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UK PIL GRANTED MAY 2012

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C. Illness

If you are ill, especially if you feel sick or are sick, the amount of insulin you need may change.

Even when you are not eating normally, you still need insulin. Test your urine or blood, follow your ‘sick rules', and tell your diabetes specialist nurse or doctor.

5. How to store Humulin M3

Keep all medicines out of the sight and reach of children.

Before the first use, store your Humulin M3 in a refrigerator at 2-8°C. Do not freeze. Do not expose to direct sunlight or excessive heat. Keep the container in the outer carton in order to protect from light.

When in use, do not keep your Humulin M3 pen or cartridge above 30°C. The cartridges can be used for up to 28 days. Do not keep your ‘in-use' pen or cartridges in the fridge.

Do not use Humulin M3 after the expiry date which is stated on the label and the carton. The expiry date refers to the last day of that month.

Do not use Humulin M3, if clumps of material are present or if solid white particles stick to the bottom or sides of the cartridge, giving it a frosted appearance. Check this each time you inject yourself.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. Further Information

What Humulin M3 contains

The active substance is human insulin. Human insulin is is made in the laboratory by a ‘recombinant DNA technology' process. It has the same structure as the natural hormone made by the pancreas. It is therefore different from animal insulins. Humulin M3 is a premixed suspension which contains 30% insulin dissolved in water and 70% insulin with protamine sulphate.

Humulin M3 contains m-cresol distilled, phenol, protamine sulphate, glycerol, zinc oxide, dibasic sodium phosphate heptahydrate and water for injections.

Hydrochloric acid or sodium hydroxide (or both) may have been used during manufacture to adjust the acidity.

What Humulin M3 looks like and contents of the pack

Your medicine is called Humulin M3 100IU/ml suspension for injection in cartridges. Its strength is 100 units per millilitre (ml). One cartridge contains 3ml equivalent to 300 IU of biphasic isophane insulin - 30% soluble insulin/70% isophane insulin.

Humulin M3 100IU/ml suspension for injection in cartridge is a sterile suspension of white crystals in a glass vial with a rubber stopper and a metal cap.

Humulin M3 cartridges come in packs of 5 cartridges.

Product Licence holder and manufacturer

POM    PL No: 06464/2728

This product is manufactured by Lilly France SAS, rue du Colonel Lilly, 67640 Fegersheim, France and is procured from within the EU and repackaged by the Product Licence holder:

Waymade plc, Miles Gray Road, Basildon, Essex SS14 3FR

Leaflet revision and issue date (Ref.) 14.6.2012

Humulin is a registered trademark of Eli Lilly and Company

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HUMULIN® M3 100 IU/ml SUSPENSION FOR INJECTION

IN CARTRIDGE (Human Insulin (prb))

Patient Information Leaflet

Your medicine is known as the above name but will be referred to as Humulin M3 throughout this leaflet.

Read all of this leaflet carefully before you start using this medicine.

•    Keep this leaflet. You may need to read it again.

•    If you have any further questions, ask your diabetes specialist nurse, doctor or pharmacist.

•    This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

•    If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your diabetes specialist nurse, doctor or pharmacist.

In this leaflet:

1.    What Humulin M3 is and what it is used for

2.    Before you use Humulin M3

3.    How to use Humulin M3

4.    Possible side effects

5.    How to store Humulin M3

6.    Further information

1. What Humulin M3 is and what it is used for

Humulin M3 contains the active substance human insulin, which is used to treat diabetes. You get diabetes if your pancreas does not make enough insulin to control the level of glucose in your blood (blood sugar). Humulin M3 is used to control glucose in the long term. It is a premixed suspension of rapid and long acting insulin. Its action is prolonged by the inclusion of protamine sulphate in the suspension.

Your doctor may tell you to use Humulin M3 as well as a longer-acting insulin.

Each kind of insulin comes with its own patient information leaflet to tell you about it. Do not change your insulin unless your doctor tells you to. Be very careful if you do change insulin.

Each type of insulin has a different colour and symbol on the pack and the cartridge so that you can easily tell the difference.

2. Before you use Humulin M3

Do not use Humulin M3 if you:

-    think hypoglycaemia (low blood sugar) is starting. Further in this leaflet it tells you how to

deal with mild hypoglycaemia (see A in Section 4).

-    are allergic (hypersensitive) to human insulin or any of the other ingredients of Humulin M3 (see Section 6).

Take special care with Humulin M3

•    If your blood sugar levels are well controlled by your current insulin therapy, you may not feel the warning symptoms when your blood sugar is falling too low. Warning signs are listed later in this leaflet. You must think carefully about when to have your meals, how often to exercise and how much to do. You must also keep a close watch on your blood sugar levels by testing your blood glucose often.

•    A few people who have had hypoglycaemia (low blood sugar) after switching from animal insulin to human insulin have reported that the early warning symptoms were less obvious or different. If you often have hypoglycaemia or have difficulty recognising the symptoms, please discuss this with your doctor.

•    If you answer YES to any of the following questions, tell your diabetes specialist nurse, doctor or pharmacist.

-    Have you recently become ill?

-    Do you have trouble with your kidneys or liver?

-    Are you exercising more than usual?

•    The amount of insulin you need may also change if you drink alcohol.

•    You should also tell your diabetes specialist nurse, doctor or pharmacist if you are planning to go abroad. The time difference between countries may mean that you have to have your injections and meals at different times to when you are at home.

•    Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible, if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Using other medicines

Please tell your doctor or diabetes specialist nurse, if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Your insulin needs may change if you are taking any of the following:

•    steroids,

•    thyroid hormone replacement therapy,

•    oral hypoglycaemics (antidiabetic medication),

•    acetylsalicylic acid (aspirin),

•    growth hormone,

•    octreotide, lanreotide,

•    beta₂ stimulants (for example ritodrine, salbutamol or terbutaline),

•    beta-blockers,

•    thiazides or some antidepressants (monoamine oxidase inhibitors),

•    danazol,

•    some angiotensin converting (ACE) inhibitors (for example captopril, enalapril) or angiotensin II receptor blockers.

Pregnancy and breast-feeding

Ask your doctor or diabetes specialist nurse for advice before taking any medicine.

The amount of insulin you need usually falls during the first three months of pregnancy and increases for the remaining six months. If you are breastfeeding, you may need to alter your insulin intake or diet.

WARNING! WE CANNOT ACCEPT RESPONSIBILITY FOR ANY ERRORS IN THIS PROOF AFTER APPROVAL. THE ARTWORK RECEIVED HAS BEEN SIGNIFICANTLY ADJUSTED, REVISED OR RESET BY US FROM DISK OR HARD COPY. WHILST WE TAKE EXTREME CARE AT ALL TIMES TO ENSURE ACCURACY, THE FINAL RESPONSIBILITY MUST BETAKEN BY OUR CUSTOMER. IF YOU SIGN THIS PROOF YOU ARE SIGNIFYING FULL APPROVAL OF DESIGN AND TEXT.

WARNING! THE COLOURS SHOWN ON THIS PROOF ARE FOR GENERAL REPRESENTATION PURPOSES ONLY. THEY ARE NOT ACCURATE AND MUST NOT BE USED AS A COLOUR MATCH FOR THE FINISHED JOB. PLEASE REFER TO THE PANTONE COLOUR GUIDES FOR ACCURATE COLOUR REFERENCES.

UK PIL GRANTED MAY 2012

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Driving and using machines

Your ability to concentrate and react may be reduced if you have hypoglycaemia (low blood sugar). Please remember this in all situations where you might put yourself and others at risk (e.g. driving a car or operating machinery). You should contact your diabetes specialist nurse or doctor about the advisability of driving if you have:

•    frequent episodes of hypoglycaemia

•    reduced or absent warning signs of hypoglycaemia.

3. How to use Humulin M3

The 3 ml cartridge is only for use in 3ml pens. It is not for use in 1.5 ml pens.

Always check the pack and the cartridge label for the name and type of the insulin when you get it from your pharmacy. Make sure you get the Humulin that your doctor has told you to use.

Always use Humulin M3 exactly as your doctor has told you. You should check with your doctor if you are not sure.

Dosage

•    Your doctor has told you which insulin to use, how much, when and how often to inject. These instructions are only for you.

Follow them exactly and visit your diabetes clinic regularly.

•    If you change your insulin type (for example from animal to human), you may have to take more or less than before. This might just be for the first injection or it may be a gradual change over several weeks or months.

•    Inject Humulin M3 under the skin. You should not administer it using a different administration route. Under no circumstances should Humulin M3 be given into a vein.

Preparing Humulin M3

•    Cartridges containing Humulin M3 should be rotated in the palms of the hands 10 times and inverted 10 times immediately before use to resuspend insulin until it appears uniformly cloudy or milky. If not, repeat the above procedure until contents are mixed. Cartridges contain a small glass bead to assist mixing. Do not shake vigorously as this may cause frothing which may interfere with the correct measurement of the dose. The cartridges should be examined frequently and should not be used if clumps of material are present or if solid white particles stick to the bottom or sides of the cartridge, giving it a frosted appearance. Check each time you inject yourself.

Getting the pen ready to use

•    First wash your hands. Disinfect the rubber membrane of the cartridge.

•    You must only use Humulin M3 cartridges in compatible CE marked pens. Please make sure that Humulin M3 or Lilly cartridges are mentioned in the leaflet accompanying your pen. The 3 ml cartridge only fits the 3 ml pen.

•    Follow the instructions that come with the pen. Put the cartridge into the pen.

•    You will set the dose to 1 or 2 units. Then hold the pen with the needle pointing up and tap the side of the pen so that any bubbles float to the top. With the pen still pointing up, press the injection mechanism. Do this until a drop of Humulin M3 comes out of the needle.There may still be some small air bubbles left in the pen. These are harmless, but if the air bubble is too big, it may make the dose of your injection less accurate.

Injecting Humulin M3

•    Before you make an injection, clean your skin as you have been instructed. Inject under the skin, as you were taught. Do not inject directly into a vein. After your injection, leave the needle in the skin for 5 seconds to make sure you have taken the whole dose. Do not rub the area you have just injected. Make sure you inject at least half an inch (1 cm) from where you last injected and that you ‘rotate' the places you inject, as you have been taught.

After injecting

•    As soon as you have done the injection, unscrew the needle from the pen using the outer needle cap. This will keep the insulin sterile and prevent leaking. It will also stop air going back into the pen and the needle clogging up. Do not share your needles or your pen. Replace the cap on your pen.

Further injections

•    Leave the cartridge in the pen. Before every injection, dial 1 or 2 units and press the injection mechanism with the pen pointing up until a drop of Humulin M3 comes out of the needle. You can see how much Humulin M3 is left by looking at the gauge on the side of the cartridge. The distance between each mark on the gauge is about 20 units. If there is not enough for your dose, change the cartridge.

Do not mix any other insulin in a Humulin M3 cartridge. Once the cartridge is empty, do not use it again.

If you take more Humulin M3 than you need

If you take more Humulin M3 than you need, your blood sugar may become low. Check your blood sugar (see A in Section 4).

If you forget to use Humulin M3

If you take less Humulin M3 than you need, your blood sugar levels may increase. Check your blood sugar.

If you stop using Humulin M3

If you take less Humulin M3 than you need, your blood sugar levels may become too high. Do not change your insulin unless your doctor tells you to.

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

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4. Possible side effects

Like all medicines, Humulin M3 can cause side effects, although not everybody gets them.

Human insulin may cause hypoglycaemia (low blood sugar). See more information on hypoglycaemia below in the subsection "Common problems of diabetes”.

Possible side effects

Systemic allergy is very rare (affects less than 1 person in 10, 000). The symptoms are as follows:

•    fall in blood pressure

•    difficulty in breathing

•    fast heart beat

•    rash over the whole body

•    wheezing

•    sweating

If you think you are having this sort of insulin allergy with Humulin M3, tell your doctor at once.

Local allergy is common (affects less than 1 person in 10). Some people get redness, swelling or itching around the area of the insulin injection. This usually clears up in anything from a few days to a few weeks. If this happens to you, tell your doctor.

Lipodystrophy (thickening or pitting of the skin) is uncommon (affects less than 1 person in 100). If you notice your skin thickening or pitting at the injection site, change your injection site and tell your doctor.

Oedema (e.g. swelling in arms, ankles; fluid retention) has been reported, particularly at the start of insulin therapy or during a change in therapy to improve control of your blood glucose.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Common problems of diabetes

A. Hypoglycaemia

Hypoglycaemia (low blood sugar) means there is not enough sugar in the blood. This can be caused if you:

•    take too much Humulin M3 or other insulin;

•    miss or delay meals or change your diet;

•    exercise or work too hard just before or after a meal;

•    have an infection or illness (especially diarrhoea or vomiting);

•    have a change in your need for insulin; or

•    have trouble with your kidneys or liver which gets worse.

Alcohol and some medicines can affect your blood sugar levels.

The first symptoms of low blood sugar usually come on quickly and include the following:

•    tiredness

•    rapid heartbeat

•    nervousness or shakiness

•    feeling sick

•    headache

•    cold sweat

Until you become confident in recognising your warning symptoms, avoid situations such as driving a car, in which you or others would be put at risk by hypoglycaemia.

Do not use Humulin M3 if you think hypoglycaemia (low blood sugar) is starting.

If your blood sugar is low, eat glucose tablets, sugar or drink a sugary drink.

Then eat fruit, biscuits, or a sandwich, as your doctor has advised you and have some rest. This will often get you over mild hypoglycaemia or a minor insulin overdose. If you get worse and your breathing is shallow and your skin gets pale, tell your doctor at once. A glucagon injection can treat quite severe hypoglycaemia. Eat glucose or sugar after the glucagon injection. If you do not respond to glucagon, you will have to go to hospital. Ask your doctor to tell you about glucagon.

B. Hyperglycaemia and diabetic ketoacidosis

Hyperglycaemia (too much sugar in the blood) means that your body does not have enough insulin. Hyperglycaemia can be brought about by:

•    not taking your Humulin M3 or other insulin;

•    taking less insulin than your doctor tells you to;

•    eating a lot more than your diet allows; or

•    fever, infection or emotional stress.

Hyperglycaemia can lead to diabetic ketoacidosis. The first symptoms come on slowly over many hours or days. The symptoms include the following:

•    feeling sleepy

•    no appetite

•    flushed face

•    fruity smell on the breath

•    thirst

•    feeling or being sick

Severe symptoms are heavy breathing and a rapid pulse. Get medical help immediately.

If hypoglycaemia (low blood sugar) or hyperglycaemia (high blood sugar) are not treated they can be very serious and cause headaches, nausea, vomiting, dehydration, unconsciousness, coma or even death.

Three simple steps to avoid hypoglycaemia or hyperglycaemia are:

•    Always keep spare syringes and a spare vial of Humulin M3.

•    Always carry something to show you are diabetic.

•    Always carry sugar with you.

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WARNING! WE CANNOT ACCEPT RESPONSIBILITY FOR ANY ERRORS IN THIS PROOF AFTER APPROVAL. THE ARTWORK RECEIVED HAS BEEN SIGNIFICANTLY ADJUSTED, REVISED OR RESET BY US FROM DISK OR HARD COPY. WHILST WE TAKE EXTREME CARE AT ALL TIMES TO ENSURE ACCURACY, THE FINAL RESPONSIBILITY MUST BETAKEN BY OUR CUSTOMER. IF YOU SIGN THIS PROOF YOU ARE SIGNIFYING FULL APPROVAL OF DESIGN AND TEXT.

WARNING! THE COLOURS SHOWN ON THIS PROOF ARE FOR GENERAL REPRESENTATION PURPOSES ONLY. THEY ARE NOT ACCURATE AND MUST NOT BE USED AS A COLOUR MATCH FOR THE FINISHED JOB. PLEASE REFER TO THE PANTONE COLOUR GUIDES FOR ACCURATE COLOUR REFERENCES.