For the treatment of adults, adolescents and children of 6 years or above with diabetes
mellitus, where
treatment with insulin is required.
 

Posology
Vivaro contains insulin glargine, an insulin analogue, and has a prolonged duration of action.
Vivaro should be administered once daily at any time but at the same time each day.
The Vivaro dose regimen (dose and timing) should be individually adjusted. In patients with
type 2 diabetes mellitus, Vivaro can also be given together with orally active antidiabetic
medicinal products.
The potency of this medicinal product is stated in units. These units are exclusive to Vivaro and
are not the same as IU or the units used to express the potency of other insulin analogues. (see
secton 5.1).
Elderly populaton (≥ 65 years old)
In the elderly, progressive deterioration of renal function may lead to a steady decrease in
insulin requirements.
Renal impairment
In patients with renal impairment, insulin requirements may be diminished due to reduced
insulin metabolism.
Hepatic impairment
In patients with hepatic impairment, insulin requirements may be diminished due to reduced
capacity for gluconeogenesis and reduced insulin metabolism.
Paediatric population
Safety and efficacy of Vivaro have been established in adolescents and children of 6 years and
above.
In children, efficacy and safety of Vivaro have only been assessed when given in the evening.
Due to limited experience on the efficacy and safety of Vivaro in children below the age of 6
years, Vivaro should only be used in this age group under careful medical supervision.
Transition from other insulins to Vivaro
When changing from a treatment regimen with an intermediate or long-acting insulin to a
regimen with Vivaro, a change of the dose of the basal insulin may be required and the
concomitant antidiabetic treatment may need to be adjusted (dose and timing of additional
regular insulins or fastacting insulin analogues or the dose of oral antidiabetic medicinal
products). To reduce the risk of nocturnal and early morning hypoglycaemia, patients who are
changing their basal insulin regimen from a twice daily NPH insulin to a once daily regimen with
Vivaro should reduce their daily dose of basal insulin by 20-30 % during the frst weeks of
treatment. During the first weeks the reduction should, at least partially, be compensated by an
increase in mealtime insulin, after this period the regimen should be adjusted individually.
As with other insulin analogues, patients with high insulin doses because of antibodies to
human insulin may experience an improved insulin response with Vivaro.
Close metabolic monitoring is recommended during the transition and in the initial weeks
thereafter. With improved metabolic control and resulting increase in insulin sensitivity a
further adjustment in dose regimen may become necessary. Dose adjustment may also be
required, for example, if the patient's weight or life-style changes, change of timing of insulin
dose or other circumstances arise that increase susceptibility to hypo-or hyperglycaemia (see
secton 4.4).
Method of administration
Vivaro is administered subcutaneously.
Vivaro should not be administered intravenously. The prolonged duration of action of Vivaro is
dependent on its injection into subcutaneous tissue. Intravenous administration of the usual
subcutaneous dose could result in severe hypoglycaemia.
There are no clinically relevant differences in serum insulin or glucose levels after abdominal,
deltoid or thigh administration of Vivaro. Injection sites must be rotated within a given injection
area from one injection to the next.
Vivaro must not be mixed with any other insulin or diluted. Mixing or diluting can change its
time/action profile and mixing can cause precipitation.
Before using Vivaro Pen, the Instructions for Use included in the Package Leaflet must be read
carefully (see secton 6.6).
 

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

Vivaro is not the insulin of choice for the treatment of diabetic ketoacidosis. Instead, regular
insulin administered intravenously is recommended in such cases.
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the
patient's adherence to the prescribed treatment regimen, injection sites and proper injection
technique and all other relevant factors must be reviewed before dose adjustment is
considered.
Transferring a patient to another type or brand of insulin should be done under strict medical
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting,
etc.), origin (animal, human, human insulin analogue) and/or method of manufacture may
result in the need for a change in dose.
Insulin administration may cause insulin antibodies to form. In rare cases, the presence of such
insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency
to hyper- or hypoglycaemia. (see secton 4.8)
Hypoglycaemia
The time of occurrence of hypoglycaemia depends on the action profile of the insulins used and
may, therefore, change when the treatment regimen is changed. Due to more sustained basal
insulin supply with Vivaro, less nocturnal but more early morning hypoglycaemia can be
expected.
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in
patients with significant stenoses of the coronary arteries or of the blood vessels supplying the
brain (risk of cardiac or cerebral complications of hypoglycaemia) as well as in patients with
proliferative retinopathy, particularly if not treated with photocoagulation (risk of transient
amaurosis following hypoglycaemia).
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or
be absent in certain risk groups. These include patients:
- in whom glycaemic control is markedly improved,
- in whom hypoglycaemia develops gradually,
- who are elderly,
- after transfer from animal insulin to human insulin,
- in whom an autonomic neuropathy is present,
- with a long history of diabetes,
- suffering from a psychiatric illness,
- receiving concurrent treatment with certain other medicinal products (see secton 4.5).
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to
the patient's awareness of hypoglycaemia.
The prolonged effect of subcutaneous insulin glargine may delay recovery from hypoglycaemia.
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent,
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. Adherence
of the patient to the dose and dietary regimen, correct insulin administration and awareness of
hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors increasing
the susceptibility to hypoglycaemia require particularly close monitoring and may necessitate
dose adjustment. These include:
- change in the injection area,
- improved insulin sensitivity (e.g., by removal of stress factors),
- unaccustomed, increased or prolonged physical activity,
- intercurrent illness (e.g. vomiting, diarrhoea),
- inadequate food intake,
- missed meals,
- alcohol consumption,
- certain uncompensated endocrine disorders, (e.g. in hypothyroidism and in anterior pituitary
or adrenocortical insufficiency),
- concomitant treatment with certain other medicinal products.
Intercurrent illness
Intercurrent illness requires intensified metabolic monitoring. In many cases urine tests for
ketones are indicated, and often it is necessary to adjust the insulin dose. The insulin
requirement is often increased. Patents with type 1 diabetes must contnue to consume at
least a small amount of carbohydrates on a regular basis; even if they are able to eat only little
or no food, or are vomiting etc. and they must never omit insulin entirely.
Handling of the pen Before using Vivaro Pen, the Instructions for Use included in the Package
Leaflet must be read carefully.
Vivaro Pen has to be used as recommended in these Instructons for Use (see secton 6.6).
Medication errors
Medication errors have been reported in which other insulins, particularly short-acting insulins,
have been accidentally administered instead of insulin glargine. Insulin label must always be
checked before each injection to avoid medication errors between insulin glargine and other
insulins.
Combination of Vivaro with pioglitazone
Cases of cardiac failure have been reported when pioglitazone was used in combination with
insulin, especially in patients with risk factors for development of cardiac heart failure. This
should be kept in mind if treatment with the combination of pioglitazone and Vivaro is
considered. If the combination is used, patients should be observed for signs and symptoms of
heart failure, weight gain and oedema. Pioglitazone should be discontinued if any deterioration
in cardiac symptoms occurs.
 

A number of substances affect glucose metabolism and may require dose adjustment of insulin
glargine.
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme
(ACE) inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors,
pentoxifylline, propoxyphene, salicylates and sulfonamide antibiotics.
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol,
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens, phenothiazine
derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine [adrenaline],
salbutamol, terbutaline), thyroid hormones, atypical antipsychotic medicinal products (e.g.
clozapine and olanzapine) and protease inhibitors.
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the bloodglucoselowering effect of insulin. Pentamidine may cause hypoglycaemia, which may
sometimes be followed by hyperglycaemia.
In addition, under the influence of sympatholytic medicinal products such as beta-blockers,
clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation may be
reduced or absent.
 

Pregnancy category C

For insulin glargine no clinical data on exposed pregnancies from controlled clinical trials are
available. A moderate amount of data on pregnant women (between 300-1000 pregnancy
outcomes) exposed to marketed insulin glargine indicate no adverse effects of insulin glargine
on pregnancy and no malformative nor feto/neonatal toxicity of insulin glargine.
Animal data do not indicate reproductive toxicity.
The use of Vivaro may be considered during pregnancy, if necessary.
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic
control throughout pregnancy. Insulin requirements may decrease during the first trimester
and generally increase during the second and third trimesters. Immediately after delivery,
insulin requirements decline rapidly (increased risk of hypoglycaemia). Careful monitoring of
glucose control is essential.
Breastfeeding
It is unknown whether insulin glargine is excreted in human milk. No metabolic effects of
ingested insulin glargine on the breastfed newborn/infant are anticipated since insulin glargine
as a peptide is digested into aminoacids in the human gastrointestinal tract.
Breastfeeding women may require adjustments in insulin dose and diet.
Fertility
Animal studies do not indicate direct harmful effects with respect to fertility.
 

The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in
situations where these abilities are of special importance (e.g. driving a car or operating
machines).
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is
particularly important in those who have reduced or absent awareness of the warning
symptoms of hypoglycaemia or have frequent episodes of hypoglycaemia. It should be
considered whether it is advisable to drive or operate machines in these circumstances.
 

Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if
the insulin dose is too high in relation to the insulin requirement.
The following related adverse reactions from clinical investigations are listed below by system
organ class and in order of decreasing incidence (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).
Within each frequency grouping, adverse reactions are presented in order of decreasing
seriousness.

Metabolism and nutrition disorders
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage.
Prolonged or severe hypoglycaemic episodes may be life-threatening.
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of
adrenergic counter-regulation. Generally, the greater and more rapid the decline in blood
glucose, the more marked is the phenomenon of counter-regulation and its symptoms.
Immune system disorders Immediate-type allergic reactions to insulin are rare. Such reactions
to insulin (including insulin glargine) or the excipients may, for example, be associated with
generalised skin reactions, angiooedema, bronchospasm, hypotension and shock, and may be
life-threatening.
Insulin administration may cause insulin antibodies to form. In clinical studies, antibodies that
crossreact with human insulin and insulin glargine were observed with the same frequency in
both NPHinsulin and insulin glargine treatment groups. In rare cases, the presence of such
insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency
to hyper- or hypoglycaemia.
Eyes disorders
A marked change in glycaemic control may cause temporary visual impairment, due to
temporary alteration in the turgidity and refractive index of the lens.
Long-term improved glycaemic control decreases the risk of progression of diabetic
retinopathy.
However, intensification of insulin therapy with abrupt improvement in glycaemic control may
be associated with temporary worsening of diabetic retinopathy. In patients with proliferative
retinopathy, particularly if not treated with photocoagulation, severe hypoglycaemic episodes
may result in transient amaurosis.
Skin and subcutaneous tissue disorders
As with any insulin therapy, lipodystrophy may occur at the injection site and delay local insulin
absorption. Continuous rotation of the injection site within the given injection area may help to
reduce or prevent these reactions.
General disorders and administration site conditions
Injection site reactions include redness, pain, itching, hives, swelling, or inflammation. Most
minor reactions to insulins at the injection site usually resolve in a few days to a few weeks.
Rarely, insulin may cause sodium retention and oedema particularly if previously poor
metabolic control is improved by intensified insulin therapy.
Paediatric population
In general, the safety profle for children and adolescents (≤ 18 years of age) is similar to the
safety profile for adults.
The adverse reaction reports received from post marketing surveillance included relatively
more frequent injection site reactions (injection site pain, injection site reaction) and skin
reactons (rash, urtcaria) in children and adolescents (≤ 18 years of age) than in adults.
No clinical study safety data are available in children below 6 years of age.

Symptoms
Insulin overdose may lead to severe and sometimes long-term and life-threatening
hypoglycaemia.
Management
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in
dose of the medicinal product, meal patterns, or physical activity may be needed.
More severe episodes with coma, seizure, or neurologic impairment may be treated with
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained
carbohydrate intake and observation may be necessary because hypoglycaemia may recur after
apparent clinical recovery.
 

Pharmacotherapeutic group: Drugs used in diabetes. Insulins and analogues for injection, longacting.
ATC Code: A10A E04.
Insulin glargine is a human insulin analogue designed to have a low solubility at neutral pH. It is
completely soluble at the acidic pH of the Vivaro injecton soluton (pH 4). Afer injecton into
the subcutaneous tissue, the acidic solution is neutralised leading to formation of microprecipitates from which small amounts of insulin glargine are continuously released, providing a
smooth, peakless, predictable concentration/time profile with a prolonged duration of action.
Insulin receptor binding: Insulin glargine is very similar to human insulin with respect to insulin
receptor binding kinetics. It can, therefore, be considered to mediate the same type of effect
via the insulin receptor as insulin.
The primary activity of insulin, including insulin glargine, is regulation of glucose metabolism.
Insulin and its analogues lower blood glucose levels by stimulating peripheral glucose uptake,
especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin
inhibits lipolysis in the adipocyte, inhibits proteolysis and enhances protein synthesis.
In clinical pharmacology studies, intravenous insulin glargine and human insulin have been
shown to be equipotent when given at the same doses. As with all insulins, the time course of
action of insulin glargine may be affected by physical activity and other variables.
In euglycaemic clamp studies in healthy subjects or in patents with type 1 diabetes, the onset
of action of subcutaneous insulin glargine was slower than with human NPH insulin, its effect
profile was smooth and peakless, and the duration of its effect was prolonged.
:The following graph shows the results from a study in patients

The longer duration of action of subcutaneous insulin glargine is directly related to its slower
rate of absorption and supports once daily administration. The time course of action of insulin
and insulin analogues such as insulin glargine may vary considerably in different individuals or
within the same individual.
In a clinical study, symptoms of hypoglycaemia or counter-regulatory hormone responses were
similar after intravenous insulin glargine and human insulin both in healthy volunteers and
patients with type 1 diabetes.
Effects of insulin glargine (once daily) on diabetic retinopathy were evaluated in an open-label 5
year
NPH-controlled study (NPH given bid) in 1024 type 2 diabetc patents in which progression of
retnopathy by 3 or more steps on the Early Treatment Diabetc Retnopathy Study (ETDRS)
scale was investigated by fundus photography. No significant difference was seen in the
progression of diabetic retinopathy when insulin glargine was compared to NPH insulin.
aediatric population
In a randomised, controlled clinical study, paediatric patents (age range 6 to 15 years) with
type 1 diabetes (n = 349) were treated for 28 weeks with a basal-bolus insulin regimen where
regular human insulin was used before each meal. Insulin glargine was administered once daily
at bedtime and NPH human insulin was administered once or twice daily. Similar effects on
glycohemoglobin and the incidence of symptomatic hypoglycemia were observed in both
treatment groups, however fasting plasma glucose decreased more from baseline in the insulin
glargine group than in the NPH group.
There was less severe hypoglycaemia in the insulin glargine group as well. One hundred forty
three of the patients treated with insulin glargine in this study continued treatment with insulin
glargine in an uncontrolled extension study with mean duration of follow-up of 2 years. No new
safety signals were seen during this extended treatment with insulin glargine.
A crossover study comparing insulin glargine plus lispro insulin to NPH plus regular human
insulin (each treatment administered for 16 weeks in random order) in 26 adolescent type 1
diabetic patients aged 12 to 18 years was also performed. As in the paediatric study described
above, fasting plasma glucose reduction from baseline was greater in the insulin glargine group
than in the NPH group.
HbA1c changes from baseline were similar between treatment groups; however blood glucose
values recorded overnight were significantly higher in the insulin glargine/ lispro group than the
NPH/regular group, with a mean nadir of 5.4 mM vs 4.1 mM. Correspondingly, the incidences of
nocturnal hypoglycaemia were 32 % in the insulin glargine / lispro group vs 52 % in the NPH /
regular group.
 

In healthy subjects and diabetic patients, insulin serum concentrations indicated a slower and
much more prolonged absorption and showed a lack of a peak after subcutaneous injection of
insulin glargine in comparison to human NPH insulin. Concentrations were thus consistent with
the time profile of the pharmacodynamic activity of insulin glargine. The graph above shows the
activity profiles over time of insulin glargine and NPH insulin.
Insulin glargine injected once daily will reach steady state levels in 2-4 days afer the frst dose.
When given intravenously the elimination half-life of insulin glargine and human insulin were
comparable.
In man, insulin glargine is partly degraded in the subcutaneous tissue at the carboxyl terminus
of the
Beta chain with formaton of the actve metabolites 21A-Gly-insulin and 21A -Gly-des-30B-Thrinsulin.
Unchanged insulin glargine and degradation products are also present in the plasma.
In clinical studies, subgroup analyses based on age and gender did not indicate any difference in
safety and efficacy in insulin glargine-treated patients compared to the entire study population.
Paediatric population
No specific pharmacokinetic study in children or adolescents was conducted.
 

Non-clinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to
reproduction.
 

Zinc chloride
m-cresol
glycerol 57
hydrochloric acid
sodium hydroxide
water for injections.
 

This medicinal product must not be mixed with other medicinal products.
 

3 years. Shelf life after first use of the pen The medicinal product may be stored for a maximum of 4 weeks not above 25°C and away from direct heat or direct light. Pens in use must not be stored in the refrigerator. The pen cap must be put back on the pen after each injection in order to protect from light.

Not in-use pens
Store in a refrigerator (2°C-8°C).
Do not freeze. Do not put Vivaro next to the freezer compartment or a freezer pack.
Keep the pre-filled pen in the outer carton in order to protect from light.
In use pens
For storage precautons, see secton 6.3.
 

3 ml soluton in a cartridge (type 1 colourless glass) with a black plunger (bromobutyl rubber)
and a flanged cap (aluminium) with a stopper (bromobutyl or laminate of polyisoprene and
bromobutyl rubber).The cartridge is sealed in a disposable pen injector. Needles are not
included in the pack.
Packs of 1, 3, 4, 5, 6, 8, 9 and 10 pens are available. Not all pack sizes may be marketed.
 

Before frst use, the pen must be stored at room temperature for 1 to 2 hours.
Inspect the cartridge before use. It must only be used if the solution is clear, colourless, with no
solid particles visible, and if it is of water-like consistency. Since Vivaro is a solution, it does not
require resuspension before use.
Vivaro must not be mixed with any other insulin or diluted. Mixing or diluting can change its
time/action profile and mixing can cause precipitation.
Empty pens must never be reused and must be properly discarded.
To prevent the possible transmission of disease, each pen must be used by one patient only.
Insulin label must always be checked before each injection to avoid medication errors between
insulin glargine and other insulins. (see secton 4.4)
Handling of the pen
The patient should be advised to read the instructions for use included in the package leaflet
carefully before using Vivaro Pen.

Important information for use of Vivaro Pen:
 Before each use, a new needle must always be carefully attached and a safety test must be
performed. Only needles that are compatible for use with Vivaro Pen must be used.
 Special caution must be taken to avoid accidental needle injury and transmission of infection.
 Vivaro Pen must never be used if it is damaged or if the patient is not sure if it is working
properly.
 The patient must always have a spare Vivaro Pen available in case the Vivaro Pen is lost or
damaged.
Storage Instructions
Please check secton 6.4 of this SPC for instructons on how to store Vivaro Pen.
If Vivaro Pen is in cool storage, it should be taken out 1 to 2 hours before injecton to allow it to
warm up. Cold insulin is more painful to inject.
The used Vivaro Pen must be discarded as required by your local authorities.
Maintenance
Vivaro Pen has to be protected from dust and dirt.
The outside of the Vivaro Pen can be cleaned by wiping it with a damp cloth.
The pen must not be soaked, washed or lubricated as this may damage it.
Vivaro Pen is designed to work accurately and safely. It should be handled with care. The
patient should avoid situations where Vivaro Pen may be damaged. If the patient is concerned
that the Vivaro Pen may be damaged, he must use a new one.
Step 1. Check the Insulin
The label on the pen should be checked to make sure it contains the correct insulin. The Vivaro
Vivaro Pen is grey with a purple injection button. After removing the pen cap, the appearance
of insulin should also be checked: the insulin solution must be clear, colorless, with no solid
particles visible, and must have a water-like consistency.
Step 2. Atach the needle
Only needles that are compatible for use with Vivaro Pen should be used.
A new sterile needle will be always used for each injection. After removing the cap, the needle
should be carefully attached straight onto the pen.
Step 3. Perform a safety test
Prior to each injection a safety test has to be performed to ensure that pen and needle work
properly and to remove air bubbles.
A dose of 2 units has to be selected.
The outer and inner needle caps should be removed.
While holding the pen with the needle pointing upwards, the insulin reservoir should be tapped
gently with the finger so that any air bubbles rise up towards the needle
Then the injection button should be pressed in completely.
If insulin has been expelled through the needle tip, then the pen and the needle are working
properly. If no insulin appears at the needle tp, step 3 should be repeated untl insulin appears
at the needle tip.
Step 4. Select the dose
The dose can be set in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If a
dose greater than 80 units is required, it should be given as two or more injectons.
The dose window must show “0” following the safety test. The dose can then be selected.
Step 5. Inject the dose
The patient should be informed on the injection technique by his health care professional.
The needle should be inserted into the skin.
The injection button should be pressed in completely. Then the injection button should be held
down 10 seconds before withdrawing the needle. This ensures that the full dose of insulin has
been injected.
Step 6. Remove and discard the needle
The needle should always be removed after each injection and discarded. This helps prevent
contamination and/or infection, entry of air into the insulin reservoir and leakage of insulin.
Needles must not be reused.
Special caution must be taken when removing and disposing the needle. Recommended safety
measures for removal and disposal of needles must be followed in order to reduce the risk of
accidental needle injury and transmission of infectious diseases.
The pen cap should be replaced on the pen.