Protaphane 40 IU/ml suspension for injection in a vial

Protaphane is human insulin to treat diabetes. Protaphane is a long-acting insulin. This means that it will start to lower your blood sugar about 1½ hours after you take it, and the effect will last for approximately 24 hours. Protaphane is often given in combination with fast-acting insulin products.

Do not use Protaphane

If you are allergic hypersensitive to this insulin product, metacresol or any of the other ingredients see 7 Further information. Look out for the signs of allergy in 5 Possible side effects If you feel a hypo coming on a hypo is short for a hypoglycaemic reaction and is a symptom of low blood sugar. See 4 What to do in an emergency for more about hypos.

Take special care with Protaphane

If you have trouble with your kidneys or liver, or with your adrenal, pituitary or thyroid glands If you are drinking alcohol watch for signs of a hypo and never drink alcohol on an empty stomach If you are exercising more than usual or if you want to change your usual diet If you are ill carry on taking your insulin If you are going abroad travelling over time zones may affect your insulin needs and the timing of your injections.

Using other medicines

Many medicines affect the way glucose works in your body and they may influence your insulin dose. Listed below are the most common medicines which may affect your insulin treatment. Talk to your doctor or pharmacist if you take or have recently taken any other medicines, even those not prescribed. Your need for insulin may change if you also take: oral antidiabetic products; monoamine oxidase inhibitors (MAOI); beta-blockers; ACE-inhibitors; acetylsalicylic acid; anabolic steroids; sulphonamides; oral contraceptives; thiazides; glucocorticoids; thyroid hormone therapy; beta-sympathomimetics; growth hormone; danazol; octreotide or lanreotide.

Pioglitazone (oral antidiabetic medicine used for the treatment of type 2 diabetes mellitus) 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).

Pregnancy and breast-feeding

If you are pregnant, planning a pregnancy or breast-feeding: please contact your doctor for advice.

Driving and using machines

If you drive or use tools or machines: watch out for signs of a hypo. Your ability to concentrate or to react will be less during a hypo. Never drive or use machinery if you feel a hypo coming on. Discuss with your doctor whether you can drive or use machines at all, if you have a lot of hypos or if you find it hard to recognise hypos.

Talk about your insulin needs with your doctor and diabetes nurse. Follow their advice carefully. This leaflet is a general guide.
If your doctor has switched you from one type or brand of insulin to another, your dose may have to be adjusted by your doctor.
It is recommended that you measure your blood glucose regularly.

Before using Protaphane

Check the label to make sure it is the right type of insulin Disinfect the rubber membrane with a medicinal swab.

Do not use Protaphane

In insulin infusion pumps If the protective cap is loose or missing. Each vial has a protective, tamper-proof plastic cap. If it isnt in perfect condition when you get the vial, return the vial to your supplier If it hasnt been stored correctly or been frozen see 6 How to store Protaphane If its not uniformly white and cloudy when its resuspended.

How to use this insulin

Protaphane is for injection under the skin (subcutaneously). Never inject your insulin directly into a vein or muscle. Always vary the sites you inject, to avoid lumps (see 5 Possible side effects). The best place to give yourself an injection are: the front of your waist (abdomen); your buttocks; the front of your thighs or upper arms may be used. Your insulin will work more quickly if you inject it around the waist.

Protaphane vials are for use with insulin syringes with the corresponding unit scale.

To inject Protaphane on its own

1. Just before injecting this insulin, roll the vial between your hands until the liquid is uniformly white and cloudy. Resuspending is easier if the insulin has reached room temperature

2. Draw air into the syringe, in the same amount as the dose of insulin you need

3. Inject the air into the vial: push the needle through the rubber stopper and press the plunger

4. Turn the vial and syringe upside down

5. Draw the right dose of insulin into the syringe

6. Pull the needle out of the vial

7. Make sure there is no air left in the syringe: point the needle upwards and push the air out

8. Check you have the right dose

9. Inject straight away.

To mix Protaphane with fast-acting insulin

1. Roll the vial of Protaphane between your hands. Do this until the liquid is uniformly white and cloudy. Resuspending is easier if the insulin has reached room temperature

2. Draw as much air into the syringe as the dose of Protaphane you need. Inject the air into the Protaphane vial, then pull out the needle

3. Draw as much air into the syringe as the dose of fast-acting insulin you need. Inject the air into the fast-acting insulin vial. Then turn the vial and syringe upside down

4. Draw the right dose of fast-acting insulin into the syringe. Pull the needle out of the vial. Make sure there is no air left in the syringe: point the needle upwards and push the air out. Check the dose

5. Now push the needle into the vial of Protaphane. Then turn the vial and syringe upside down

6. Draw the right dose of Protaphane into the syringe. Pull the needle out of the vial. Make sure there is no air left in the syringe, and check the dose

7. Inject the mixture straight away.

Always mix fast-acting and long-acting insulin in this order.

Inject the insulin

Inject the insulin under the skin. Use the injection technique advised by your doctor or diabetes nurse Keep the needle under your skin for at least 6 seconds to make sure that the full dose has been delivered.

Like all medicines, Protaphane can cause side effects, although not everybody gets them. Protaphane may cause hypoglycaemia (low blood sugar). See the advice in 4 What to do in an emergency.

Side effects reported uncommonly (in less than 1 patient in 100)

Changes at the injection site (Lipodystrophy). If you inject yourself too often at the same site, fatty tissue under the skin at this site may shrink (lipoatrophy) or thicken (lipohypertrophy). Changing the site with each injection may help to prevent such skin changes. If you notice your skin pitting or thickening at the injection site, tell your doctor or diabetes nurse because these reactions can become more severe, or they may change the absorption of your insulin if you inject in such a site.

Signs of allergy. Reactions (redness, swelling, itching) at the injection site may occur (local allergic reactions). These reactions usually disappear after a few weeks of taking your insulin. If they do not disappear, see your doctor.
Seek medical advice immediately:

• if signs of allergy spread to other parts of the body, or
• if you suddenly feel unwell and you start sweating; start being sick (vomiting); have difficulty in breathing; have a rapid heart beat; feel dizzy; feel like fainting. You may have a very rare serious allergic reaction to Protaphane or one of its ingredients (called a systemic allergic reaction). See also warning in 2 Before you use Protaphane.

Diabetic retinopathy (eye background changes). If you have diabetic retinopathy and your blood glucose levels improve very fast, the retinopathy may get worse. Ask your doctor about this.

Swollen joints. When you start taking insulin, water retention may cause swelling around your ankles and other joints. This soon disappears.

Side effects reported very rarely (in less than 1 patient in 10,000)

Vision problems. When you first start your insulin treatment, it may disturb your vision, but the reaction usually disappears.

Painful neuropathy (nerve related pain). If your blood glucose levels improve very fast it may cause a burning, tingling or electric pain. This is called acute painful neuropathy and it usually disappears. If it does not disappear, see your doctor.

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

Keep out of the reach and sight of children.

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

The vials that arenot being used are to be stored in a refrigerator (2°C - 8°C).
Do not store them in or too near the freezer section or cooling element.
Do not freeze.
Keep the vials in the original package.
The vials that are being used or about to be used are not to be kept in a refrigerator. After removing the vial from the refrigerator it is recommended to let it reach room temperature before resuspending the insulin as instructed for the first time use. See 3 How to useProtaphane. You can carry them with you and keep them at room temperature (not above 25°C) for up to 4 weeks.
Always keep the vial in the outer carton when you?re not using it in order to protect it from light. Protaphane must be protected from excessive heat and sunlight.

Protaphane 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.

What Protaphanecontains

The active substance is insulin human made by recombinant biotechnology. Protaphane is an isophane insulin suspension NPH. 1 ml contains 40 IU of insulin human. 1 vial contains 10 ml equivalent to 400 IU

The other ingredients are zinc chloride, glycerol, metacresol, phenol, disodium phosphate dihydrate, sodium hydroxide, hydrochloric acid, protamine sulphate and water for injections.

What Protaphanelooks like and contents of the pack

The suspension for injection comes as a cloudy, white, aqueous suspension.
It is supplied in packs of 1 or 5 vials of 10 ml or in a multipack of 5 x (1 x 10 ml) vials. Not all packs may be marketed.

Marketing Authorisation Holder and Manufacturer

Novo Nordisk A/S
Novo Allé, DK-2880 Bagsværd, Denmark

This leaflet was last approved in

WHAT TO DO IN AN EMERGENCY

If you get a hypo

A hypo means your blood sugar level is too low.
Thewarning signs of a hypo may come on suddenly and can include: cold sweat; cool pale skin; headache; rapid heart beat; feeling sick; feeling very hungry; temporary changes in vision; drowsiness; unusual tiredness and weakness; nervousness or tremor; feeling anxious; feeling confused; difficulty in concentrating.
If you get any of these signs. eat glucose tablets or a high sugar snack (sweets, biscuits, fruit juice), then rest.
Don?t take any insulin if you feel a hypo coming on.
Carry glucose tablets, sweets, biscuits or fruit juice with you, just in case.
Tell your relatives, friends and close colleagues that if you pass out (become unconscious), they must: turn you on your side and seek medical advice straight away. They must not give you any food or drink as it could choke you.
- If severe hypoglycaemia is not treated, it can cause brain damage (temporary or permanent) and even death
- If you have a hypo that makes you pass out, or a lot of hypos, talk to your doctor. The amount or timing of insulin, food or exercise may need to be adjusted.

Using glucagon

You may recover more quickly from unconsciousness with an injection of the hormone glucagon by someone who knows how to use it. If you are given glucagon you will need glucose or a sugary snack as soon as you are conscious. If you do not respond to glucagon treatment, you will have to be treated in a hospital. Seek medical advice after an injection of glucagon; you need to find the reason for your hypo to avoid getting more.

Causes of a hypo

You get a hypo if your blood sugar gets too low. This might happen:

• If you take too much insulin
• If you eat too little or miss a meal
• If you exercise more than usual.

If your blood sugar gets too high

Your blood sugar may get too high (this is called hyperglycaemia).
Thewarning signs appear gradually. They include: increased urination; feeling thirsty; losing your appetite; feeling sick (nausea or vomiting); feeling drowsy or tired; flushed, dry skin; dry mouth and a fruity (acetone) smell of the breath.
If you get any of these signs. test your blood sugar level and test your urine for ketones if you can. Then seek medical advice straight away.
These may be signs of a very serious condition called diabetic ketoacidosis. If you don?t treat it, this could lead to diabetic coma and death.

Causes of hyperglycaemia

• Having forgotten to take your insulin
• Repeatedly taking less insulin than you need
• An infection or a fever
• Eating more than usual
• Less exercise than usual.