, events reported as liver disorder,

abnormal liver function and liver injury have

been received.

Reporting of side effects

If you get any side effects, talk to your doctor or

pharmacist. This includes any possible side effects

not listed in this leaflet. You can also report side

effects directly via the Yellow Card Scheme at:

www.mhra.gov.uk/yellowcard. By reporting side

effects you can help provide more information on the

safety of this medicine.

5. How to store Acarbose

Keep this medicine out of the sight and reach

of children.

Do not use this medicine after the expiry date,

which is stated on the carton and blister after ‘EXP’.

The expiry date refers to the last day of that month.

This medicine does not require any special

temperature storage conditions. Store in the

original package in order to protect from moisture.

Do not use this medicine if you notice

any discolouration.

Do not throw away any medicines via wastewater

or household waste. Ask your pharmacist how to

throw away medicines you no longer use. These

measures will help protect the environment.

6. Contents of the pack and

other information

What Acarbose contains

The active substance is acarbose. Each tablet

contains either 50 mg or 100 mg of acarbose.

The other ingredients are silica, colloidal anhydrous;

maize starch; magnesium stearate; cellulose,

microcrystalline.

What Acarbose looks like and contents

of the pack

Your medicine comes as a white to off-white round

biconvex tablet. Acarbose 50 mg tablets are marked

“A” over “50” on one side of the tablet and “M” on the

other side. Acarbose 100 mg tablets are marked “AB”

(breakline) “100” on one side of the tablet and “M” on

the other side.

Acarbose is available in blister packs of 90 and

100 tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Mylan, Potters Bar, Hertfordshire, EN6 1TL,

United Kingdom

Manufacturer

Gerard Laboratories, 35/36 Baldoyle Industrial Estate,

Grange Road, Dublin 13, Ireland

Mylan Hungary Kft, H-2900 Komarom, Mylan utca 1,

Hungary

Generics [UK] Ltd, Potters Bar, Hertfordshire, EN6 1TL,

United Kingdom

This leaflet was last revised in May 2016.

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT

Acarbose 100mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 100 mg acarbose.

For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM

Tablet

White to off-white, round biconvex tablet intagliated with AB breakline 100 on one

side and M on the reverse.

The score line is not intended for breaking the tablet.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

Acarbose is indicated in adults and adolescents aged over 18 years.

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

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.

Patients with hepatic impairment

No dose adjustment is required in patients with pre-existing impaired hepatic function,

however, liver enzymes should be closely monitored (see section 4.4).

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.

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. In addition, acarbose 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.

Severe kidney impairment (creatinine clearance <25 ml/min/1.73m

) as acarbose has

not been studied in patients with severe renal impairment.

Severe hepatic impairment (e.g. liver cirrhosis).

Pregnancy and in nursing mothers.

4.4

Special warnings and precautions for use

Hypoglycaemia

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. 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. If acute hypoglycaemia develops

glucose should be used for rapid correction of hypoglycaemia (see section 4.5).

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. It is recommended that liver

enzyme monitoring is considered during the first six to twelve months of treatment (see

section 4.8). 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.

4.5

Interaction with other medicinal products and other forms of interaction

Acarbose has an anti-hyperglycaemic effect but, by itself, does not cause hypoglycaemia. In

patients treated simultaneously with acarbose and sulfonylurea, metformin or insulin, the

glycaemia values may drop to hypoglycaemic levels and so dose adjustment of these

medicinal products may be necessary. 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).

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.

Sucrose (cane sugar) and foods containing sucrose often cause abdominal discomfort or even

diarrhoea during treatment with acarbose as a result of increased carbohydrate fermentation in

the colon.

Intestinal adsorbents (e.g. charcoal) and digestive enzyme preparations containing

carbohydrate splitting enzymes (e.g. amylase, pancreatin) may reduce the effect of acarbose

and should not therefore be taken concomitantly.

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.

The concomitant administration of colestyramine may enhance the effects of acarbose,

particularly with respect to reducing postprandial insulin levels. Simultaneous administration

of acarbose and colestyramine should, therefore, be avoided. In the rare circumstance that

both acarbose 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 isolated cases acarbose may affect the bioavailability of digoxin, making dose adjustment

necessary. Monitoring of serum digoxin levels should be considered.

The administration of antacid preparations containing magnesium and aluminium salts, e.g.

hydrotalcite, has been shown not to ameliorate the acute gastrointestinal symptoms of

acarbose and should, therefore, not be recommended to patients for this purpose.

In a pilot study to investigate a possible interaction between acarbose and nifedipine, no

significant or reproducible changes were observed in the plasma nifedipine profiles.

4.6

Fertility, pregnancy and lactation

Pregnancy

Acarbose should not be administered during pregnancy as no information is available from

clinical studies on its use in pregnant women.

Breast-feeding

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 breast-feeding.

Fertility

No impairment of fertility was observed in male or female rats at doses of up to 540

mg/kg/day (see section 5.3).

4.7

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 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

Immune

system

disorders

Drug

hypersensitivity

hypersensitivity

(rash, erythema,

exanthema,

urticaria)

Vascular

disorders

Oedema

Gastrointestina

l disorders

Flatulenc

Diarrhoea

Gastrointestina

l and

abdominal

pains

Nausea

Vomiting

Dyspepsia

Subileus/Ileus

Pneumatosis

cystoides

intestinalis

Hepatobiliary

disorders

Increase in

transaminase

Jaundic

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. Abnormal values may be transient during treatment with

acarbose (see section 4.4).

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.

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 internet at

www.mhra.gov.uk/yellowcard.

4.9

Overdose

Symptoms

When acarbose is taken with beverages and/or meals containing carbohydrates

(polysaccharides, oligosaccharides or disaccharides), overdose may lead to meteorism,

flatulence and diarrhoea. However, in the event that acarbose has been ingested in overdose

outside meal times, no excessive intestinal symptoms should be expected.

Management

In the event of overdose the intake of beverages or meals containing carbohydrates should be

avoided over the next 4-6 hours.

No specific antidotes to acarbose are known.

Diarrhoea should be treated by standard conservative measures.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Drugs used in diabetes, Alpha glucosidase inhibitors, ATC code:

A10BF01.

Mechanism of action

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 (

-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.

Under the influence of acarbose, 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. Treatment with acarbose also results in a reduction of fasting

blood glucose and to modest changes in levels of glycated haemoglobin (HbA

, HbA

5.2

Pharmacokinetic properties

The pharmacokinetics of acarbose were investigated after oral administration of the

C-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

g/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

g/l after 2.1 ± 1.6 h). The second peak is on average 586.3 ± 282.7

g/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 and toxicity to

reproduction.

Acute toxicity

studies were performed in mice, rats and dogs. Oral LD

values were estimated to be >

10 g/kg body-weight. Intravenous LD

values ranged from 3.8 g/kg (dog) to 7.7 g/kg

(mouse).

Sub-chronic toxicity

Three month studies have been conducted in rats and dogs in which acarbose was

administered orally by gavage.

In rats, daily doses of up to 450 mg/kg body-weight were tolerated without drug-related

toxicity.

In the dog study, daily doses of 50-450 mg/kg were associated with decreases in body-weight.

This occurred because dosing of the animals took place shortly before the feed was

administered, resulting in the presence of acarbose in the gastro-intestinal tract at the time of

feeding. The pharmacodynamic action of acarbose led to a reduced availability of

carbohydrate from the feed, and hence to weight loss in the animals. A greater time interval

between dosing and feeding in the rat study resulted in most of the drug being eliminated

prior to feed intake, and hence no effect on body-weight development was observed.

Owing to a shift in the intestinal

-amylase synthesis feedback mechanism a reduction in

serum

-amylase activity was also observed in the dog study. Increases in blood urea

concentrations in acarbose-treated dogs also occurred, probably as a result of increased

catabolic metabolism associated with the weight loss.

Chronic toxicity

In rats treated for one year with up to 4500 ppm acarbose in their feed, no drug-related

toxicity was observed. In dogs, also treated for one year with daily doses of up to 400 mg/kg

by gavage, a pronounced reduction in body-weight development was observed, as seen in the

sub-chronic study. Again this effect was due to an excessive pharmacodynamic activity of

acarbose and was reversed by increasing the quantity of feed.

Carcinogenicity

In a study in which Sprague-Dawley rats received up to 4500ppm acarbose in their feed for

24-26 months, malnutrition was observed in animals receiving the drug substance. A dose-

dependent increase in tumours of the renal parenchyma (adenoma, hypernephroid carcinoma)

was also observed against a background of a decrease in the overall tumour rate. When this

study was repeated, an increase in benign tumours of testicular Leydig cells was also

observed. Owing to the malnutrition and excessive decrease in bodyweight gain these studies

were considered inadequate to assess the carcinogenic potential of acarbose.

In further studies with Sprague-Dawley rats in which the malnutrition and glucose deprivation

were avoided by either dietary glucose supplementation or administration of acarbose by

gavage, no drug-related increases in the incidences of renal or Leydig cell tumours were

observed.

In an additional study using Wistar rats and doses of up to 4500ppm acarbose in the feed,

neither drug-induced malnutrition nor changes in the tumour profile occurred. Tumour

incidences were also unaffected in hamsters receiving up to 4000ppm acarbose in the feed for

80 weeks (with and without dietary glucose supplementation).

Reproductive toxicity

There was no evidence of a teratogenic effect of acarbose in studies with oral doses of up to

480mg/kg/day in rats and rabbits.

In rats no impairment of fertility was observed in males or females at doses of up to 540

mg/kg/day. The oral administration of up to 540 mg/kg/day to rats during foetal development

and lactation had no effect on parturition or on the offspring.

Mutagenicity

The results of a number of mutagenicity studies show no evidence of a genotoxic potential of

acarbose.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Silica, colloidal anhydous

Maize starch

Magnesium stearate

Cellulose, microcrystalline

6.2

Incompatibilities

Not applicable.

6.3

Shelf life

2 years.

6.4

Special precautions for storage

This medicinal product does not require any special temperature storage conditions.

Store in the original package in order to protect from moisture.

6.5

Nature and contents of container

Clear Aclar – PVC / Aluminium blisters in cardboard carton containing 90 and 100

tablets.

Not all pack sizes may be marketed.

6.6

Special precautions for disposal

No special requirements.

Any unused medicinal product or waste material should be disposed of in

accordance with local requirements.

7

MARKETING AUTHORISATION HOLDER

Generics [UK] Limited t/a Mylan

Station Close

Potters Bar,

Hertfordshire

EN6 1TL

United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)

PL 04569/1620

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

13/12/2012

10

DATE OF REVISION OF THE TEXT

05/07/2016

Read the complete document

Public Assessment Report

Decentralised Procedure

ACARBOSE 50MG TABLETS

ACARBOSE 100MG TABLETS

(Acarbose)

Procedure No: UK/H/1362/001-2/DC

UK Licence No: PL 00289/1114-5

TEVA UK LIMITED

PAR Acarbose 50mg and 100mg tablets

UK/H/1362/001-2/DC

2

LAY SUMMARY

On 08 June 2011, Germany, France, Hungary, Poland, Portugal and the UK agreed to grant

Marketing Authorisations to Teva UK Limited for the medicinal products Acarbose 50mg

and 100mg tablets (PL 00289/1114-5; UK/H/1362/001-2/DC) via the Decentralised

Procedure (DCP), with the UK as Reference Member State (RMS). After a subsequent

national phase, Marketing Authorisations were granted in the UK on 28 June 2011.

These are prescription-only medicines (POM) used in the management of Type II diabetes. If

you have Type II diabetes then levels of sugar (glucose) in your blood are too high. This

medicine works by slowing down digestion and absorption of sugars from your diet and stops

levels of blood sugar from rising too high. This medicine can be used alone or in combination

with a sulphonylurea and/or metformin.

Acarbose 50mg and 100mg tablets contains the active ingredient acarbose, which belongs to

a class of medicines called “alpha glucosidase inhibitors”.

No new or unexpected safety concerns arose from these applications and it was, therefore,

judged that the benefits of taking Acarbose 50mg and 100mg tablets outweigh the risks,

hence Marketing Authorisations have been granted.

PAR Acarbose 50mg and 100mg tablets

UK/H/1362/001-2/DC

3

TABLE OF CONTENTS

Module 1: Information about initial procedure

Page 4

Module 2: Summary of Product Characteristics

Page 5

Module 3: Product Information Leaflets

Page 15

Module 4: Labelling

Page 17

Module 5: Scientific Discussion

Page 19

I Introduction

II About the product

III Scientific Overview and discussion

III.1 Quality aspects

III.2 Non-clinical aspects

III.3 Clinical aspects

IV Overall Conclusions and benefit-risk assessment

Module 6

Steps taken after initial procedure

Page 27

PAR Acarbose 50mg and 100mg tablets

UK/H/1362/001-2/DC

4

Module 1

Product Name

Acarbose 50mg tablets

Acarbose 100mg tablets

Type of Application

Hybrid, Article 10.3

Active Substances

Acarbose

Form

Tablets

Strength

50mg and 100mg

MA Holder

Teva UK Limited, Brampton Road, Hampden Park,

Eastbourne, BN22 9AG, UK.

Reference Member State (RMS)

CMS

Germany, France, Hungary, Poland and Portugal

Procedure Number

UK/H1362/001-2/DC

Timetable

Day 210 – 08 June 2011

PAR Acarbose 50mg and 100mg tablets

UK/H/1362/001-2/DC

5

Module 2

Summary of Product Characteristics

1

NAME OF THE MEDICINAL PRODUCT

Acarbose 50mg tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 50mg Acarbose.

For a full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM

Tablet.

Acarbose 50mg tablets are round, biconvex, white to off-white tablets, with bossing "ACA 50" on one

side.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

Acarbose is recommended for the treatment of non-insulin dependent (NIDDM) diabetes mellitus in

patients inadequately controlled on diet alone, or on diet and (i) metformin and / or (ii) a

sulphonylurea.

4.2

Posology and 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.

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.

Acarbose is intended for continuous long-term treatment.

If adverse events occur in spite of strict adherence to the diabetic diet, the dose should not be increased

and if necessary should be reduced (see section 4.8).

Elderly patients

No modification of the normal adult dosage regimen is necessary.

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.

Renal or hepatic impairment

See section 4.3.

4.3

Contraindications

Hypersensitivity to acarbose or any of the excipients. Acarbose is also contraindicated in patients with

inflammatory bowel disease, colonic ulceration, partial intestinal obstruction or in patients predisposed

to intestinal obstruction. In addition, Acarbose 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.

Acarbose is contraindicated in patients with hepatic impairment.

PAR Acarbose 50mg and 100mg tablets

UK/H/1362/001-2/DC

6

As Acarbose 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.

4.4

Special warnings and precautions for use

Hypoglycaemia:

When administered alone, Acarbose 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 Acarbose in

higher dosage and should, therefore, not be recommended to patients for this purpose.

If ileus or sub-ileus is suspected, treatment must be stopped immediately (see section 4.8).

It is essential to adhere to a strict diabetic diet when taking Acarbose.

Regular use of Acarbose should not be interrupted without medical advice as this may lead to a rise in

blood glucose.

Since the information available on its effects and tolerability in children and adolescents is still

insufficient, Acarbose should not be used in patients under 18 years of age.

4.5

Interaction with other medicinal products and other forms of interaction

Sucrose (cane sugar) and foods containing sucrose often cause abdominal discomfort or even diarrhoea

during treatment with Acarbose as a result of increased carbohydrate fermentation in the colon.

Intestinal adsorbents (e.g. charcoal) and digestive enzyme preparations containing carbohydrate

splitting enzymes (e.g. amylase, pancreatin) may reduce the effect of Acarbose 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 Acarbose may be warranted.

The concomitant administration of colestyramine may enhance the effects of Acarbose, particularly

with respect to reducing postprandial insulin levels. Simultaneous administration of Acarbose and

colestyramine should, therefore, be avoided. In the rare circumstance that both Acarbose 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 Acarbose 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 Acarbose and nifedipine, no significant or

reproducible changes were observed in the plasma nifedipine profiles.

Several therapeutic agents including thiazide and other diuretics, corticosteroids, phenothiazines,

thyroid hormones, oestrogens and oral contraceptives, phenytoin, nicotinic acid, sympathomimetics,

calcium channel blockers and isoniazid can cause hyperglycaemia, which may attenuate the

pharmacodynamic effects of Acarbose. Blood glucose levels should be closely monitored if any of

PAR Acarbose 50mg and 100mg tablets

UK/H/1362/001-2/DC

7

these agents are used by patients receiving Acarbose, or if treatment with Acarbose is contemplated in

patients already receiving any of these agents.

If Acarbose is prescribed in addition to other oral hypoglycaemic agents (

e.g.

a sulphonylurea or

metformin), a fall of the blood glucose into the hypoglycaemic range may necessitate a decrease in the

dose of the concomitant medication.

4.6

Pregnancy and lactation

Pregnancy

The safety of this medicinal product for use in human pregnancy has not been established. An

evaluation of experimental animal studies does not indicate direct or indirect harmful effects with

respect to reproduction, development of the embryo or fetus, the course of gestation, and peri- and

postnatal development.

Acarbose is not recommended during pregnancy.

When the patient plans to become pregnant and during pregnancy, diabetes should be treated with

insulin to maintain blood glucose levels as close to normal as possible in order to lower the risk of fetal

malformations associated with abnormal blood glucose levels.

Lactation

It is unknown whether acarbose is excreted in human breast milk. Animal studies have shown

excretion of acarbose in breast milk. Acarbose should not be used during breast-feeding.

4.7

Effects on ability to drive and use machines

Acarbose monotherapy does not cause hypoglycaemia and is therefore unlikely to have effects on the

ability to drive or to use machines. However, patients should be alerted to the risk of hypoglycaemia

when acarbose is used in combination with metformin and / or a sulphonylurea.

4.8

Undesirable effects

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.

Frequencies are defined as very common (≥1/10); common (>1/100 to <1/10); uncommon (>1/1000 to

<1/100); rare (>1/10 000 to <1/1000); very rare (<1/10 000).

Blood and the lymphatic system disorders:

Not known (cannot be estimated from the available data): Thrombo-cytopenia*

Immune System Disorders:

Not known (cannot be estimated from the available data): Allergic reaction (rash, erythema,

exanthema, urticaria)*

Vascular Disorders:

Rare: Oedema

Gastrointestinal Disorders:

Very common: Flatulence

Common: Diarrhoea, Gastrointestinal and abdominal pains

Uncommon: Nausea, Vomiting, Dyspepsia

Not known (cannot be estimated from the available data):

Subileus/ileus, Pneumatosis cystoides

intestinalis*

Hepatobiliary Disorders:

Uncommon: Transient increase in liver enzymes

Rare: Jaundice

Not known (cannot be estimated from the available data): Hepatitis*

*ADRs derived from post marketing reports (status: 31 Dec 2005).

If ileus or subileus is suspected, treatment must be stopped immediately.

Individual cases of fulminant hepatitis with fatal outcome have been reported in Japan. The

relationship to acarbose is unclear.

PAR Acarbose 50mg and 100mg tablets

UK/H/1362/001-2/DC

8

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 Acarbose, clinically relevant

abnormal liver function tests (three times above upper limit of normal range) were rarely observed.

Abnormal values may be transient under ongoing Acarbose therapy.

(See Section 4.4).

4.9

Overdose

When Acarbose tablets are taken with drinks and/or meals containing carbohydrates overdose may lead

to meteorism, flatulence and diarrhoea. If Acarbose tablets are taken independently of food, excessive

intestinal symptoms need not be anticipated.

No specific antidotes to Acarbose are known.

Intake of carbohydrate-containing meals or beverages should be avoided for 4-6 hours.

Diarrhoea should be treated by standard conservative measures.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group:

Alpha glucosidase inhibitors

ATC code: A10BF01

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 (α-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.

In contrast to sulphonylureas acarbose has no stimulatory action on the pancreas.

Treatment with acarbose also results in a reduction of fasting blood glucose and to modest changes in

levels of glycated haemoglobin (HbA

, HbA

). The changes may be a reduction or reduced

deterioration in HbA

or HbA

levels, depending upon the patient's clinical status and disease

progression. These parameters are affected in a dose-dependent manner by acarbose.

5.2

Pharmacokinetic properties

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

The pharmacokinetics of acarbose were investigated after oral administration of the

C-labelled

substance (200mg) 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 ± 15.7μg/l after 1.1 ± 0.3 h, is in agreement with corresponding data

for the concentration course of the inhibitor substance (49.5 ± 26.9μg/l after 2.1 ± 1.6 h). The second

peak is on average 586.3 ± 282.7μg/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.

PAR Acarbose 50mg and 100mg tablets

UK/H/1362/001-2/DC

9

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.

A markedly reduced body weight gain in rats and dogs after repeated administration of acarbose was

considered as pharmacodynamic effect (loss of carbohydrates) and could be counteracted by increase

of food or glucose supplementation.

Carcinogenicity was studied in Sprague-Dawley rats, Wistar rats and hamsters. An increased tumour

incidence in certain tissues (kidney, testis) was observed if malnutrition due to acarbose was not

corrected. No increase in tumour rate was observed if the body weight gain was kept normal by food or

glucose supplementation.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Cellulose, microcrystalline

Starch pregelatinized, maize

Silica, colloidal anhydrous

Magnesium stearate

6.2

Incompatibilities

Not applicable

6.3

Shelf life

3 years.

6.4

Special precautions for storage

Do not store above 25 °C. Store in the original packaging in order to protect from moisture.

6.5

Nature and contents of container

20, 21, 30, 40, 50, 60, 90, 100, 105, 120, 270 tablets in PVC/PE/PVDC aluminium blisters. 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

Teva UK Limited

Brampton Road

Hampden Park

Eastbourne

BN22 9AG

United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)

PL 00289/1114

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

28/06/2011

10

DATE OF REVISION OF THE TEXT

28/06/2011

PAR Acarbose 50mg and 100mg tablets

UK/H/1362/001-2/DC

10

1

NAME OF THE MEDICINAL PRODUCT

Acarbose 100mg tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 100mg Acarbose.

For a full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM

Tablet.

Acarbose 100mg tablets are round, biconvex, white to off-white tablets, with a score-line on one side

and bossing “ACA 100” on the other 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 non-insulin dependent (NIDDM) diabetes mellitus in

patients inadequately controlled on diet alone, or on diet and (i) metformin and / or (ii) a

sulphonylurea.

4.2

Posology and 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.

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.

Acarbose is intended for continuous long-term treatment.

If adverse events occur in spite of strict adherence to the diabetic diet, the dose should not be increased

and if necessary should be reduced (see section 4.8).

Elderly patients

No modification of the normal adult dosage regimen is necessary.

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.

Renal or hepatic impairment

See section 4.3.

4.3

Contraindications

Hypersensitivity to acarbose or any of the excipients. Acarbose is also contraindicated in patients with

inflammatory bowel disease, colonic ulceration, partial intestinal obstruction or in patients predisposed

to intestinal obstruction. In addition, Acarbose 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.

Acarbose is contraindicated in patients with hepatic impairment.

As Acarbose 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.

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