Consumer medicine information

Optisulin

Insulin glargine

BRAND INFORMATION

Brand name

Optisulin

Active ingredient

Insulin glargine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Optisulin.

SUMMARY CMI

OPTISULIN® and OPTISULIN® SoloSTAR

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Optisulin or Optisulin SoloSTAR?

Optisulin contains the active ingredient insulin glargine. Optisulin is used to reduce high blood sugar (glucose) levels in people with diabetes mellitus.

For more information, see Section 1. Why am I using Optisulin? in the full CMI.

2. What should I know before I use Optisulin or Optisulin SoloSTAR?

Do not use if you have ever had an allergic reaction to Optisulin or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Optisulin or Optisulin SoloSTAR? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Optisulin and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Optisulin or Optisulin SoloSTAR?

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

More instructions can be found in Section 4. How do I use Optisulin or Optisulin SoloSTAR? in the full CMI.

5. What should I know while using Optisulin or Optisulin SoloSTAR?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using Optisulin.
  • Measure your blood sugar level regularly.
  • Keep using Optisulin even if you feel well.
  • Tell your doctor if you often have hypoglycaemia or if you have ever become unconscious after using Optisulin.
  • Always carry some sugary food or drink with you.
  • Tell your doctor or anybody else treating you if you are travelling.
Drinking alcohol
  • Tell your doctor if you drink alcohol.
  • Alcohol may mask the symptoms of hypoglycemia.
Looking after your medicine
  • Keep unopened cartridges and pens of Optisulin in a refrigerator where the temperature is between 2-8°C. Do not allow it to freeze. Discard if frozen.

For more information, see Section 5. What should I know while using Optisulin or Optisulin SoloSTAR? in the full CMI.

6. Are there any side effects?

Serious side effects may include low blood sugar (hypoglycaemia or ‘hypo’) or an allergic reaction. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

OPTISULIN® and OPTISULIN® SoloSTAR

Active ingredient: insulin glargine (in-sue-lin glar-jeen)

Consumer Medicine Information (CMI)

This leaflet provides important information about using Optisulin. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Optisulin.

Where to find information in this leaflet:

1. Why am I using Optisulin?
2. What should I know before I use Optisulin?
3. What if I am taking other medicines?
4. How do I use Optisulin?
5. What should I know while using Optisulin?
6. Are there any side effects?
7. Product details

1. Why am I using Optisulin or Optisulin SoloSTAR?

Optisulin contains the active ingredient insulin glargine. Optisulin is an antidiabetic agent used to reduce high blood sugar.

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

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

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

Optisulin is not addictive.

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

2. What should I know before I use Optisulin or Optisulin SoloSTAR?

Warnings

Do not use Optisulin if:

  • you are allergic to insulin glargine, or any of the ingredients listed at the end of this leaflet.
Always check the ingredients to make sure you can use this medicine.
  • any medicine containing insulin

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 Optisulin 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 appears damaged.

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

Do not give Optisulin to children less than 6 years of age.

There is no experience with the use of Optisulin in children less than 6 years.

Check with your doctor if you:

  • have any other medical conditions such as kidney problems or liver problems
  • take any medicines for any other conditions

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 Optisulin.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Pregnancy may make managing your diabetes more difficult.

3. What if I am taking other medicines?

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

Medicines that may increase the blood sugar lowering the effect of Optisulin 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 the effect of Optisulin 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 Optisulin. Please check with your doctor or pharmacist before starting any new medicines or over the counter products.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Optisulin.

4. How do I use Optisulin or Optisulin SoloSTAR?

How much to use

  • Your doctor will tell you how much Optisulin 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 Optisulin

  • Your doctor will tell you when to use Optisulin.
  • Optisulin should be used once a day, at the same time every day.

How to use Optisulin

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

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

Inject Optisulin into your thighs, upper arms or the front of your waist (abdomen).

Change the place within the area you inject each day. This will reduce the risk of skin shrinking or thickening or lumps at the site (see "Side effects").

Do not use the exact same spot for each injection.

Do not inject where the skin has pits, is thickened, or has lumps.

Do not inject where the skin is tender, bruised, scaly or hard, or into scars or damaged skin.

Carefully follow all the directions.

Do not dilute Optisulin.

Do not mix Optisulin with any other insulin or solution.

Do not inject Optisulin into a vein.

Optisulin 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.

ALWAYS CHECK YOUR OPTISULIN INJECTION PEN OR CARTRIDGE.

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

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

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

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

If you develop skin changes at the injection site. The injection site should be rotated to prevent skin changes such as lumps under the skin. The insulin may not work very well if you inject into a lumpy area. Contact your doctor if you are currently injecting into a lumpy area before you start injecting in a different area. Your doctor may tell you to check your blood sugar more closely, and to adjust your insulin or your other antidiabetic medications dose.

For Optisulin 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

Optisulin 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, Optisulin may be withdrawn from the cartridge into a syringe. Ask your doctor, pharmacist or diabetes educator for help.

Pre-filled disposable pens

Optisulin 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 Optisulin 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

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

Choose a site for injection.

Inject Optisulin into the abdomen, thighs or upper arms.

  1. With one hand, stabilise the skin by spreading it or pinching up a large area, as recommended by your healthcare professional.
  2. Insert the needle into the skin as recommended by your healthcare professional.
  3. Inject the full dose of Optisulin by pushing the plunger as far as it will go.
  4. 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 than 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.

If you forget to use Optisulin - Hyperglycemia

Optisulin should be used regularly at the same time each day. If you forget to take your insulin dose, test your blood sugar level as soon as possible.

Optisulin 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 Optisulin 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 Optisulin or other insulin, or use less Optisulin 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.

If you use too much Optisulin - Hypoglycemia, a "Hypo"

If you accidentally use too much Optisulin your blood sugar level may become too low (hypoglycaemia) and you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26 in Australia, or 0800 POISON or 0800 764 766 in New Zealand)
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

The risk of hypoglycaemia is increased if you:

  • accidentally use too much Optisulin
  • 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 heartbeat
  • 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 Optisulin.

Your dose of Optisulin or other medicines may need to be changed

5. What should I know while using Optisulin or Optisulin SoloSTAR?

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 Optisulin even if you feel well.

Optisulin 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 Optisulin.

Your doctor may need to adjust your dose of Optisulin 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 Optisulin.

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 Optisulin 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 Optisulin readily available; take enough Optisulin for your expected needs whilst travelling - you may not be able to get Optisulin 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 Optisulin unless your doctor tells you to.

Do not skip meals while using Optisulin.

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

Do not reuse empty cartridges.

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

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Optisulin affects you. Be careful not to let your blood sugar levels fall too low.

Drinking alcohol

Tell your doctor if you drink alcohol.

Alcohol may mask the symptoms of hypoglycemia.

Things to be careful of

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 Optisulin, 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 Optisulin. Exercise may also speed up the effect of a dose of Optisulin, 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.

Looking after your medicine

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

Storage

CARTRIDGES

Keep unopened cartridges of Optisulin 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 Optisulin 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.

When to discard your medicine (as relevant)

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

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

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Optisulin 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").

Less serious side effectsWhat to do
General:
  • hypoglycaemia (mild to moderate)
Skin related:
  • 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
Speak to your doctor if you have any of these less serious side effects and they worry you.

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

Skin changes at the injection site:
If you inject insulin too often at the same place, the fatty tissue may either shrink (lipoatrophy) or thicken (lipohypertrophy). Lumps under the skin may also be caused by build-up of a protein called amyloid (localized cutaneous amyloidosis). The insulin may not work very well if you inject into a lumpy area. Change the injection site with each injection to help prevent these skin changes.

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

Serious side effectsWhat to do
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
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

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.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects as follows:

For Australia: Therapeutic Goods Administration online at: www.tga.gov.au/reporting-problems.

New Zealand: Medsafe online at: www.medsafe.govt.nz/safety/report-a-problem.asp

By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What Optisulin contains

Active ingredient
(main ingredient)		Insulin glargine (100 IU/mL)
Other ingredients
(inactive ingredients)		metacresol
glycerol
zinc chloride
hydrochloric acid
sodium hydroxide
water for injections
Potential allergensN/A

Do not take this medicine if you are allergic to any of these ingredients.

What Optisulin and Optisulin SoloSTAR look like

Optisulin is a clear, colourless solution available in 3mL cartridges. AUST R 159295

Optisulin SoloSTAR is a pre-filled disposable pen containing a 3mL cartridge of Optisulin. AUST R 159302

Who distributes Optisulin and Optisulin SoloSTAR

Optisulin is supplied in Australia by:

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

Optisulin is supplied in New Zealand by:

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

® = Registered Trademark

This leaflet was prepared in November 2021

Full Product Information is available from sanofi-aventis australia pty ltd at
www.sanofi.com.au/PI-prescription
or by calling 1800 818 806

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

optisulin-ccdsv20-cmiv22-nov21

Published by MIMS February 2022

BRAND INFORMATION

Brand name

Optisulin

Active ingredient

Insulin glargine

Schedule

S4

 

1 Name of Medicine

Insulin glargine.

2 Qualitative and Quantitative Composition

Optisulin 3 mL cartridge contains 3 mL of insulin glargine 100 units/mL.
Optisulin pre-filled pen contains 3 mL of insulin glargine 100 units/mL.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection.
Optisulin is a clear to colourless, particle free solution.

4 Clinical Particulars

4.1 Therapeutic 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.

4.2 Dose and Method of Administration

Optisulin 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.
Optisulin is for individual patient use only.

Dosage.

Optisulin is given subcutaneously once a day. It may be administered at any time during the day, however, at the same time every day.
Optisulin is not intended for intravenous administration.
Blood glucose monitoring is recommended for all individuals with diabetes.
The desired blood glucose levels as well as the doses and timing of any antidiabetic medication, including Optisulin, must be determined and adjusted individually. In a clinical study in insulin-naive patients with type 2 diabetes, Optisulin was started at a dose of 10.8 ± 4.9 IU (mean ± SD; median dose 10 IU) Optisulin once daily and subsequently adjusted individually.
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 hypo- or hyperglycaemia. Any change of insulin dose should be made cautiously and only under medical supervision.

Dosage in paediatrics.

Optisulin can be safely administered to paediatric patients > 6 years of age. In a study comparing Optisulin to NPH insulin in children from 2-5 years, non-inferiority was not demonstrated in relation to the primary outcome of hypoglycaemia (see Section 5.1 Pharmacodynamic Properties, Clinical trials). 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 Optisulin is the same as described for adults.

Changeover to Optisulin.

The initial dose of Optisulin 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 Optisulin, 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 Optisulin, the recommended initial Optisulin 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 Optisulin, the initial dose was usually not changed. In studies when patients were transferred from twice-daily NPH human insulin to Optisulin 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 Optisulin, 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 Optisulin 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 Optisulin and other insulin or oral antidiabetic agents in the regimen may become necessary.

Method of administration.

Although absorption of Optisulin 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 in order to reduce the risk of lipodystrophy and localised cutaneous amyloidosis. Do not inject into areas of lipodystrophy and localised cutaneous amyloidosis. (See Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)).

Before first use.

Before first use, Optisulin must be kept at room temperature for 1 to 2 hours.
Optisulin must only be used if the solution is clear, colourless with no particles visible, and if it is of water-like consistency.
An empty cartridge or pre-filled pen must never be reused and must be properly discarded.
Optisulin 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.

Cartridges and pre-filled pens.

Manufacturer instructions for using Optisulin in reusable or pre-filled 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, Optisulin may be withdrawn from the cartridge into a U100 syringe and injected subcutaneously. The syringe must not contain any other medicinal product or residue.

Pens to be used with Optisulin cartridges.

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

4.3 Contraindications

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

4.4 Special Warnings and Precautions for Use

Optisulin must not be diluted or mixed with any other insulin or solution.
Optisulin 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.
As with all insulins, the time course of Optisulin 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 hyper- or hypoglycaemia, and know what actions to take.
In case of insufficient glucose control or a tendency to hyper- 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.
Patients must be instructed to perform continuous rotation of the injection site to reduce the risk of developing lipodystrophy and localised cutaneous amyloidosis. There is a potential risk of delayed insulin absorption and worsened glycaemic control following insulin injections at sites with these reactions. A sudden change in the injection site to an unaffected area has been reported to result in hypoglycaemia. Blood glucose monitoring is recommended after the change in the injection site, and dose adjustment of antidiabetic medications may be considered (see Section 4.8 Adverse Effects (Undesirable Effects)).
Medication errors have been reported in which other insulins, particularly short-acting insulins, have been accidentally administered instead of insulin glargine.
Patients with diabetes should be advised to inform their doctor if they are pregnant or are contemplating becoming pregnant.

Diabetic ketoacidosis.

Optisulin is not the insulin of choice for the treatment of diabetic ketoacidosis. Instead, intravenous human insulin is recommended in such cases.

Hypoglycaemia.

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.
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.

Use in 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.

Use in renal impairment.

Although no studies were performed 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.

Use in the elderly.

Progressive deterioration of renal function may lead to a steady decrease in insulin requirements. Furthermore, the warning signs of hypoglycaemia may be changed, diminished or absent in elderly patients. See Section 4.4 Special Warnings and Precautions for Use, Hypoglycaemia; Section 5.2 Pharmacokinetic Properties, Special populations.

Use with intercurrent conditions.

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

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.

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.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of 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.

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.

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.

Others.

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.

4.6 Fertility, Pregnancy and Lactation

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.
(Category B3)
There are no randomised controlled clinical studies of the use of insulin glargine in pregnant women.
A large number (more than 1000 retrospective and prospective pregnancy outcomes with Optisulin) 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 Optisulin 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.
 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.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Clinical trial data.

See Tables 1, 2 and 3.
Over the course of this 6 year study severe hypoglycaemia was reported in 5.7% of the Optisulin 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 non-severe symptomatic hypoglycaemia are shown in Table 4.
Over the course of this 6-year study, 42% of the Optisulin group and 74% of the Standard Care group did not experience any hypoglycaemia.
The median of the change in body weight from baseline to the last on-treatment visit was 2.2 kg greater in the Optisulin group than in the Standard Care group i.e. weight gain of 1.4 kg in Optisulin group compared to weight loss of 0.8 kg in standard care group.

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 Optisulin 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 5 for both the per-protocol (primary) and Intent-to-Treat (ITT) populations, and indicate non-inferiority of Optisulin to NPH in the progression of diabetic retinopathy as assessed by this outcome.

Skin and subcutaneous tissue disorders.

As with any insulin therapy, lipodystrophy may occur at the injection site and delay local insulin absorption. In clinical studies, in regimens, which included insulin glargine, lipohypertrophy was observed in 1 to 2% of patients, whereas lipoatrophy was uncommon.
Localised cutaneous amyloidosis at the injection site has occurred with insulins. Hyperglycaemia has been reported with repeated insulin injections into areas of cutaneous amyloidosis; hypoglycaemia has been reported with a sudden change to an unaffected injection site.
Continuous rotation of the injection site within the given injection area may help to reduce or prevent these reactions. (See Section 4.4 Special Warnings and Precautions for Use).

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.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

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 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Drugs used in diabetes, Insulins and analogue for injection, long-acting, ATC code: A10AE04.

Mechanism 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 Optisulin 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 Optisulin 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 Optisulin 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 Optisulin 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.

Clinical trials.

Efficacy studies. The overall efficacy of once-daily Optisulin 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 9.)
In Phase 3 studies, patients with type 1 diabetes (Studies 3001 and 3004, n=1119) were randomised to basal-bolus treatment with Optisulin once daily or to NPH human insulin once or twice daily and treated for 28 weeks. Regular human insulin was administered before each meal. Optisulin was administered at bedtime. NPH human insulin was administered once daily at bedtime or in the morning and at bedtime when used twice daily. Optisulin 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, Optisulin 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 Optisulin 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. Optisulin was administered once daily at bedtime and NPH human insulin was administered once or twice daily. Optisulin 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 10.)
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. Optisulin 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 Optisulin compared to NPH (given twice daily in most patients) was 1.18 (95% CI: 0.97-1.44), therefore, not meeting the non-inferiority 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 6 summarises the primary outcome results between Optisulin and NPH insulin.
Optisulin has not been studied in children below 2 years.

Type 2 diabetes in adults.

(See Table 9.)
In one Phase 3 study (Study 3002, n=570), Optisulin 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). Optisulin 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 Optisulin reported a nocturnal hypoglycaemic episode after initial titration, from study month 2 to end of study (Table 7).
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 Optisulin 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. Optisulin had similar effectiveness as either once- or twice-daily NPH human insulin in reducing GHb and fasting glucose. Fewer patients treated with Optisulin reported nocturnal hypoglycaemia from study month 2 to end of study (Table 8).

Type 1 and type 2 adult diabetes.

Table 9 compares regimens of Optisulin 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 10 compares regimens of Optisulin 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 Optisulin (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 Optisulin were still on treatment.
The primary objective of the trial was to demonstrate that Optisulin use could significantly lower the risk of major cardiovascular endpoints compared to standard care. There were two co-primary 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 co-primary events, or revascularization procedure (cardiac, carotid, or peripheral), or hospitalisation 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, Optisulin did not alter the relative risk for CV disease and CV mortality when compared with standard care. There were no significant differences between Optisulin and standard care for the two co-primary outcomes, for any individual components of the co-primary outcomes, for all-cause mortality or for the composite microvascular outcomes. The results are displayed in Table 11.
Median on-treatment HbA1c values ranged from 5.9 to 6.4% in the Optisulin 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 Optisulin 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 Optisulin 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 non-severe symptomatic hypoglycaemia are shown in Table 12.
Over the course of this 6-year study, 42% of the Optisulin group and 74% of the Standard Care group did not experience any hypoglycaemia.
The median of the change in body weight from baseline to the last on-treatment visit was 2.2 kg greater in the Optisulin group than in the Standard Care group i.e. weight gain of 1.4 kg in Optisulin 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 13.

5.2 Pharmacokinetic Properties

Absorption.

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 Tmax 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, Optisulin with polysorbate 20 was found to be bioequivalent to Optisulin.

Metabolism.

After subcutaneous injection of Optisulin in healthy subjects and diabetic patients, insulin glargine is rapidly metabolised at the carboxyl terminus of the Beta chain with formation of two active metabolites M1 (21AGly-insulin) and M2 (21A-Gly-des-30B-Thr-insulin). In plasma, the principal circulating compound is the metabolite M1. The exposure to M1 increases with the administered dose of Optisulin. The pharmacokinetic and pharmacodynamic findings indicate that the effect of the subcutaneous injection with Optisulin 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 Optisulin.

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.

5.3 Preclinical Safety Data

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).

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.

6 Pharmaceutical Particulars

6.1 List of Excipients

The excipients contained in Optisulin solution are glycerol, hydrochloric acid, metacresol sodium hydroxide for adjustment to pH 4, zinc chloride and water for injection.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.
See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.
See Section 6.4 Special Precautions for Storage, for shelf life after first use and open (in use) or unrefrigerated cartridges and pre-filled pens.

6.4 Special Precautions for Storage

Store at 2 to 8 degrees Celsius. Do not freeze.

Unopened cartridges and pre-filled pens.

Unopened cartridges and pre-filled pens (Optisulin 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.

Open (in use) or unrefrigerated cartridges and pre-filled pens.

Optisulin cartridges or pre-filled pens, whether or not refrigerated, must be discarded after 28 days from first use. Do not freeze. Discard if frozen.
Unrefrigerated cartridges or pre-filled pens, whether or not in use, must be discarded after 28 days. This applies irrespective of whether the cartridge or pre-filled pen is used immediately or is first carried as a spare for a while.

Cartridges and pre-filled pens.

Once in use, pre-filled pens (such as Optisulin SoloStar) or a reusable injection pen containing a cartridge of Optisulin must not be stored in the refrigerator. Optisulin 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.

6.5 Nature and Contents of Container

Optisulin 100 units per mL (U 100) is available as:
3 mL cartridges: 5 pack;
Solostar prefilled disposable devices: 5 pack, 1 pack (patient starter pack).

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

Optisulin is a sterile clear to colourless solution of insulin glargine in cartridges for use as an injection. The 3 mL cartridges contain 100 IU/mL (3.6378 mg/mL) insulin glargine.
Optisulin [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. The structural formula is shown below:
Molecular Formula: C267H404N72O78S6.
Molecular Weight: 6063.
Chemical Name: 21A-Gly-30Ba-L-Arg-30Bb-L-Arg-human insulin.

CAS number.

The CAS number is 160337-95-1.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (Schedule 4).

Summary Table of Changes