Vildagluse

1.NAME OF THE MEDICINAL PRODUCT

Vildagluse 50mg Tablets


2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 50mg of vildagliptin.


3. PHARMACEUTICAL FORM

Tablet


4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Vildagliptin is indicated in the treatment of type 2 diabetes mellitus:

As dual oral therapy in combination with

- metformin, in patients with insufficient glycaemic control despite maximal

tolerated dose of monotherapy with metformin,

- a sulphonylurea, in patients with insufficient glycaemic control despite

maximal tolerated dose of a sulphonylurea and for whom metformin is

inappropriate due to contraindications or intolerance,

- a thiazolidinedione, in patients with insufficient glycaemic control and for

whom the use of a thiazolidinedione is appropriate.

4.2 Posology and method of administration

Adults

When used in dual combination with metformin or a thiazolidinedione, the

recommended daily dose of vildagliptin is 100mg, administered as one dose of

50 mg in the morning and one dose of 50 mg in the evening.

When used in dual combination with a sulphonylurea, the recommended dose

of vildagliptin is 50mg once daily administered in the morning. In this patient

population, vildagliptin 100mg daily was no more effective than vildagliptin

50mg once daily.

Doses higher than 100mg are not recommended.

The safety and efficacy of vildagliptin as triple oral therapy in combination with

metformin and a thiazolidinedione or with metformin and a sulphonylurea has

not been established.

Vildagluse can be administered with or without a meal (see also section 5.2).

Additional information on special populations

Renal impairment

No dose adjustment is required in patients with mild renal impairment

(creatinine clearance50 ml/min). The use of Vildagluse is not recommended

in patients with moderate or severe renal impairment or in haemodialysis

patients with end-stage renal disease (ESRD) (see also sections 4.4 and 5.2).

Hepatic impairment

Vildagluse should not be used in patients with hepatic impairment, including

patients with pre-treatment alanine aminotransferase (ALT) or aspartate

aminotransferase (AST)> 3x the upper limit of normal (ULN) (see also

sections 4.4 and 5.2).

Elderly (≥65 years)

No dose adjustments are necessary in elderly patients (see also sections 5.1 and

5.2).

Paediatric population (< 18 years)

Vildagluse is not recommended for use in children and adolescents due to a

lack of data on safety and efficacy.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients.

4.4 Special warnings and precautions for use

General

Vildagluse is not a substitute for insulin in insulin-requiring patients.

Vildagluse should not be used in patients with type 1 diabetes or for the

treatment of diabetic ketoacidosis.

Renal impairment

There is limited experience in patients with moderate to severe renal

impairment or in patients with ESRD on haemodialysis. Therefore, the use of

Vildagluse is not recommended in these patients.

Hepatic impairment

Vildagluse should not be used in patients with hepatic impairment, including

patients with pre-treatment ALT or AST> 3x ULN.

Liver enzyme monitoring

Rare cases of hepatic dysfunction (including hepatitis) have been reported. In

these cases, the patients were generally asymptomatic without clinical sequelae

and liver function test results returned to normal after discontinuation of

treatment. Liver Function tests should be performed prior to the initiation of

treatment with Vildagluse in order to know the patient’s baseline value. Liver

function should be monitored during treatment with Vildagluse at

three-month intervals during the first year and periodically thereafter. Patients

who develop increased transaminase levels should be monitored with a second

liver function evaluation to confirm the finding and be followed thereafter with

frequent liver function tests until the abnormality(ies) return(s) to normal.

Should an increase in AST or ALT of 3x ULN or greater persist, withdrawal of

Vildagluse therapy is recommended.

Patients who develop jaundice or other signs suggestive of liver dysfunction

should discontinue Vildagluse.

Following withdrawal of treatment with Vildagluse and LFT normalisation,

treatment with Vildagluse should not be reinitiated.

Cardiac failure

Experience with vildagliptin therapy in patients with congestive heart failure of

New York Heart Association (NYHA) functional class I-II is limited and

therefore vildagliptin should be used cautiously in these patients. There is no

experience of vildagliptin use in clinical trials in patients with NYHA

 

functional class III-IV and therefore use is not recommended in these patients.

Skin disorders

Skin lesions, including blistering and ulceration have been reported in

extremities of monkeys in non-clinical toxicology studies (see section 5.3).

Although skin lesions were not observed at an increased incidence in clinical

trials, there was limited experience in patients with diabetic skin complications.

Therefore, in keeping with routine care of the diabetic patient, monitoring for

skin disorders, such as blistering or ulceration, is recommended.

Excipients

The tablets contain lactose. Patients with rare hereditary problems of galactose

intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption

should not take this medicinal product.

4.5 Interaction with other medicinal products and other forms of

interaction

Vildagliptin has a low potential for interactions with co-administered medicinal

products. Since vildagliptin is not a cytochrome P (CYP) 450 enzyme substrate

and does not inhibit or induce CYP 450 enzymes, it is not likely to interact

with active substances that are substrates, inhibitors or inducers of these

enzymes.

Combination with pioglitazone, metformin and glyburide

Results from studies conducted with these oral antidiabetics have shown no

clinically relevant pharmacokinetic interactions.

Digoxin (Pgp substrate), warfarin (CYP2C9 substrate)

Clinical studies performed with healthy subjects have shown no clinically

relevant pharmacokinetic interactions. However, this has not been established

in the target population.

Combination with amlodipine, ramipril, valsartan or simvastatin

Drug-drug interaction studies in healthy subjects were conducted with

amlodipine, ramipril, valsartan and simvastatin. In these studies, no clinically

relevant pharmacokinetic interactions were observed after co-administration

with vildagliptin.

As with other oral antidiabetic medicinal products the hypoglycaemic effect of

vildagliptin may be reduced by certain active substances, including thiazides,

corticosteroids, thyroid products and sympathomimetics.

4.6 Pregnancy and lactation

Pregnancy

There are no adequate data from the use of vildagliptin in pregnant women.

Studies in animals have shown reproductive toxicity at high doses (see section

5.3). The potential risk for humans is unknown. Due to lack of human data,

Vildagluse should not be used during pregnancy.

Breast-feeding

It is unknown whether vildagliptin is excreted in human milk. Animal studies

have shown excretion of vildagliptin in milk. Vildagluse should not be used

during lactation.

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been

performed. Patients who experience dizziness as an undesirable effect should

avoid driving vehicles or using machines.

4.8 Overdose

Information regarding overdose with vildagliptin is limited.

Information on the likely symptoms of overdose was taken from a rising dose

tolerability study in healthy subjects given Vildagluse for 10 days. At 400 mg,

there were three cases of muscle pain, and individual cases of mild and

transient paraesthesia, fever, oedema and a transient increase in lipase levels. At

600 mg, one subject experienced oedema of the feet and hands, and increases in

creatine phosphokinase (CPK), aspartate aminotransferase (AST), C-reactive

protein (CRP) and myoglobin levels. Three other subjects experienced oedema

of the feet, with paraesthesia in two cases. All symptoms and laboratory

abnormalities resolved without treatment after discontinuation of the study

medicinal product.

Management

In the event of an overdose, supportive management is recommended.

Vildagliptin cannot be removed by haemodialysis. However, the major

hydrolysis metabolite (LAY 151) can be removed by haemodialysis.

 

 

5. PHARMACEUTICAL PARTICULARS

5.1 List of excipients

Lactose anhydrous , microcrystalline Cellulose ,Sodium starch glycolate

,Magnesium stearate

5.2 Incompatibilities

Not applicable.

5.3 Shelf life

2 years

5.4 Special precautions for storage

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

Store at a temperature not exceeding 30˚ C, in a dry place.

Keep out of reach of children.

5.5 Nature and contents of container

A carton box of 1 aluminum / aluminum strip of 10 tablets and inner leaflet