Consumer medicine information

Lantus

Insulin glargine

BRAND INFORMATION

Brand name

Lantus

Active ingredient

Insulin glargine

Schedule

What is in this leaflet

This leaflet answers some common questions about Lantus.

It does not contain all the available information. It does not take the place of talking to your doctor, pharmacist or diabetes educator.

All medicines have risks and benefits. Your doctor has weighed the risks of you using Lantus against the benefits they expect it will have for you.

If you have any concerns about using this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What Lantus is used for

Lantus is used to reduce high blood sugar (glucose) levels in people with diabetes mellitus.

Lantus is a modified insulin that is very similar to human insulin. It is a substitute for the insulin produced by the pancreas.

Lantus is a long-acting insulin. Your doctor may tell you to use a rapid-acting human insulin or oral diabetes medication in combination with Lantus.

Lantus is not addictive.

Ask your doctor if you have any questions about why Lantus has been prescribed for you.

Before you use Lantus

When you must not use Lantus

Do not use Lantus:

- If you have an allergy to:

any medicine containing insulin
any of the ingredients contained in Lantus listed at the end of this leaflet

Some of the symptoms of an allergic reaction may include:

redness, swelling, rash and itching at the injection site
rash, itching or hives on the skin
shortness of breath
wheezing or difficulty breathing
swelling of the face, lips, tongue or other parts of the body

- If you are experiencing low blood sugar levels (hypoglycaemia - a "hypo").

If you have a lot of hypos discuss appropriate treatment with your doctor.

- After the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.

If you use Lantus after the expiry date has passed, it may not work as well. If it has expired or is damaged, return it to your pharmacist for disposal.

- If the product appears cloudy, discoloured or contains particles, or if the injection pen/cartridge/vial appears damaged.

If you are not sure whether you should start using this medicine, talk to your doctor.

Do not give Lantus to children less than 6 years of age. There is no experience with the use of Lantus in children less than 6 years.

Before you start to use Lantus

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

kidney problems
liver problems

Tell your doctor if you are pregnant or plan to become pregnant. Pregnancy may make managing your diabetes more difficult.

Tell your doctor if you are breastfeeding or plan to breastfeed.

Tell your doctor if:

you drink alcohol
you do not eat regular meals
you do a lot of exercise
you are ill or feeling unwell

Alcohol, diet, exercise and your general health all affect the control of your diabetes.

If you have not told your doctor about any of the above, tell them before you start using Lantus.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Medicines that may increase the blood sugar lowering effect of Lantus include:

oral antidiabetic medicines that are used to treat type 2 diabetes
blood pressure, blood flow, cholesterol and heart medications
medications for pain and inflammation
some antidepressants
sulfonamide antibiotics

Medicines that may reduce the blood sugar lowering effect of Lantus include:

corticosteroids, glucagon and other hormonal therapies
estrogens, progestogens, oral contraceptives and gynaecological medications
fluid and glaucoma medications
tuberculosis and HIV/AIDS treatments
some psychiatric medications
adrenaline (epinephrine) and asthma medications such as salbutamol, terbutaline

Certain heart medications, especially beta-blockers, may mask the symptoms of hypoglycaemia.

Your doctor and pharmacist have a full list of medicines with which you must be careful or avoid while using Lantus. Please check with your doctor or pharmacist before starting any new medicines or over the counter products.

How to use Lantus

Lantus is a clear solution that does not require shaking before use.

Your doctor, pharmacist or diabetes educator will have shown you how to use Lantus.

Carefully follow all the directions.

Do not dilute Lantus.

Do not mix Lantus with any other insulin or solution.

Do not inject Lantus into a vein. Lantus is intended for injection under the skin. It can be injected at any time during the day, however, at the same time every day.

Any change in this medicine should be made cautiously and only under medical supervision.

If you do not understand the instructions, ask your doctor, pharmacist or diabetes educator for help.

How much to use

Your doctor will tell you how much Lantus you need to use each day. Your doctor may increase or decrease the dose, depending on your blood sugar levels.

It is very important that you manage your diabetes carefully. Too much or too little insulin can cause serious effects.

When to use Lantus

Your doctor will tell you when to use Lantus.

Lantus should be used once a day, at the same time every day.

How to use Lantus

ALWAYS CHECK YOUR LANTUS INJECTION PEN, CARTRIDGE OR VIAL

Do not use Lantus if it is no longer clear and colourless or if it contains particles.

Make sure you are using the correct injection pen, cartridge or vial.

Always check the insulin label on the cartridge, reusable pen or vial before each injection to make sure you are using the right insulin.

Keep the cartridge, injection pen or vial at room temperature for 1 or 2 hours before use. Cold insulin is more painful to inject.

For Lantus cartridges or injection pens

PREPARING A DOSE FOR INJECTION

Always do a safety test before use. The safety test may highlight a problem with your injection pen. The safety test also removes any air bubbles and helps indicate whether or not a needle is bent or broken.

Becton Dickinson (BD Micro-Fine™+) needles should be used with injection pens.

Reusable pens

Lantus cartridges should only be used with the AllStar, AllStar Pro, JuniorStar or ClikStar reusable pens.

Carefully follow the instructions provided with the pen, for loading a cartridge, attaching a needle, performing a safety test and administering the insulin injection.

If the reusable injection pen does not work properly, Lantus may be withdrawn from the cartridge into a syringe. Ask your doctor, pharmacist or diabetes educator for help.

Pre-filled disposable pens

Lantus SoloStar disposable pens are pre-filled and ready to use. Once all the insulin is used you cannot replace the cartridge.

Carefully follow the instructions provided with the Lantus SoloStar pen for attaching a needle, performing a safety test and administering the insulin injection.

Never use an injection pen if it is damaged or you are not sure that it is working properly. Use a new pen.

INJECTING A DOSE

Lantus should be injected under the skin, being careful not to inject it into a muscle or vein.

Choose a site for injection.

Inject Lantus into the abdomen, thighs or upper arms.

With one hand, stabilise the skin by spreading it or pinching up a large area, as recommended by your healthcare professional.
Insert the needle into the skin as recommended by your healthcare professional.
Inject the full dose of Lantus by pushing the plunger as far as it will go.
Slowly count to 10 before removing the needle from the skin.

Use a different injection site each injection so that the same site is not used more often that once a month. This will reduce the chance of local skin reactions developing.

AFTER INJECTING

Using the outer needle cap, unscrew the needle and dispose of it safely into a sharps container.

Do not share needles, cartridges or injection devices. Do not reuse needles.

Leave the cartridge in the reusable pen until it needs to be replaced.

Do not attempt to replace the cartridge in a pre-filled disposable pen. Empty disposable pens must never be reused and must be properly discarded.

For Lantus vials

PREPARING A DOSE FOR INJECTION

Wash your hands.
Draw air into a U100 insulin syringe equal to the dose of Lantus to be injected.
Push the needle through the rubber top of the vial and inject the air into the vial.
Leave the needle in the vial. Hold the vial and syringe firmly in one hand, with the vial above the syringe.
Make sure the tip of the needle is in the insulin and withdraw the correct dose into the syringe.
Before removing the needle from the vial, check the syringe for air bubbles. If bubbles are present, hold the syringe vertically (needle pointed upwards) and tap firmly until the bubbles float to the top. Push the bubbles out with the plunger and then withdraw the correct dose. Remove the needle from the vial.
If you need to put the syringe down, make sure the needle does not touch anything.

INJECTING A DOSE

Lantus should be injected under the skin, being careful not to inject it into a muscle or vein.

Choose a site for injection.

Inject Lantus into the abdomen, thighs or upper arms.

With one hand, stabilise the skin by spreading it or pinching up a large area, as recommended by your healthcare professional.
Insert the needle into the skin as recommended by your healthcare professional.
Inject the full dose of Lantus by pushing the plunger as far as it will go.
Slowly count to 10 before removing the needle from the skin.

Use a different injection site each injection so the same site is not used more often than once a month. This will reduce the chance of local skin reactions developing.

AFTER INJECTING

Dispose of your insulin syringes safely into a sharps container.

Do not share vials, needles or syringes. Do not reuse needles.

How long to use Lantus

Continue using Lantus for as long as your doctor recommends.

Make sure you keep enough Lantus to last over weekends and holidays.

If you take too much (overdose) - Hypoglycaemia, a "Hypo"

If you accidentally use too much Lantus your blood sugar level may become too low (hypoglycaemia).

Immediately telephone your doctor or the Poisons Information Centre (13 11 26 in Australia; 0800 POISON or 0800 764 766 in New Zealand) if you think that you or anyone else may have used too much Lantus.

Do this even if there are no signs of discomfort or poisoning.

The risk of hypoglycaemia is increased if you:

accidentally use too much Lantus
have too much or unexpected exercise
delay eating meals or snacks
eat too little food
are ill

The first symptoms of mild to moderate hypoglycaemia can come on suddenly. They may include:

cold sweat, cool pale skin
fatigue, drowsiness, unusual tiredness and weakness
nervousness, anxious feeling, tremor, rapid heart beat
confusion, difficulty concentrating
excessive hunger
vision changes
headache, nausea

Always carry some sugary food or drink with you.

If you experience any of these symptoms of hypoglycaemia, you need to raise your blood sugar urgently. You can do this by taking one of the following:

5-7 jelly beans
3 teaspoons of sugar or honey
1/2 can of a sugar-containing soft drink (not a diet soft drink)
2-3 concentrated glucose tablets

Follow up with extra carbohydrates, e.g. plain biscuits, fruit or milk, when over the initial symptoms. Taking this extra carbohydrate will prevent a second drop in your blood sugar level.

If not treated quickly, the initial symptoms of hypoglycaemia may progress to loss of co-ordination, slurred speech, confusion, loss of consciousness and seizures.

If severe hypoglycaemia is not treated, it can cause brain damage and death.

Tell your relatives, friends, close workmates or carers that you have diabetes. It is important that they recognise the signs and symptoms of a "hypo".

Make sure they know to turn you on your side and get medical help immediately if you lose consciousness.

Make sure they know not to give you anything to eat or drink if you are unconscious. This is because you could choke.

Provide them with the telephone number for your doctor, the Poisons Information Centre (13 11 26 in Australia; 0800 POISON or 0800 764 766 in New Zealand) and Emergency Services.

An injection of the hormone glucagon may speed up recovery from unconsciousness. This can be given by a relative, friend, workmate or carer who knows how to give it.

If glucagon is used, have some sugary food or drink as soon as you are conscious again.

If you do not feel better after this, contact your doctor, diabetes educator, or the closest hospital.

If you do not respond to glucagon treatment, you will have to be treated in a hospital.

See your doctor if you keep having "hypos" or if you have ever become unconscious after using Lantus. Your dose of Lantus or other medicines may need to be changed.

If you miss a dose - Hyperglycaemia

If you forget to take your insulin dose, test your blood sugar level as soon as possible.

Lantus is a long-acting insulin that works for 24 hours and should be taken regularly at the same time each day. If you miss taking your dose at the regular scheduled time, your blood sugar levels may become high (hyperglycaemia).

However, taking a dose of Lantus at another time may increase your risk of having a hypo. You should therefore plan in advance with your doctor or healthcare professional so that you know what to do in case you miss a dose.

If you have missed a dose and are not sure what you should do, contact your doctor or healthcare professional for specific advice.

Do NOT use a double dose of your insulin. If you double a dose, this may cause low blood sugar levels.

The risk of hyperglycaemia is increased if you:

miss doses of Lantus or other insulin, or use less Lantus than you need
have uncontrolled diabetes
exercise less than usual
eat more carbohydrates than usual
are ill or stressed
take certain other medications

High blood sugar levels over a period of time can lead to too much acid in the blood (diabetic ketoacidosis).

Contact your doctor immediately if your blood sugar level is very high or you experience any of the following symptoms.

Symptoms of mild to moderate hyperglycaemia include:

drowsy feeling
flushed face
thirst, loss of appetite
fruity odour on the breath
blurred vision
passing larger amounts of urine than usual
getting up at night more often than usual to pass urine
high levels of glucose and acetone in the urine

Symptoms of severe hyperglycaemia include:

heavy breathing
fast pulse
nausea, vomiting
dehydration
loss of consciousness

Severe hyperglycaemia can lead to unconsciousness and, in extreme cases, death if untreated.

Discuss any worries you may have about this with your doctor, pharmacist or diabetes educator.

While you are using Lantus

Things you must do

Measure your blood sugar level regularly. This is the best way to tell if your diabetes is being controlled properly. Your doctor or diabetes educator will show you how and when to do this.

It is important to keep using Lantus even if you feel well. Lantus helps to control your condition, but does not cure it.

Tell your doctor if you often have hypoglycaemia or if you have ever become unconscious after using Lantus. Your doctor may need to adjust your dose of Lantus or of other medicines you are taking.

Always carry some sugary food or drink with you. If you experience any of the symptoms of hypoglycaemia, immediately eat some sugary food or have a drink, e.g. jelly beans, sugar, honey, sugar-containing soft drink, glucose tablets. Diet and low calorie soft drinks do NOT contain sugar and are unsuitable to take for hypoglycaemia.

Make sure that you tell every doctor, dentist, pharmacist or other healthcare professional who is treating you that you have diabetes and are using Lantus.

Tell your doctor, pharmacist or diabetes educator if you are travelling.

Ask your doctor for a letter explaining why you are taking injecting pens and needles with you. Each country you visit will need to see this letter, so you should take several copies.

You may need to inject Lantus and eat your meals at different times because of time differences in and between countries.

If you are travelling, it is a good idea to:

wear some form of identification showing you have diabetes
carry some form of sugar to treat hypoglycaemia if it occurs, e.g. sugar sachets or jelly beans
carry emergency food rations in case of a delay, e.g. dried fruit, biscuits or muesli bars
keep Lantus readily available; take enough Lantus for your expected needs whilst travelling - you may not be able to get Lantus in the country you are visiting

Your doctor, pharmacist or diabetes educator can provide you with some helpful information.

Tell your doctor if you are having trouble or difficulty with your eyesight.

Visit your doctor for regular checks of your eyes, feet, kidneys, heart, circulation, blood and blood pressure.

Carefully follow your doctor's and/or dietician's advice on diet, drinking alcohol and exercise.

Things you must not do

Do not stop using Lantus unless your doctor tells you to.

Do not skip meals while using Lantus.

Do not use Lantus if you think it has been frozen or exposed to excessive heat (temperatures above 30°C).

Do not reuse empty cartridges.

Do not give Lantus to anyone else, even if they have the same condition as you.

Things to be careful of

Be careful driving or operating machinery until you know how Lantus affects you. Be careful not to let your blood sugar levels fall too low.

Tell your doctor if you drink alcohol. Alcohol may mask the symptoms of hypoglycaemia.

Tell your doctor if you are ill. Illness, especially with nausea and vomiting, may cause your insulin needs to change. Even if you are not eating, you still require insulin. You and your doctor should design an insulin plan for those times when you are sick.

If you become sick with a cold or flu, it is very important to continue using Lantus, even if you feel unable to eat your normal meal. If you have trouble eating solid foods, use sugar-sweetened drinks as a carbohydrate substitute or eat small amounts of bland food. Your diabetes educator or dietician can give you a list of foods to use for sick days.

Tell your doctor if you are exercising more than usual. Exercise may lower your need for Lantus. Exercise may also speed up the effect of a dose of Lantus, especially if the exercise involves the area of the injection site (e.g. the thighs should not be used for injection prior to jogging or running).

Tell your doctor if your diet changes. Changes in diet may cause your insulin needs to change.

Side effects

Tell your doctor, pharmacist or diabetes educator as soon as possible if you do not feel well while you are using Lantus.

Lantus helps most people with diabetes, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor, pharmacist or diabetes educator to answer any questions you may have.

The most common side effect when using insulin is low blood sugar levels (hypoglycaemia - a "hypo").

Tell your doctor if you notice any of the following and they worry you:

hypoglycaemia (mild to moderate)
redness, swelling or itching at the injection site; usually these symptoms disappear within a few weeks during continued use
a depression or thickening of the skin around the injection site (lipodystrophy); this can often occur if you inject too often at the same injection site

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

- More severe symptoms of hypoglycaemia, including:

disorientation
seizures, fits or convulsions
loss of consciousness

- Signs of a serious allergic reaction, including:

skin rashes over a large part of the body
shortness of breath, wheezing
swelling of the face, lips or tongue
fast pulse
sweating

The above list includes some very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are very rare.

Tell your doctor if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After using Lantus

Storage

All medicines should be kept where children cannot reach them.

CARTRIDGES

Keep unopened cartridges of Lantus in a refrigerator where the temperature is between 2-8°C. Do not allow it to freeze. Discard if frozen.

When the cartridge has been inserted into the injection pen, the cartridge-pen combination should not be put in the refrigerator and should be kept below 30°C. Do not leave it near heat or in direct light. Discard the cartridge within 28 days of first use. Cartridges that are first carried as a spare for a while must also be discarded 28 days after being removed from the refrigerator.

PRE-FILLED DISPOSABLE PENS

Before use, keep unopened Lantus pre-filled pens in a refrigerator where the temperature is between 2-8°C. Do not allow it to freeze. Discard if frozen.

Before first use, store the pre-filled pen at room temperature for 1 to 2 hours. Once in use, the pre-filled pen should not be put in the refrigerator and it should be kept below 30°C. Do not leave it near heat or in direct light. Discard the pre-filled pen within 28 days of first use. Pre-filled pens that are first carried as a spare for a while must also be discarded 28 days after being removed from the refrigerator.

VIALS

Keep unopened Lantus vials in a refrigerator where the temperature is between 2-8°C. Do not allow it to freeze. Discard if frozen.

Once opened, the vial should be refrigerated between 2-8°C, but may be kept unrefrigerated for up to 28 days as long as it is kept below 30°C. Do not leave it near heat or in direct light. Discard the vial within 28 days of first use. Vials that are first carried as a spare for a while must also be discarded 28 days after being removed from the refrigerator.

Disposal

Dispose of your insulin syringes, needles and disposable injection devices safely into a sharps container.

If your doctor tells you to stop using Lantus or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

Lantus is a clear, colourless solution available in 3mL cartridges and 10mL vials.

Lantus SoloSTAR is a pre-filled disposable pen containing a 3mL cartridge of Lantus.

Ingredients

Active Ingredient:

insulin glargine (100IU/mL)

Inactive Ingredients:

meta-cresol
glycerol
zinc chloride
polysorbate 20 (10mL vial only)
hydrochloric acid
sodium hydroxide
water for injections

Supplier

Lantus is supplied in Australia by:

sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113
Freecall No: 1800 818 806

Lantus is supplied in New Zealand by:

sanofi-aventis new zealand limited
Level 856 Cawley Street
Ellerslie, Auckland
Freecall No: 0800 283 684

® = Registered Trademark

Lantus SoloSTAR 3mL injector pen AUST R 128468

Lantus 3mL cartridge AUST R 77737

Lantus 10mL vial AUST R 122335

This leaflet was prepared in March 2020

Further information

You can get more information about diabetes and insulin from:

Diabetes Australia:
freecall helpline 1300 136 588
www.diabetesaustralia.com.au
Diabetes NZ:
freecall helpline: 0800 369 636
www.diabetes.org.nz

lantus-ccdsv19-cmiv19-30apr20

Published by MIMS July 2020

BRAND INFORMATION

Brand name

Lantus

Active ingredient

Insulin glargine

Schedule

Name of the medicine

Insulin glargine (rDNA origin).

Excipients.

3 mL cartridge.

Zinc chloride, metacresol, glycerol, hydrochloric acid and sodium hydroxide for adjustment to pH 4, and water for injections.

10 mL vial.

Zinc chloride, metacresol, polysorbate 20, glycerol, hydrochloric acid and sodium hydroxide for adjustment to pH 4, and water for injections.

Description

Chemical name: 21^A-gly-30^Ba-L-arg-30^Bb-L-arg human insulin. Molecular formula: C₂₆₇H₄₀₄N₇₂O₇₈S₆. MW: 6063. CAS: 160337-95-1. Lantus (insulin glargine injection (rDNA origin)) is a recombinant human insulin analogue produced by DNA technology. Insulin glargine differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and two arginines are added to the C terminus of the B chain.
Lantus is a sterile clear to colourless solution of insulin glargine in vials and cartridges for use as an injection. The 3 mL cartridges contain 100 IU/mL (3.6378 mg/mL) insulin glargine. The 10 mL vials contain 100 IU/mL (3.6378 mg/mL) insulin glargine.

Pharmacology

Site and mode of action.

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.

Pharmacodynamics.

Insulin glargine is a human insulin analogue that has been designed to have low solubility at neutral pH. At pH 4, the pH of the Lantus injection solution, it is completely soluble. After injection 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 time/ concentration profile and a prolonged duration of action. This allows once daily dosing to meet a patient's basal insulin needs.
Insulin glargine is metabolised into 2 active metabolites M1 and M2.

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 the one of human insulin.

IGF-1 receptor binding.

The affinity of insulin glargine for the human IGF-1 receptor is approximately 5 to 8-fold greater than that of human insulin (but approximately 70 to 80-fold lower than the one of IGF-1), whereas M1 and M2 bind the IGF-1 receptor with slightly lower affinity compared to human insulin.
The total therapeutic insulin concentration (insulin glargine and its metabolites) found in type 1 diabetic patients was markedly lower than what would be required for a half maximal occupation of the IGF-1 receptor and the subsequent activation of the mitogenic proliferative pathway initiated by the IGF-1 receptor. Physiological concentrations of endogenous IGF-1 may activate the mitogenic proliferative pathway; however, the therapeutic concentrations found in insulin therapy, including in Lantus therapy, are considerably lower than the pharmacological concentrations required to activate the IGF-1 pathway.
In clinical studies, intravenous insulin glargine and human insulin have been shown to be equipotent when given at the same doses.
In euglycaemic clamp studies in healthy subjects or in patients with type 1 diabetes, the onset of action of subcutaneous insulin glargine was slower than NPH (neutral protamine Hagedorn) human insulin. The effect profile of insulin glargine was smooth and peakless, and the duration of its effect was prolonged compared to NPH human insulin. Figure 1 shows results from a study in patients with type 1 diabetes. The median time between injection and the end of pharmacological effect was 14.5 hours for NPH human insulin, and 24 hours (the end of the observation period) for insulin glargine.

The longer duration of Lantus is directly related to its slower rate of absorption and supports once daily subcutaneous administration. The time course of action of insulin and insulin analogues such as Lantus may vary considerably in different individuals or within the same individual but is, due to the lack of a peak, less variable with insulin glargine than with NPH insulin.

Pharmacokinetics.

After subcutaneous injection of insulin glargine in healthy subjects and patients with diabetes, the insulin serum concentrations indicated a slower, more prolonged absorption and a lack of a peak in comparison to NPH human insulin. However, the assay was unable to differentiate between the two forms of insulin (native human insulin and insulin glargine). Concentrations were thus consistent with the time profile of the pharmacodynamic activity of insulin glargine.
After subcutaneous injection of 0.3 IU/kg insulin glargine in patients with type 1 diabetes, a flat concentration time profile has been demonstrated; this is also reflected in the wide range of T_max values (0 to 22.5 h) compared to 0.3 IU/kg NPH human insulin (2.5 to 10.5 h).
There were no relevant differences in serum insulin glargine levels and the duration of action after abdominal, deltoid or thigh subcutaneous administration.
In a randomised, controlled, double blind, four way crossover trial in healthy male volunteers, Lantus with polysorbate 20 was found to be bioequivalent to Lantus.

Metabolism.

After subcutaneous injection of Lantus in healthy subjects and diabetic patients, insulin glargine is rapidly metabolized at the carboxyl terminus of the beta-chain with formation of two active metabolites M1 (21^A-gly insulin) and M2 (21^A-gly-des-30^B-thr insulin). In plasma, the principal circulating compound is the metabolite M1. The exposure to M1 increases with the administered dose of Lantus. The pharmacokinetic and pharmacodynamic findings indicate that the effect of the subcutaneous injection with Lantus is principally based on exposure to M1. Insulin glargine and the metabolite M2 were not detectable in the vast majority of subjects and, when they were detectable their concentration was independent of the administered dose of Lantus.

Special populations.

Age and gender.

There were no phase 1 studies to evaluate the effects of age and race. In clinical trials, subgroup analysis based on age and gender did not indicate any difference in safety and efficacy in insulin glargine treated patients compared to the total study population.

Obesity.

In clinical trials, subgroup analysis based on BMI showed no differences in safety and efficacy in insulin glargine treated patients compared to the total study population. The same was true for NPH insulin.

Renal and hepatic impairment.

No studies were performed in patients with renal or hepatic impairment. Careful glucose monitoring and dose adjustments of insulin or insulin analogues including insulin glargine may be necessary.

Clinical Trials

Efficacy studies.

The overall efficacy of once daily Lantus on metabolic control was compared to that of once daily and twice daily NPH human insulin in open label, randomised, active control, parallel studies of 2327 adult patients and 349 paediatric patients with type 1 diabetes mellitus and 1563 patients with type 2 diabetes mellitus.

Type 1 diabetes in adults.

(See Table 3.) In phase 3 studies, patients with type 1 diabetes (studies 3001 and 3004, n = 1119) were randomised to basal bolus treatment with Lantus once daily or to NPH human insulin once or twice daily and treated for 28 weeks. Regular human insulin was administered before each meal. Lantus was administered at bedtime. NPH human insulin was administered once daily at bedtime or in the morning and at bedtime when used twice daily. Lantus had a larger effect in reducing fasting glucose than NPH human insulin administered twice daily, but was comparable with NPH human insulin twice daily in its effect on glycohaemoglobin (GHb) and incidence of nocturnal and severe hypoglycaemia. Compared to once daily NPH human insulin, Lantus had a similar effect on fasting glucose and GHb. Hypoglycaemia was reported with similar frequency during the first month of the studies (during initial titration period) after starting treatment with Lantus compared to NPH human insulin.
In another phase 3 study, patients with type 1 diabetes (study 3005, n = 619) were treated for 16 weeks with a basal bolus insulin regimen where insulin lispro was used before each meal. Lantus was administered once daily at bedtime and NPH human insulin was administered once or twice daily. Lantus and NPH human insulin had a similar effect on GHb, with similar numbers of patients reporting a hypoglycaemic episode.

Type 1 diabetes in children.

(See Table 4.) In a randomised, controlled clinical study, paediatric patients (ranging in age from 6 to 15 years) with type 1 diabetes (study 3003, n = 349) were treated for 28 weeks with a basal bolus insulin regimen where regular human insulin was used before each meal. Lantus was administered once daily at bedtime and NPH human insulin was administered once or twice daily. Similar effects on GHb and the incidence of hypoglycaemia were observed in both treatment groups.

Type 1 paediatric diabetes (2 to 6 years).

A 24 week parallel group study was conducted in 125 children with type 1 diabetes mellitus aged 1 to 6 years (61 children from 2 to 5 in the insulin glargine group and 64 children from 1 to 6 in the NPH insulin group), comparing insulin glargine given once daily in the morning to NPH insulin given once or twice daily as basal insulin. Both groups received bolus insulin before meals.
Comparison of the two treatment regimens in terms of hypoglycaemia was the primary objective of the study. The composite primary outcome consisted of: continuous glucose monitoring excursions below 3.9 mmol/L, confirmed by fingerstick blood glucose (FSBG) measurements; other FSBG measurements < 3.9 mmol/L; and episodes of symptomatic hypoglycaemia.
Overall, the event rate ratio of this composite outcome for once daily Lantus compared to NPH (given twice daily in most patients) was 1.18 (95% CI: 0.97-1.44), therefore, not meeting the noninferiority margin of 1.15.
The rate of symptomatic hypoglycaemia events is the most commonly used and clinically relevant component of the composite outcome. Rates of symptomatic hypoglycaemia events were numerically lower in the insulin glargine group, both overall (25.5 episodes per patient year, vs 33.0 for NPH) and overnight (2.38 episodes per patient year, vs 3.65 for NPH).
Glycohaemoglobin and glucose variabilities were comparable in both treatment groups. No new safety signals were observed in this trial.
Table 1 summarises the primary outcome results between Lantus and NPH insulin.

Lantus has not been studied in children below 2 years.

Type 2 diabetes in adults.

(See Table 3.) In one phase 3 study (study 3002, n = 570), Lantus was evaluated for 52 weeks as part of a regimen of combination therapy with insulin and oral antidiabetic agents (a sulfonylurea, metformin, acarbose, or combinations of these drugs). Lantus administered once daily at bedtime was as effective as NPH human insulin administered once daily at bedtime in reducing GHb and fasting glucose. However, fewer patients treated with Lantus reported a nocturnal hypoglycaemic episode after initial titration, from study month 2 to end of study. (See Table 2.)

In another phase 3 study in patients with type 2 diabetes not using oral antidiabetic agents (study 3006, n = 518), a basal bolus regimen of Lantus once daily at bedtime or NPH human insulin administered once or twice daily was evaluated for 28 weeks. Regular human insulin was used before meals as needed. Lantus had similar effectiveness as either once or twice daily NPH human insulin in reducing GHb and fasting glucose. Fewer patients treated with Lantus reported nocturnal hypoglycaemia from study month 2 to end of study. (See Table 3.)

Type 1 and type 2 adult diabetes.

Table 4 compares regimens of Lantus once daily to NPH human insulin either once or twice daily in subgroups of patients from phase 3 studies based upon prior basal insulin regimens.

Type 1 diabetes in children.

Table 5 compares regimens of Lantus once daily to NPH human insulin either once or twice daily in subgroups of patients from phase 3 studies based upon prior basal insulin regimens.

ORIGIN trial (study HOE901/4032).

The ORIGIN (Outcome Reduction with Initial Glargine Intervention) trial was an international, multicenter, randomised, open label, 2 x 2 factorial design study conducted in 12,537 participants with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or early type 2 diabetes mellitus and evidence of CV disease. Participants were randomised to receive Lantus (n = 6264) (participants with IFG and/or IGT = 11.7%, early type 2 diabetes mellitus = 88.3%), titrated to a FPG of 5.3 mmol/L or less, or standard care (n = 6273) (participants with IFG and/or IGT = 11.4%, early type 2 diabetes mellitus = 88.6%). At baseline participants had a mean age of 63.5 years, mean duration of diabetes of 5.8 years in those with pre-existing diabetes, and median HbA1c of 6.4%. Median duration of follow-up was approximately 6.2 years. At the end of the trial 81% of participants randomised to take Lantus were still on treatment.
The primary objective of the trial was to demonstrate that Lantus use could significantly lower the risk of major cardiovascular endpoints compared to standard care. There were two coprimary composite efficacy outcomes. The first one was the time to the first occurrence of CV death, nonfatal myocardial infarction (MI), or nonfatal stroke, and the second one was the time to the first occurrence of any of the first coprimary events, or revascularization procedure (cardiac, carotid, or peripheral), or hospitalization for heart failure.
Secondary endpoints were: all cause mortality; a composite microvascular outcome; development of type 2 diabetes, in participants with IGT and/or IFG at baseline.
After a median treatment duration of 6.2 years, Lantus did not alter the relative risk for CV disease and CV mortality when compared with standard care. There were no significant differences between Lantus and standard care for the two coprimary outcomes, for any individual components of the coprimary outcomes, for all cause mortality or for the composite microvascular outcomes. The results are displayed in Table 6.

Median on treatment HbA1c values ranged from 5.9 to 6.4% in the Lantus group, and 6.2% to 6.6% in the standard care group throughout the duration of follow-up. Median FPG at the end of study in the Lantus group was 5.4 mmol/L, and for the standard care group was 6.8 mmol/L.
Over the course of this 6 year study severe hypoglycaemia was reported in 5.7% of the Lantus group compared to 1.9% of the standard care group. The rates (per 100 patient years) of confirmed all hypoglycaemia events, severe hypoglycaemia events and nonsevere symptomatic hypoglycaemia are shown in Table 7.
Over the course of this 6 year study, 42% of the Lantus group and 74% of the standard care group did not experience any hypoglycaemia.

The median of the change in bodyweight from baseline to the last on treatment visit was 2.2 kg greater in the Lantus group than in the standard care group, i.e. weight gain of 1.4 kg in Lantus group compared to weight loss of 0.8 kg in standard care group.

Cancer.

In the ORIGIN trial, the overall incidence of cancer (all types combined) or death from cancers was similar between the treatment groups as shown in Table 8.

Indications

Insulin glargine is an insulin analogue indicated for once daily subcutaneous administration in the treatment of type 1 diabetes mellitus in adults and children and type 2 diabetes mellitus in adults who require insulin for the control of hyperglycaemia.

Contraindications

Lantus must not be used in patients hypersensitive to insulin glargine or any of its excipients.

Precautions

Lantus must not be diluted or mixed with any other insulin or solution.
Lantus is not intended for intravenous administration. The prolonged duration of activity of insulin glargine is dependent on injection into subcutaneous space. Intravenous administration of the usual subcutaneous dose could result in severe hypoglycaemia.
Lantus is not the insulin of choice for the treatment of diabetic ketoacidosis. Instead, intravenous regular insulin is recommended in such cases.
As with all insulins, the time course of Lantus action may vary in different individuals or at different times in the same individual and the rate of absorption is dependent on blood supply, temperature and physical activity.
Patients, and if appropriate, their relatives, must also be alert to the possibility of hyperglycaemia or hypoglycaemia, and know what actions to take.
In case of insufficient glucose control or a tendency to hyperglycaemic or hypoglycaemic episodes, the patient's compliance with all prescribed treatment regimens, injection sites and proper injection technique, the handling of the pen and all other relevant factors must be reviewed before dose adjustment is considered.
Medication errors have been reported in which other insulins, particularly short acting insulins, have been accidentally administered instead of insulin glargine.

Hypoglycaemia.

Hypoglycaemia is the most common adverse effect of insulins. The incidence of nocturnal hypoglycaemia in regimens that include insulin glargine is significantly reduced in patients with type 2 diabetes compared with regimens containing NPH human insulin. The time of occurrence of hypoglycaemia depends on the action profile of the insulins and may, therefore, change when the treatment regimen is changed.
As with all insulins, particular caution (including intensified blood glucose monitoring) should be exercised in patients who are at greater risk of clinically significant sequelae from hypoglycaemic episodes.
The prolonged effect of subcutaneous insulin glargine may delay recovery from hypoglycaemia.
In clinical studies, symptoms of hypoglycaemia or counter regulatory hormone responses were similar after insulin glargine and human insulin both in healthy volunteers and patients with type 1 diabetes. However, the warning symptoms of hypoglycaemia may be changed, be less pronounced or be absent in certain risk groups as, for example, in patients whose glycaemic control is markedly improved, in elderly patients, where an autonomic neuropathy is present, in patients with a long history of diabetes, in patients receiving concurrent treatment with certain other drugs.
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the patient's awareness of hypoglycaemia.

Renal impairment.

In patients with renal impairment, insulin requirements may be diminished because of reduced insulin metabolism. In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin requirements.

Hepatic impairment.

Although no studies have been performed in patients with diabetes and hepatic impairment, insulin requirements may be diminished due to reduced capacity for gluconeogenesis and reduced insulin metabolism.

Intercurrent conditions.

Insulin requirements may be altered during intercurrent conditions such as illness, emotional disturbances or stress.

Information for patients.

Patients should be instructed on self management procedures including glucose monitoring, proper injection technique and hypoglycaemia and hyperglycaemia management. Patients must be instructed on handling of special situations such as intercurrent conditions (illness, stress or emotional disturbances), an inadequate food intake or skipped meals.
Patients must be advised that Lantus must not be diluted or mixed with any other insulin or solution.
Accidental mix-ups between insulin glargine and other insulins, particularly short acting insulins, have been reported. To avoid medication errors between insulin glargine and other insulins, patients should be instructed to always check the insulin label before each injection.
As with all patients who have diabetes, the ability to concentrate and/or react may be impaired as a result of hypoglycaemia or hyperglycaemia.
Patients with diabetes should be advised to inform their doctor if they are pregnant or are contemplating becoming pregnant.

Pens to be used with Lantus cartridges.

Lantus cartridges should only be used with the following pens: AllStar and AllStar Pro which deliver Lantus in 1 unit dose increments; or JuniorSTAR which delivers Lantus in 0.5 unit dose increments from 1 unit; or ClikSTAR which delivers Lantus in 1 unit dose increments.
Lantus cartridges should not be used with any other reusable pen as dosing accuracy has only been established with the listed pens.

Effects on fertility.

In a combined fertility, prenatal and postnatal study in male and female rats at subcutaneous doses up to 10 IU/kg/day (approximately 5 times anticipated clinical exposure based on BSA), insulin glargine was maternotoxic due to dose dependent hypoglycaemia leading to death at the highest dose. There were no effects of treatment on fertility. Similar effects were seen with NPH insulin.

Use in pregnancy.

(Category B3)
There are no randomized controlled clinical studies of the use of insulin glargine in pregnant women.
A large number (more than 1000 retrospective and prospective pregnancy outcomes with Lantus) of exposed pregnancies from postmarketing surveillance indicate no specific adverse effects on pregnancy or on the health of the foetus and newborn child.
Furthermore a meta-analysis of eight observational clinical studies including 331 women using Lantus and 371 women using insulin NPH was performed to assess the safety of insulin glargine and insulin NPH in gestational or pregestational diabetes. No significant differences in safety related maternal or neonatal outcomes were seen between insulin glargine and insulin NPH during pregnancy.
It is essential to maintain good control of the insulin treated patient (insulin dependent or gestational diabetes) throughout pregnancy to prevent adverse outcomes associated with hyperglycaemia. Insulin requirements usually fall during the first trimester, increase during the second and third trimesters and rapidly decline after delivery. Careful monitoring of glucose control is essential.
Patients with diabetes must inform their doctor if they are pregnant or are contemplating pregnancy and insulin glargine should be used during pregnancy only if the potential benefits outweigh potential risk.
Embryofetal development studies in rats and rabbits have been performed at subcutaneous doses up to 20 IU/kg/day and 2 IU/kg/day, respectively (approximately 10 times and twice anticipated clinical exposure, respectively, based on BSA). The effects of insulin glargine generally did not differ from those observed with NPH insulin in rats or rabbits. However, in rabbits dosed with 2 IU/kg/day there was an increased incidence of dilatation of the cerebral ventricles.

Use in lactation.

It is not known whether insulin glargine is excreted in significant amounts in human milk or animal milk. Many drugs, including insulin, are excreted in human milk. For this reason, caution should be exercised when insulin glargine is administered to a nursing mother. Lactating women may require adjustments in insulin dose and diet.

Paediatric use.

In general, the safety profile for patients ≤ 18 years of age is similar to the safety profile for patients > 18 years. The adverse events reports received from postmarketing surveillance included relatively more frequent injection site reactions (injection site pain, injection site reaction) and skin reactions (rash, urticaria) in patients ≤ 18 years of age than in patients > 18 years.
Data from pooled clinical trials in adults and children aged 6 to 18 years did not show a greater incidence of either injection site reaction or skin reactions in the paediatric population compared to adults.
Pharmacokinetics in children aged 2 to less than 6 years of age with type 1 diabetes mellitus was assessed in one clinical study. Plasma ‘trough’ levels of insulin glargine and its main metabolites M1 and M2 were measured in children treated with insulin glargine, revealing plasma concentration patterns similar to adults, and providing no evidence for accumulation of insulin glargine or its metabolites with chronic dosing.

Carcinogenicity.

Two year carcinogenicity studies were performed in mice and rats at subcutaneous doses up to 12.5 IU/kg/day (approximately 3 and 7 times anticipated clinical exposure based on BSA). Malignant fibrous histiocytomas were found at insulin glargine injection sites in male rats and mice. The incidence of these tumours was not dose dependent and tumours were also present at acid vehicle control injection sites but not at saline control injection sites or insulin comparator groups using a different vehicle. The relevance of these findings to humans is unknown.
Other insulin preparations are known to cause an increase in mammary tumours in female rats. No such increase in tumours was seen with insulin glargine, probably because of the lower doses of insulin glargine used in the mouse and rat carcinogenicity studies.

Genotoxicity.

Insulin glargine was negative in tests for mutagenicity in bacterial and mammalian cells and for clastogenicity (in vitro in V79 cells and in vivo in Chinese hamsters).

Interactions

A number of substances affect glucose metabolism and may require insulin dose adjustment.
Substances that may enhance the blood glucose lowering effect and susceptibility to hypoglycaemia include: oral antidiabetic agents, ACE inhibitors, pentoxifylline (oxpentifylline), perhexiline, disopyramide, fibrates, fluoxetine, MAO inhibitors, dextropropoxyphene, salicylates, sulfonamide antibiotics.
Substances that may reduce the blood glucose lowering effect include: corticosteroids, danazol, diazoxide, diuretics, glucagon, isoniazid, estrogens, progestogens, oral contraceptives, phenothiazine derivatives, somatotrophin, sympathomimetic agents (e.g. adrenaline (epinephrine), salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic medications (e.g. olanzapine and clozapine).
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the blood glucose lowering effect of insulin. Pentamidine may cause hypoglycaemia, which may be sometimes 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 induced by hypoglycaemia may be reduced or absent.

Adverse Effects

Clinical trial data.

(See Tables 9, 10 and 11.)

Over the course of this 6 year study severe hypoglycaemia was reported in 5.7% of the Lantus group compared to 1.9% of the standard care group. The rates (per 100 patient years) of confirmed all hypoglycaemia events, severe hypoglycaemia events and nonsevere symptomatic hypoglycaemia are shown in Table 12.
Over the course of this 6 year study, 42% of the Lantus group and 74% of the standard care group did not experience any hypoglycaemia.

Hypoglycaemia.

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.
As with all insulins, 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 neuroglycopaenia 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.

Eyes.

A marked change in glycaemic control may cause temporary visual impairment, due to temporary alteration in the turgidity and refractive index of the lens.
As with all insulin regimens, intensification of insulin therapy with abrupt improvement in glycaemic control may be associated with temporary visual impairment or worsening of diabetic retinopathy. However, long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy.
In patients with proliferative retinopathy, particularly if not treated with photocoagulation, severe hypoglycaemic episodes may result in transient partial or complete blindness.
Retinopathy was evaluated in clinical studies by means of retinal adverse events reported and fundus photography. The numbers of retinal adverse events reported for Lantus and NPH treatment groups were similar for patients with type 1 and type 2 diabetes. Progression of retinopathy was investigated by fundus photography using a grading protocol derived from the Early Treatment Diabetic Retinopathy Study (ETDRS). In a 5 year NPH controlled study, the primary outcome was progression by 3 or more steps on the ETDRS scale at study endpoint. The results of this analysis are shown in Table 13 for both the per protocol (primary) and intent to treat (ITT) populations, and indicate noninferiority of Lantus to NPH in the progression of diabetic retinopathy as assessed by this outcome.

Injection site and allergic reactions.

As with any insulin therapy, lipodystrophy may occur at the injection site and delay insulin absorption. Other injection site reactions with insulin therapy include redness, pain, itching, hives, swelling and inflammation. Most minor reactions to insulins usually resolve in a few days to a few weeks.
Immediate type allergic reactions are rare. Such reactions to insulin (including insulin glargine) or the excipients may, for example, be associated with generalised skin reactions, angioedema, bronchospasm, hypotension or shock and may be life threatening.
Animal studies with insulin glargine have identified significant local tolerance toxicity at the injection site following repeat subcutaneous administration. Care should be taken to rotate the site of injection.

Antibody production.

Insulin administration may cause the formation of antibodies to insulin. In clinical studies, antibodies that cross react with human insulin and insulin glargine were observed in both NPH human insulin and insulin glargine treatment groups with similar incidences. In rare cases, the presence of such insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to hyperglycaemia or hypoglycaemia.

Other reactions.

Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is improved by intensified insulin therapy.
Medication errors have been reported in which other insulins have been accidentally administered instead of insulin glargine.

Dosage and Administration

Lantus is an insulin analogue, equipotent to human insulin, with a peakless glucose lowering profile and a prolonged duration of action that permits once daily dosing.
Lantus is for individual patient use only.
Lantus is given subcutaneously once a day. It may be administered at any time during the day, however, at the same time every day.
Lantus is not intended for intravenous administration.
The desired blood glucose levels as well as the doses and timing of any antidiabetic medication, including Lantus, must be determined and adjusted individually. In a clinical study in insulin naïve patients with type 2 diabetes, Lantus was started at a dose of 10.8 ± 4.9 IU (mean ± SD; median dose 10 IU) Lantus once daily and subsequently adjusted individually. Blood glucose monitoring is recommended for all individuals with diabetes.
Dose adjustment may also be required, for example, if the patient's weight or lifestyle change, change in timing of insulin dose or other circumstances arise that increase susceptibility to hypoglycaemia or hyperglycaemia. Any change of insulin dose should be made cautiously and only under medical supervision.
Although absorption of Lantus does not differ between abdominal, thigh or deltoid subcutaneous injection sites, as with all insulins, injection sites must be rotated from one injection to the next.

Paediatric use.

Lantus can be safely administered to paediatric patients > 6 years of age. In a study comparing Lantus to NPH insulin in children from 2-5 years, noninferiority was not demonstrated in relation to the primary outcome of hypoglycaemia (see Clinical Trials for details). Efficacy in terms of HbA1c (a secondary efficacy endpoint) was similar between groups.
Based on the result of a study in paediatric patients, the dose recommendation for changeover to Lantus is the same as described for adults.

Changeover to Lantus.

The initial dose of Lantus should be determined individually, depending on the desired blood glucose levels.
When changing from a treatment regimen with an intermediate or long acting insulin to a regimen with Lantus, the amount and timing of a short acting insulin or fast acting insulin analogue or the dose of any oral antidiabetic drug may need to be adjusted.
To reduce the risk of hypoglycaemia, when patients are transferred from once daily insulin glargine 300 units/mL to once daily Lantus, the recommended initial Lantus dose is approximately 80% of the insulin glargine 300 units/mL that is being discontinued.
In clinical studies, when adult patients were transferred from once daily NPH human insulin or ultralente human insulin to once daily Lantus, the initial dose was usually not changed. In studies when patients were transferred from twice daily NPH human insulin to Lantus once daily at bedtime, the initial dose (IU) was usually reduced by approximately 20% (compared to total daily IU of NPH human insulin) within the first week of treatment and then adjusted based on patient response. There was also a slightly higher rate of injection site pain seen with Lantus, possibly related to the acidic nature of insulin glargine when compared with NPH insulin. The majority of injection site reactions were mild, with only one subject in each of the Lantus and NPH treatment groups discontinuing study medication due to injection site adverse events.
A programme of close metabolic monitoring under medical supervision is recommended during changeover and in the initial weeks thereafter. As with all insulin analogues, this is particularly true for patients who, due to antibodies to human insulin, need high insulin doses and may experience markedly improved insulin response with insulin glargine.
With improved metabolic control and resultant increase in insulin sensitivity (reduced insulin requirements) further adjustment of the dose of Lantus and other insulin or oral antidiabetic agents in the regimen may become necessary.

Preparation and handling.

Unopened vials, cartridges and prefilled pens.

Unopened vials, cartridges and prefilled pens (Lantus SoloStar) should be stored in a refrigerator where the temperature is between +2°C and +8°C. Do not freeze. Discard if frozen. Keep in the outer carton in order to protect from light. Do not store next to the freezer compartment or freezer packs.
Before first use, Lantus must be kept at room temperature for 1 to 2 hours.
Lantus must only be used if the solution is clear, colourless with no particles visible, and if it is of water-like consistency.

Open (in use) or unrefrigerated vials, cartridges and prefilled pens.

Lantus vials, cartridges or prefilled pens, whether or not refrigerated, must be discarded after 28 days from first use. Do not freeze. Discard if frozen.
Unrefrigerated vials, cartridges or prefilled pens, whether or not in use, must be discarded after 28 days. This applies irrespective of whether the vial, cartridge or prefilled pen is used immediately or is first carried as a spare for a while.
An empty vial, cartridge or prefilled pen must never be reused and must be properly discarded.

Vials.

Before withdrawing Lantus from the vial for the first time, remove the plastic protective cap. Do not shake the vial vigorously as this may cause frothing. Froth may interfere with the correct measurement of dose.
Once in use, vials of Lantus should be stored away from direct light between +2°C and +8°C. Do not freeze. Discard if frozen. If refrigeration is impossible, the vial of Lantus in use may be kept unrefrigerated for up to 28 days as long as the temperature is not greater than 30°C and it is kept away from direct heat and light. Whether or not it is refrigerated, the vial that is in use must be used within a 28 day period. Any unused contents must be discarded 28 days after opening.

Cartridges and prefilled pens.

Once in use, prefilled pens (such as Lantus SoloStar) or a reusable injection pen containing a cartridge of Lantus must not be stored in the refrigerator. Lantus that is in use in injection pens may be kept unrefrigerated for up to 28 days, as long as the temperature is not greater than 30°C and it is kept away from direct heat and light. It must be used within a 28 day period or must be discarded 28 days after commencement of use.
Manufacturer instructions for using Lantus in reusable or prefilled disposable injection devices must be followed carefully for loading the cartridge into a reusable pen, and for attaching the needle, performing the safety test and administering the insulin injection. If the injection device is damaged, it should be discarded and a new injection device should be used.
If the reusable injection device malfunctions (see instructions for using the pen), or no pen is available, Lantus may be withdrawn from the cartridge into a U100 syringe and injected subcutaneously. The syringe must not contain any other medicinal product or residue.
Lantus must not be mixed with any other insulin nor be diluted. Mixing or diluting can change its time/ action profile and mixing can cause precipitation.

Overdosage

Symptoms.

An excess of insulin relative to food intake, energy expenditure or both may lead to severe and sometimes prolonged and life threatening hypoglycaemia.

Management.

Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in drug dosage, meal patterns or exercise may be needed.
More severe episodes with coma, seizure or neurologic impairment may be treated with intramuscular/ subcutaneous glucagon or concentrated intravenous glucose. After apparent clinical recovery from hypoglycaemia, continued observation and additional carbohydrate intake may be necessary to avoid recurrence of hypoglycaemia.
For information on the management of overdose, contact the Poisons Information Centre on 131 126.

Presentation

Solution for injection (sterile, clear to colourless), 100 units/mL (U 100) (≡ 3.6378 mg/mL): 3 mL (cartridge); 10 mL (vial); 3 mL cartridge in SoloStar prefilled disposable device.

Poison Schedule

S4.

Log in

Consumer medicine information

Lantus

Insulin glargine

Keep track of your medicines

BRAND INFORMATION