GLUCO-RITE

Patient leaflet in accordance with the

Pharmacists‘ Regulations

)Preparations( - 1986

This medicine is dispensed with a doctor’s

prescription only

GLUCO-RITE

5 mg Tablets

Each tablet contains 5 mg glipizide

Inactive

ingredients

allergens

medicine: see section 2 ‘Important information

about some of the ingredients of Gluco-Rite’

and section 6 in the leaflet.

Read the entire leaflet carefully before using

the

medicine.

This

leaflet

contains

concise

information about the medicine. If you have any

further questions, refer to the doctor or pharmacist.

Keep this leaflet, you may want to read it again. This

medicine has been prescribed for the treatment

of your illness. Do not pass it on to others. It may

harm them, even if it seems to you that their illness

is similar.

1. WHAT IS THE MEDICINE INTENDED

FOR?

Gluco-Rite is used for control of hyperglycemia

)high blood sugar levels( and the accompanying

symptoms in patients with type 2 diabetes in

addition to a change in diet.

Therapeutic group: Medicine to lower blood

sugar level from the sulphonylurea group.

2. BEFORE USING THE MEDICINE

Do not use Gluco-Rite if:

You are hypersensitive )allergic( to the active

ingredient glipizide, to another similar antidiabetic

drug or to any of the other ingredients this

medicine contains )see section 6(.

You have juvenile diabetes )type 1 diabetes

which probably began in your childhood and is

an insulin-dependent diabetes(.

Ketone bodies or sugar have appeared in your

urine )you may suffer from diabetic ketoacidosis(.

You suffer from episodes of unconsciousness

)you may suffer from diabetic coma(.

You suffer from problems with the kidneys or

liver.

You are pregnant, planning to become pregnant

or breastfeeding.

You are currently taking miconazole to treat

fungal infections.

!

Special warnings regarding the use of

the medicine

Before starting treatment with Gluco-Rite, tell

the doctor if:

You have been told that you have a problem with

the adrenal gland or the pituitary gland.

You are about to undergo major surgery, have

had a recent injury )trauma(, or if you develop

a fever or severe infection )see in section 3

"

If

you are about to undergo surgery

"

for further

information(.

You suffer from G6PD deficiency )a disease that

causes abnormal destruction of your red blood

cells(.

You should check your blood and urine glucose level

regularly, particularly if you are elderly, disabled

or malnourished. If the test results are outside the

limits recommended by your doctor, you should

contact him immediately.

Gluco-Rite can cause hypoglycemia )low blood sugar

levels(, which is characterized by confusion, fainting,

sweating, dizziness, drowsiness, headache, tremor

and visual disturbances )these symptoms may also

be unrelated to hypoglycemia(. Low blood sugar

levels can be prevented by regular consumption of

carbohydrates )for example, bread or other products

containing starch/sugar(. It is recommended to eat

regular meals, and not exercise heavily or for a

long period without eating something first.

!

Children and adolescents

Safety and efficacy of use in children have not

been determined.

!

Drug interactions

If

you

are

taking

or

have

recently

taken

other medicines including non-prescription

medicines, nutritional supplements and herbal

preparations, tell the doctor or pharmacist,

especially if you are taking:

The following medicines may reduce your blood

sugar levels excessively when given together

with Gluco-Rite:

Miconazole, fluconazole or voriconazole )used to

treat fungal infections(

Non-steroidal anti-inflammatory drugs )NSAIDs(

)used to treat muscle and joint pain, such as

phenylbutazone(

Aspirin

aspirin-like

medicines

known

salicylates )usually used as pain killers(

Beta-blockers )used to treat high blood pressure

and certain heart problems, such as propranolol(

ACE )angiotensin converting enzyme( inhibitors

)used

treat

high

blood

pressure,

such

captopril(

Cimetidine )used to treat stomach and duodenal

ulcers and other digestive disorders(

Sulphonamides or chloramphenicol )used to treat

bacterial infections(

Quinolones )used to treat bacterial infections(

Monoamine oxidase )MAO( inhibitors )used to

treat depression(

Probenecid )used to treat gout(

Coumarin anticoagulants )used to treat blood

clots, such as warfarin(

Fibrates )used to treat high cholesterol, such as

clofibrate(

following

medicines

increase

your

blood

sugar

levels

excessively

when

given

together with Gluco-Rite:

Danazol )a hormone treatment(

Phenothiazine

tranquilizers

)used

treat

psychiatric conditions, such as chlorpromazine,

thioridazine(

Corticosteroids

)used

treat

inflammatory

conditions, such as prednisolone(

Sympathomimetic

substances,

such

nasal

decongestants and bronchodilators used to treat

asthma )such as salbutamol, isoprenaline(

Hormonal agents, including oral contraceptives

)the

pill(

hormone

replacement

therapy

)HRT(

Thiazides

other

diuretics

)such

bendroflumethiazide(

Thyroid preparations )used to treat patients with

low production levels of thyroid hormones(

Phenytoin )used to treat epilepsy(

Nicotinic acid )found in vitamin supplements and

used to lower cholesterol and other lipid levels(

Calcium channel blockers )used to treat angina

pectoris

high

blood

pressure,

such

nifedipine or verapamil(

Isoniazid )used to treat tuberculosis(

Preparations

containing

colesevelam:

take

Gluco-Rite

least

hours

before

taking

colesevelam preparations in order to ensure that

colesevelam does not impair the absorption of

Gluco-Rite.

!

Use of the medicine and food

Food may delay absorption of the medicine,

therefore each dose should be taken 30 minutes

before eating.

Try to avoid alcohol. Alcoholic beverages )wine,

beer, liquors( can further increase the reduction

of blood sugar levels and may cause loss of

consciousness )hypoglycemic coma(.

!

Pregnancy, breastfeeding and fertility

Gluco-Rite

pregnant,

planning to become pregnant or breastfeeding.

!

Driving and using machines

Gluco-Rite is not supposed to affect your ability

to drive or use machinery. However, you should

be cautious when you have just started taking

this medicine or if you do not use it regularly. Be

aware of the symptoms of low blood sugar levels

)hypoglycemia(.

These

characterized

confusion, fainting, sweating, dizziness, drowsiness,

headache, tremor and visual disturbances.

If you experience any effect, do not drive or operate

machinery.

!

Important information about some of

the ingredients of Gluco-Rite

Gluco-Rite contains lactose, a type of sugar. If

you have been told that you have an intolerance

to certain sugars, refer to your doctor before

taking this medicine.

3. HOW SHOULD YOU USE THE

MEDICINE?

Always use the medicine according to the doctor’s

instructions. You should check with the doctor or

pharmacist if you are not sure about the dosage

and treatment regimen with the medicine.

Do not take more Gluco-Rite than your doctor has

recommended. The dosage and treatment regimen

will be determined by the doctor only. The usual

recommended dosage is:

Adults

The initial dose is usually 5 mg, taken approximately

30 minutes before breakfast or lunch, although

initial dose may be lower in some patients. If you

are elderly, have mild diabetes or suffer from liver

or kidney problems, you may be asked to start

with a dose of 2.5 mg daily. If your doctor feels

your dose needs to be altered, he will instruct you

to adjust the dose in small increments, usually in

2.5-5 mg steps.

The maximum recommended daily dose is 20 mg.

Do not stop taking the tablets or adjust your

dosage without consulting the doctor. Stopping

the medicine may make your diabetes worse.

Your dose will be adapted for you individually, in

accordance with your medical condition. Some

patients, whose condition is usually controlled

by nutrition alone, may require Gluco-Rite for a

short time only.

Do not exceed the recommended dose.

Method of administration

Gluco-Rite should only be taken by mouth. The

tablet can be halved. There is no information

regarding crushing/chewing.

If you have accidentally taken a higher

dosage of Gluco-Rite than required

If you have taken an overdose, or if a child or

someone else has accidentally swallowed the

medicine, refer immediately to a doctor or proceed to

a hospital emergency room, and bring the package

of the medicine with you.

If you suffer from a sense of fainting, confusion,

drowsiness, headache, dizziness, sweating or

tremor and visual disturbances, these may be

symptoms of low blood sugar level. You should

eat or drink something that contains sugar.

If you suffer from convulsive seizures or in cases

of loss of consciousness, someone should seek

urgent medical assistance for you.

If you forgot to take Gluco-Rite

If you forgot to take this medicine at the required

time, it is important to take your medicine as soon

as you remember or when you feel weakness;

otherwise your blood sugar level will become

too high and you may go into a coma )or fall

unconscious(. Do not take a double dose to

make up for a forgotten dose. Adhere to the

treatment as recommended by the doctor. Even

if there is an improvement in your health, do not

stop treatment with the medicine without consulting

the doctor.

If you stop taking the medicine

Do not stop taking the tablets or alter your

dosage without consulting the doctor. Stopping

treatment with the medicine may worsen your

diabetes.

If you are about to undergo surgery

If you are about to undergo major surgery or

you have recently suffered from a severe illness

or infection, it is possible that diabetic control

will be lost. At such times it may be necessary

to temporarily stop using Gluco-Rite and take

insulin.

Do not take medicines in the dark! Check the

label and the dose each time you take the

medicine. Wear glasses if you need them.

If you have any further questions regarding

the use of the medicine, consult the doctor

or pharmacist.

4. SIDE EFFECTS

As with any medicine, the use of Gluco-Rite may

cause side effects in some users. Do not be

alarmed when reading the list of side effects. You

may not suffer from any of them. Most of them

are temporary and disappear upon reducing the

dose or stopping treatment. Do not stop taking

the tablets or adjust your dosage without seeing

your doctor.

Refer

to

your

doctor

immediately

experience any of the following symptoms after

taking this medicine. Although they are very rare,

these symptoms can be serious:

An allergic reaction such as sudden wheezing,

difficulty in breathing, swelling of eyelids, face or

lips, rash or itching )especially when appearing

all over the body(. Allergic reactions )including

death,

very

rarely(

have

been

reported

with

medicines similar to Gluco-Rite.

Common side effects )may affect up to 1 in

10 patients(:

Hypoglycemia )low blood sugar level(

Nausea

Diarrhoea

Pain in the stomach

Uncommon side effects )may affect up to 1

in 100 users(:

Dizziness

Drowsiness

Tremor

Blurred vision

Vomiting

Jaundice )yellowing of the skin and eyes, itching

and dark urine(

Eczema )inflammation of the skin(

Side effects of unknown frequency )frequency

has not yet been determined(:

Agranulocytosis )deficiency of a type of white

blood cells(

Leukopenia )reduction in white blood cells count(

Thrombocytopenia )reduction in platelet count(

Hemolytic anaemia )abnormal breakdown of red

blood cells(

Pancytopenia )decreased count of all type of

blood cells(

Non-acute porphyria

Redness )erythema(

Itching

Rash )red, bumpy, or measle-like(

Itching, skin redness or inflammation )allergic

dermatitis(

Pale red, raised, itchy bumps )urticaria(

Sensitivity to light

Reduction in blood sodium )hyponatremia(

Confusion

Headache

Visual disturbances and double vision

Constipation

Inflammation of the liver )hepatitis( and abnormal

hepatic function

Malaise )general discomfort(

Abnormal laboratory test results

If a side effect appears, if any of the side effects

gets worse, or when you suffer from a side

effect not mentioned in the leaflet, consult

the doctor.

Reporting side effects

Side effects can be reported to the Ministry of

Health by clicking on the link

"

Reporting Side

Effects

from

Drug

Treatment

"

found

Ministry of Health homepage www.health.gov.il,

that directs you to the online form for reporting

side effects, or by entering the link:

https://sideeffects.health.gov.il

In addition, you can report to Perrigo via the

following address: www.perrigo-pharma.co.il

5. HOW SHOULD THE MEDICINE BE

STORED?

Avoid poisoning! This medicine and any other

medicine must be kept in a closed place out of

the reach and sight of children and/or infants in

order to avoid poisoning. Do not induce vomiting

unless explicitly instructed to do so by the doctor.

Do not use the medicine after the expiry date

)exp. date( that appears on the package. The

expiry date refers to the last day of that month.

Store below 25ºC.

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 to protect the environment.

6. FURTHER INFORMATION

In addition to the active ingredient, the medicine

also contains:

Lactose 200, Microcrystalline cellulose, Maize

starch, Stearic acid.

Each tablet contains 154 mg lactose

What the medicine looks like and the contents

of the package:

Gluco-Rite 5 mg tablets are round and white,

marked with an A on one side and on the other

side a score line, in a package of 30 tablets in

blisters.

Manufacturer, registration holder and address:

Perrigo Israel Pharmaceuticals Ltd., POB 16,

Yeruham.

Revised in February 2020.

Registration number of the medicine in the

National Drug Registry of the Ministry of

Health: 13227.27134

26.2.20

Gluco-Rite PIL PB0520-05

تيار-وكولچ لوانت تيسن اذإ لوانتت نأ مهملا نم ,ددحملا تقولا يف ءاودلا اذه لوانت تيسن اذإ ىوتسم نإف لاإو ,نهولاب رعشت امدنع وأ كركذت دنع ا

روف كئاود وأ( ةبوبيغ يف لخدت دقو مزلالا نم رثكأ عفتريس كمد يف ركسلا ةعرجلا نع ضيوعتلل ةفعاضم ةعرج لوانت زوجي لا .)يعولا دقفت ىتح .بيبطلا لبق نم يصوأ امك جلاعلا ىلع ةبظاوملا بجي .ةيسنملا ءاودلاب جلاعلا فاقيإ زوجي لا ,يحصلا كعضو ىلع نسحت أرط اذإ .بيبطلا ةراشتسا نود ءاودلا لوانت نع تفقوت اذإ ةراشتسا نود كتعرج رييغت وأ صارقلأا لوانت نع فقوتلازوجي لا .كيدل يركسلا مقافي دق ءاودلاب جلاعلا فاقيإ .بيبطلا

ة

ّ

يحارج ة

ّ

يلمعل عوضخلا كشو ىلع تنك اذإ

رخؤم تيناع اذإ وأ ة

يدج ة

يحارج ة

يلمعل عوضخلا كشو ىلع تنك اذإ نع يركسلا ةلاح جرخت نأ نكمملا نم ,ديدش ثولت وأ ضرم نم لامعتسا فاقيلإ ةرورض كلانه نوكت دق تاقولأا هذه لثم يف .نزاوتلا .نيلوسنإ لوانتو تقؤم لكشب تيار-وكولچ يف ةعرجلاو قصلملا نم ققحت !ملاظلا يف ةيودأ لوانت زوجي لا .اهل ةجاحب تنك اذإ ةيبطلا تاراظنلا عض .ءاود اهيف لوانتت ةرم لك رشتسإ ,ءاودلا لامعتسا صوصخب ةيفاضإ ةلئسأ كيدل تناك اذإ .يلديصلا وأ بيبطلا

ة

ّ

يبناجلا ضارعلأا .4 ىدل

يبناج ا

ضارعأ تيار-وكولچ لامعتسا ببسي دق ,ءاود يأ يف امك

يبناجلا ضارعلأا ةمئاق ةءارق دنع عزفت لا .نيمدختسملا نم ءزج عم يفتختو هتقؤم اهمظعم .اهنم ةدحاو يأب باصت لا نأ نكمملا نم صارقلأا لوانت نع فقوتلا زوجي لا .جلاعلا فاقيإ وأ ةعرجلا ليلقت .كبيبط ىلإ هجوتلا نود كتعرج رييغت وأ دعب ةيلاتلا ضارعلأا دحأ نم يناعت تنك اذإ ا

ً

روف بيبطلا ىلإ هجوت ضارعلأا هذه نوكت دق ,ا

دج ةردان اهنأ نم مغرلاب .ءاودلا اذه لوانت :ةميخو

خافتنا ,سفنت تابوعص ,سفنتلا دنع يئاجف زيزأ لثم يسسحت لعف در ىلع رهظت امدنع ا

صوصخ( ةكح وأ حفط ,نيتفشلا وأ هجولا ,نينفجلا يف ةافولا كلذ يف امب( ةيسسحت لعف دودر نع غيلبتلا

مت .)مسجلا لك .تيار-وكولچلاب ةهيبش ةيودأ عم )ا

دج ةردان تلااح مدختسم ىتح ةريتوب رهظت( )common( ةعئاش ة

ّ

يبناج ضارعأ :)10 نيب نم 1 )مدلا يف ركسلا نم ضفخنم ىوتسم( مدلا ركس صقن نايثغ لاهسإ نطب ملأ ىتح ةريتوب رهظت( )uncommon( ةعئاش ريغ ة

ّ

يبناج ضارعأ :)100 نيب نم 1 مدختسم ةخود ساع

شاع

ةيبابض ةيؤر تاؤيقت )نكاد لوبو ةكح ,نينيعلاو دلجلا رارفصا( ناقري )دلجلا باهتلا( اميزكإ اهعويش ديدحت متي مل ضارعأ( فورعم ريغ اهعويش ةيبناج ضارعأ :)دعب )ءاضيبلا مدلا ايلاخ نم ن

يعم عونب صقن( تاب

َّ

ملا ة

)ءاضيبلا مدلا تايرك دادعت يف ضافخنا( ض

بلا تا

َّ

كلا ة

َّ

)مدلا يف تاحيفصلا ددع يف ضافخنا( تاحيف

ُّ

صلا ة

َّ

)ءارمحلا مدلا ايلاخل ذاش ريمدت( يللاحنلإا مدلا رقف )مدلا ايلاخ عيمج ددع يف ضافخنا( ة

ما

َّ

شلا تا

َّ

كلا ة

َّ

ةداح ريغ ة

يريفرب )ىمام

ح( رارمحا ةكح )ةبصحلا هيبش وأ نردتم ,رمحا( حفط )يسسحت دلج باهتلا( باهتلا وأ دلجلا يف رارمحا ,ةكح )ىرش( ة

كحلل ةريثمو ةزراب ,ةبحاش ءارمح تافآ ءوضلل ةيساسح )مدلا مويدوص صقن( مدلا مويدوص يف ضافخنا كابترا سأر ملأ ةجودزم ةيؤرو ةيؤرلا يف تابارطضا كاسمإ دبكلا ةفيظو يف تابارطضاو )hepatitis( دبك باهتلا ضرملاب ماع روعش ةيربخملا تاصوحفلا يف ةذاش جئاتن تيناع اذإ وأ ة

ّ

يبناجلا ضارعلأا دحأ مقافت اذإ ,

ّ

يبناج ضرع رهظ اذإ .بيبطلا ةراشتسا كيلع ,ةرشنلا يف ركذ

ُ

ي مل

ّ

يبناج ضرع نم

ة

ّ

يبناج ضارعأ نع غيلبتلا ىلع طغضلا للاخ نم ةحصلا ةرازول ة

يبناج ضارعأ نع غيلبتلا نكمي يف دوجوملا "يئاود جلاع بقع ة

يبناج ضارعأ نع غيلبتلا" طبارلا يذلا www.health.gov.il ةحصلا ةرازو عقوم يف ةيسيئرلا ةحفصلا نع وأ ,ة

يبناج ضارعأ نع غيلبتلل ة

يتنرتنلإا ةرامتسلاا ىلإ هجوي :طبارلل لوخدلا قيرط

https://sideeffects.health.gov.il

:يلاتلا ناونعلا ةطساوب وچيريپ ةكرشل غيلبتلا نكمي ,ةفاضلإاب

www.perrigo-pharma.co.il

؟ءاودلا نيزخت ةيفيك .5

قلغم ناكم يف رخآ ءاود لكو ءاودلا اذه ظفح بجي !ممستلا بنجت عنمت كلذبو مهتيؤر لاجمو عضرلا وأ/و لافطلأا يديأ لوانتم نع ا

ديعب .بيبطلا نم ةحيرص تاميلعت نودب ؤيقتلا ببست لا .ممستلا

)exp. date( ةيحلاصلا ءاهتنا خيرات دعب ءاودلا لامعتسا زوجي لا ريخلأا مويلا ىلإ عجري ةيحلاصلا ءاهتنا خيرات .ةوبعلا ىلع رهظي يذلا .رهشلا سفن نم

.ةيوئم ةجرد 25 تحت نيزختلا بجي

تايافنلا وأ هايملا فرصم قيرط نع ةيودلأا نم صلختلا زوجي لا

عت مل يتلا ةيودلأا نم صلختلا ة

يفيك نع

يلديصلا لأسا .ةيلزنملا .ةئيبلا ىلع ظافحلا يف مهاس

ت تاوطخلا هذه .ةيرورض

ة

ّ

يفاضإ تامولعم .6

:ىلع ا

ً

ضيا ءاودلا يوتحي ةلا

ّ

عفلا ةداملل ةفاضلإاب

Lactose 200, Microcrystalline сellulose, Maize

starch, Stearic acid.

.زوتكلا علم 154 ىلع يوتحي صرق لك

:ةوبعلا ىوتحم وه امو ءاودلا ودبي فيك ةدحاو ةهج نم ,ءاضيبو ةريدتسم يه غلم 5 تيار-وكولچ صارقأ يف صرق 30 نم ةوبع يف ,رطش طخ ةيناثلا ةهجلا نمو ,A م

.)تاحيول( تارتسيلب

ليئارسإ وچيريپ :هناونعو ليجستلا بحاص ,جتنملا مسإ .ماحوري ,16 .ب.ص ,.ض.م سلاكيتوسامراف

.2020 طابش يف حيقنتلا

مت

:ةحصلا ةرازو يف يموكحلا ةيودلأا لجس يف ءاودلا ليجست مقر

13227.27134

ىلع .ركذملا ةغيصب ةرشنلا هذه ةغايص تمت ,ةءارقلا ليهستو طيسبتلل .نيسنجلا لاكل صصخ

م ءاودلا ,كلذ نم مغرلا

26.2.20

Summary of Product

Characteristics

1. Name of the medicinal product

Gluco-Rite 5mg Tablets

2. Qualitative and quantitative composition

Glipizide 5 mg

Excipient with known effect:

Each tablet contains 153 mg lactose monohydrate.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Tablet.

White tablets, convex, scored with a break line on one side and with 'A' on the

other side.

4. Clinical particulars

4.1 Therapeutic indications

Gluco-Rite is indicated as an adjunct to diet for the control of hyperglycemia and its

associated symptomatology in patients with diabetes mellitus type II.

4.2 Posology and method of administration

PosologyAs for any hypoglycaemic agent, dosage must be adapted for each

individual case.

Short term administration of glipizide may be sufficient during periods of transient

loss of control in patients usually controlled well on diet.

In general, glipizide should be given shortly before a meal to achieve the greatest

reduction in post-prandial hyperglycaemia.

Initial Dose

The recommended starting dose is 5 mg, given before breakfast or the midday

meal. Mild diabetics, geriatric patients or those with liver disease may be started

on 2.5 mg.

Titration

Dosage adjustments should ordinarily be in increments of 2.5 to 5 mg, as

determined by blood glucose response. At least several days should elapse

between titration steps. The maximum recommended single dose is 15 mg. If this

is not sufficient, splitting the daily dosage may prove effective. Doses above 15 mg

should ordinarily be divided.

Maintenance

Some patients may be effectively controlled on a once-a-day regimen. Total daily

dosage above 15 mg should ordinarily be divided.

The maximum recommended daily dosage is 20 mg.

Paediatric population

Safety and effectiveness in children have not been established.

Use in Elderly and High Risk Patients

In elderly, debilitated and malnourished patients or patients with an impaired renal

or hepatic function, the initial and maintenance dosing should be conservative to

avoid hypoglycaemic reactions (see Initial Dose section 4.4).

Patients Receiving Other Oral Hypoglycaemic Agents

As with other sulphonylurea class hypoglycaemics, no transition period is

necessary when transferring patients to glipizide. Patients should be observed

carefully (1-2 weeks) for hypoglycaemia when being transferred from longer half-

life sulphonylureas (e.g. chlorpropamide) to glipizide due to potential overlapping

of drug effect.

Method of administration

For oral use only.

4.3 Contraindications

1. Hypersensitivity to the active substance glipizide, other sulphonylureas or

sulphonamides, or to any of the excipients listed in section 6.1.

2. Insulin-dependent diabetes mellitus , diabetic ketoacidosis, diabetic coma;

3. Severe renal or hepatic insufficiency;

4. Patients treated with miconazole (see section 4.5);

5. Pregnancy and lactation

4.4 Special warnings and precautions for use

Glucose-6-phosphate dehydrogenase deficiency

Since glipizide belongs to the class of sulfonylurea agents, caution should be used

in patients with G6PD-deficiency. Treatment of patients with G6PD-deficiency with

sulfonylurea agents can lead to haemolytic anaemia and a non-sulfonylurea

alternative should be considered.

Hypoglycaemia

All sulphonylurea agents are capable of producing severe hypoglycaemia. Renal

or hepatic insufficiency may cause elevated blood levels of glipizide and the latter

may also diminish gluconeogenic capacity, both of which increase the risk of

serious hypoglycaemic reactions. Elderly, debilitated or malnourished patients and

those with adrenal or pituitary insufficiency are particularly susceptible to the

hypoglycaemic action of glucose-lowering drugs.

Hypoglycaemia may be difficult to recognise in the elderly, and in people who are

taking beta-adrenergic blocking drugs (see section 4.5.). Hypoglycaemia is more

likely to occur when caloric- intake is deficient, after severe or prolonged exercise,

when alcohol is ingested, or when more than one glucose-lowering drug is used.

Loss of control of blood glucose

When a patient stabilised on a diabetic regimen is exposed to stress such as fever,

trauma, infection, or surgery, a loss of control may occur. At such times, it may be

necessary to discontinue glipizide and administer insulin.

The effectiveness of any oral hypoglycaemic drug, including glipizide, in lowering

blood glucose to a desired level decreases in many patients over a period of time,

which may be due to progression of the severity of diabetes or due to diminished

responsiveness to the drug. This phenomenon is known as secondary failure, to

distinguish it from primary failure in which the drug is ineffective in an individual

patient when first given. Adequate adjustment of dose and adherence to diet

should be assessed before classifying a patient as a secondary failure.

Renal and Hepatic Disease

The pharmacokinetics and/or pharmacodynamics of glipizide may be affected in

patients with impaired renal or hepatic function. If hypoglycaemia should occur in

such patients, it may be prolonged and appropriate management should be

instituted.

Information for Patients

Patients should be informed of the potential risks and advantages of glipizide and

of alternative modes of therapy. They should also be informed about the

importance of adherence to dietary instructions, of a regular exercise program, and

of regular testing of urine and/or blood glucose.

The risks of hypoglycaemia, its symptoms and treatment, and conditions that

predispose to its development should be explained to patients and responsible

family members. Primary and secondary failure should also be explained.

Laboratory Tests

Blood and urine glucose should be monitored periodically. Measurement of

glycosylated haemoglobin may be useful.

This product contains lactose. Patients with rare hereditary problems of galactose

intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption should

not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

The following products are likely to increase the hypoglycaemic effect:

- Contraindicated combinations

Miconazole

Increase in hypoglycaemic effect, possibly leading to symptoms of hypoglycaemia

or even coma.

- Inadvisable combinations

Nonsteroidal Anti-inflammatory Drugs (e.g. phenylbutazone) Increase in

hypoglycaemic effect of sulphonylureas (displacement of sulphonylurea binding to

plasma proteins and/or decrease in sulphonylurea elimination).

Alcohol

Increase in hypoglycaemic reaction which can lead to hypoglycaemic coma.

- Combinations requiring precaution

Fluconazole

Increase in the half-life of the sulphonylurea, possibly giving rise to symptoms of

hypoglycaemia.

Voriconazole

Although not studied, voriconazole may increase the plasma levels of

sulfonylureas, (e.g. tolbutamide, glipizide and glyburide) and therefore cause

hypoglycaemia. Careful monitoring of blood glucose is recommended during co-

administration.

Salicylates (acetylsalicylic acid)

Increase in hypoglycaemic effect by high doses of acetylsalicylic acid

(hypoglycaemic action of the acetylsalicylic acid).

Beta-blockers

All beta-blockers mask some of the symptoms of hypoglycaemia, (i.e. palpitations

and tachycardia). Most non cardio selective beta-blockers increase the incidence

and severity of hypoglycaemia.

Angiotensin converting Enzyme inhibitors

The use of angiotensin converting enzyme inhibitors may lead to an increased

hypoglycaemic effect in diabetic patients treated with sulphonylureas.

Cimetidine

The use of cimetidine may be associated with a reduction in post prandial blood

glucose in patients treated with glipizide.

The hypoglycaemic action of sulphonylureas in general may also be potentiated by

monoamine oxidase inhibitors, quinolones and drugs that are highly protein bound,

such as sulfonamides, chloramphenicol, probenecid, coumarins and fibrates.

When such drugs are administered to (or withdrawn from) a patient receiving

glipizide, the patient should be observed closely for hypoglycaemia (or loss of

control).

The following products could lead to hyperglycaemia:

- Inadvisable combinations

Danazol

Diabetogenic effect of danazol. If it cannot be avoided, warn the patient and step

up self monitoring of blood glucose and urine. Possibly adjust the dosage of

antidiabetic agent during treatment with danazol and after its discontinuation.

- Combinations requiring precaution

Colesevelam: In studies assessing the effect of colesevelam on the

pharmacokinetics of glipizide in healthy volunteers, reductions in glipizide AUC and

Cmax of 12% and 13%, respectively were observed when colesevelam was

coadministered with glipizide. When glipizide was administered 4 hours prior to

colesevelam, there was no significant change in glipizide AUC or Cmax, -4% and

0%, respectively. Therefore, Gluco-Rite should be administered at least 4 hours

prior to colesevelam to ensure that colesevelam does not reduce the absorption of

glipizide.

Phenothiazines (e.g. chlorpromazine) at High doses (> 100 mg /day of

chlorpromazine)

Elevation in blood glucose (reduction in insulin release).

Corticosteroids

Elevation in blood glucose.

Sympathomimetics (e.g. ritodrine, salbutamol, terbutaline)

Elevation in blood glucose due to beta-2-adrenoceptor stimulation.

Progestogens

Diabetogenic effects of high-dose progestogens. Warn the patient and step up

self-monitoring of blood glucose and urine. Possibly adjust the dosage of

antidiabetic agent during treatment with the neuroleptics, corticoids or progestogen

and after discontinuation.

Other drugs that may produce hyperglycaemia and lead to a loss of control include

the thiazides and other diuretics, thyroid products, oestrogens, oral contraceptives,

phenytoin, nicotinic acid, calcium channel blocking drugs, and isoniazid.

When such drugs are administrated to (or withdrawn from) a patient receiving

glipizide, the patient should be observed closely for hypoglycaemia.

4.6.Fertility, pregnancy and lactation

Pregnancy

Glipizide is contraindicated in pregnancy.

Glipizide was found to be mildly fetotoxic in rat reproductive studies. No

teratogenic effects were found in rat or rabbit studies.

Prolonged severe hypoglycaemia (4 -10 days) has been reported in neonates born

to mothers who were receiving a sulphonylurea drug at the time of delivery.

Because recent information suggests that abnormal blood glucose levels during

pregnancy are associated with a higher incidence of congenital abnormalities,

many experts recommend that insulin be used during pregnancy to maintain blood

glucose levels as close to normal as possible.

Breast feeding

No data are available on secretion into breast milk. Therefore glipizide is

contraindicated in lactation.

4.7 Effects on ability to drive and use machines

The effect of glipizide on the ability to drive or operate machines has not been

studied. However, there is no evidence to suggest that glipizide may affect these

abilities. Patients should be aware of the symptoms of hypoglycaemia and be

careful about driving and the use ofmachines, especially when optimum

stabilisation has not been achieved, for example during the change-over from

other medications or during irregular use.

4.8 Undesirable effects

The majority of side effects have been dose related, transient, and have

responded to dose reduction or withdrawal of the medication. However, clinical

experience thus far has shown that, as with other sulphonylureas, some side

effects associated with hypersensitivity may be severe and deaths have been

reported in some instances.

The reported adverse reactions, which may possibly be associated with glipizide,

are listed in the following table by system organ class and frequency group: 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), Not known (cannot be

estimated from available data).

Blood and lymphatic system disorders:

Not known - Leukopenia, agranulocytosis, thrombocytopenia, haemolytic anaemia,

pancytopenia

Metabolism and nutrition disorders:

Common – Hypoglycaemia

Not known – Hyponatraemia

Psychiatric disorders:

Not known – Confusional state

Nervous system disorders:

Uncommon – Dizziness

, somnolence

, tremor

Not known – Headache

Eye disorders:

Uncommon – Vision blurred

Not known – Diplopia

, visual impairment

, visual acuity reduced

Gastrointestinal disorders:

Common – Nausea

, diarrhoea

, abdominal pain and upper

abdominal pain

Uncommon – Vomiting

Not known – Constipation

Hepatobiliary disorders:

Uncommon – Jaundice cholestatic

Not known – Hepatic function abnormal, hepatitis

Skin and subcutaneous tissue disorders:

Uncommon – Eczema

Not known – Dermatitis allergic

, erythema

, rash morbilliform

, rash

maculopapular

, urticaria

, pruritus

, photosensitivity reaction

Congenital, familial and genetic disorders:

Not known – Porphyria non-acute

General disorders and administration site conditions:

Not known – Malaise

Investigations:

Not known – Aspartate aminotransferase increased

, blood lactate dehydrogenase

(BLT) increased

, blood alkaline phosphatase increased

, blood urea increased

(BUN)

, blood creatinine increased

They are This is usually transient and do not require discontinuance of therapy;

however, they may also be symptoms of hypoglycaemia.

Appear to be dose related and usually disappear on division or reduction of

dosage.

Discontinue treatment if cholestatic jaundice occurs.

They frequently disappear with continued therapy. However, if they persist, the

drug should be discontinued.

The relationship of these abnormalities to glipizide is uncertain, and they have

rarely been associated with clinical symptoms.

Aplastic anaemia and disulfiram-like reactions have been reported with other

sulphonylureas.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product

is important. It allows continued monitoring of the benefit/risk balance of the

medicinal product.

Any suspected adverse events should be reported to the Ministry of Health

according to the National Regulation by using an online form

/https://sideeffects.health.gov.il

Additionally, you can also report to www.perrigo-pharma.co.il.

4.9 Overdose

There is no well documented experience with glipizide overdosage.

Overdosage of sulphonylureas including glipizide can produce glycaemia. Mild

hypoglycaemic symptoms without loss of consciousness or neurologic findings

should be treated actively with oral glucose and adjustments in drug dosage and/or

meal patterns. Close monitoring should continue until the physician is assured that

the patient is out of danger. Severe hypoglycaemic reactions with coma, seizure,

or other neurological impairment occur infrequently, but constitute medical

emergencies requiring immediate hospitalisation. If hypoglycaemic coma is

diagnosed or suspected, the patient should be given a rapid intravenous injection

of concentrated (50%) glucose solution. This should be followed by a continuous

infusion of a more dilute (10%) glucose solution at a rate that will maintain the

blood glucose at a level above 100 mg/dL (5.55 mmol/L). Patients should be

closely monitored for a minimum of 48 hours and depending on the status of the

patient at this time the physician should decide whether further monitoring is

required. Clearance of glipizide from plasma may be prolonged in people with liver

disease. Because of the extensive protein binding of glipizide, dialysis is unlikely to

be of benefit.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Drugs used in diabetes, blood glucose lowering drugs

excl. insulins, sulfonylureas, ATC code: A10BB07.

Glipizide is an oral blood glucose lowering drug of the sulphonylurea class. The

primary mode of action of glipizide is the stimulation of insulin secretion from the

beta-cells of pancreatic islet tissue. Stimulation of insulin secretion by glipizide in

response to a meal is of major importance. Fasting insulin levels are not elevated

even on long-term glipizide administration, but the post-prandial insulin response

continues to be enhanced after at least 6 months of treatment. The insulinotropic

response to a meal occurs within 30 minutes after oral dose of glipizide in diabetic

patients, but elevated insulin levels do not persist beyond the time of the meal

challenge. There is also increasing evidence that extrapancreatic effects involving

potentiation of insulin action form a significant component of the activity of

glipizide.

Blood sugar control persists for up to 24 hours after a single dose of glipizide, even

though plasma levels have declined to a small fraction of peak levels by that time

(see section 5.2).

5.2 Pharmacokinetic properties

Absorption

Gastrointestinal absorption of glipizide in hummans is uniform, rapid and

essentially complete. Peak plasma concentrations occur 1to 3 hours after a single

oral dose. The half-life of elimination ranges from 2to 4 hours in normal subjects,

whether given intravenously or orally. The metabolic and excretory patterns are

similar with the two routes of administration, indicating that first-pass metabolism is

not significant. Glipizide does not accumulate in plasma on repeated oral

administration. Total absorption and disposition of an oral dose were unaffected by

food in normal volunteers, but absorption was delayed by about 40 minutes. Thus,

glipizide was more effective when administered about 30 minutes before, rather

than with, a test meal in diabetic patients.

Distribution

Protein binding was studied in serum from volunteers who received either oral or

intravenous glipizide and found to be 98%to 99% one hour after either route of

administration. The apparent volume of distribution of glipizide after intravenous

administration was 11L, indicative of localisation within the extracellular fluid

compartment. In mice, no glipizide or metabolites were detectable

autoradiographically in the brain or spinal cord of males or females, nor in the

foetuses of pregnant females. In another study, however, very small amounts of

radioactivity were detected in the foetuses of rats given labelled drug.

Biotransformation

The metabolism of glipizide is extensive and occurs mainly in the liver.

Elimination

The primary metabolites are inactive hydroxylation products and polar conjugates

and are excreted mainly in the urine. Less than 10% unchanged glipizide is found

in urine.

5.3 Preclinical safety data

Acute toxicity studies showed no specific susceptibility. The acute oral toxicity of

glipizide was extremely low in all species tested (LD50 greater than 4 g/kg).

Chronic toxicity tests in rats and dogs at doses up to 8.0 mg/kg did not show any

evidence of toxic effects.

A 20-month study in rats and an 18-month study in mice at doses up to 75 times

the maximum human dose revealed no evidence of drug related carcinogenicity.

Bacterial and in vivo mutagenicity tests were uniformly negative. Studies in rats of

both sexes at doses up to 75 times the maximum human dose showed no effects

on fertility.

6. Pharmaceutical particulars

6.1 List of excipients

Lactose 200, Microcrystalline сellulose, Maize starch, Stearic acid

6.2 Incompatibilities

None stated.

6.3 Shelf life

36 months. The expiry date of the product is indicated on the packaging materials

6.4 Special precautions for storage

Store below 25

6.5 Nature and contents of container

Blister strips containing 30 tablets

6.6 Special precautions for disposal and other handling

None.

7. Manufacturer and Registration authorisation holder

Perrigo Israel Pharmaceuticals, P.O.B 16, Yeruham Israel

8. Registration authorisation number

13227.27134

This leaflet format has been determined by the Ministry of Health and the content

has been checked and approved in November 2015 and updated according to the

guidelines of the Ministry of Health in February 2020.