1.NAME OF THE MEDICINAL PRODUCT
Vildagluse 50mg Tablets
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 50mg of vildagliptin.
3. PHARMACEUTICAL FORM
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
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
No dose adjustment is required in patients with mild renal impairment
(creatinine clearance≥50 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).
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
Paediatric population (< 18 years)
Vildagluse is not recommended for use in children and adolescents due to a
lack of data on safety and efficacy.
Hypersensitivity to the active substance or to any of the excipients.
4.4 Special warnings and precautions for use
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.
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.
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.
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 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.
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
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
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
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
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.
It is unknown whether vildagliptin is excreted in human milk. Animal studies
have shown excretion of vildagliptin in milk. Vildagluse should not be used
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.
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
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
5.3 Shelf life
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