Active ingredients: Insulin (insulin glargine)
Lantus 100 units / ml solution for injection in a vial
Lantus package inserts are available for pack sizes:- Lantus 100 units / ml solution for injection in a vial
- Lantus 100 units / ml solution for injection in a cartridge
- Lantus 100 units / ml solution for injection in a cartridge for OptiClik
- Lantus OptiSet 100 units / ml solution for injection in a pre-filled pen.
- Lantus SoloStar 100 units / ml solution for injection in a pre-filled pen
Indications Why is Lantus used? What is it for?
Lantus contains insulin glargine. This is a modified insulin, very similar to human insulin.
Lantus is used to treat diabetes mellitus in adults, adolescents and children from 2 years of age. Diabetes mellitus is a disease in which the body does not produce enough insulin to control blood sugar levels. Insulin glargine has a constant and prolonged action and lowers high blood sugar levels.
Contraindications When Lantus should not be used
Do not use Lantus
If you are allergic to insulin glargine or any of the other ingredients of this medicine
Precautions for use What you need to know before taking Lantus
Talk to your doctor, pharmacist or nurse before using Lantus.
Strictly follow the instructions that your doctor has given you for the dosage, the checks to be performed (blood and urine tests), diet and physical activity (work and exercise).
If your blood sugar level is too low (hypoglycaemia), follow the guide for hypoglycaemia (see box at the end of this leaflet).
Trips
Before starting a trip, consult your doctor. You may need to discuss the following:
- availability of insulin in the country of destination,
- sufficient supplies of insulin, syringes, etc.,
- correct storage of insulin during travel,
- interval between meals and insulin administration during travel,
- possible effects of changing the time zone,
- possible risks of contracting new diseases in the countries visited,
- what to do in emergency situations if you feel unwell or get sick.
Diseases and injuries
In the following situations, diabetes control may require a lot of attention (for example, an adjustment of the insulin dose, blood and urine tests):
- If you are ill or have severe injuries there is a risk of your blood sugar level going up (hyperglycaemia).
- If you don't eat enough, there is a risk that your blood sugar level will drop (hypoglycemia).
In most cases, medical attention is required. Contact your doctor quickly.
Also, if you have type 1 diabetes (insulin-dependent diabetes mellitus) do not stop taking your insulin or taking carbohydrates. It is also necessary to keep the people close to you informed of your need for insulin. Insulin treatment can cause the formation of antibodies to insulin (substances that work against insulin).
However, only very rarely does this necessitate an adjustment of the insulin dose.
Some patients with long-standing type 2 diabetes mellitus and heart disease or a previous stroke treated with pioglitazone (orally administered anti-diabetic medicine used to treat type 2 diabetes mellitus) and insulin have developed heart failure. Tell your doctor as soon as possible if you have signs of heart failure such as unusually shortness of breath or rapid weight gain or localized swelling (edema).
Children
There is no experience with the use of Lantus in children less than 2 years of age.
Interactions Which drugs or foods may change the effect of Lantus
Some medicines can cause your blood sugar to change (decrease or increase or both, depending on the situation). In any case, an optimization of the insulin dose is necessary to avoid too low or too high blood sugar levels. Take care when you start or stop using another medicine.
Tell your doctor or pharmacist if you are taking or have recently taken or might take any other medicines. Before taking a medicine ask your doctor if, and in what way, it can affect your blood sugar and if you need to take countermeasures.
Medicines that can cause low blood sugar levels (hypoglycemia) include:
- all other medicines used to treat diabetes,
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),
- disopyramide (used to treat some heart conditions),
- fluoxetine (used to treat depression),
- fibrates (used to lower high blood fat levels),
- mono-amino oxidase (MAO) inhibitors (used to treat depression),
- pentoxifylline, propoxyphene, salicylates (such as acetylsalicylic acid, used to relieve pain and lower fever),
- sulfonamide antibiotics.
Medicines that can cause blood sugar levels to rise (hyperglycemia) include:
- corticosteroids (such as "cortisone" used to treat inflammation),
- danazol (a medicine that acts on ovulation),
- diazoxide (used to treat high blood pressure),
- diuretics (used to treat high blood pressure or excessive fluid retention),
- glucagon (pancreatic hormone used to treat severe hypoglycaemia),
- isoniazid (used to treat tuberculosis),
- estrogen and progesterone (as in the birth control pill used for birth control),
- phenothiazine derivatives (used to treat psychiatric disorders),
- somatotropin (growth hormone),
- sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),
- thyroid hormones (used to treat thyroid disorders),
- atypical antipsychotic medicines (such as clozapine, olanzapine),
- protease inhibitors (used to treat HIV).
Your blood sugar levels may go down or up if you take:
- beta blockers (used to treat high blood pressure),
- clonidine (used to treat high blood pressure),
- lithium salts (used to treat psychiatric disorders).
Pentamidine (used to treat some infections caused by parasites) can cause hypoglycemia, sometimes followed by hyperglycemia.
Beta-blockers, as well as other sympatholytic medicines (such as clonidine, guanethidine and reserpine), can reduce or completely cancel the warning signs that help you recognize hypoglycaemia.
If you are not sure if you are taking any of these medicines ask your doctor or pharmacist.
Lantus with alcohol
Your blood sugar levels can go down or up if you drink alcohol.
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Tell your doctor if you are planning to become pregnant or if you are already pregnant. Your insulin dose may need to be adjusted during pregnancy and after delivery. It is important to control diabetes carefully and prevent hypoglycemia for the health of the baby.
If you are breast-feeding, consult your doctor as changes in your insulin dose and diet may be required.
Driving and using machines
The ability to concentrate or react may be impaired in case of:
- hypoglycemia (low blood sugar levels),
- hyperglycemia (high blood sugar levels),
- vision problems.
Be aware of the possibility of this occurring in all situations where it could pose a risk to both yourself and others (such as driving a car or using machinery).
Talk to your doctor for advice on whether you should drive if:
- have frequent hypoglycaemic episodes,
- the typical signs that help you identify a "hypoglycemia are reduced or absent
Important information about some of the ingredients of Lantus
This medicinal product contains less than 1 mmol (23 mg) sodium per dose, i.e. essentially sodium-free.
Dosage and method of use How to use Lantus: Dosage
Always use this medicine exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.
Although Lantus contains the same active substance as Toujeo (insulin glargine 300 units / ml), these medicines are not interchangeable. Switching from one insulin therapy to another requires a prescription, medical check-up and blood sugar monitoring. Consult your doctor for further information.
Dose
Based on your lifestyle, your blood sugar (blood sugar) test results, and your previous use of insulin, your doctor will:
- will determine the daily dosage of Lantus you need and at what time,
- will inform you when to check your blood sugar and if you need to do other urine checks,
- will inform you if a lower or higher dose of Lantus is needed.
Lantus is a "long-acting" insulin. Your doctor will advise you if you need to use it together with "other short-acting" insulin or tablets used to treat high blood sugar levels. Many factors can affect blood sugar levels.
He should know these factors so that he can act appropriately in the event of changes in blood sugar levels and thus prevent them from becoming too high or too low. For more information, see the box at the end of this sheet.
Use in children and adolescents
Lantus can be used in adolescents and children from 2 years of age. Take this medicine exactly as your doctor has told you.
Frequency of administration
An injection of Lantus is needed every day at the same time of day.
Method of administration
Lantus is injected under the skin. Lantus must NOT be injected into a vein, as this route of administration will alter its action and may result in hypoglycaemia.
Your doctor will tell you which area of your skin to inject Lantus. For each injection, change the injection site within the chosen skin area.
How to use the vials
Check the vial carefully before use. Use it only if the solution appears clear, colorless, water-like and free from visible particles. Do not shake or mix before use.
Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin. Do not mix Lantus with any other insulin or medicine, and do not dilute it, as these procedures may change the action of Lantu.
Exchanges of insulins
You must always check the insulin label before each injection to avoid mix-ups between Lantus and other insulins.
Always use a new vial if you notice that your blood sugar control has unexpectedly deteriorated. This is because the insulin may have lost some of its effectiveness. If you think you may have a problem with Lantus, have it checked by your doctor or pharmacist.
Overdose What to do if you have taken too much Lantus
If you use more Lantus than you should
- If you have injected too much Lantus, your blood sugar levels may become too low (hypoglycaemia).
Check your blood sugar frequently. In general, to prevent hypoglycemia, you need to eat more substantial meals and control your blood sugar. For information on treating hypoglycemia, see the box at the end of this leaflet.
If you forget to use Lantus
- If you have forgotten a dose of Lantus or if you have not injected enough insulin, your blood sugar levels may become too high (hyperglycaemia). Check your blood sugar frequently. For information on treating hyperglycaemia, see the box at the end of this leaflet.
- Do not take a double dose to make up for a forgotten dose.
If you stop taking Lantus
This can lead to severe hyperglycemia (very high blood sugar levels) and ketoacidosis (buildup of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Lantus without consulting a doctor, who will tell you what needs to be done.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.
Side Effects What are the side effects of Lantus
Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you notice that your blood sugar levels are too low (hypoglycaemia), take immediate action to raise your blood sugar levels (see box at the end of this leaflet).
Hypoglycaemia (low blood sugar levels) can be very serious and is very common with insulin treatment (may affect more than 1 in 10 people). Low sugar means there is not enough blood sugar If your blood sugar levels drop too low, you can pass out (lose consciousness). Severe hypoglycemic episodes can cause brain damage and can be life-threatening. For more information, see the box at the end of this sheet.
Severe allergic reactions (rare may affect up to 1 in 1000 patients): signs may include extensive skin reactions (rash and itching all over the body), severe edema of the skin or mucous membranes (angioedema), dyspnoea, low blood pressure blood pressure with rapid heartbeats and sweating.
A severe allergic reaction to insulins could be life-threatening. Tell your doctor immediately if you notice any signs of severe allergic reactions.
Common reported side effects (may affect up to 1 in 10 patients)
- Skin changes at the injection site
If you inject insulin too often into the same area of the skin, the subcutaneous fatty tissue in this area may shrink (lipoatrophy may affect up to one in 100 patients) or harden (lipohypertrophy). Insulin may not be adequately effective. Change the site of each injection to help prevent this type of skin change.
- Skin and allergic reactions at the injection site
The signs may include redness, unusually severe pain when injecting, itching, hives, edema and inflammation. These reactions can spread to the area around the injection site. Most minor insulin reactions usually go away within a few days or weeks.
Rare side effects reported (may affect up to 1 in 1,000 patients)
- Ocular reactions
A marked change (improvement or worsening) in blood sugar levels can temporarily disturb vision. If you have proliferative retinopathy (an eye disease associated with diabetes), severe hypoglycaemic episodes can cause temporary loss of vision.
- Systemic pathologies
In rare cases, insulin treatment can result in a temporary increase in water retention in the body with swelling of the calves and ankles.
Very rare side effects reported (may affect up to 1 in 10,000 patients)
In very rare cases, dysgeusia (taste disturbance) and myalgia (muscle pain) can occur.
Use in children and adolescents
In general, side effects in children and adolescents aged 18 years and younger are similar to those seen in adults.
Reports of injection site reactions (injection site pain, injection site reaction) and skin reactions (redness, hives) were relatively more frequent in children and adolescents aged 18 years and younger than in adults.
There is no experience in children less than 2 years of age.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. 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.
Expiry and Retention
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 carton and vial label after "EXP" / "Exp". The expiry date refers to the last day of that month.
Unopened vials
Store in a refrigerator (2 ° C-8 ° C). Do not freeze or put in direct contact with the freezer or refrigerated bags. Keep the vial in the outer carton to protect the medicine from light
Open vials
Once in use, the 5 ml vial can be stored for up to 4 weeks in the original packaging at a temperature not exceeding 25 ° C and away from direct heat or direct light
Once in use, the 10 ml vial can be stored for up to 4 weeks in the original packaging at a temperature not exceeding 30 ° C and away from direct heat or direct light.
Do not use it after this period. It is recommended to note on the label itself the date of first use.
Do not use Lantus if you observe particles inside.Only use Lantus if the solution appears clear, colorless and water-like.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What Lantus contains
- The active ingredient is insulin glargine. Each ml of solution contains 100 units of insulin glargine (equivalent to 3.64 mg).
- The other ingredients are: zinc chloride, meta-cresol, glycerol, sodium hydroxide (for pH adjustment) (see section "Important information about some of the components of Lantus"), hydrochloric acid (for pH adjustment), polysorbate 20 (only 10 ml vial) and water for injections.
What Lantus looks like and contents of the pack
Lantus 100 units / ml solution for injection in a vial is a clear, colorless and aqueous solution.
Each vial contains 5 ml of solution for injection (equivalent to 500 units) or 10 ml of solution for injection (equivalent to 1000 units)
Pack sizes of 1, 2, 5 and 10 vials of 5 ml or 1 vial of 10 ml.
Not all pack sizes may be marketed.
HYPERGLYCEMIA AND HYPOGLYCEMIA
Always carry some sugar with you (at least 20 grams).
Bring information with you to indicate that you are diabetic.
HYPERGLYCEMIA (high blood sugar levels) If your blood sugar levels are too high (hyperglycaemia), you may not have injected enough insulin.
Why does hyperglycemia occur?
Examples include:
- has not injected insulin or has administered an insufficient amount of it or when the insulin becomes less effective, for example because it is not stored correctly,
- are exercising less than usual, or are particularly stressed (emotionally or physically), or in cases of injury, surgery, infection or fever,
- you are taking or have taken certain other medicines (see section, "Lantus and other medicines").
Hyperglycemia Warning Symptoms
Thirst, increased need to urinate, weakness, dry skin, redness of the face, loss of appetite, low blood pressure, rapid heartbeat, and presence of glucose or ketone bodies in the urine. Abdominal pain, deep and rapid breathing, drowsiness or even loss of knowledge may indicate a serious condition (ketoacidosis) resulting from insulin deficiency
What should you do in case of hyperglycaemia?
Check your blood sugar and urine for ketone bodies as soon as possible if any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis should always be treated by your doctor, usually in a hospital setting.
Hypoglycaemia (low blood sugar levels)
If your blood sugar levels drop too low, you can lose consciousness. Severe hypoglycemic episodes can cause heart attack or brain damage and can be life-threatening. You usually need to be able to recognize when your blood sugar levels are getting too low so that you can take adequate precautions.
Why does hypoglycemia occur?
Examples include:
- injected too much insulin,
- missed or delayed meals,
- is not eating enough, or the food consumed contains less carbohydrates than is normally consumed (carbohydrates are sugar and sugar-like substances; however artificial sweeteners are NOT carbohydrates),
- lost carbohydrates due to vomiting or diarrhea,
- drinks alcoholic beverages, particularly if you are eating little,
- are doing more exercise than usual, or a different type of physical activity,
- is recovering from injury, surgery or stress,
- recovering from an illness or fever,
- you are taking or have taken certain other medicines (see section, "Lantus and other medicines").
Hypoglycemia can also occur more easily if
- you are at the beginning of your insulin treatment or have switched to a different type of insulin, (when you switch from a previous basal insulin to Lantus, if hypoglycaemia occurs, it will more likely occur in the morning than at night),
- blood sugar levels are nearly normal or show changes,
- the area of the skin where the insulin is injected has changed (for example from the thigh to the upper arm),
- suffer from severe kidney or liver disease, or from other diseases such as hypothyroidism.
Warning symptoms of hypoglycemia
- In the body
Examples of symptoms that indicate blood sugar levels are falling too much or too fast: sweating, clammy skin, anxiety, rapid heartbeat, high blood pressure, palpitations, and an irregular heartbeat. These symptoms can often develop earlier than those that indicate a decrease in brain sugar levels.
- In the brain
Examples of symptoms that indicate decreased brain sugar levels: headache, insatiable hunger, nausea, vomiting, fatigue, sleepiness, sleep disturbance, restlessness, aggression, difficulty concentrating, decreased ability to react, depressed mood, confusion, difficulty speech (sometimes aphasia), visual disturbances, tremor, paralysis, sensory disturbances (paraesthesia), tingling and numbness in the mouth, dizziness, loss of self-control, inability to provide for oneself, seizures, loss of consciousness.
The first symptoms characteristic of a state of hypoglycemia ("warning symptoms") may vary, be less evident or even completely absent
- if you are elderly, have had diabetes for a long time or suffer from a certain type of neurological disease (diabetic autonomic neuropathy),
- after a recent hypoglycemic episode (for example the day before) or if the hypoglycaemia appears slowly,
- if your blood sugar levels are nearly normal or at least significantly improved,
- if you have recently switched from an "animal insulin to a" human insulin such as Lantus,
- if you are taking or have taken certain other medicines (see section, "Lantus and other medicines")
In these cases, severe hypoglycemia (even fainting) can develop without recognizing it in time. Therefore, you learn about the warning symptoms of hypoglycemia. If necessary, more frequent blood glucose checks can help identify mild hypoglycemic episodes that may otherwise go unnoticed. If you are unable to recognize the warning symptoms of hypoglycemia. "hypoglycemia, avoid all those situations (such as driving a car) that can be risky for you and others due to hypoglycemia.
What should you do in case of hypoglycaemia?
- Do not inject insulin. Immediately take 10-20 g of sugar, such as glucose, sugar cubes or a sugar-sweetened drink. Warning: Artificial sweeteners and foods containing artificial sweeteners (such as diet drinks) do not help treat hypoglycemia.
- At this point, you consume food that can cause a release of sugar into the blood over a long period of time (such as bread or pasta). Your doctor or nurse should discuss these measures with you in advance. Normalization of hypoglycaemia may be delayed as Lantus has a long duration of action.
- If another hypoglycemia occurs, take 10-20g of sugar again.
- Talk to your doctor as soon as you notice that your hypoglycaemia cannot be controlled or if it occurs again.
Tell your relatives, friends and colleagues who are close to you that:
If you are unable to swallow or if you lose consciousness, you should have an "injection of glucose or glucagon (a medicine that raises blood sugar levels). These injections are justified even if you are not sure if this has occurred. a hypoglycemic event.
You should check your blood sugar immediately after taking sugar to confirm that a hypoglycaemic episode is in progress.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
LANTUS 100 UNITS / ML SOLUTION FOR INJECTION IN A VIAL
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml contains 100 units of insulin glargine (equivalent to 3.64 mg).
Each vial contains 5 ml of solution for injection, equivalent to 500 units, or 10 ml of solution for injection, equivalent to 1,000 units.
Insulin glargine is produced by the recombinant DNA technique in Escherichia coli.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Injectable solution.
Clear and colorless solution.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Treatment of diabetes mellitus in adults, adolescents and children from 2 years of age.
04.2 Posology and method of administration
Dosage
Lantus contains insulin glargine, an insulin analogue, and has a prolonged duration of action.
Lantus should be given once a day, at any time of the day but always at the same time every day.
The dosage regimen of Lantus (dose and timing of administration) must be individually adapted. In patients with type 2 diabetes mellitus, Lantus can be given together with orally active antidiabetic medicines.
The potency of this medicine is expressed in units. These units refer to Lantus only and do not correspond to the IU or units used to express the potency of other insulin analogues (See section 5.1).
Special populations
Elderly population (≥ 65 years)
In the elderly, progressive deterioration of kidney function can cause a steady decrease in insulin demand.
Kidney failure
In patients with renal insufficiency the insulin requirement may decrease due to reduced insulin clearance.
Hepatic insufficiency
Insulin requirements may decrease in patients with hepatic insufficiency due to impaired gluconeogenesis and reduced insulin metabolism.
Pediatric population
The efficacy and safety of Lantus have been demonstrated in adolescents and children aged 2 years and above. Lantus has not been studied in children less than 2 years of age.
Switching from other insulins to Lantus
When replacing an intermediate-acting or prolonged-acting insulin regimen with a Lantus regimen, a change in the basal insulin dose may be required and concomitant antidiabetic treatment (the dose and timing of additional insulin administration) must be adjusted. regular human or fast-acting insulin analogs or the dose of oral antidiabetic medicines).
To reduce the risk of nocturnal and morning hypoglycaemia, patients who change their basal insulin regimen from NPH insulin twice daily to Lantus once daily will need to reduce their daily basal insulin dose by 20-30% during the first few weeks. of treatment. During the first few weeks the decrease should, at least in part, be compensated for by an increase in insulin before meals; after this period the regime will have to be adjusted individually.
As with other insulin analogues, patients treated with high doses of insulin due to the presence of antibodies to human insulin may show improved insulin response when treated with Lantus.
Frequent metabolic checks are recommended during the transition from one type of insulin to another and in the first few weeks thereafter.
It may occur that due to improved metabolic control and consequent increase in insulin sensitivity, further dose adjustment may be required. Dose adjustment may also be necessary if, for example, the patient's weight or patient's weight changes. lifestyle, time of administration or other circumstances that may cause increased sensitivity to hypo- or hyperglycaemia (see section 4.4).
Method of administration
Lantus is administered subcutaneously.
Lantus must not be administered intravenously. The prolonged duration of action of Lantus depends on its injection into the subcutaneous tissue. Intravenous administration of the dose that is usually used subcutaneously can cause severe hypoglycaemia.
There are no clinically relevant differences in serum insulin or glucose levels following administration of Lantus in the abdominal wall, deltoid muscle or thigh. It is necessary to rotate the injection sites within the chosen area between one injection and the next.
Lantus must not be mixed with any other type of insulin or diluted. By mixing or diluting it, its duration / action profile can be changed and mixing can cause it to precipitate.
For further details on use, see section 6.6.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
04.4 Special warnings and appropriate precautions for use
Lantus is not the insulin of choice for the treatment of diabetic ketoacidosis. In such cases, regular insulin administered intravenously is recommended instead.
If glycemic control is not optimal or if the patient exhibits a tendency to hyperglycemic or hypoglycemic episodes, the patient's adherence to the prescribed treatment regimen, injection sites and techniques, and all other relevant factors should be reviewed before considering a dose adjustment.
Switching a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type (regular, NPH, slow, long-acting, etc.), origin (animal, human, human insulin analogue) and / or method of preparation may necessitate a dose adjustment.
The administration of insulin can lead to the formation of anti-insulin antibodies. In rare cases, the presence of such insulin antibodies may require adjustment of the insulin dosage to correct a tendency to hyperglycemia or hypoglycemia (see section 4.8).
Hypoglycemia
The frequency of hypoglycaemic events depends on the action profile of the various types of insulin used and can therefore change when the treatment regimen is changed. Due to an increased basal insulin intake with Lantus, hypoglycaemia may occur less frequently at night and more frequently in the early morning.
Special precautions should be taken and more frequent blood glucose monitoring is recommended in patients in whom hypoglycaemic episodes may be of particular clinical relevance, for example in patients with significant stenosis of the coronary arteries or blood vessels supplying the brain ( risk of cardiac or cerebral complications of hypoglycemia), as well as in patients with proliferative retinopathy, particularly if they are not treated with photocoagulation (risk of transient amaurosis following hypoglycemia).
Patients should be able to recognize the circumstances in which the warning symptoms of hypoglycemia have diminished. The warning symptoms of hypoglycemia may change, be less noticeable or absent in certain risk groups. These include patients:
- with marked improvement in glycemic control,
- in which hypoglycaemia develops gradually,
- Senior citizens,
- who have switched from an "animal insulin to a" human insulin,
- with autonomic neuropathy,
- with a long history of diabetes,
- suffering from psychiatric disorders,
- who are receiving treatment with some other medicines at the same time (see section 4.5).
Such situations can cause severe hypoglycemia (and possible loss of consciousness) before the patient is aware of it.
The prolonged effects of subcutaneous administration of insulin glargine may delay the normalization of a hypoglycaemia.
If normal or decreased glycosylated hemoglobin values are observed, the possibility of recurrent, unrecognized (especially nocturnal) episodes of hypoglycaemia should be considered.
Patient adherence to the dose and dietary regimen, correct insulin administration and recognition of hypoglycemic symptoms are essential to reduce the risk of hypoglycemia. Factors that increase susceptibility to hypoglycemia require particularly careful monitoring and the dose may need to be adjusted. These factors include:
- variation of the injection area,
- improvement of insulin sensitivity (for example, by eliminating stressors),
- unusual, increased or prolonged physical exercise,
- intercurrent disturbances (e.g. vomiting, diarrhea),
- inadequate food intake,
- omission of meals,
- alcohol consumption,
- uncompensated disorders of the endocrine system (for example, in hypothyroidism and in adrenocortical and anterior pituitary insufficiency),
- concomitant treatment with some other medicines.
Intercurrent illnesses
Intercurrent illnesses require intensified metabolic monitoring. In some cases it is advisable to do urine tests for ketones and often it is necessary to adjust the dose of insulin. The demand for insulin usually increases. Patients with type 1 diabetes must maintain a regular intake of carbohydrates, albeit in small amounts, even if they eat little or are unable to eat, or vomit, etc. and they must never completely stop insulin administration.
Medication administration errors
Medication errors have been reported in which other insulins, particularly rapid insulins, have been accidentally administered in place of insulin glargine. The insulin label should always be checked before each injection to avoid medication errors. between insulin glargine and other insulins.
Combination of Lantus with pioglitazone
Cases of heart failure have been reported when pioglitazone was used in combination with insulin, especially in patients with risk factors for developing heart failure. This should be taken into consideration when setting up treatment with the combination of pioglitazone and Lantus. If the combination is used, patients should be observed for signs and symptoms of heart failure, weight gain and edema.
Pioglitazone should be discontinued if any deterioration in cardiac symptoms occurs.
04.5 Interactions with other medicinal products and other forms of interaction
Concomitant administration of some substances affects glucose metabolism and may require dose adjustment of insulin glargine.
Substances that may increase the blood glucose lowering effect and susceptibility to hypoglycaemia include oral antidiabetic drugs, angiotensin converting enzyme (ACE) inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, propoxyphene, salicylates and sulfonamide antibiotics.
Substances that may reduce the hypoglycemic effect include: corticosteroids, danazol, diazoxide, diuretics, glucagon, isoniazid, estrogens and progestins, phenothiazine derivatives, somatropin, sympathomimetic drugs (eg epinephrine [adrenaline], salbutamol, terbutaline), hormones , atypical antipsychotic medicines (e.g. clozapine and olanzapine) and protease inhibitors.
Beta-blockers, clonidine, lithium salts or alcohols can potentiate or reduce the blood sugar lowering effect of insulin. Pentamidine can cause hypoglycemia, which can sometimes be followed by hyperglycemia.
Furthermore, under the effect of sympatholytic drugs such as beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent.
04.6 Pregnancy and lactation
Pregnancy
For insulin glargine, no clinical data on exposed pregnancies are available in controlled clinical trials.
A limited amount of data on pregnant women (between 300 and 1000 pregnancy outcomes) exposed to the marketed medicinal product indicate neither any adverse effects on pregnancy nor any malformation or toxicity on fetal and neonatal health of insulin glargine.
Animal data do not indicate reproductive toxicity.
The use of Lantus may be considered during pregnancy if needed.
It is essential that patients with pre-existing or pregnant diabetes maintain satisfactory metabolic control throughout their pregnancy. Insulin requirements may decrease during the first trimester and generally increase during the second and third trimesters. Immediately after delivery, the amount of insulin needed decreases rapidly (the risk of hypoglycemia increases). Careful blood sugar control is therefore essential.
Feeding time
It is not known whether insulin glargine is excreted in human milk. No metabolic effects are expected from ingestion of insulin glargine in the nursing infant / child since insulin glargine as a peptide is digested into individual amino acids in the human gastrointestinal tract.
Breastfeeding women may require adjustment of insulin dosage and diet.
Fertility
Animal studies do not indicate direct harmful effects on fertility.
04.7 Effects on ability to drive and use machines
The patient's ability to concentrate and react may be compromised by "hypoglycemia or" hyperglycemia or, for example, as a consequence of visual impairment. This can result in a risky situation where the aforementioned ability is of particular importance (for example driving vehicles or using machines).
Patients should be advised to take the necessary precautions to avoid hypoglycemia while driving, this is particularly important for those in whom the perception of the warning signs of the onset of a hypoglycemic state is reduced or completely absent or who are subject to frequent hypoglycemic episodes. It is therefore necessary to consider whether in such circumstances it is appropriate to drive or operate machinery.
04.8 Undesirable effects
Hypoglycaemia, which is generally the most frequent adverse reaction to insulin therapy, may be caused by too high a dose of insulin than required.
Table of adverse reactions
The following related adverse reactions from clinical studies are listed below by system organ class and by decreasing incidence (very common: ≥1 / 10; common: ≥1 / 100,
Within each frequency class, adverse reactions are reported in order of decreasing severity.
Description of selected adverse reactions
Metabolism and nutrition disorders
Severe hypoglycemic attacks, especially if recurrent, can cause neurological damage. Prolonged or severe hypoglycemic episodes can be life threatening.
In many patients, the signs and symptoms of central hypoglycemia are preceded by signs of adrenergic counter-regulation. Generally, the higher and faster the lowering of blood glucose levels, the more marked are the counter-regulation phenomena and related symptoms.
Disorders of the immune system
Immediate-type allergic reactions to insulin are rare. Such reactions to insulin (and insulin glargine) or to the excipients may be associated, for example, with generalized skin reactions, angioedema, bronchospasm, hypotension and shock and may represent a life threatening.
The administration of insulin can lead to the formation of anti-insulin antibodies. In some clinical studies, antibodies that cross-reacted with human insulin and insulin glargine were observed with the same frequency in the NPH insulin groups and in the insulin glargine groups. In rare cases, the presence of such insulin antibodies may require adjustment of the insulin dosage in order to correct a tendency to hyperglycemia or hypoglycemia.
Eye disorders
A marked change in glycemic control can cause temporary visual impairment, due to a temporary alteration in the imbibition and refractive index of the lens.
Long-term improvement in glycemic control decreases the risk of progression of diabetic retinopathy. However, the intensification of insulin therapy and the resulting sudden improvement in glycemic control may be associated with a temporary worsening of diabetic retinopathy. In patients with proliferative retinopathy, particularly those not treated with photocoagulation, severe hypoglycemic episodes can cause transient amaurosis. .
Skin and subcutaneous tissue disorders
As with all insulin therapies, injection site lipodystrophy can occur which slows local insulin absorption. Continuous rotation of the injection site within the chosen injection site can help reduce or prevent these reactions.
General disorders and administration site conditions
Injection site reactions include redness, pain, itching, hives, edema, or inflammation. Most minor reactions to insulins at the injection site usually resolve within a few days to weeks.
Rarely, insulin can cause sodium retention and edema, particularly if previous poor metabolic control has been improved with intensive insulin therapy.
Pediatric population
In general, the safety profile in children and adolescents (age ≤ 18 years) is similar to that seen in adults.
Adverse reactions reported post-marketing include injection site reactions (injection site pain, injection site reaction) and skin reactions (rash, urticaria) relatively more frequent in children and adolescents (age ≤ 18 years) than to adults.
There are no clinical data on safety in children less than 2 years of age.
Reporting of suspected adverse reactions.
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous 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. in "Annex V.
04.9 Overdose
Symptoms
Insulin overdose can lead to severe, sometimes long-term, and life-threatening hypoglycaemia.
Treatment
Mild episodes of hypoglycemia can usually be treated with oral carbohydrates. It may be necessary to adjust the dose of the medicine and change the diet or exercise.
More severe episodes accompanied by coma, seizures or neurological disorders can be treated with intramuscular / subcutaneous glucagon or concentrated intravenous glucose. It may also be necessary to ensure a long-acting carbohydrate intake and to keep the patient under observation since hypoglycaemia may recur even after an initial recovery.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: drugs used in diabetes, insulins and analogues for injection, slow acting.
ATC code: A10AE04.
Mechanism of action
Insulin glargine is a human insulin analog with low solubility at neutral pH. It is completely soluble at the acidic pH (pH 4) of the Lantus injectable solution. After being injected into the subcutaneous tissue, the acid solution is neutralized and gives rise to the formation of microprecipitates from which small quantities of insulin glargine are continuously released. This process ensures a uniform, peak-free, predictable concentration / duration profile with a prolonged duration of action.
Insulin glargine is metabolised to 2 active metabolites M1 and M2 (see section 5.2).
Insulin receptor binding: In vitro studies indicate that the affinity of insulin glargine and its metabolites M1 and M2 for the human insulin receptor is similar to that of human insulin.
IGF-1 receptor binding: the affinity of insulin glargine for the human IGF-1 receptor is approximately 5-8 times greater than that of human insulin (but approximately 70-80 times lower than that of IGF-1 ), while M1 and M2 bind to the IGF-1 receptor with a slightly lower "affinity than" human insulin.
The total concentration of insulin (insulin glargine and its metabolites) found in patients with type 1 diabetes was markedly lower than that which would be required for an occupation of the IGF-1 receptor such as to have a semi-maximal effect and the consequent activation of the mitogenic-proliferative pathway from starts from the IGF-1 receptor. Physiological concentrations of endogenous IGF-1 can activate the mitogenic-proliferative pathway; however, the therapeutic concentrations found during insulin therapy, including Lantus therapy, are significantly lower than the pharmacological concentrations required to activate the IGF-1 pathway.
The main activity of insulin, including insulin glargine, is the regulation of glucose metabolism.
Insulin and its analogues lower blood glucose levels by stimulating peripheral glucose uptake, especially from skeletal muscle and adipose tissue, and by inhibiting hepatic glucose production. Insulin inhibits adipocyte lipolysis and proteolysis and increases protein synthesis.
Clinical pharmacology studies have shown that intravenous insulin glargine and human insulin are equipotent when given at the same doses. As with all insulin treatments, the duration of action of insulin glargine can be influenced by exercise and other variables.
In euglycemic clamp studies in healthy subjects or in patients with type 1 diabetes, the onset of activity of subcutaneously administered insulin glargine was slower than that of human NPH insulin, and its effect was uniform. and without any peak and the duration of its effect was prolonged.
The longer duration of action of subcutaneous insulin glargine is directly related to its slower rate of absorption and justifies the administration of a single daily dose. The temporal profile of the action of insulin and its analogues such as insulin glargine can vary considerably in different individuals or in the same individual.
In a clinical study, symptoms of hypoglycemia or counter-regulating hormone responses were similar after intravenous administration of insulin glargine and human insulin in both healthy volunteers and patients with type 1 diabetes.
The effects of insulin glargine (once daily) on diabetic retinopathy were evaluated in an open-label 5-year NPH-controlled study (NPH administered twice daily) in 1024 patients with type II diabetes in whom the progression of retinopathy of 3 or more steps on the Early Tretament scale
Diabetic Retinopathy Study (ETDRS) was evaluated with fundus photography. No significant differences were seen in the progression of diabetic retinopathy with insulin glargine versus NPH insulin.
The Origin study (Outcome Reduction with Initial Glargine INtervention) is a multicenter, randomized, 2x2 factorial design study conducted in 12,537 high risk cardiovascular (CV) subjects with impaired fasting glucose (IGF) or impaired glucose tolerance (IGT) ( 12% of participants) or type 2 diabetes mellitus treated with ≤ 1 oral antidiabetic agent (88% of participants). Subjects were randomized (1: 1) to treatment with insulin glargine (n = 6264), titrated to achieve a fasting glucose (FPG) ≤ 95 mg / dL (5.3 mM / L), or to standard therapy (n = 6273).
The first co-primary efficacy outcome was time to first occurrence of CV death, non-fatal myocardial infarction (MI), or non-fatal stroke, and the second co-primary efficacy outcome was time to first occurrence of any of the primary events, or a revascularization procedure (coronary, carotid or peripheral), or hospitalization for heart failure.
Secondary endpoints included all cause mortality and a composite microvascular outcome.
Insulin glargine did not change the relative risk of CV disease and CV mortality compared with standard therapy. There were no differences between insulin glargine and standard therapy with regard to the two co-primary results, for each component endpoint, including the above results, for all-cause mortality, or for composite microvascular outcome.
The mean insulin glargine dose at the end of the study was 0.42 U / kg. Upon entry into the study, subjects had a median HbA1c value of 6.4% and median HbA1c values during treatment ranging from 5.9 to 6.4% in the insulin glargine group, and ranging from 6.2% to 6.6% in the standard therapy group throughout the follow-up period.
Rates of severe hypoglycemia (subjects affected by the event per 100 subject-exposure years) were 1.05 in the insulin glargine group and 0.30 in the standard therapy group, and confirmed non-severe hypoglycemia rates were 7.71 in the insulin group. glargine and 2.44 in the standard therapy group During this 6-year study, 42% of subjects in the insulin glargine group experienced no hypoglycemic episodes.
At the last visit during treatment there was a mean increase in body weight of 1.4 kg in the insulin glargine group and a mean decrease of 0.8 kg in the standard therapy group from baseline.
Pediatric population
In a randomized controlled clinical trial, pediatric patients (ages 6 to 15 years) with type I diabetes (n = 349) were treated for 28 weeks with a basal-bolus insulin regimen in which insulin was used before each meal. regular human. Insulin glargine was administered once daily at bedtime and human NPH insulin was administered once or twice daily. Similar effects on glycated hemoglobin and the incidence of hypoglycaemia were observed in both treatment groups. symptomatic; however, fasting glucose decreased more from baseline in the insulin glargine group than in the NPH group. In addition, there were fewer episodes of severe hypoglycaemia in the insulin glargine group. 143 patients treated with insulin glargine in the study continued insulin treatment glargine in an uncontrolled extension study with a mean follow-up duration of 2 years No safety warning signs were seen during this extended treatment with insulin glargine.
A crossover study comparing insulin glargine plus insulin lispro versus NPH plus regular human insulin (each treatment administered for 16 weeks in random order) was also conducted in 26 adolescents with type I diabetes aged 12 to 18 years. As in the pediatric study described above, the decrease in fasting glucose from baseline was greater in the insulin glargine group than in the NPH insulin group.
Changes in HbA1c from baseline were similar in the two treatment groups; however, overnight blood glucose values were significantly higher in the insulin glargine / lispro group than in the NPH / regular insulin group, with a mean nadir of 5.4 mM versus 4.1 mM.
Correspondingly, the incidence of nocturnal hypoglycemia was 32% in the insulin glargine / lispro group compared to 52% in the NPH / regular insulin group.
A 24-week, parallel group study was conducted in 125 children with type I diabetes mellitus aged 2 to 6 years, comparing insulin glargine administered once daily in the morning versus NPH administered once or twice. per day as basal insulin. Both groups received a bolus of insulin before meals.
The primary objective of demonstrating non-inferiority of insulin glargine to NPH in all hypoglycemia was not met and there was a trend for an increase in hypoglycemic events with insulin glargine [insulin glargine frequency ratio: NPH (95% CI) ) = 1.18 (0.97-1.44)].
Glycated hemoglobin and blood glucose variability were comparable in the two groups. No new safety signals were observed in this study.
05.2 Pharmacokinetic properties
In healthy subjects and diabetic patients, serum insulin concentrations indicated slower and much more prolonged absorption and showed a lack of a peak after subcutaneous injection of insulin glargine compared to human NPH insulin. Concentrations were therefore consistent with the time profile of insulin glargine. Pharmacodynamic activity of insulin glargine. The graph above shows the time profiles of insulin glargine and NPH insulin activity.
Insulin glargine given by injection once daily will reach steady state levels in 2-4 days after the first dose.
When administered intravenously, the elimination half-lives of insulin glargine and human insulin were comparable.
After subcutaneous injection of Lantus in diabetic patients, insulin glargine is rapidly metabolized at the carboxy terminus of the Beta chain, with the formation of the two active metabolites M1 (21A-Gly-insulin) and M2 (21A-Gly-des-30B-Thr- insulin). In plasma, the major circulating compound is the metabolite M1. Exposure to M1 increases with increasing dose of Lantus administered.
Pharmacokinetic and pharmacodynamic data indicate that the effect of subcutaneous injection of Lantus is mainly due to exposure to M1. Insulin glargine and metabolite M2 were not measurable in the vast majority of subjects and, when measurable, their concentration it was independent of the dose of Lantus administered.
In clinical studies, subgroup analysis based on age and gender showed no difference in safety and efficacy in patients treated with insulin glargine compared to the entire study population.
Pediatric population
Pharmacokinetics in children aged 2 to 6 years with type I diabetes mellitus were evaluated in a clinical study (see section 5.1). The trough plasma concentrations of insulin glargine and its major metabolites M1 and M2 were measured in children treated with insulin glargine, and showed a pattern of plasma concentrations similar to adults, with no evidence of accumulation of insulin glargine or its metabolites with the chronic administration.
05.3 Preclinical safety data
Non-clinical data reveal no risk for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, reproductive toxicity.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
5 ml vial:
Zinc chloride,
m-cresol,
glycerol,
hydrochloric acid,
sodium hydroxide,
water for injections.
10 ml vial:
Zinc chloride,
m-cresol,
glycerol,
hydrochloric acid,
polysorbate 20
sodium hydroxide,
water for injections.
06.2 Incompatibility
This medicinal product must not be mixed with other medicinal products. It is important to make sure that the syringes do not contain traces of other substances.
06.3 Period of validity
2 years.
Shelf life after first use of the vial
The medicine can be stored for up to 4 weeks at a temperature not exceeding 25 ° C and away from direct heat or direct light. Keep the vial in the outer carton to protect the medicine from light.
It is recommended to write the date on which the contents of the vial are used for the first time on the label.
06.4 Special precautions for storage
Unopened vials
Store in a refrigerator (2 ° C - 8 ° C).
Do not freeze.
Do not put Lantus in the freezer or in direct contact with refrigerated bags.
Keep the vial in the outer carton to protect the medicine from light.
Open vials
For storage conditions after first opening of the medicinal product, see section 6.3.
06.5 Nature of the immediate packaging and contents of the package
5 ml of solution in a vial (type 1 colorless glass), with a flanged cap (aluminum), a stopper (chlorobutyl rubber (type 1)) and a flip off cap (polypropylene).
Packs of 1, 2, 5 and 10 vials are available.
10 ml solution in a vial (type 1 colorless glass), with a flanged cap (aluminum), with a stopper (type 1 rubber, polyisoprene and bromobutyl laminate) and with a flip off cap (polypropylene). Packs of 1 vial are available.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
Check the vial before use. Use only if the solution is clear, colorless, with no visible solid particles and has an aqueous consistency. As Lantus is a solution, it does not require resuspension prior to use.
Lantus must not be mixed with other insulins or diluted. Mixing or dilution can change the time / action profile and mixing can cause precipitation.
The insulin label should always be checked before each injection to avoid medication errors between insulin glargine and other insulins (see section 4.4).
07.0 MARKETING AUTHORIZATION HOLDER
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany
08.0 MARKETING AUTHORIZATION NUMBER
EU / 1/00/134 / 001-004
035724018
035724020
035724032
035724044
EU / 1/00/134/012
035724121
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 9 June 2000
Date of most recent renewal: 9 June 2010
10.0 DATE OF REVISION OF THE TEXT
December 2013
