Getryl

Main information

  • Trade name:
  • Getryl 3mg Tablet
  • Dosage:
  • 3mg
  • Pharmaceutical form:
  • Tablet
  • Units in package:
  • Alu-Alu Blister Pack x 10's (box of 20's)
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug
  • Manufactured by:
  • Getz Pharma (Pvt) Limited

Documents

Localization

  • Available in:
  • Getryl 3mg Tablet
    Philippines
  • Language:
  • English

Therapeutic information

  • Therapeutic area:
  • Anti-Diabetic
  • Therapeutic indications:
  • As an adjunct to diet and exercise to lower blood glucose in patients with non-insulin-dependent (type 2) diabetes mellitus.

Status

  • Source:
  • FDA - Food And Drug Administration - Philippines
  • Authorization number:
  • DR-XY32079
  • Authorization date:
  • 04-08-2019
  • Last update:
  • 19-05-2017

Summary of Product characteristics: dosage, interactions, side effects

DESCRIPTION

Glimepiride (Getryl

) is an oral blood glucose lowering drug of the

sulfonylurea class. Chemically glimepiride is 1-[[p-[2-(3-Ethyl-4-methyl-

2-oxo-3-pyrroline-1-carboxamido) ethyl]phe nyl]-sulphonyl]-3-(trans-4-

methylcyclohexyl)urea. The molecular formula is C

S and the

structural formula is:

FORMULATION

Glimepiride (Getryl

) is available for oral administration as:

1. Glimepiride (Getryl

) Tablets 1mg

Each tablet contains:

Glimepiride…1mg

2. Glimepiride (Getryl

) Tablets 2mg

Each tablet contains:

Glimepiride…2mg

3. Glimepiride (Getryl

) Tablets 3mg

Each tablet contains:

Glimepiride…3mg

4. Glimepiride (Getryl

) Tablets 4mg

Each tablet contains:

Glimepiride…4mg

CLINICAL PHARMACOLOGY

Mechanism of Action

The primary mechanism of action of glimepiride appears to be dependent

on stimulating the release of insulin from functioning pancreatic beta

cells. In addition, extra-pancreatic effects (e.g. reduction of basal hepatic

glucose production and increased peripheral tissue sensitivity to insulin

and glucose uptake) may also play a role in the activity of glimepiride.

However, as with other sulfonylureas, the mechanism by which glimepiride

lowers blood glucose during long-term administration has not been

clearly established.

Pharmacokinetics

After oral administration glimepiride is completely absorbed from the GI

tract. The oral bioavailability is approximately 100%. Peak plasma

concentrations occur in 2-3 hours. More than 99% of the drug is bound

to plasma proteins. Glimepiride is completely metabolized by oxidative

biotransformation into two main metabolites, a hydroxy derivative and

a carboxy derivative.

The elimination half-life (t

after multiple doses is about 5-8 hours.

Approximately 60% of dose is eliminated in the urine and 40% in the

feces.

Special populations

Renal Insufficiency

A single-dose clinical study glimepiride showed that glimepiride serum

levels decreased as renal function decreased. However, metabolite

serum levels (mean AUC values) increased. The apparent terminal half-

life (t

) for glimepiride did not change, while the half-lives for metabolites

increased as renal function decreased. Mean urinary excretion of

metabolites

percent

dos e,

however,

de c r ea s ed .

INDICATIONS

Glimepiride (Getryl

) is indicated as an adjunct to diet and exercise to

lower the blood glucose in patients with noninsulin-dependent (Type 2)

diabetes mellitus (NIDDM) whose hyperglycemia cannot be controlled

by diet and exercise alone.

Glimepiride (Getryl

) may be used concomitantly with metformin when

diet, exercise, and Glimepiride (Getryl

) or metformin alone do not result

in adequate glycemic control.

Glimepiride (Getryl

) is also indicated for use in combination with insulin

to lower blood glucose in patients whose hyperglycemia cannot be

controlled by diet and exercise in conjunction with an oral hypoglycemic

agent.

DOSAGE & ADMINISTRATION

In initiating treatment for noninsulin-dependent diabetes, diet and

exercise should be emphasized as the primary form of treatment. There

is no fixed dosage regimen for the management of diabetes mellitus

with Glimepiride (Getryl

) or any other hypoglycemic agent. The patient’s

fasting blood glucose and HbA

must be measured periodically to

determine

minimum

effective

dose

p a ti e n t .

Short-term administration of Glimepiride (Getryl

) may be sufficient

during periods of transient loss of control in patients usually well controlled

on diet and exercise.

Usual Starting Dose

The usual starting dose of Glimepiride (Getryl

) as initial therapy is 1-

2mg once daily, administered with breakfast or the first main meal.

Those patients who may be more sensitive to hypoglycemic drugs should

be started at 1mg once daily, and should be titrated carefully. The

maximum starting dose of Glimepiride (Getryl

) should be not more than

2mg.

Usual Maintenance Dose

The usual maintenance dose of Glimepiride (Getryl

) is 1 to 4mg once

daily. The maximum recommended dose is 8mg once daily. After reaching

a dose of 2mg, dose increases should be made in increments of no

more than 2mg at 1-2 week intervals based upon the patient’s blood

glucose response. Long-term efficacy should be monitored by

measurement of HbA

levels, for example, every 3 to 6 months.

Glimepiride (Getryl

®

) – Metformin Combination Therapy

If patients do not respond adequately to the maximal dose of Glimepiride

(Getryl

) monotherapy, addition of metformin may be considered. With

concomitant Glimepiride (Getryl

) and metformin therapy, the desired

control of blood glucose may be obtained by adjusting the dose of each

drug.

Glimepiride (Getryl

®

) – Insulin Combination Therapy

Combination therapy with Glimepiride (Getryl

) and insulin may also be

used in secondary failure patients. The fasting glucose level for instituting

combination therapy is in the range of >150mg/dL in plasma or serum

depending on the patient. The recommended Glimepiride (Getryl

) dose

is 8mg once daily administered with the first main meal. After starting

with low-dose insulin, upward adjustments of insulin can be done

approximately weekly as guided by fr equent measurements of fasting

blood glucose.

Special populations

In elderly, debilitated, or malnourished patients, or in patients with

hepatic insufficiency, the initial dosing, dose increments, and maintenance

dosage should be conservative to avoid hypoglycemic reactions.

Renal impaired patients

In patients with mild to moderate renal impairment, a starting dose of

1mg once daily must not be exceeded. The dose may then be carefully

titrated upwards if necessary based on fasting blood glucose levels in

increments of 1mg at intervals of one to two weeks.

ADVERSE REACTIONS

Glimepiride is generally well tolerated. However following are the side

effects reported during treatment with glimepiride.

Hypoglycemia: Hypoglycemia is the greatest potential risk with all

sulfonylureas.

Visual reactions: There may be temporary visual impairment (e.g.,

changes in accommodation and/or blurred vision) due to the change in

Glimepiride

blood

glucose

levels,

especially at

the start

tr eatment.

Gastrointestinal reactions: Occasionally gastrointestinal symptoms such

as nausea, vomiting, sensations of pressure or fullness in the epigastrium,

abdominal pain and diarrhea may occur.

Hematologic reactions: Rarely, thrombocytopenia and in isolated cases,

leukopenia may develop. In isolated instances, thrombocytopenic purpura,

agranulocytosis, pancytopenia due to myelosuppression, eosinophilia,

hemolytic

anemia,

aplastic

anaemia,

erythrocytopenia

granulocytopenia may occur.

Dermatologic reactions: Occasionally, allergic or pseudo-allergic skin

reactions (e.g., pruritus, erythema, urticaria, erythematous and maculo-

papular and bullous skin eruptions or psoriasiform drug eruption) may

occur in patients treated with sulfonylureas.

Hepatic reactions: Increased liver enzymes (AST, ALT), abnormal liver

function, cholestasis, cholestatic hepatitis, granulomatous hepatitis,

bilirubinemia aernia and liver failure have been reported with sulfonylureas

in isolated cases.

Electrolyte disturbance: In isolated cases, hyponatremia has been

reported in patients receiving glimepiride and other sulfonylureas, most

often in patients who are on other medications or have medical conditions

known to cause hyponatremia or to increase release of anti-diuretic

hormone.

Others: Isolated cases of allergic vasculitis have been reported with

sulfonylureas.

CONTRAINDICATIONS

l

Glimepiride

contraindicated

patients

with

known

hypersensitivity to the drug.

l

Diabetic ketoacidosis, with or without coma. This condition

should be treated with insulin.

PRECAUTIONS

The patient’s fasting blood glucose and HbA

must be measured

periodically to determine the minimum effective dose for the patient; to

detect primary failure, i.e., inadequate lowering of blood glucose at the

maximum recommended dose of medication; and to detect secondary

failure, i.e., loss of adequate blood glucose lowering response. After an

initial period of effectiveness glycosylated hemoglobin levels should be

performed

monitor

patient’s

response

ther apy.

Hypoglycemia

All sulfonylurea drugs are capable of producing severe hypoglycemia.

Proper patient selection, dosage, and instructions are important to avoid

hypoglycemic episodes.

Debilitated patients, malnourished patients and patients with adrenal,

pituitary, renal or hepatic insufficiency are particularly susceptible to the

hypoglycemic action of sulfonylureas and should therefore be carefully

monitored. The dosage of glimepiride should be carefully adjusted in

these patients.

Hepatic insufficiency may cause increased serum concentrations of

glimepiride and may diminish gluconeogenic capacity, both of which

increase the risk of severe hypoglycemic reactions.

Alcohol ingestion, severe or prolonged exercise, deficient caloric intake

or use of more than one antidiabetic agent may predispose patients to

the development of hypoglycemia.

Loss of control of blood glucose

When a patient stabilized on any 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 add insulin in com bination with

glimepiride or even use insulin monotherapy.

Pregnancy

Glimepiride is not recommended for use during pregnancy.

Nursing mothers

It is not known whether glimepiride is distributed into human breast milk.

However, some sulfonylureas are distributed into human breast milk.

Because of its potential to cause hypoglycemia in nursing infants,

glimepiride is not recommended for use by nursing mothers.

Pediatric use

Glimepiride is not recommended for use in children.

Drug Interactions

l

The hypoglycemic a ction of sulfonylureas may be potentiated by

certain drugs, including nonsteroidal anti-inflammatory

drugs and other drugs that are highly protein bound,

s u c h

s ali c y la te s ,

sulfonamides,

chl or ampheni col ,

coumarins, probenecid, monoamine oxidase inhibitors, and

beta adrenergic blocking agents. When these drugs are

administered to a patient receiving glimepiride, the patient

should be observed closely for hypoglycemia.

l

Certain drugs tend to produce hyperglycemia and may lead to

loss of control. These drugs include the thiazides and other

diuretics, corticosteroids, phenothiazines, thyroid products,

estrogens, oral contraceptives, phenytoin, nicotinic acid,

sympathomimetics, and isoniazid. When these drugs are

administered to a patient receiving glimepiride, the patient

should be closely observed for loss of control.

l

Glimepiride

metabolised

cytochrome

P450

(CYP2C9). This should be taken into account when glimepiride

is co-administered with inducers, inhibitors or substrates

CYP2C9

(e.g.,

rifampicin, fluconazole, amiodarone,

tolbutamide, diclofenac, ibuprofen, naproxen).

l

receptor antagonists, beta-blockers, clonidine and reserpine

may lead to either potentiation or weakening of the blood

glucose-lowering effect.

l

Concomitant treatment with a beta-receptor bloc ker,

clonidine, guanethidine or reserpine may mask the warning

symptoms of a hypoglycemic attack.

l

Acute and chronic alcohol intake may either potentiate or

attenuate the activity of glimepiride in an unpredictable fashion.

STORAGE CONDITIONS

Store at temperatures not exceeding 30

Protect from sunlight and moisture.

The expiration date refers to the product correctly stored at the required

conditions.

AVAILABILITY

Glimepiride (Getryl

) Tablets 1mg are available in blister pack of 10’s (Box

of 20’s).

Glimepiride (Getryl

) Tablets 2mg are available in blister pack of 10’s (Box

of 20’s).

Glimepiride (Getryl

) Tablets 3mg are available in blister pack of 10’s (Box

of 20’s).

Glimepiride (Getryl

) Tablets 4mg are available in blister pack of 10’s (Box

of 20’s).

CAUTION

Foods, Drugs, Devices and Cosmetics Act prohibits dispensing without

prescription.

Keep out of reach of children.

1mg, 2mg, 3mg, 4mg Tablet

Oral Hypoglycemic

Glimepiride

DESCRIPTION

Glimepiride (Getryl

) is an oral blood glucose lowering drug of the

sulfonylurea class. Chemically glimepiride is 1-[[p-[2-(3-Ethyl-4-methyl-

2-oxo-3-pyrroline-1-carboxamido)ethyl]phenyl]-sulphonyl]-3-(trans-4-

methylcyclohexyl)urea. The molecular formula is C

S and the

structural formula is:

FORMULATION

Glimepiride (Getryl

) is available for oral administration as:

1. Glimepiride (Getryl

) Tablets 1mg

Each tablet contains:

Glimepiride…1mg

2. Glimepiride (Getryl

) Tablets 2mg

Each tablet contains:

Glimepiride…2mg

3. Glimepiride (Getryl

) Tablets 3mg

Each tablet contains:

Glimepiride…3mg

4. Glimepiride (Getryl

) Tablets 4mg

Each tablet contains:

Glimepiride…4mg

CLINICAL PHARMACOLOGY

Mechanism of Action

The primary mechanism of action of glimepiride appears to be dependent

on stimulating the release of insulin from functioning pancreatic beta

cells. In addition, extra-pancreatic effects (e.g. reduction of basal hepatic

glucose production and increased peripheral tissue sensitivity to insulin

and glucose uptake) may also play a role in the activity of glimepiride.

However, as with other sulfonylureas, the mechanism by which glimepiride

lowers blood glucose during long-term administration has not been

clearly established.

Pharmacokinetics

After oral administration glimepiride is completely absorbed from the GI

tract. The oral bioavailability is approximately 100%. Peak plasma

concentrations occur in 2-3 hours. More than 99% of the drug is bound

to plasma proteins. Glimepiride is completely metabolized by oxidative

biotransformation into two main metabolites, a hydroxy derivative and

a carboxy derivative.

The elimination half-life (t

after multiple doses is about 5-8 hours.

Approximately 60% of dose is eliminated in the urine and 40% in the

feces.

Special populations

Renal Insufficiency

A single-dose clinical study glimepiride showed that glimepiride serum

levels decreased as renal function decreased. However, metabolite

serum levels (mean AUC values) increased. The apparent terminal half-

life (t

) for glimepiride did not change, while the half-lives for metabolites

increased as renal function decreased. Mean urinary excretion of

metabolites

percent

dos e,

however,

de c r ea s ed .

INDICATIONS

Glimepiride (Getryl

) is indicated as an adjunct to diet and exercise to

lower the blood glucose in patients with noninsulin-dependent (Type 2)

diabetes mellitus (NIDDM) whose hyperglycemia cannot be controlled

by diet and exercise alone.

Glimepiride (Getryl

) may be used concomitantly with metformin when

diet, exercise, and Glimepiride (Getryl

) or metformin alone do not result

in adequate glycemic control.

Glimepiride (Getryl

) is also indicated for use in combination with insulin

to lower blood glucose in patients whose hyperglycemia cannot be

controlled by diet and exercise in conjunction with an oral hypoglycemic

agent.

DOSAGE & ADMINISTRATION

In initiating treatm ent for noninsulin-dependent diabetes, diet and

exercise should be emphasized as the primary form of treatment. There

is no fixed dosage regimen for the management of diabetes mellitus

with Glimepiride (Getryl

) or any other hypoglycemic agent. The patient’s

fasting blood glucose and HbA

must be measured periodically to

determine

minimum

effective

dose

p a t i e n t .

Short-term administration of Glimepiride (Getryl

) may be sufficient

during periods of transient loss of control in patients usually well controlled

on diet and exercise.

Usual Starting Dose

The usual starting dose of Glimepiride (Getryl

) as initial therapy is 1-

2mg once daily, administered wi th breakfast or the first main meal.

Those patients who may be more sensitive to hypoglycemic drugs should

be started at 1mg once daily, and should be titrated carefully. The

maximum starting dose of Glimepiride (Getryl

) should be not more than

2mg.

Usual Maintenance Dose

The usual maintenance dose of Glimepiride (Getryl

) is 1 to 4mg once

daily. The maximum recommended dose is 8mg once daily. After reaching

a dose of 2mg, dose increases should be made in increments of no

more than 2mg at 1-2 week intervals based upon the patient’s blood

glucos e respons e. Long-ter m efficac y should

be moni tor ed by

measurement of HbA

levels, for example, every 3 to 6 months.

Glimepiride (Getryl

®

) – Metformin Combination Therapy

If patients do not respond adequately to the maximal dose of Glimepiride

(Getryl

) monotherapy, addition of metformin may be considered. With

concomitant Glimepiride (Getryl

) and metformin therapy, the desired

control of blood glucose may be obtained by adjusting the dose of each

drug.

Glimepiride (Getryl

®

) – Insulin Combination Therapy

Combination therapy with Glimepiride (Getryl

) and insulin may also be

used in secondary failure patients. The fasting glucose level for instituting

combination therapy is in the range of >150mg/dL in plasma or serum

depending on the patient. The recommended Glimepiride (Getryl

) dose

is 8mg once daily administered with the first main meal. After starting

with low-dose insulin, upward adjustments of insulin can be done

approximately weekly as guided by frequent measurements of fasting

blood glucose.

Special populations

In elderly, debilitated, or malnourished patients, or in patients with

hepatic insufficiency, the initial dosing, dose increments, and maintenance

dosage should be conservat ive to avoid hypoglycemic reactions.

Renal impaired patients

In patients with mild to moderate renal impairment, a starting dose of

1mg once daily must not be exceeded. The dose may then be carefully

titrated upwards if necessary based on fasting blood glucose levels in

increments of 1mg at intervals of one to two weeks.

ADVERSE REACTIONS

Glimepiride is generally well tolerated. However following are the side

effects reported during treatment with glimepiride.

Hypoglycemia: Hypoglycemia is the greatest potential risk with all

sulfonylureas.

Visual reactions: There may be temporary visual impairment (e.g.,

changes in accommodation and/or blurred vision) due to the change in

blood

glucose

levels,

especially at

the start

tr eatment.

Gastrointestinal reactions: Occasionally gastrointestinal symptoms such

as nausea, vomiting, sensations of pressure or fullness in the epigastrium,

abdominal pain and diarrhea may occur.

Hematologic reactions: Rarely, thrombocytopenia and in isolated cases,

leukopenia may develop. In isolated instances, thrombocytopenic purpura,

agranulocytosis, pancytopenia due to myelosuppression, eosinophilia,

hemolytic

anemia,

aplastic

anaemia,

erythrocytopenia

granulocytopenia may occur.

Dermatologic reactions: Occasionally, allergic or pseudo-allergic skin

reactions (e.g., pruritus, erythema, urticaria, erythematous and maculo-

papular and bullous skin eruptions or psoriasiform drug eruption) may

occur in patients treated with sulfonylureas.

Hepatic reactions: Increased liver enzymes (AST, ALT), abnormal liver

function, cholestasis, cholestatic hepatitis, granulomatous hepatitis,

bilirubinemia aernia and liver failure have been reported with sulfonylureas

in isolated cases.

Electrolyte disturbance: In isolated cases, hyponatremia has been

reported in patients receiving glimepiride and other sulfonylureas, most

often in patients who are on other medications or have medical conditions

known to cause hyponatremia or to increase release of anti-diuretic

hormone.

Others: Isolated cases of allergic vasculitis have been reported with

sulfonylureas.

CONTRAINDICATIONS

l

Glimepiride

contraindicated

patients

with

known

hypersensitivity to the drug.

l

Diabetic ketoacidosis, with or without coma. This condition

should be treated with insulin.

PRECAUTIONS

The patient’s fasting blood glucose and HbA

must be measured

periodically to determine the minimum effective dose for the patient; to

detect primary failure, i.e., inadequate lowering of blood glucose at the

maximum recommended dose of medication; and to detect secondary

failure, i.e., loss of adequate blood glucose lowering response. After an

initial period of effectiveness glycosylated hemoglobin levels should be

performed

monitor

patient’s

response

ther apy.

Hypoglycemia

All sulfonylurea drugs are capable of producing severe hypoglycemia.

Proper patient selection, dosage, and instructions are important to avoid

hypoglycemic episodes.

Debilitated patients, malnourished patients and patients with adrenal,

pituitary, renal or hepatic insufficiency are particularly susceptible to the

hypoglycemic action of sulfonylureas and should therefore be carefully

monitored. The dosage of glimepiride should be carefully adjusted in

these patients.

Hepatic insufficiency may cause increased serum concentrations of

glimepiride and may diminish gluconeogenic capacity, both of which

increase the risk of severe hypoglycemic reactions.

Alcohol ingestion, severe or prolonged exercise, deficient caloric intake

or use of more than one antidiabetic agent may predispose patients to

the development of hypoglycemia.

Loss of control of blood glucose

When a patient stabilized on any 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 add insulin in com bination with

glimepiride or even use insulin monotherapy.

Pregnancy

Glimepiride is not recommended for use during pregnancy.

Nursing mothers

It is not known whether glimepiride is distributed into human breast milk.

However, some sulfonylureas are distributed into human breast milk.

Because of its potential to cause hypoglycemia in nursing infants,

glimepiride is not recommended for use by nursing mothers.

Pediatric use

Glimepiride is not recommended for use in children.

Drug Interactions

l

The hypoglycemic a ction of sulfonylureas may be potentiated by

certain drugs, including nonsteroidal anti-inflammatory

drugs and other drugs that are highly protein bound,

s u c h

s ali c y la te s ,

sulfonamides,

chl or ampheni col ,

coumarins, probenecid, monoamine oxidase inhibitors, and

beta adrenergic blocking agents. When these drugs are

administered to a patient receiving glimepiride, the patient

should be observed closely for hypoglycemia.

l

Certain drugs tend to produce hyperglycemia and may lead to

loss of control. These drugs include the thiazides and other

diuretics, corticosteroids, phenothiazines, thyroid products,

estrogens, oral contraceptives, phenytoin, nicotinic acid,

sympathomimetics, and isoniazid. When these drugs are

administered to a patient receiving glimepiride, the patient

should be closely observed for loss of control.

l

Glimepiride

metabolised

cytochrome

P450

(CYP2C9). This should be taken into account when glimepiride

is co-administered with inducers, inhibitors or substrates

CYP2C9

(e.g.,

rifampicin, fluconazole, amiodarone,

tolbutamide, diclofenac, ibuprofen, naproxen).

l

receptor antagonists, beta-blockers, clonidine and reserpine

may lead to either potentiation or weakening of the blood

glucose-lowering effect.

l

Concomitant treatment with a beta-receptor bloc ker,

clonidine, guanethidine or reserpine may mask the warning

symptoms of a hypoglycemic attack.

l

Acute and chronic alcohol intake may either potentiate or

attenuate the activity of glimepiride in an unpredictable fashion.

STORAGE CONDITIONS

Store at temperatures not exceeding 30

Protect from sunlight and moisture.

The expiration date refers to the product correctly stored at the required

conditions.

AVAILABILITY

Glimepiride (Getryl

) Tablets 1mg are available in blister pack of 10’s (Box

of 20’s).

Glimepiride (Getryl

) Tablets 2mg are available in blister pack of 10’s (Box

of 20’s).

Glimepiride (Getryl

) Tablets 3mg are available in blister pack of 10’s (Box

of 20’s).

Glimepiride (Getryl

) Tablets 4mg are available in blister pack of 10’s (Box

of 20’s).

CAUTION

Foods, Drugs, Devices and Cosmetics Act prohibits dispensing without

prescription.

Keep out of reach of children.

Please read the contents carefully before use.

This package insert is continually updated from time to time.

Manufactured by: Getz Pharma (Pvt.) Ltd., 29-30/27, K.I.A., Karachi - 74900, Pakistan.

Imported by: Getz Pharma (Phils.) Inc., 2/F Tower 1, The Rockwell Business Center,

Ortigas Ave., Pasig City, Philippines.

PH07-200006661