Zomarist

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



2 

1. NAME OF THE MEDICINAL PRODUCT 

 

Zomarist 50 mg/850 mg film-coated tablets 

Zomarist 50 mg/1000 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Zomarist 50 mg/850 mg film-coated tablets 

 

Each film-coated tablet contains 50 mg of vildagliptin and 850 mg of metformin hydrochloride 

(corresponding to 660 mg of metformin). 

 

Zomarist 50 mg/1000 mg film-coated tablets 

 

Each film-coated tablet contains 50 mg of vildagliptin and 1000 mg of metformin hydrochloride 

(corresponding to 780 mg of metformin). 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet. 

 

Zomarist 50 mg/850 mg film-coated tablets 

 

Yellow, ovaloid film-coated tablet with bevelled edge, imprinted with “NVR” on one side and “SEH” 

on the other side. 

 

Zomarist 50 mg/1000 mg film-coated tablets 

 

Dark yellow, ovaloid film-coated tablet with bevelled edge, imprinted with “NVR” on one side and 

“FLO” on the other side. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 

 

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

- Zomarist is indicated in the treatment of adult patients who are unable to achieve sufficient 
glycaemic control at their maximally tolerated dose of oral metformin alone or who are already 

treated with the combination of vildagliptin and metformin as separate tablets. 

- Zomarist is indicated in combination with a sulphonylurea (i.e. triple combination therapy) as an 
adjunct to diet and exercise in adult patients inadequately controlled with metformin and a 

sulphonylurea. 

- Zomarist is indicated in triple combination therapy with insulin as an adjunct to diet and 
exercise to improve glycaemic control in adult patients when insulin at a stable dose and 

metformin alone do not provide adequate glycaemic control. 

 

  



3 

4.2 Posology and method of administration 

 

Posology 

 

Adults with normal renal function (GFR ≥ 90 ml/min) 

The dose of antihyperglycaemic therapy with Zomarist should be individualised on the basis of the 

patient’s current regimen, effectiveness and tolerability while not exceeding the maximum 

recommended daily dose of 100 mg vildagliptin. Zomarist may be initiated at either the 50 mg/850 mg 

or 50 mg/1000 mg tablet strength twice daily, one tablet in the morning and the other in the evening. 

 

- For patients inadequately controlled at their maximal tolerated dose of metformin monotherapy: 

The starting dose of Zomarist should provide vildagliptin as 50 mg twice daily (100 mg total daily 

dose) plus the dose of metformin already being taken. 

 

- For patients switching from co-administration of vildagliptin and metformin as separate tablets: 

Zomarist should be initiated at the dose of vildagliptin and metformin already being taken. 

 

- For patients inadequately controlled on dual combination with metformin and a sulphonylurea: 

The doses of Zomarist should provide vildagliptin as 50 mg twice daily (100 mg total daily dose) and 

a dose of metformin similar to the dose already being taken. When Zomarist is used in combination 

with a sulphonylurea, a lower dose of the sulphonylurea may be considered to reduce the risk of 

hypoglycaemia. 

 

- For patients inadequately controlled on dual combination therapy with insulin and the maximal 

tolerated dose of metformin 

The dose of Zomarist should provide vildagliptin dosed as 50 mg twice daily (100 mg total daily dose) 

and a dose of metformin similar to the dose already being taken. 

 

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

thiazolidinedione have not been established. 

 

Special populations 

Elderly (≥ 65 years) 

As metformin is excreted via the kidney, and elderly patients have a tendency to decreased renal 

function, elderly patients taking Zomarist should have their renal function monitored regularly (see 

sections 4.4 and 5.2). 

 

Renal impairment 

A GFR should be assessed before initiation of treatment with metformin-containing products and at 

least annually thereafter. In patients at increased risk of further progression of renal impairment and in 

the elderly, renal function should be assessed more frequently, e.g. every 3-6 months. 

 

The maximum daily dose of metformin should preferably be divided into 2-3 daily doses. Factors that 

may increase the risk of lactic acidosis (see section 4.4) should be reviewed before considering 

initiation of metformin in patients with GFR<60 ml/min. 

 

If no adequate strength of Zomarist is available, individual monocomponents should be used instead of 

the fixed dose combination. 

 



4 

GFR ml/min Metformin Vildagliptin 

60-89 Maximum daily dose is 3000 mg. 

Dose reduction may be considered in 

relation to declining renal function. 

No dose adjustment. 

45-59 Maximum daily dose is 2000 mg. 

The starting dose is at most half of the 

maximum dose. 

Maximal daily dose is 50 mg. 

30-44 Maximum daily dose is 1000 mg. 

The starting dose is at most half of the 

maximum dose. 

<30 Metformin is contraindicated. 

 

Hepatic impairment 

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

alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 times the upper limit of 

normal (ULN) (see sections 4.3, 4.4 and 4.8). 

 

Paediatric population 

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

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

 

Method of administration 

 

Oral use. 

Taking Zomarist with or just after food may reduce gastrointestinal symptoms associated with 

metformin (see also section 5.2). 

 

4.3 Contraindications 

 

 Hypersensitivity to the active substances or to any of the excipients listed in section 6.1 

 Any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis) 

 Diabetic pre-coma 

 Severe renal failure (GFR < 30 ml/min) (see section 4.4) 

 Acute conditions with the potential to alter renal function, such as: 
- dehydration, 
- severe infection, 
- shock, 
- intravascular administration of iodinated contrast agents (see section 4.4). 

 Acute or chronic disease which may cause tissue hypoxia, such as: 
- cardiac or respiratory failure, 
- recent myocardial infarction, 
- shock. 

 Hepatic impairment (see sections 4.2, 4.4 and 4.8) 

 Acute alcohol intoxication, alcoholism 

 Breast-feeding (see section 4.6) 
 

4.4 Special warnings and precautions for use 

 

General 

 

Zomarist is not a substitute for insulin in insulin-requiring patients and should not be used in patients 

with type 1 diabetes. 

 

  



5 

Lactic acidosis 

 

Lactic acidosis, a very rare but serious metabolic complication, most often occurs at acute worsening 

of renal function or cardiorespiratory illness or sepsis. Metformin accumulation occurs at acute 

worsening of renal function and increases the risk of lactic acidosis. 

 

In case of dehydration (severe diarrhoea or vomiting, fever, or reduced fluid intake), metformin should 

be temporarily discontinued and contact with a healthcare professional is recommended. 

 
Medicinal products that can acutely impair renal function (such as antihypertensives, diuretics and 

NSAIDs) should be initiated with caution in metformin-treated patients. Other risk factors for lactic 

acidosis are excessive alcohol intake, hepatic insufficiency, inadequately controlled diabetes, ketosis, 

prolonged fasting and any conditions associated with hypoxia, as well as concomitant use of medicinal 

products that may cause lactic acidosis (see also sections 4.3 and 4.5). 

 

Patients and/or care-givers should be informed of the risk of lactic acidosis. Lactic acidosis is 

characterised by acidotic dyspnoea, abdominal pain, muscle cramps, asthenia and hypothermia 

followed by coma In case of suspected symptoms, the patient should stop taking metformin and seek 

immediate medical attention. Diagnostic laboratory findings are decreased blood pH (< 7.35), 

increased plasma lactate levels (> 5 mmol/l) and an increased anion gap and lactate/pyruvate ratio. 

 

Administration of iodinated contrast agents 

Intravascular administration of iodinated contrast agents lead to contrast-induced nephropathy, 

resulting in metformin accumulation and increased risk of lactic acidosis. Metformin should be 

discontinued prior to or at the time of the imaging procedure and not restarted until at least 48 hours 

after, provided that renal function has been re-evaluated and found to be stable (see sections 4.2 and 

4.5). 

 

Renal function 

 

GFR should be assessed before treatment initiation and regularly thereafter (see section 4.2). 

Metformin is contraindicated in patients with GFR <30 ml/min and should be temporarily 

discontinued in the presence of conditions that alter renal function (see section 4.3). 

 

Hepatic impairment 

 

Patients with hepatic impairment, including those with pre-treatment ALT or AST > 3x ULN, should 

not be treated with Zomarist (see sections 4.2, 4.3 and 4.8). 

 

Liver enzyme monitoring 

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

cases, the patients were generally asymptomatic without clinical sequelae and liver function tests 

(LFTs) returned to normal after discontinuation of treatment. LFTs should be performed prior to the 

initiation of treatment with Zomarist in order to know the patient’s baseline value. Liver function 

should be monitored during treatment with Zomarist 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 LFTs 

until the abnormality(ies) return(s) to normal. Should an increase in AST or in ALT of 3x ULN or 

greater persist, withdrawal of Zomarist therapy is recommended. Patients who develop jaundice or 

other signs suggestive of liver dysfunction should discontinue Zomarist. 

 

Following withdrawal of treatment with Zomarist and LFT normalisation, treatment with Zomarist 

should not be re-initiated. 

 

  



6 

Skin disorders 

 

Skin lesions, including blistering and ulceration have been reported with vildagliptin 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 beenassociated with a risk of developing of 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 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. 

 

Surgery 

 

Metformin must be discontinuedat the time of surgery under general, spinal or epidural anaesthesia. 

Therapy may be restarted no earlier than 48 hours following surgery or resumption of oral nutrition 

and provided that renal function has been re-evaluated and found to be stable. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

There have been no formal interaction studies for Zomarist. The following statements reflect the 

information available on the individual active substances. 

 

Vildagliptin 

 

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. 

 

Results from clinical trials conducted with the oral antidiabetics pioglitazone, metformin and 

glyburide in combination with vildagliptin have shown no clinically relevant pharmacokinetic 

interactions in the target population. 

 

Drug-drug interaction studies with digoxin (P-glycoprotein substrate) and warfarin (CYP2C9 

substrate) in healthy subjects have shown no clinically relevant pharmacokinetic interactions after co-

administration with vildagliptin. 

 

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. However, this has not been established in the target 

population. 

 

  



7 

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. 

 

Metformin 

 

Combinations not recommended 

Alcohol 

Alcohol intoxication is associated with an increased risk of lactic acidosis, particularly in cases of 

fasting, malnutrition or hepatic impairment. 

 

Iodinated contrast agents 

Metformin must be discontinued prior to or at the time of the imaging procedure and not restarted until 

at least 48 hours after, provided that renal function has been re-evaluated and found to be stable (see 

sections 4.2 and 4.4). 

 

Cationic active substances 

Cationic active substances that are eliminated by renal tubular secretion (e.g. cimetidine) may interact 

with metformin by competing for common renal tubular transport systems and hence delay the 

elimination of metformin, which may increase the risk of lactic acidosis. A study in healthy volunteers 

showed that cimetidine, administered as 400 mg twice daily, increased metformin systemic exposure 

(AUC) by 50%. Therefore, close monitoring of glycaemic control, dose adjustment within the 

recommended posology and changes in diabetic treatment should be considered when cationic 

medicinal products that are eliminated by renal tubular secretion are co-administered (see section 4.4). 

 

Combinations requiring precautions for use 

Some medicinal products can adversely affect renal function which may increase the risk of lactic 

acidosis, e.g. NSAIDs, including selective cyclo-oxygenase (COX) II inhibitors, ACE inhibitors, 

angiotensin II receptor antagonists and diuretics, especially loop diuretics. When starting or using such 

products in combination with metformin, close monitoring of renal function is necessary. 

 

Glucocorticoids, beta-2-agonists, and diuretics have intrinsic hyperglycaemic activity. The patient 

should be informed and more frequent blood glucose monitoring performed, especially at the 

beginning of treatment. If necessary, the dosage of Zomarist may need to be adjusted during 

concomitant therapy and on its discontinuation. 

 

Angiotensin converting enzyme (ACE) inhibitors may decrease the blood glucose levels. If necessary, 

the dosage of the antihyperglycaemic medicinal product should be adjusted during therapy with the 

other medicinal product and on its discontinuation. 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

 

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

animals have shown reproductive toxicity at high doses. For metformin, studies in animals have not 

shown reproductive toxicity. Studies in animals performed with vildagliptin and metformin have not 

shown evidence of teratogenicity, but foetotoxic effects at maternotoxic doses (see section 5.3). The 

potential risk for humans is unknown. Zomarist should not be used during pregnancy. 

 

  



8 

Breast-feeding 

 

Studies in animals have shown excretion of both metformin and vildagliptin in milk. It is unknown 

whether vildagliptin is excreted in human milk, but metformin is excreted in human milk in low 

amounts. Due to both the potential risk of neonate hypoglycaemia related to metformin and the lack of 

human data with vildagliptin, Zomarist should not be used during breast-feeding (see section 4.3). 

 

Fertility 

 

No studies on the effect on human fertility have been conducted for Zomarist (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 

may experience dizziness as an adverse reaction should avoid driving vehicles or using machines. 

 

4.8 Undesirable effects 
 

There have been no therapeutic clinical trials conducted with Zomarist. However, bioequivalence of 

Zomarist with co-administered vildagliptin and metformin has been demonstrated (see section 5.2). 

The data presented here relate to the co-administration of vildagliptin and metformin, where 

vildagliptin has been added to metformin. There have been no studies of metformin added to 

vildagliptin. 

 

Summary of the safety profile 

 

The majority of adverse reactions 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 with vildagliptin. 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. 

 

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 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 vildagliptin in double-blind studies as 

monotherapy and add-on therapies are listed below by system organ class and absolute frequency. 

Adverse reactions listed in Table 5 are based on information available from the metformin Summary 

of Product Characteristics available in the EU. 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. 

 



9 

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

add-on therapy to metformin compared to placebo plus 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 plus metformin, no 

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

metformin or the placebo plus metformin treatment groups. 

 

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

 

Combination with a sulphonylurea 

 

Table 2 Adverse reactions reported in patients who received vildagliptin 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 

 

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). 

 



10 

Combination with insulin 

 

Table 3 Adverse reactions reported in patients who received vildagliptin 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). 

 

Additional information on the individual active substances of the fixed combination 

 

Vildagliptin 

 

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

monotherapy in double-blind studies (N=1855) 

 

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 

The overall incidence of withdrawals from controlled monotherapy trials 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. 

 



11 

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. 

 

Metformin 

 

Table 5 Adverse reactions for metformin component 

 

Metabolism and nutrition disorders 

 Very Rare Decrease of vitamin B12 absorption and lactic acidosis* 

Nervous system disorders 
 Common Metallic taste 

Gastrointestinal disorders 

 Very common Nausea, vomiting, diarrhoea, abdominal pain and loss of appetite 

Hepatobiliary disorders 

 Very rare Liver function test abnormalities or hepatitis** 

Skin and subcutaneous tissue disorders 

 Very rare Skin reactions such as erythema, pruritus and urticaria 

*A decrease in vitamin B12 absorption with decrease in serum levels has been very rarely observed 

in patients treated long-term with metformin. Consideration of such aetiology is recommended if a 

patient presents with megaloblastic anaemia. 

**Isolated cases of liver function test abnormalities or hepatitis resolving upon metformin 

discontinuation have been reported. 

 

Gastrointestinal adverse reactions occur most frequently during initiation of therapy and resolve 

spontaneously in most cases. To prevent them, it is recommended that metformin be taken in 2 daily 

doses during or after meals. A slow increase in the dose may also improve gastrointestinal tolerability. 

 

Post-marketing experience 

 

Table 6 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 

 
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. 

 
  



12 

4.9 Overdose 
 

No data are available with regard to overdose of Zomarist. 

 

Vildagliptin 

Information regarding overdose with vildagliptin is limited. 

 

Symptoms 

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

tolerability study in healthy subjects given vildagliptin 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), 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. 

 

Metformin 

A large overdose of metformin (or co-existing risk of lactic acidosis) may lead to lactic acidosis, 

which is a medical emergency and must be treated in hospital. 

 

Management 

The most effective method of removing metformin is haemodialysis. However, vildagliptin cannot be 

removed by haemodialysis, although the major hydrolysis metabolite (LAY 151) can. Supportive 

management is recommended. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Drugs used in diabetes, combinations of oral blood glucose lowering 

drugs, ATC code: A10BD08 

 

Mechanism of action 

 

Zomarist combines two antihyperglycaemic agents with complimentary mechanisms of action to 

improve glycaemic control in patients with type 2 diabetes: vildagliptin, a member of the islet 

enhancer class, and metformin hydrochloride, a member of the biguanide class. 

 

Vildagliptin, a member of the islet enhancer class, is a potent and selective dipeptidyl-peptidase-4 

(DPP-4) inhibitor. Metformin acts primarily by decreasing endogenous hepatic glucose production. 

 

Pharmacodynamic effects 

 

Vildagliptin 

Vildagliptin acts primarily by inhibiting DPP-4, the enzyme responsible for the degradation of the 

incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic 

polypeptide). 

 

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 and GIP. 

 

  



13 

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. 

 

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. 

 

Metformin 

Metformin is a biguanide with antihyperglycaemic effects, lowering both basal and postprandial 

plasma glucose. It does not stimulate insulin secretion and therefore does not produce hypoglycaemia 

or increased weight gain. 

 

Metformin may exert its glucose-lowering effect via three mechanisms: 

- by reduction of hepatic glucose production through inhibition of gluconeogenesis and 
glycogenolysis; 

- in muscle, by modestly increasing insulin sensitivity, improving peripheral glucose uptake and 
utilisation; 

- by delaying intestinal glucose absorption. 
Metformin stimulates intracellular glycogen synthesis by acting on glycogen synthase and increases 

the transport capacity of specific types of membrane glucose transporters (GLUT-1 and GLUT-4). 

 

In humans, independently of its action on glycaemia, metformin has favourable effects on lipid 

metabolism. This has been shown at therapeutic doses in controlled, medium-term or long-term 

clinical studies: metformin reduces serum levels of total cholesterol, LDL cholesterol and 

triglycerides. 

 

The prospective randomised UKPDS (UK Prospective Diabetes Study) study has established the long-

term benefit of intensive blood glucose control in type 2 diabetes. Analysis of the results for 

overweight patients treated with metformin after failure of diet alone showed: 

- a significant reduction in the absolute risk of any diabetes-related complication in the metformin 
group (29.8 events/1,000 patient-years) versus diet alone (43.3 events/1,000 patient-years), 

p=0.0023, and versus the combined sulphonylurea and insulin monotherapy groups 

(40.1 events/1,000 patient-years), p=0.0034; 

- a significant reduction in the absolute risk of diabetes-related mortality: metformin 
7.5 events/1,000 patient-years, diet alone 12.7 events/1,000 patient-years, p=0.017; 

- a significant reduction in the absolute risk of overall mortality: metformin 
13.5 events/1,000 patient-years versus diet alone 20.6 events/1,000 patient-years (p=0.011), and 

versus the combined sulphonylurea and insulin monotherapy groups 18.9 events/1,000 patient-

years (p=0.021); 

- a significant reduction in the absolute risk of myocardial infarction: metformin 
11 events/1,000 patient-years, diet alone 18 events/1,000 patient-years (p=0.01). 

 

  



14 

Clinical efficacy and safety 

 

Vildagliptin added to patients whose glycaemic control was not satisfactory despite treatment with 

metformin monotherapy resulted after 6-month treatment in additional statistically significant mean 

reductions in HbA1c compared to placebo (between group differences of -0.7% to -1.1% for 

vildagliptin 50 mg and 100 mg, respectively). The proportion of patients who achieved a decrease in 

HbA1c of ≥ 0.7% from baseline was statistically significantly higher in both vildagliptin plus 

metformin groups (46% and 60%, respectively) versus the metformin plus placebo group (20%). 

 

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. 

 

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 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). 

 

  



15 

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%). 

 

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). 

 

Paediatric population 

 

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

vildagliptin in combination with metformin 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 

 

Zomarist 

 

Absorption 

Bioequivalence has been demonstrated between Zomarist at three dose strengths (50 mg/500 mg, 

50 mg/850 mg and 50 mg/1000 mg) versus free combination of vildagliptin and metformin 

hydrochloride tablets at the corresponding doses. 
 

Food does not affect the extent and rate of absorption of vildagliptin from Zomarist. The rate and 

extent of absorption of metformin from Zomarist 50 mg/1000 mg were decreased when given with 

food as reflected by the decrease in Cmax by 26%, AUC by 7% and delayed Tmax (2.0 to 4.0 h). 

 

The following statements reflect the pharmacokinetic properties of the individual active substances of 

Zomarist. 

 

Vildagliptin 

 

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%) compared to dosing in the fasting state. However, the magnitude of 

change is not clinically significant, so that vildagliptin can be given with or without food. The absolute 

bioavailability is 85%. 

 

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. 

 



16 

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 amide hydrolysis product (4% of 

dose). 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, 

and 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 was 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 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. 

 

Age: 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 not considered to be clinically relevant, however. 

DPP-4 inhibition by vildagliptin is not affected by age. 

 

Hepatic impairment: In subjects with mild, moderate or severe hepatic impairment (Child-Pugh A-C) 

there were no clinically significant changes (maximum ~30%) in exposure to vildagliptin. 

 

Renal impairment: In subjects with mild, moderate, or severe renal impairment, systemic exposure to 

vildagliptin was increased (Cmax 8-66%; AUC 32-134%) and total body clearance was reduced 

compared to subjects with normal renal function. 

 

Ethnic group: Limited data suggest that race does not have any major influence on vildagliptin 

pharmacokinetics. 

 

Metformin 

 

Absorption 

After an oral dose of metformin, the maximum plasma concentration (Cmax) is achieved after about 

2.5 h.. Absolute bioavailability of a 500 mg metformin tablet is approximately 50-60% in healthy 

subjects. After an oral dose, the non-absorbed fraction recovered in faeces was 20-30%. 

 

After oral administration, metformin absorption is saturable and incomplete. It is assumed that the 

pharmacokinetics of metformin absorption are non-linear. At the usual metformin doses and dosing 

schedules, steady state plasma concentrations are reached within 24-48 h and are generally less than 

1 µg/ml. In controlled clinical trials, maximum metformin plasma levels (Cmax) did not exceed 

4 µg/ml, even at maximum doses. 

 



17 

Food slightly delays and decreases the extent of the absorption of metformin. Following 

administration of a dose of 850 mg, the plasma peak concentration was 40% lower, AUC was 

decreased by 25% and time to peak plasma concentration was prolonged by 35 minutes. The clinical 

relevance of this decrease is unknown. 

 

Distribution 

Plasma protein binding is negligible. Metformin partitions into erythrocytes. The mean volume of 

distribution (Vd) ranged between 63-276 litres. 

 

Biotransformation 

Metformin is excreted unchanged in the urine. No metabolites have been identified in humans. 

 

Elimination 

Metformin is eliminated by renal excretion. Renal clearance of metformin is > 400 ml/min, indicating 

that metformin is eliminated by glomerular filtration and tubular secretion. Following an oral dose, the 

apparent terminal elimination half-life is approximately 6.5 h. When renal function is impaired, renal 

clearance is decreased in proportion to that of creatinine and thus the elimination half-life is 

prolonged, leading to increased levels of metformin in plasma. 

 

5.3 Preclinical safety data 
 

Animal studies of up to 13-week duration have been conducted with the combined substances in 

Zomarist. No new toxicities associated with the combination were identified. The following data are 

findings from studies performed with vildagliptin or metformin individually. 

 

Vildagliptin 

 

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. Embryofoetal 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. 

 

  



18 

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 1000 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. 

 

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. 

 

Metformin 

 

Non-clinical data on metformin reveal no special hazard for humans based on conventional studies of 

safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential and toxicity to 

reproduction. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Tablet core 

 

Hydroxypropylcellulose 

Magnesium stearate 

 

Film-coating 

 

Hypromellose 

Titanium dioxide (E 171) 

Iron oxide, yellow (E 172) 

Macrogol 4000 

Talc 

 

6.2 Incompatibilities 
 

Not applicable. 

 

6.3 Shelf life 
 

PA/alu/PVC/alu 2 years 

PCTFE/PVC/alu 18 months 

PVC/PE/PVDC/alu 18 months 

 

  



19 

6.4 Special precautions for storage 

 

Do not store above 30C. 

Store in the original package (blister) in order to protect from moisture. 

 

6.5 Nature and contents of container 

 

Aluminium/Aluminium (PA/alu/PVC/alu) blister 

Available in packs containing 10, 30, 60, 120,180 or 360 film-coated tablets and in multi-packs 

containing 120 (2 packs of 60), 180 (3 packs of 60) or 360 (6 packs of 60) film-coated tablets. 

 

Polychlorotrifluoroethylene (PCTFE/PVC/alu) blister 

Available in packs containing 10, 30, 60, 120, 180 or 360 film-coated tablets and in multi-packs 

containing 120 (2 packs of 60), 180 (3 packs of 60) or 360 (6 packs of 60) film-coated tablets. 

 

Polyvinylchloride/Polyethylene/Polyvinylidene chloride/Aluminium (PVC/PE/PVDC/alu) blister 

Available in packs containing 10, 30, 60, 120, 180 or 360 film-coated tablets and in multi-packs 

containing 120 (2 packs of 60), 180 (3 packs of 60) or 360 (6 packs of 60) film-coated tablets. 

 

Not all pack sizes and tablet strengths 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 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

Zomarist 50 mg/850 mg film-coated tablets 

 

EU/1/08/483/001-006 

EU/1/08/483/013-015 

EU/1/08/483/019-024 

EU/1/08/483/031-033 

EU/1/08/483/037-045 

 

Zomarist 50 mg/1000 mg film-coated tablets 

 

EU/1/08/483/007-012 

EU/1/08/483/016-018 

EU/1/08/483/025-030 

EU/1/08/483/034-036 

EU/1/08/483/046-054 

 

 



20 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 01 December 2008 

Date of latest renewal: 31 July 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 

  



21 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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 

 



22 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer responsible for batch release 

 

Lek d.d, PE PROIZVODNJA LENDAVA 

Trimlini 2D 

Lendava, 9220 

Slovenia 

 

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. 

 

  



23 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



24 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 
  



25 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

FOLDING BOX FOR UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Zomarist 50 mg/850 mg film-coated tablets 

vildagliptin/metformin hydrochloride 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 50 mg vildagliptin and 850 mg metformin hydrochloride (corresponding to 

660 mg of metformin). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

10 film-coated tablets 

30 film-coated tablets 

60 film-coated tablets 

120 film-coated tablets 

180 film-coated tablets 

360 film-coated 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 

 

 



26 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30C. 

Store in the original package (blister) 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/1/08/483/001 10 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/002 30 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/003 60 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/004 120 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/005 180 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/006 360 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/019 10 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/020 30 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/021 60 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/022 120 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/023 180 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/024 360 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/037 10 film-coated tablets (PVC/PE/PVDC/alu) 

EU/1/08/483/038 30 film-coated tablets (PVC/PE/PVDC/alu) 

EU/1/08/483/039 60 film-coated tablets (PVC/PE/PVDC/alu) 

EU/1/08/483/040 120 film-coated tablets (PVC/PE/PVDC/alu) 

EU/1/08/483/041 180 film-coated tablets (PVC/PE/PVDC/alu) 

EU/1/08/483/042 360 film-coated tablets (PVC/PE/PVDC/alu) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

  



27 

16. INFORMATION IN BRAILLE 

 

Zomarist 50 mg/850 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



28 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Zomarist 50 mg/850 mg film-coated tablets 

vildagliptin/metformin hydrochloride 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

  



29 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 
Zomarist 50 mg/850 mg film-coated tablets 

vildagliptin/metformin hydrochloride 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 
Each tablet contains 50 mg vildagliptin and 850 mg metformin hydrochloride (corresponding to 

660 mg of metformin). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

60 film-coated 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 

 

Do not store above 30C. 

Store in the original package (blister) in order to protect from moisture. 

 



30 

 

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/1/08/483/013 120 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/014 180 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/015 360 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/031 120 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/032 180 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/033 360 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/043 120 film-coated tablets (PVC/PE/PVDC/alu) 

EU/1/08/483/044 180 film-coated tablets (PVC/PE/PVDC/alu) 

EU/1/08/483/045 360 film-coated tablets (PVC/PE/PVDC/alu) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 
Zomarist 50 mg/850 mg 

  



31 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACKS (INCLUDING BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 
Zomarist 50 mg/850 mg film-coated tablets 

vildagliptin/metformin hydrochloride 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 
Each tablet contains 50 mg vildagliptin and 850 mg metformin hydrochloride (corresponding to 

660 mg of metformin). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

Multipack: 120 (2 packs of 60) film-coated tablets. 

Multipack: 180 (3 packs of 60) film-coated tablets. 

Multipack: 360 (6 packs of 60) film-coated 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 

 

 



32 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30C. 

Store in the original package (blister) 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/1/08/483/013 120 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/014 180 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/015 360 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/031 120 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/032 180 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/033 360 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/043 120 film-coated tablets (PVC/PE/PVDC/alu) 

EU/1/08/483/044 180 film-coated tablets (PVC/PE/PVDC/alu) 

EU/1/08/483/045 360 film-coated tablets (PVC/PE/PVDC/alu) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Zomarist 50 mg/850 mg 

 

 

  



33 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



34 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

FOLDING BOX FOR UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Zomarist 50 mg/1000 mg film-coated tablets 

vildagliptin/metformin hydrochloride 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 50 mg vildagliptin and 1000 mg metformin hydrochloride (corresponding to 

780 mg of metformin). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

10 film-coated tablets 

30 film-coated tablets 

60 film-coated tablets 

120 film-coated tablets 

180 film-coated tablets 

360 film-coated 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 

 

 



35 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30C. 

Store in the original package (blister) 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/1/08/483/007 10 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/008 30 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/009 60 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/010 120 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/011 180 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/012 360 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/025 10 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/026 30 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/027 60 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/028 120 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/029 180 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/030 360 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/046 10 film-coated tablets (PVC/PE/PVDC/alu) 

EU/1/08/483/047 30 film-coated tablets (PVC/PE/PVDC/alu) 

EU/1/08/483/048 60 film-coated tablets (PVC/PE/PVDC/alu) 

EU/1/08/483/049 120 film-coated tablets (PVC/PE/PVDC/alu) 

EU/1/08/483/050 180 film-coated tablets (PVC/PE/PVDC/alu) 

EU/1/08/483/051 360 film-coated tablets (PVC/PE/PVDC/alu) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

  



36 

16. INFORMATION IN BRAILLE 

 

Zomarist 50 mg/1000 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



37 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Zomarist 50 mg/1000 mg film-coated tablets 

vildagliptin/metformin hydrochloride 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

  



38 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 
Zomarist 50 mg/1000 mg film-coated tablets 

vildagliptin/metformin hydrochloride 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 
Each tablet contains 50 mg vildagliptin and 1000 mg metformin hydrochloride (corresponding to 

780 mg of metformin). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

60 film-coated 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 

 

Do not store above 30C. 

Store in the original package (blister) in order to protect from moisture. 

 



39 

 

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/1/08/483/016 120 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/017 180 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/018 360 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/034 120 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/035 180 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/036 360 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/052 120 film-coated tablets (PVC/PE/PVDC/alu) 

EU/1/08/483/053 180 film-coated tablets (PVC/PE/PVDC/alu) 

EU/1/08/483/054 360 film-coated tablets (PVC/PE/PVDC/alu) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 
Zomarist 50 mg/1000 mg 

  



40 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACKS (INCLUDING BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 
Zomarist 50 mg/1000 mg film-coated tablets 

vildagliptin/metformin hydrochloride 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 
Each tablet contains 50 mg vildagliptin and 1000 mg metformin hydrochloride (corresponding to 

780 mg of metformin). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

Multipack: 120 (2 packs of 60) film-coated tablets. 

Multipack: 180 (3 packs of 60) film-coated tablets. 

Multipack: 360 (6 packs of 60) film-coated 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 

 

 



41 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30C. 

Store in the original package (blister) 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/1/08/483/016 120 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/017 180 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/018 360 film-coated tablets (PA/alu/PVC/alu) 

EU/1/08/483/034 120 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/035 180 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/036 360 film-coated tablets (PCTFE/PVC/alu) 

EU/1/08/483/052 120 film-coated tablets (PVC/PE/PVDC/alu) 

EU/1/08/483/053 180 film-coated tablets (PVC/PE/PVDC/alu) 

EU/1/08/483/054 360 film-coated tablets (PVC/PE/PVDC/alu) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Zomarist 50 mg/1000 mg 

 

 

  



42 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 
NN: 

  



43 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 
 



44 

Package leaflet: Information for the user 

 

Zomarist 50 mg/850 mg film-coated tablets 

Zomarist 50 mg/1000 mg film-coated tablets 

vildagliptin/metformin hydrochloride 

 

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 Zomarist is and what it is used for 

2. What you need to know before you take Zomarist 

3. How to take Zomarist 

4. Possible side effects 

5. How to store Zomarist 

6. Contents of the pack and other information 

 

 

1. What Zomarist is and what it is used for 

 

The active substances of Zomarist, vildagliptin and metformin, belong to a group of medicines called 

“oral antidiabetics”. 

 

Zomarist is used to treat adult patients with type 2 diabetes. This type of diabetes is also known as 

non-insulin-dependent diabetes mellitus. 

 

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. 

 

Both insulin and glucagon are made in the pancreas. Insulin helps to lower the level of sugar in the 

blood, especially after meals. Glucagon triggers the liver to make sugar, causing the blood sugar level 

to rise. 

 

How Zomarist works 

Both active substances, vildagliptin and metformin, help to control the level of sugar in the blood. The 

substance vildagliptin works by making the pancreas produce more insulin and less glucagon. The 

substance metformin works by helping the body to make better use of insulin. This medicine has been 

shown to reduce blood sugar, which may help to prevent complications from your diabetes. 

 

 

2. What you need to know before you take Zomarist 

 

Do not take Zomarist 
- if you are allergic to vildagliptin, metformin or any of the other ingredients of this medicine 

(listed in section 6). If you think you may be allergic to any of these, talk to your doctor before 

taking Zomarist. 

  



45 

- if you have uncontrolled diabetes, with, for example, severe hyperglycaemia (high blood 
glucose), nausea, vomiting, diarrhoea, rapid weight loss, lactic acidosis (see “Risk of lactic 

acidosis” below) or ketoacidosis. Ketoacidosis is a condition in which substances called ketone 

bodies accumulate in the blood and which can lead to diabetic pre-coma. Symptoms include 

stomach pain, fast and deep breathing, sleepiness or your breath developing an unusual fruity 

smell. 

- if you have recently had a heart attack or if you have heart failure or serious problems with your 
blood circulation or difficulties in breathing which could be a sign of heart problems. 

- if you have severely reduced kidney function. 
- if you have a severe infection or are seriously dehydrated (have lost a lot of water from your 

body). 

- if you are going to have a contrast x-ray (a specific type of x-ray involving an injectable dye). 
Please also see information about this in section “Warnings and precautions”. 

- if you have liver problems. 
- if you drink alcohol excessively (whether every day or only from time to time). 
- if you are breast-feeding (see also “Pregnancy and breast-feeding”). 
 

Warnings and precautions 

Risk of lactic acidosis 

Zomarist may cause a very rare, but very serious side effect called lactic acidosis, particularly if your 

kidneys are not working properly. The risk of developing lactic acidosis is also increased with 

uncontrolled diabetes, serious infections, prolonged fasting or alcohol intake, dehydration (see further 

information below), liver problems and any medical conditions in which a part of the body has a 

reduced supply of oxygen (such as acute severe heart disease). 

If any of the above apply to you, talk to your doctor for further instructions. 

 

Stop taking Zomarist for a short time if you have a condition that may be associated with 

dehydration (significant loss of body fluids) such as severe vomiting, diarrhoea, fever, exposure to 

heat or if you drink less fluid than normal. Talk to your doctor for further instructions. 
 

Stop taking Zomarist and contact a doctor or the nearest hospital immediately if you experience 

some of the symptoms of lactic acidosis, as this condition may lead to coma. 

Symptoms of lactic acidosis include: 

- vomiting 
- stomach ache (abdominal pain) 
- muscle cramps 
- a general feeling of not being well with severe tiredness 
- difficulty in breathing 
- reduced body temperature and heartbeat 
 

Lactic acidosis is a medical emergency and must be treated in a hospital. 

 

Zomarist is not a substitute for insulin. Therefore, you should not receive Zomarist for the treatment of 

type 1 diabetes. 

 

Talk to your doctor, pharmacist or nurse before taking Zomarist if you have or have had a disease of 

the pancreas. 

 

Talk to your doctor, pharmacist or nurse before taking Zomarist 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 Zomarist in order to avoid low blood glucose (hypoglycaemia). 

 

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

not take this medicine. 

 

  



46 

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 Zomarist. Should 

these occur, you should promptly consult your doctor. 

 

If you need to have major surgery you must stop taking Zomarist during and for some time after the 

procedure. Your doctor will decide when you must stop and when to restart your treatment with 

Zomarist. 

 

A test to determine your liver function will be performed before the start of Zomarist 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. 

 

During treatment with Zomarist, your doctor will check your kidney function at least once a year or 

more frequently if you are elderly and/or have worsening renal function. 

 

Your doctor will test your blood and urine for sugar regularly. 

 

Children and adolescents 

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

 

Other medicines and Zomarist 
If you need to have an injection of a contrast medium that contains iodine into your bloodstream, for 

example in the context of an X-ray or scan, you must stop taking Zomarist before or at the time of the 

injection. Your doctor will decide when you must stop and when to restart your treatment with 

Zomarist. 

 

Tell your doctor if you are taking, have recently taken or might take any other medicines. You may 

need more frequent blood glucose and kidney function tests or your doctor may need to adjust the 

dosage of Zomarist. It is especially important to mention the following: 

- glucocorticoids generally used to treat inflammation 
- beta-2 agonists generally used to treat respiratory disorders 
- other medicines used to treat diabetes 
- medicines which increase urine production (diuretics) 

- medicines used to treat pain and inflammation (NSAID and COX-2-inhibitors, such as 

ibuprofen and celecoxib) 

- certain medicines for the treatment of high blood pressure (ACE inhibitors and angiotensin II 
receptor antagonists) 

- certain medicines affecting the thyroid, or 
- certain medicines affecting the nervous system. 
 

Zomarist with alcohol 
Avoid excessive alcohol intake while taking Zomarist since this may increase the risk of lactic acidosis 

(please see section “Warnings and precautions”). 

 

Pregnancy and breast-feeding 

- If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor 
for advice before taking this medicine. Your doctor will discuss with you the potential risk of 

taking Zomarist during pregnancy. 

- Do not use Zomarist if you are pregnant or breast-feeding (see also “Do not take Zomarist”). 
 

Ask your doctor or pharmacist for advice before taking any medicine. 

 

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

 

 



47 

3. How to take Zomarist 

 

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

tell you exactly the dose of Zomarist to take. 

 

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

if you are not sure. 

 

The recommended dose is one film-coated tablet of either 50 mg/850 mg or 50 mg/1000 mg taken 

twice a day 

 

If you have reduced kidney function, your doctor may prescribe a lower dose. Also if you are taking 

an anti-diabetic medicine known as a sulphonylurea your doctor may prescribe a lower dose. 

 

Your doctor may prescribe this medicine alone or with certain other medicines that lower the 

level of sugar in your blood. 
 

When and how to take Zomarist 

- Swallow the tablets whole with a glass of water, 
- Take one tablet in the morning and the other in the evening with or just after food. Taking the 

tablet just after food will lower the risk of an upset stomach. 

 

Continue to follow any advice about diet that your doctor has given you. In particular, if you are 

following a diabetic weight control diet, continue with this while you are taking Zomarist. 

 

If you take more Zomarist than you should 

If you take too many Zomarist tablets, or if someone else takes your tablets, talk to a doctor or 

pharmacist immediately. Medical attention may be necessary. If you have to go to a doctor or 

hospital, take the pack and this leaflet with you. 

 

If you forget to take Zomarist 
If you forget to take a tablet, take it with your next meal unless you are due to take one then anyway. 

Do not take a double dose (two tablets at once) to make up for a forgotten tablet. 

 

If you stop taking Zomarist 
Continue to take this medicine as long as your doctor prescribes it so that it can continue to control 

your blood sugar. Do not stop taking Zomarist unless your doctor tells you to. If you have any 

questions about how long to take this medicine, talk to your doctor. 

 

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 

 

 

4. Possible side effects 
 

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

 

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

side effects: 

 Lactic acidosis (very rare: may affect up to 1 user in 10,000): 
Zomarist may cause a very rare, but very serious side effect called lactic acidosis (see section 

“Warnings and precautions”). If this happens you must stop taking Zomarist and contact a 

doctor or the nearest hospital immediately, as lactic acidosis may lead to coma. 

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



48 

 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 experienced the following side effects while taking Zomarist: 

 Very common (may affect more than 1 in 10 people): nausea, vomiting, diarrhoea, pain in and 
around the stomach (abdominal pain), loss of appetite. 

 Common (may affect up to 1 in 10 people): dizziness, headache, trembling that cannot be 
controlled, metallic taste, low blood glucose. 

 Uncommon (may affect up to 1 in 100 people): joint pain, tiredness, constipation, swollen 
hands, ankle or feet (oedema). 

 Very rare (may affect up to 1 in 10,000 people): sore throat, runny nose, fever; signs of a high 
level of lactic acid in the blood (known as lactic acidosis) such as drowsiness or dizziness, 

severe nausea or vomiting, abdominal pain, irregular heart beat or deep, rapid breathing; redness 

of the skin, itching; decreased vitamin B12 levels (paleness, tiredness, mental symptoms such as 

confusion or memory disturbances). 

 

Some patients have experienced the following side effects while taking Zomarist and a sulphonylurea: 

 Common: dizziness, tremor, weakness, low blood glucose, excessive sweating. 
 

Some patients have had the following side effects while taking Zomarist and insulin: 

 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. 

 

 

5. How to store Zomarist 

 

- 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 carton after 

“EXP”. The expiry date refers to the last day of that month. 

- Do not store above 30C. 
- Store in the original package (blister) in order to protect from moisture. 
 

 

6. Contents of the pack and other information 

 

What Zomarist contains 

- The active substances are vildagliptin and metformin hydrochloride. 
- Each Zomarist 50 mg/850 mg film-coated tablet contains 50 mg vildagliptin and 850 mg 

metformin hydrochloride (corresponding to 660 mg of metformin). 

- Each Zomarist 50 mg/1000 mg film-coated tablet contains 50 mg vildagliptin and 1000 mg 
metformin hydrochloride (corresponding to 780 mg of metformin). 

- The other ingredients are: Hydroxypropylcellulose, magnesium stearate, hypromellose, titanium 
dioxide (E 171), yellow iron oxide (E 172), macrogol 4000 and talc. 

 



49 

What Zomarist looks like and contents of the pack 

Zomarist 50 mg/850 mg film-coated tablets are yellow, oval tablets with “NVR” on one side and 

“SEH” on the other. 

Zomarist 50 mg/1000 mg film-coated tablets are dark yellow, oval tablets with “NVR” on one side 

and “FLO” on the other. 

 

Zomarist is available in packs containing 10, 30, 60, 120, 180 or 360 film-coated tablets and in multi-

packs containing 120 (2x60), 180 (3x60) or 360 (6x60) film-coated tablets. Not all pack sizes and 

tablet strengths may be available in your country. 

 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Lek d.d, PE PROIZVODNJA LENDAVA 

Trimlini 2D 

Lendava, 9220 

Slovenia 

 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

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 



50 

Ελλάδα 

Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

ή 

WIN MEDICA ΦΑΡΜΑΚΕΥΤΙΚΗ A.E. 

Tηλ: +30 210 74 88 821 

 

Österreich 

Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Esteve Pharmaceuticals, S.A. 

Tel: +34 93 446 60 00 

 

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 

Bialport-Produtos Farmacêuticos, S.A. 

Tel: +351 22 986 61 00 

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 

 

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