Xiliarx

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 

 

Xiliarx 50 mg tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each tablet contains 50 mg of vildagliptin. 

 

Excipient with known effect: Each tablet contains 47.82 mg lactose (anhydrous). 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Tablet. 

 

White to light yellowish, round (8 mm diameter), flat-faced, bevelled-edge tablet. One side is 

debossed with “NVR”, and the other side with “FB”. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 

 

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

 

As monotherapy 

- in patients inadequately controlled by diet and exercise alone and for whom metformin is 

inappropriate due to contraindications or intolerance. 

 

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. 

 

As triple oral therapy in combination with 

- a sulphonylurea and metformin when diet and exercise plus dual therapy with these medicinal 
products do not provide adequate glycaemic control. 

 

Vildagliptin is also indicated for use in combination with insulin (with or without metformin) when 

diet and exercise plus a stable dose of insulin do not provide adequate glycaemic control. 

 
  



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4.2 Posology and method of administration 

 

Posology 

 

Adults 

When used as monotherapy, in combination with metformin, in combination with thiazolidinedione, in 

combination with metformin and a sulphonylurea, or in combination with insulin (with or without 

metformin), the recommended daily dose of vildagliptin is 100 mg, 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 50 mg 

once daily administered in the morning. In this patient population, vildagliptin 100 mg daily was no 

more effective than vildagliptin 50 mg once daily. 

 

When used in combination with a sulphonylurea, a lower dose of the sulphonylurea may be considered 

to reduce the risk of hypoglycaemia. 

 

Doses higher than 100 mg are not recommended. 

 

If a dose of Xiliarx is missed, it should be taken as soon as the patient remembers. A double dose 

should not be taken on the same day. 

 

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

thiazolidinedione have not been established. 

 

Additional information on special populations 

Elderly (≥ 65 years) 

No dose adjustments are necessary in elderly patients (see also sections 5.1 and 5.2). 

 

Renal impairment 

No dose adjustment is required in patients with mild renal impairment (creatinine clearance 

≥ 50 ml/min). In patients with moderate or severe renal impairment or with end-stage renal disease 

(ESRD), the recommended dose of Xiliarx is 50 mg once daily (see also sections 4.4, 5.1 and 5.2). 

 

Hepatic impairment 

Xiliarx 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). 

 

Paediatric population 

Xiliarx is not recommended for use in children and adolescents under (< 18 years). The safety and 

efficacy of Xiliarx in children and adolescents (< 18 years) have not been established. No data are 

available (see also section 5.1). 

 

Method of administration 

 

Oral use 

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

 

  



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4.3 Contraindications 

 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

 

4.4 Special warnings and precautions for use 

 

General 

 

Xiliarx is not a substitute for insulin in insulin-requiring patients. Xiliarx 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 ESRD on haemodialysis. Therefore Xiliarx should be used 

with caution in these patients (see also sections 4.2, 5.1 and 5.2). 

 

Hepatic impairment 

 

Xiliarx should not be used in patients with hepatic impairment, including patients with pre-treatment 

ALT or AST > 3x ULN (see also sections 4.2 and 5.2). 

 

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 Xiliarx in order to know the patient’s baseline value. Liver function should 

be monitored during treatment with Xiliarx 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 Xiliarx therapy is recommended. 

 

Patients who develop jaundice or other signs suggestive of liver dysfunction should discontinue 

Xiliarx. 

 

Following withdrawal of treatment with Xiliarx and LFT normalisation, treatment with Xiliarx should 

not be reinitiated. 

 

Cardiac failure 

 

A clinical trial of vildagliptin in patients with New York Heart Association (NYHA) functional 

class I-III showed that treatment with vildagliptin was not associated with a change in left-ventricular 

function or worsening of pre-existing congestive heart failure (CHF) versus placebo. Clinical 

experience in patients with NYHA functional class III treated with vildagliptin is still limited and 

results are inconclusive (see section 5.1). 

 

There is no experience of vildagliptin use in clinical trials in patients with NYHA functional class IV 

and therefore use is not recommended in these patients. 

 

  



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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. 

Furthermore, there have been post-marketing reports of bullous and exfoliative skin lesions. 

Therefore, in keeping with routine care of the diabetic patient, monitoring for skin disorders, such as 

blistering or ulceration, is recommended. 

 

Acute pancreatitis 

 

Use of vildagliptin has been associated with a risk of developing acute pancreatitis. Patients should be 

informed of the characteristic symptom of acute pancreatitis. 

 

If pancreatitis is suspected, vildagliptin should be discontinued; if acute pancreatitis is confirmed, 

vildagliptin should not be restarted. Caution should be exercised in patients with a history of acute 

pancreatitis. 

 

Hypoglycaemia 

 

Sulphonylureas are known to cause hypoglycaemia. Patients receiving vildagliptin in combination 

with a sulphonylurea may be at risk for hypoglycaemia. Therefore, a lower dose of sulphonylurea may 

be considered to reduce the risk of hypoglycaemia. 

 

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. 

 

  



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Combination with ACE-inhibitors 

 

There may be an increased risk of angioedema in patients concomitantly taking ACE-inhibitors.(see 

section 4.8). 

 

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 Fertility, 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, Xiliarx 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. Xiliarx should not be used during breast-feeding. 

 

Fertility 

 

No studies on the effect on human fertility have been conducted for Xiliarx (see section 5.3). 

 

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 adverse reaction should avoid driving vehicles or using machines. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

Safety data were obtained from a total of 3,784 patients exposed to vildagliptin at a daily dose of 

50 mg (once daily) or 100 mg (50 mg twice daily or 100 mg once daily) in controlled trials of at least 

12 weeks duration. Of these patients, 2,264 patients received vildagliptin as monotherapy and 

1,520 patients received vildagliptin in combination with another medicinal product. 2,682 patients 

were treated with vildagliptin 100 mg daily (either 50 mg twice daily or 100 mg once daily) and 

1,102 patients were treated with vildagliptin 50 mg once daily. 

 

The majority of adverse reactions in these trials were mild and transient, not requiring treatment 

discontinuations. No association was found between adverse reactions and age, ethnicity, duration of 

exposure or daily dose. 

 

Rare cases of hepatic dysfunction (including hepatitis) have been reported. In these cases, the patients 

were generally asymptomatic without clinical sequelae and liver function returned to normal after 

discontinuation of treatment. In data from controlled monotherapy and add-on therapy trials of up to 

24 weeks in duration, the incidence of ALT or AST elevations  3x ULN (classified as present on at 

least 2 consecutive measurements or at the final on-treatment visit) was 0.2%, 0.3% and 0.2% for 

vildagliptin 50 mg once daily, vildagliptin 50 mg twice daily and all comparators, respectively. These 

elevations in transaminases were generally asymptomatic, non-progressive in nature and not 

associated with cholestasis or jaundice. 

 

  



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Rare cases of angioedema have been reported on vildagliptin at a similar rate to controls. A greater 

proportion of cases were reported when vildagliptin was administered in combination with an 

angiotensin converting enzyme inhibitor (ACE-Inhibitor). The majority of events were mild in 

severity and resolved with ongoing vildagliptin treatment. 

 

Tabulated list of adverse reactions 

 

Adverse reactions reported in patients who received Xiliarx in double-blind studies as monotherapy 

and add-on therapies are listed below for each indication by system organ class and absolute 

frequency. 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), very rare (<1/10,000), not known (cannot be 

estimated from the available data). Within each frequency grouping, adverse reactions are presented in 

order of decreasing seriousness. 

 

Combination with metformin 

 

Table 1 Adverse reactions reported in patients who received Xiliarx 100 mg daily in 

combination with metformin in double-blind studies (N=208) 

 

Metabolism and nutrition disorders 
 Common Hypoglycaemia 

Nervous system disorders 

 Common Tremor 

 Common Headache 

 Common Dizziness 

 Uncommon Fatigue 

Gastrointestinal disorders 

 Common Nausea 

 

Description of selected adverse reactions 

In controlled clinical trials with the combination of vildagliptin 100 mg daily + metformin, no 

withdrawal due to adverse reactions was reported in either the vildagliptin 100 mg daily + metformin 

or the placebo + metformin treatment groups. 

 

In clinical trials, the incidence of hypoglycaemia was common in patients receiving vildagliptin 

100 mg daily in combination with metformin (1%) and uncommon in patients receiving placebo + 

metformin (0.4%). No severe hypoglycaemic events were reported in the vildagliptin arms. 

 

In clinical trials, weight did not change from baseline when vildagliptin 100 mg daily was added to 

metformin (+0.2 kg and -1.0 kg for vildagliptin and placebo, respectively). 

 

Clinical trials of up to more than 2 years’ duration did not show any additional safety signals or 

unforeseen risks when vildagliptin was added on to metformin. 

 



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Combination with a sulphonylurea 

 

Table 2 Adverse reactions reported in patients who received Xiliarx 50 mg in combination 

with a sulphonylurea in double-blind studies (N=170) 

 

Infections and infestations 

 Very rare Nasopharyngitis 

Metabolism and nutrition disorders 
 Common Hypoglycaemia 

Nervous system disorders 

 Common Tremor 

 Common Headache 

 Common Dizziness 

 Common Asthenia 

Gastrointestinal disorders 

 Uncommon Constipation 

 

Description of selected adverse reactions 

In controlled clinical trials with the combination of vildagliptin 50 mg + a sulphonylurea, the overall 

incidence of withdrawals due to adverse reactions was 0.6% in the vildagliptin 50 mg + sulphonylurea 

vs 0% in the placebo + sulphonylurea treatment group. 

 

In clinical trials, the incidence of hypoglycaemia when vildagliptin 50 mg once daily was added to 

glimepiride was 1.2% versus 0.6% for placebo + glimepiride. No severe hypoglycaemic events were 

reported in the vildagliptin arms. 

 

In clinical trials, weight did not change from baseline when vildagliptin 50 mg daily was added to 

glimepiride (-0.1 kg and -0.4 kg for vildagliptin and placebo, respectively). 

 

Combination with a thiazolidinedione 

 

Table 3 Adverse reactions reported in patients who received Xiliarx 100 mg daily in 

combination with a thiazolidinedione in double-blind studies (N=158) 

 

Metabolism and nutrition disorders 

 Common Weight increase 

 Uncommon Hypoglycaemia 

Nervous system disorders 

 Uncommon Headache 

 Uncommon Asthenia 

Vascular disorders 

 Common Oedema peripheral 

 

Description of selected adverse reactions 

In controlled clinical trials with the combination of vildagliptin 100 mg daily+ a thiazolidinedione, no 

withdrawal due to adverse reactions was reported in either the vildagliptin 100 mg daily + 

thiazolidinedione or the placebo + thiazolidinedione treatment groups. 

 

In clinical trials, the incidence of hypoglycaemia was uncommon in patients receiving vildagliptin + 

pioglitazone (0.6%) but common in patients receiving placebo + pioglitazone (1.9%). No severe 

hypoglycaemic events were reported in the vildagliptin arms. 

 

In the pioglitazone add-on study, the absolute weight increases with placebo, Xiliarx 100 mg daily 

were 1.4 and 2.7 kg, respectively. 

 

  



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The incidence of peripheral oedema when vildagliptin 100 mg daily was added to a maximum dose of 

background pioglitazone (45 mg once daily) was 7.0%, compared to 2.5% for background 

pioglitazone alone. 

 

Monotherapy 

 

Table 4 Adverse reactions reported in patients who received Xiliarx 100 mg daily as 

monotherapy in double-blind studies (N=1,855) 

 

Infections and infestations 
 Very rare Upper respiratory tract infection 

 Very rare Nasopharyngitis 

Metabolism and nutrition disorders 

 Uncommon Hypoglycaemia 

Nervous system disorders 
 Common Dizziness 

 Uncommon Headache 

Vascular disorders 

 Uncommon Oedema peripheral 

Gastrointestinal disorders 

 Uncommon Constipation 

Musculoskeletal and connective tissue disorders 

 Uncommon Arthralgia 

 

Description of selected adverse reactions 

In addition, in controlled monotherapy trials with vildagliptin the overall incidence of withdrawals due 

to adverse reactions was no greater for patients treated with vildagliptin at doses of 100 mg daily 

(0.3%) than for placebo (0.6%) or comparators (0.5%). 

 

In comparative controlled monotherapy studies, hypoglycaemia was uncommon, reported in 0.4% (7 

of 1,855) of patients treated with vildagliptin 100 mg daily compared to 0.2% (2 of 1,082) of patients 

in the groups treated with an active comparator or placebo, with no serious or severe events reported. 

 

In clinical trials, weight did not change from baseline when vildagliptin 100 mg daily was 

administered as monotherapy (-0.3 kg and -1.3 kg for vildagliptin and placebo, respectively). 

 

Clinical trials of up to 2 years’ duration did not show any additional safety signals or unforeseen risks 

with vildagliptin monotherapy. 

 

Combination with metformin and a sulphonylurea 

 

Table 5 Adverse reactions reported in patients who received Xiliarx 50 mg twice daily in 

combination with metformin and a sulphonylurea (N=157) 
 

Metabolism and nutritional disorders 
 Common Hypoglycaemia 

Nervous system disorders 
 Common Dizziness, tremor 

Skin and subcutaneous tissue disorders 

 Common Hyperhidrosis 

General disorders and administration site conditions 
 Common Asthenia 

 

  



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Description of selected adverse reactions 

There were no withdrawals due to adverse reactions reported in the vildagliptin + metformin + 

glimepiride treatment group versus 0.6% in the placebo + metformin + glimepiride treatment group. 

 

The incidence of hypoglycaemia was common in both treatment groups (5.1% for the vildagliptin + 

metformin + glimepiride group versus 1.9% for the placebo + metformin + glimepiride group). One 

severe hypoglycaemic event was reported in the vildagliptin group. 

 

At the end of the study, effect on mean body weight was neutral (+0.6 kg in the vildagliptin group 

and -0.1 kg in the placebo group). 

 
Combination with insulin 

 

Table 6 Adverse reactions reported in patients who received Xiliarx 100 mg daily in 

combination with insulin (with or without metformin) in double-blind studies 

(N=371) 

 

Metabolism and nutrition disorders 

 Common Decreased blood glucose 

Nervous system disorders 

 Common Headache, chills 

Gastrointestinal disorders 

 Common Nausea, gastro-oesophageal reflux disease 

 Uncommon Diarrhoea, flatulence 

 

Description of selected adverse reactions 

In controlled clinical trials using vildagliptin 50 mg twice daily in combination with insulin, with or 

without concomitant metformin, the overall incidence of withdrawals due to adverse reactions was 

0.3% in the vildagliptin treatment group and there were no withdrawals in the placebo group. 

 

The incidence of hypoglycaemia was similar in both treatment groups (14.0% in the vildagliptin group 

vs 16.4% in the placebo group). Two patients reported severe hypoglycaemic events in the vildagliptin 

group, and 6 patients in the placebo group. 

 

At the end of the study, effect on mean body weight was neutral (+0.6 kg change from baseline in the 

vildagliptin group and no weight change in the placebo group). 

 

Post-marketing experience 

 

Table 7 Post-marketing adverse reactions 
 

Gastrointestinal disorders 
 Not known Pancreatitis 

Hepatobiliary disorders 
 Not known Hepatitis (reversible upon discontinuation of the medicinal product) 

Abnormal liver function tests (reversible upon discontinuation of the 

medicinal product) 

Musculoskeletal and connective tissue disorders 
 Not known Myalgia 

Skin and subcutaneous tissue disorders 
 Not known Urticaria 

Exfoliative and bullous skin lesions, including bullous pemphigoid 

 

  



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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 national reporting system 

listed in Appendix V. 

 

4.9 Overdose 
 

Information regarding overdose with vildagliptin is limited. 

 

Symptoms 

 

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

healthy subjects given Xiliarx 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. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Drugs used in diabetes, dipeptidyl peptidase 4 (DPP-4) inhibitors, ATC 

code: A10BH02 

 

Vildagliptin, a member of the islet enhancer class, is a potent and selective DPP-4 inhibitor. 

 

Mechanism of action 

 

The administration of vildagliptin results in a rapid and complete inhibition of DPP-4 activity, 

resulting in increased fasting and postprandial endogenous levels of the incretin hormones GLP-1 

(glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic polypeptide). 

 

Pharmacodynamic effects 

 

By increasing the endogenous levels of these incretin hormones, vildagliptin enhances the sensitivity 

of beta cells to glucose, resulting in improved glucose-dependent insulin secretion. Treatment with 

vildagliptin 50-100 mg daily in patients with type 2 diabetes significantly improved markers of beta 

cell function including HOMA- (Homeostasis Model Assessment–), proinsulin to insulin ratio and 

measures of beta cell responsiveness from the frequently-sampled meal tolerance test. In non-diabetic 

(normal glycaemic) individuals, vildagliptin does not stimulate insulin secretion or reduce glucose 

levels. 

 

By increasing endogenous GLP-1 levels, vildagliptin also enhances the sensitivity of alpha cells to 

glucose, resulting in more glucose-appropriate glucagon secretion. 

 



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The enhanced increase in the insulin/glucagon ratio during hyperglycaemia due to increased incretin 

hormone levels results in a decrease in fasting and postprandial hepatic glucose production, leading to 

reduced glycaemia. 

 

The known effect of increased GLP-1 levels delaying gastric emptying is not observed with 

vildagliptin treatment. 

 

Clinical efficacy and safety 

 

More than 15,000 patients with type 2 diabetes participated in double-blind placebo- or active-

controlled clinical trials of up to more than 2 years’ treatment duration. In these studies, vildagliptin 

was administered to more than 9,000 patients at daily doses of 50 mg once daily, 50 mg twice daily or 

100 mg once daily. More than 5,000 male and more than 4,000 female patients received vildagliptin 

50 mg once daily or 100 mg daily. More than 1,900 patients receiving vildagliptin 50 mg once daily or 

100 mg daily were ≥ 65 years. In these trials, vildagliptin was administered as monotherapy in drug-

naïve patients with type 2 diabetes or in combination in patients not adequately controlled by other 

antidiabetic medicinal products. 

 

Overall, vildagliptin improved glycaemic control when given as monotherapy or when used in 

combination with metformin, a sulphonylurea, and a thiazolidinedione, as measured by clinically 

relevant reductions in HbA1c from baseline at study endpoint (see Table 8). 

 

In clinical trials, the magnitude of HbA1c reductions with vildagliptin was greater in patients with 

higher baseline HbA1c. 

 

In a 52-week double-blind controlled trial, vildagliptin (50 mg twice daily) reduced baseline HbA1c 

by -1% compared to -1.6% for metformin (titrated to 2 g/day) statistical non-inferiority was not 

achieved. Patients treated with vildagliptin reported significantly lower incidences of gastrointestinal 

adverse reactions versus those treated with metformin. 

 

In a 24-week double-blind controlled trial, vildagliptin (50 mg twice daily) was compared to 

rosiglitazone (8 mg once daily). Mean reductions were -1.20% with vildagliptin and -1.48% with 

rosiglitazone in patients with mean baseline HbA1c of 8.7%. Patients receiving rosiglitazone 

experienced a mean increase in weight (+1.6 kg) while those receiving vildagliptin experienced no 

weight gain (-0.3 kg). The incidence of peripheral oedema was lower in the vildagliptin group than in 

the rosiglitazone group (2.1% vs. 4.1% respectively). 

 

In a clinical trial of 2 years’ duration, vildagliptin (50 mg twice daily) was compared to gliclazide (up 

to 320 mg/day). After two years, mean reduction in HbA1c was -0.5% for vildagliptin and -0.6% for 

gliclazide, from a mean baseline HBA1c of 8.6%. Statistical non-inferiority was not achieved. 

Vildagliptin was associated with fewer hypoglycaemic events (0.7%) than gliclazide (1.7%). 

 

In a 24-week trial, vildagliptin (50 mg twice daily) was compared to pioglitazone (30 mg once daily) 

in patients inadequately controlled with metformin (mean daily dose: 2020 mg). Mean reductions from 

baseline HbA1c of 8.4% were -0.9% with vildagliptin added to metformin and -1.0% with pioglitazone 

added to metformin. A mean weight gain of +1.9 kg was observed in patients receiving pioglitazone 

added to metformin compared to +0.3 kg in those receiving vildagliptin added to metformin. 

 

In a clinical trial of 2 years’ duration, vildagliptin (50 mg twice daily) was compared to glimepiride 

(up to 6 mg/day – mean dose at 2 years: 4.6 mg) in patients treated with metformin (mean daily dose: 

1894 mg). After 1 year mean reductions in HbA1c were -0.4% with vildagliptin added to metformin 

and -0.5% with glimepiride added to metformin, from a mean baseline HbA1c of 7.3%. Body weight 

change with vildagliptin was -0.2 kg vs +1.6 kg with glimepiride. The incidence of hypoglycaemia 

was significantly lower in the vildagliptin group (1.7%) than in the glimepiride group (16.2%). At 

study endpoint (2 years), the HbA1c was similar to baseline values in both treatment groups and the 

body weight changes and hypoglycaemia differences were maintained. 

 



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In a 52-week trial, vildagliptin (50 mg twice daily) was compared to gliclazide (mean daily dose: 

229.5 mg) in patients inadequately controlled with metformin (metformin dose at baseline 

1928 mg/day). After 1 year, mean reductions in HbA1c were -0.81% with vildagliptin added to 

metformin (mean baseline HbA1c 8.4%) and -0.85% with gliclazide added to metformin (mean 

baseline HbA1c 8.5%); statistical non-inferiority was achieved (95% CI -0.11 – 0.20). Body weight 

change with vildagliptin was +0.1 kg compared to a weight gain of +1.4 kg with gliclazide. 

 

In a 24-week trial the efficacy of the fixed dose combination of vildagliptin and metformin (gradually 

titrated to a dose of 50 mg/500 mg twice daily or 50 mg/1000 mg twice daily) as initial therapy in 

drug-naïve patients was evaluated. Vildagliptin/metformin 50 mg/1000 mg twice daily reduced HbA1c 

by -1.82%, vildagliptin/metformin 50 mg/500 mg twice daily by -1.61%, metformin 1000 mg twice 

daily by -1.36% and vildagliptin 50 mg twice daily by -1.09% from a mean baseline HbA1c of 8.6%. 

The decrease in HbA1c observed in patients with a baseline ≥10.0% was greater. 

 

A 24-week, multi-centre, randomised, double-blind, placebo-controlled trial was conducted to evaluate 

the treatment effect of vildagliptin 50 mg once daily compared to placebo in 515 patients with type 2 

diabetes and moderate renal impairment (N=294) or severe renal impairment (N=221). 68.8% and 

80.5% of the patients with moderate and severe renal impairment respectively were treated with 

insulin (mean daily dose of 56 units and 51.6 units respectively) at baseline. In patients with moderate 

renal impairment vildagliptin significantly decreased HbA1c compared with placebo (difference 

of -0.53%) from a mean baseline of 7.9%. In patients with severe renal impairment, vildagliptin 

significantly decreased HbA1c compared with placebo (difference of -0.56%) from a mean baseline of 

7.7%. 

 

A 24-week randomised, double-blind, placebo-controlled trial was conducted in 318 patients to 

evaluate the efficacy and safety of vildagliptin (50 mg twice daily) in combination with metformin 

(≥1500 mg daily) and glimepiride (≥4 mg daily). Vildagliptin in combination with metformin and 

glimepiride significantly decreased HbA1c compared with placebo.The placebo-adjusted mean 

reduction from a mean baseline HbA1c of 8.8% was -0.76%. 

 

A 24-week randomised, double-blind, placebo-controlled trial was conducted in 449 patients to 

evaluate the efficacy and safety of vildagliptin (50 mg twice daily) in combination with a stable dose 

of basal or premixed insulin (mean daily dose 41 units), with concomitant use of metformin (N=276) 

or without concomitant metformin (N=173). Vildagliptin in combination with insulin significantly 

decreased HbA1c compared with placebo. In the overall population, the placebo-adjusted mean 

reduction from a mean baseline HbA1c 8.8% was -0.72%. In the subgroups treated with insulin with or 

without concomitant metformin the placebo-adjusted mean reduction in HbA1c was -0.63% 

and -0.84%, respectively. The incidence of hypoglycaemia in the overall population was 8.4% and 

7.2% in the vildagliptin and placebo groups, respectively. Patients receiving vildagliptin experienced 

no weight gain (+0.2 kg) while those receiving placebo experienced weight reduction (-0.7 kg). 

 

In another 24-week study in patients with more advanced type 2 diabetes not adequately controlled on 

insulin (short and longer acting, average insulin dose 80 IU/day), the mean reduction in HbA1c when 

vildagliptin (50 mg twice daily) was added to insulin was statistically significantly greater than with 

placebo plus insulin (0.5% vs. 0.2%). The incidence of hypoglycaemia was lower in the vildagliptin 

group than in the placebo group (22.9% vs. 29.6%). 

 

A 52-week multi-centre, randomised, double-blind trial was conducted in patients with type 2 diabetes 

and congestive heart failure (NYHA functional class I-III) to evaluate the effect of vildagliptin 50 mg 

twice daily (N=128) compared to placebo (N=126) on left-ventricular ejection fraction (LVEF). 

Vildagliptin was not associated with a change in left-ventricular function or worsening of pre-existing 

CHF. Adjudicated cardiovascular events were balanced overall. There were more cardiac events in 

vildagliptin treated patients with NYHA class III heart failure compared to placebo. However, there 

were imbalances in baseline cardiovascular risk favouring placebo and the number of events was low, 

precluding firm conclusions. Vildagliptin significantly decreased HbA1c compared with placebo 

(difference of 0.6%) from a mean baseline of 7.8% at week 16. In the subgroup with NYHA class III, 

the decrease in HbA1c compared to placebo was lower (difference 0.3%) but this conclusion is limited 



14 

by the small number of patients (n=44). The incidence of hypoglycaemia in the overall population was 

4.7% and 5.6% in the vildagliptin and placebo groups, respectively. 

 

Cardiovascular risk 

A meta-analysis of independently and prospectively adjudicated cardiovascular events from 37 phase 

III and IV monotherapy and combination therapy clinical studies of up to more than 2 years duration 

(mean exposure 50 weeks for vildagliptin and 49 weeks for comparators) was performed and showed 

that vildagliptin treatment was not associated with  an increase in cardiovascular risk versus 

comparators. The composite endpoint of adjudicated major adverse cardiovascular events (MACE) 

including acute myocardial infarction, stroke or cardiovascular death was similar for vildagliptin 

versus combined active and placebo comparators [Mantel–Haenszel risk ratio (M-H RR) 0.82 (95% CI 

0.61-1.11)]. A MACE occurred in 83 out of 9,599 (0.86%) vildagliptin-treated patients and in 85 out 

of 7,102 (1.20%) comparator-treated patients. Assessment of each individual MACE component 

showed no increased risk (similar M-H RR). Confirmed heart failure (HF) events defined as HF 

requiring hospitalisation or new onset of HF were reported in 41 (0.43%) vildagliptin-treated patients 

and 32 (0.45%) comparator-treated patients with M-H RR 1.08 (95% CI 0.68-1.70). 

 

Table 8 Key efficacy results of vildagliptin in placebo-controlled monotherapy trials and in 

add-on combination therapy trials (primary efficacy ITT population) 

 

Monotherapy placebo 

controlled studies 

Mean 

baseline 

HbA1c (%) 

Mean change 

from baseline in 

HbA1c (%) at 

week 24 

Placebo-corrected 

mean change in 

HbA1c (%) at 

week 24 (95% CI) 

Study 2301: Vildagliptin 50 mg 

twice daily (N=90) 

8.6 -0.8 -0.5* (-0.8, -0.1) 

Study 2384: Vildagliptin 50 mg 

twice daily (N=79) 

8.4 -0.7 -0.7* (-1.1, -0.4) 

  * p< 0.05 for comparison versus placebo 

Add-on / Combination studies    
Vildagliptin 50 mg twice daily + 

metformin (N=143) 

8.4 -0.9 -1.1* (-1.4, -0.8) 

Vildagliptin 50 mg daily + 

glimepiride (N=132) 

8.5 -0.6 -0.6* (-0.9, -0.4) 

Vildagliptin 50 mg twice daily + 

pioglitazone (N=136) 

8.7 -1.0 -0.7* (-0.9, -0.4) 

Vildagliptin 50 mg twice daily + 

metformin + glimepiride (N=152) 

8.8 -1.0 -0.8* (-1.0, -0.5) 

  * p< 0.05 for comparison versus placebo + 

comparator 

 

Paediatric population 

 

The European Medicines Agency has waived the obligation to submit the results of studies with 

vildagliptin in all subsets of the paediatric population with type 2 diabetes mellitus (see section 4.2 for 

information on paediatric use). 

 

5.2 Pharmacokinetic properties 

 

Absorption 

 

Following oral administration in the fasting state, vildagliptin is rapidly absorbed, with peak plasma 

concentrations observed at 1.7 hours. Food slightly delays the time to peak plasma concentration to 

2.5 hours, but does not alter the overall exposure (AUC). Administration of vildagliptin with food 

resulted in a decreased Cmax (19%). However, the magnitude of change is not clinically significant, so 

that Xiliarx can be given with or without food. The absolute bioavailability is 85%. 

 



15 

Distribution 

 

The plasma protein binding of vildagliptin is low (9.3%) and vildagliptin distributes equally between 

plasma and red blood cells. The mean volume of distribution of vildagliptin at steady-state after 

intravenous administration (Vss) is 71 litres, suggesting extravascular distribution. 

 

Biotransformation 

 

Metabolism is the major elimination pathway for vildagliptin in humans, accounting for 69% of the 

dose. The major metabolite (LAY 151) is pharmacologically inactive and is the hydrolysis product of 

the cyano moiety, accounting for 57% of the dose, followed by the glucuronide (BQS867) and the 

amide hydrolysis products (4% of dose). In vitro data in human kidney microsomes suggest that the 

kidney may be one of the major organs contributing to the hydrolysis of vildagliptin to its major 

inactive metabolite, LAY151. DPP-4 contributes partially to the hydrolysis of vildagliptin based on an 

in vivo study using DPP-4 deficient rats. Vildagliptin is not metabolised by CYP 450 enzymes to any 

quantifiable extent. Accordingly, the metabolic clearance of vildagliptin is not anticipated to be 

affected by co-medications that are CYP 450 inhibitors and/or inducers. In vitro studies demonstrated 

that vildagliptin does not inhibit/induce CYP 450 enzymes. Therefore, vildagliptin is not likely to 

affect metabolic clearance of co-medications metabolised by CYP 1A2, CYP 2C8, CYP 2C9, CYP 

2C19, CYP 2D6, CYP 2E1 or CYP 3A4/5. 

 

Elimination 

 

Following oral administration of [14C] vildagliptin, approximately 85% of the dose was excreted into 

the urine and 15% of the dose is recovered in the faeces. Renal excretion of the unchanged vildagliptin 

accounted for 23% of the dose after oral administration. After intravenous administration to healthy 

subjects, the total plasma and renal clearances of vildagliptin are 41 and 13 l/h, respectively. The mean 

elimination half-life after intravenous administration is approximately 2 hours. The elimination half-

life after oral administration is approximately 3 hours. 

 

Linearity / non-linearity 

 

The Cmax for vildagliptin and the area under the plasma concentrations versus time curves (AUC) 

increased in an approximately dose proportional manner over the therapeutic dose range. 

 

Characteristics in specific groups of patients 

 

Gender 

No clinically relevant differences in the pharmacokinetics of vildagliptin were observed between male 

and female healthy subjects within a wide range of age and body mass index (BMI). DPP-4 inhibition 

by vildagliptin is not affected by gender. 

 

Elderly 

In healthy elderly subjects (≥ 70 years), the overall exposure of vildagliptin (100 mg once daily) was 

increased by 32%, with an 18% increase in peak plasma concentration as compared to young healthy 

subjects (18-40 years). These changes are, however, not considered to be clinically relevant. DPP-4 

inhibition by vildagliptin is not affected by age. 

 

Hepatic impairment 

The effect of impaired hepatic function on the pharmacokinetics of vildagliptin was studied in patients 

with mild, moderate and severe hepatic impairment based on the Child-Pugh scores (ranging from 6 

for mild to 12 for severe) in comparison with healthy subjects. The exposure to vildagliptin after a 

single dose in patients with mild and moderate hepatic impairment was decreased (20% and 8%, 

respectively), while the exposure to vildagliptin for patients with severe impairment was increased by 

22%. The maximum change (increase or decrease) in the exposure to vildagliptin is ~30%, which is 

not considered to be clinically relevant. There was no correlation between the severity of the hepatic 

disease and changes in the exposure to vildagliptin. 



16 

 

Renal impairment 

A multiple-dose, open-label trial was conducted to evaluate the pharmacokinetics of the lower 

therapeutic dose of vildagliptin (50 mg once daily) in patients with varying degrees of chronic renal 

impairment defined by creatinine clearance (mild: 50 to <80 ml/min, moderate: 30 to <50 ml/min and 

severe: <30 ml/min) compared to normal healthy control subjects. 

 

Vildagliptin AUC increased on average 1.4, 1.7 and 2-fold in patients with mild, moderate and severe 

renal impairment, respectively, compared to normal healthy subjects. AUC of the metabolites 

LAY151 and BQS867 increased on average about 1.5, 3 and 7-fold in patients with mild, moderate 

and severe renal impairment, respectively. Limited data from patients with end stage renal disease 

(ESRD) indicate that vildagliptin exposure is similar to that in patients with severe renal impairment. 

LAY151 concentrations were approximately 2-3-fold higher than in patients with severe renal 

impairment. 

 

Vildagliptin was removed by haemodialysis to a limited extent (3% over a 3-4 hour haemodialysis 

session starting 4 hours post dose). 

 

Ethnic group 

Limited data suggest that race does not have any major influence on vildagliptin pharmacokinetics. 

 

5.3 Preclinical safety data 
 

Intra-cardiac impulse conduction delays were observed in dogs with a no-effect dose of 15 mg/kg (7-

fold human exposure based on Cmax). 

 

Accumulation of foamy alveolar macrophages in the lung was observed in rats and mice. The no-

effect dose in rats was 25 mg/kg (5-fold human exposure based on AUC) and in mice 750 mg/kg (142-

fold human exposure). 

 

Gastrointestinal symptoms, particularly soft faeces, mucoid faeces, diarrhoea and, at higher doses, 

faecal blood were observed in dogs. A no-effect level was not established. 

 

Vildagliptin was not mutagenic in conventional in vitro and in vivo tests for genotoxicity. 

 

A fertility and early embryonic development study in rats revealed no evidence of impaired fertility, 

reproductive performance or early embryonic development due to vildagliptin. Embryo-foetal toxicity 

was evaluated in rats and rabbits. An increased incidence of wavy ribs was observed in rats in 

association with reduced maternal body weight parameters, with a no-effect dose of 75 mg/kg (10-fold 

human exposure). In rabbits, decreased foetal weight and skeletal variations indicative of 

developmental delays were noted only in the presence of severe maternal toxicity, with a no-effect 

dose of 50 mg/kg (9-fold human exposure). A pre- and postnatal development study was performed in 

rats. Findings were only observed in association with maternal toxicity at ≥ 150 mg/kg and included a 

transient decrease in body weight and reduced motor activity in the F1 generation. 

 

A two-year carcinogenicity study was conducted in rats at oral doses up to 900 mg/kg (approximately 

200 times human exposure at the maximum recommended dose). No increases in tumour incidence 

attributable to vildagliptin were observed. Another two-year carcinogenicity study was conducted in 

mice at oral doses up to 1,000 mg/kg. An increased incidence of mammary adenocarcinomas and 

haemangiosarcomas was observed with a no-effect dose of 500 mg/kg (59-fold human exposure) and 

100 mg/kg (16-fold human exposure), respectively. The increased incidence of these tumours in mice 

is considered not to represent a significant risk to humans based on the lack of genotoxicity of 

vildagliptin and its principal metabolite, the occurrence of tumours only in one species and the high 

systemic exposure ratios at which tumours were observed. 

  



17 

 

In a 13-week toxicology study in cynomolgus monkeys, skin lesions have been recorded at doses 

≥ 5 mg/kg/day. These were consistently located on the extremities (hands, feet, ears and tail). At 

5 mg/kg/day (approximately equivalent to human AUC exposure at the 100 mg dose), only blisters 

were observed. They were reversible despite continued treatment and were not associated with 

histopathological abnormalities. Flaking skin, peeling skin, scabs and tail sores with correlating 

histopathological changes were noted at doses ≥ 20 mg/kg/day (approximately 3 times human AUC 

exposure at the 100 mg dose). Necrotic lesions of the tail were observed at ≥ 80 mg/kg/day. Skin 

lesions were not reversible in the monkeys treated at 160 mg/kg/day during a 4-week recovery period.  

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Lactose, anhydrous 

Cellulose, microcrystalline 

Sodium starch glycolate (type A) 

Magnesium stearate 

 

6.2 Incompatibilities 
 

Not applicable. 

 

6.3 Shelf life 
 

3 years 

 

6.4 Special precautions for storage 
 

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

 

6.5 Nature and contents of container 

 

Aluminium/Aluminium (PA/Al/PVC//Al) blister 

Available in packs containing 7, 14, 28, 30, 56, 60, 90, 112, 180 or 336 tablets and in multipacks 

containing 336 (3 packs of 112) tablets. 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal 
 

No special requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

  



18 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/08/486/001-011 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 19 November 2008 

Date of latest renewal: 28 November 2013 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu 

  



19 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 



20 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer responsible for batch release 

 

Novartis Farmacéutica SA 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 

Spain 

 

Novartis Pharma GmbH 

Roonstrasse 25 

D-90429 Nürnberg 

Germany 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch. 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to medical prescription. 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

 Periodic Safety Update Reports 

 

The requirements for submission of periodic safety update reports for this medicinal product are set 

out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 

2001/83/EC and any subsequent updates published on the European medicines web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

 Risk Management Plan (RMP) 
 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in 

the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed 

subsequent updates of the RMP. 

 

An updated RMP should be submitted: 

 At the request of the European Medicines Agency; 

 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

 

An updated RMP shall be submitted every three years. 

 

  



21 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



22 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 
  



23 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Xiliarx 50 mg tablets 

vildagliptin 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 50 mg vildagliptin. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose (see leaflet for further information). 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Tablet 

 

7 tablets 

14 tablets 

28 tablets 

30 tablets 

56 tablets 

60 tablets 

90 tablets 

112 tablets 

180 tablets 

336 tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

  



24 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/08/486/001 7 tablets 

EU/1/08/486/002 14 tablets 

EU/1/08/486/003 28 tablets 

EU/1/08/486/004 30 tablets 

EU/1/08/486/005 56 tablets 

EU/1/08/486/006 60 tablets 

EU/1/08/486/007 90 tablets 

EU/1/08/486/008 112 tablets 

EU/1/08/486/009 180 tablets 

EU/1/08/486/010 336 tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

  



25 

 

16. INFORMATION IN BRAILLE 

 

Xiliarx 50 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



26 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK (INCLUDING BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Xiliarx 50 mg tablets 

vildagliptin 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 50 mg vildagliptin. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose (see leaflet for further information). 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Tablet 

 

Multipack: 336 (3 packs of 112) tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

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

 

  



27 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/08/486/011 336 tablets (3 packs of 112) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Xiliarx 50 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



28 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Xiliarx 50 mg tablets 

vildagliptin 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 50 mg vildagliptin. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose (see leaflet for further information). 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Tablet 

 

112 tablets. Component of a multipack. Not to be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

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

 

  



29 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/08/486/011 336 tablets (3 packs of 112) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Xiliarx 50 mg 

  



30 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Xiliarx 50 mg tablets 

vildagliptin 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

  



31 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 
 



32 

Package leaflet: Information for the user 

 

Xiliarx 50 mg tablets 

vildagliptin 

 

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, pharmacist or nurse. 
- 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, pharmacist or nurse. This includes any possible 
side effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 
 

1. What Xiliarx is and what it is used for 

2. What you need to know before you take Xiliarx 

3. How to take Xiliarx 

4. Possible side effects 

5. How to store Xiliarx 

6. Contents of the pack and other information 

 

 

1. What Xiliarx is and what it is used for 

 

The active substance of Xiliarx, vildagliptin, belongs to a group of medicines called “oral 

antidiabetics”. 

 

Xiliarx is used to treat adult patients with type 2 diabetes. It is used when diabetes cannot be 

controlled by diet and exercise alone. It helps to control the level of sugar in the blood. Your doctor 

will prescribe Xiliarx either alone or together with certain other antidiabetic medicines which you will 

already be taking, if these have not proved sufficiently effective to control diabetes. 

 

Type 2 diabetes develops if the body does not make enough insulin or if the insulin that the body 

makes does not work as well as it should. It can also develop if the body produces too much glucagon. 

 

Insulin is a substance which helps to lower the level of sugar in the blood, especially after meals. 

Glucagon is a substance which triggers the production of sugar by the liver, causing the blood sugar 

level to rise. The pancreas makes both of these substances. 

 

How Xiliarx works 

Xiliarx works by making the pancreas produce more insulin and less glucagon. This helps to control 

the blood sugar level. This medicine has been shown to reduce blood sugar, which may help to prevent 

complications from your diabetes. Even though you are now starting a medicine for your diabetes, it is 

important that you continue to follow the diet and/or exercise which has been recommended for you. 

 

 

  



33 

2. What you need to know before you take Xiliarx  

 

Do not take Xiliarx: 

 if you are allergic to vildagliptin or any of the other ingredients of this medicine (listed in 
section 6). If you think you may be allergic to vildagliptin or any of the other ingredients of 

Xiliarx, do not take this medicine and talk to your doctor. 

 

Warnings and precautions 

Talk to your doctor, pharmacist or nurse before taking Xiliarx 

 if you have type 1 diabetes (i.e. your body does not produce insulin) or if you have a condition 
called diabetic ketoacidosis. 

 if you are taking an anti-diabetic medicine known as a sulphonylurea (your doctor may want to 
reduce your dose of the sulphonylurea when you take it together with Xiliarx in order to avoid 

low blood glucose [hypoglycaemia]). 

 if you have moderate or severe kidney disease (you will need to take a lower dose of Xiliarx). 

 if you are on dialysis. 

 if you have liver disease. 

 if you suffer from heart failure. 

 if you have or have had a disease of the pancreas. 
 

If you have previously taken vildagliptin but had to stop taking it because of liver disease, you should 

not take this medicine. 

 

Diabetic skin lesions are a common complication of diabetes. You are advised to follow the 

recommendations for skin and foot care that you are given by your doctor or nurse. You are also 

advised to pay particular attention to new onset of blisters or ulcers while taking Xiliarx. Should these 

occur, you should promptly consult your doctor. 

 

A test to determine your liver function will be performed before the start of Xiliarx treatment, at three-

month intervals for the first year and periodically thereafter. This is so that signs of increased liver 

enzymes can be detected as early as possible. 

 

Children and adolescents 

The use of Xiliarx in children and adolescents up to 18 years of age is not recommended. 

 

Other medicines and Xiliarx 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. 
 

Your doctor may wish to alter your dose of Xiliarx if you are taking other medicines such as: 

- thiazides or other diuretics (also called water tablets) 

- corticosteroids(generally used to treat inflammation) 

- thyroid medicines 

- certain medicines affecting the nervous system. 

 

Pregnancy and breast-feeding 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor or pharmacist for advice before taking this medicine. 

 

You should not use Xiliarx during pregnancy. It is not known if Xiliarx passes into breast milk. You 

should not use Xiliarx if you are breast-feeding or plan to breast-feed. 

 

  



34 

Driving and using machines 
If you feel dizzy while taking Xiliarx, do not drive or use machines. 

 

Xiliarx contains lactose 

Xiliarx contains lactose (milk sugar). If you have been told by your doctor that you have an 

intolerance to some sugars, contact your doctor before taking this medicine. 

 

 

3. How to take Xiliarx 

 

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 

if you are not sure. 

 

How much to take and when 

The amount of Xiliarx people have to take varies depending on their condition. Your doctor will tell 

you exactly how many tablets of Xiliarx to take. The maximum daily dose is 100 mg. 

 

The usual dose of Xiliarx is either: 

 50 mg daily taken as one dose in the morning if you are taking Xiliarx with another medicine 
called a sulphonylurea. 

 

 100 mg daily taken as 50 mg in the morning and 50 mg in the evening if you are taking Xiliarx 
alone, with another medicine called metformin or a glitazone, with a combination of metformin 

and a sulphonylurea, or with insulin. 

 

 50 mg daily in the morning if you have moderate or severe kidney disease or if you are on 
dialysis. 

 

How to take Xiliarx 

 Swallow the tablets whole with some water. 
 

How long to take Xiliarx 

 Take Xiliarx every day for as long as your doctor tells you. You may have to take this treatment 
over a long period of time. 

 Your doctor will regularly monitor your condition to check that the treatment is having the 
desired effect. 

 

If you take more Xiliarx than you should 

If you take too many Xiliarx tablets, or if someone else has taken your medicine, talk to your doctor 

straight away. Medical attention may be needed. If you need to see a doctor or go to the hospital, take 

the pack with you. 

 

If you forget to take Xiliarx 

If you forget to take a dose of this medicine, take it as soon as you remember. Then take your next 

dose at the usual time. If it is almost time for your next dose, skip the dose you missed. Do not take a 

double dose to make up for a forgotten tablet. 

 

If you stop taking Xiliarx 
Do not stop taking Xiliarx unless your doctor tells you to. If you have questions about how long to 

take this medicine, talk to your doctor. 

 

 



35 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Some symptoms need immediate medical attention: 

You should stop taking Xiliarx and see your doctor immediately if you experience the following side 

effects: 

 Angioedema (rare: may affect up to 1 in 1,000 people): Symptoms include swollen face, tongue 
or throat, difficulty swallowing, difficulties breathing, sudden onset rash or hives, which may 

indicate a reaction called “angioedema”. 

 Liver disease (hepatitis) (rare): Symptoms include yellow skin and eyes, nausea, loss of appetite 
or dark-coloured urine, which may indicate liver disease (hepatitis). 

 Inflammation of the pancreas (pancreatitis) (frequency not known): Symptoms include severe 
and persistent pain in the abdomen (stomach area), which might reach through to your back, as 

well as nausea and vomiting. 

 

Other side effects 

Some patients have had the following side effects while taking Xiliarx and metformin: 

 Common (may affect up to 1 in 10 people): Trembling, headache, dizziness, nausea, low blood 
glucose 

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

Some patients have had the following side effects while taking Xiliarx and a sulphonylurea: 

 Common: Trembling, headache, dizziness, weakness, low blood glucose 

 Uncommon: Constipation 

 Very rare (may affect up to 1 in 10,000 people): Sore throat, runny nose 
 

Some patients have had the following side effects while taking Xiliarx and a glitazone: 

 Common: Weight increase, swollen hands, ankle or feet (oedema) 

 Uncommon: Headache, weakness, low blood glucose 
 

Some patients have had the following side effects while taking Xiliarx alone: 

 Common: Dizziness 

 Uncommon: Headache, constipation, swollen hands, ankle or feet (oedema), joint pain, low 
blood glucose 

 Very rare: Sore throat, runny nose, fever 
 

Some patients have had the following side effects while taking Xiliarx, metformin and a 

sulphonylurea: 

 Common: Dizziness, tremor, weakness, low blood glucose, excessive sweating 
 

Some patients have had the following side effects while taking Xiliarx and insulin (with or without 

metformin): 

 Common: Headache, chills, nausea (feeling sick), low blood glucose, heartburn 

 Uncommon: Diarrhoea, flatulence 
 

Since this product has been marketed, the following side effects have also been reported: 

 Frequency not known (cannot be estimated from the available data): Itchy rash, inflammation of 
the pancreas, localised peeling of skin or blisters, muscle pain 

 

Reporting of side effects 

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 

effects not listed in this leaflet. You can also report side effects directly via the national reporting 

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 



36 

 

5. How to store Xiliarx 

 

 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 blister and the carton after 
“EXP”. The expiry date refers to the last day of that month. 

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

 Do not use any Xiliarx pack that is damaged or shows signs of tampering. 
 

 

6. Contents of the pack and other information 

 

What Xiliarx contains 

 The active substance is vildagliptin. 
Each tablet contains 50 mg vildagliptin. 

 The other ingredients are lactose anhydrous, microcrystalline cellulose, sodium starch glycolate 
(type A) and magnesium stearate. 

 

What Xiliarx looks like and contents of the pack 

Xiliarx 50 mg tablets are round, white to light yellowish and flat, with “NVR” on one side and “FB” 

on the other. 

 

Xiliarx 50 mg tablets are available in packs containing 7, 14, 28, 30, 56, 60, 90, 112, 180 or 

336 tablets and in multipacks comprising 3 cartons, each containing 112 tablets. 

 

Not all pack sizes may be marketed in your country. 

 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Novartis Farmacéutica SA 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 

Spain 

 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

  



37 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 
SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

Česká republika 
Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 
Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 
Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 
Novartis Pharma B.V. 

Tel: +31 88 04 52 111 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 
Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 
Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 
Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Mylan Pharmaceuticals, S.L. 

Tel: +34 900 102 712 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 
Merck, S.A. 

Tel. +351 21 3613 500 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 
Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 
Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 
Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 
Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 



38 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

This leaflet was last revised in 

 

Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency website: 

http://www.ema.europa.eu 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET