Consumer medicine information

Humalog U200 KwikPen

Insulin lispro

BRAND INFORMATION

Brand name

Humalog U200

Active ingredient

Insulin lispro

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Humalog U200 KwikPen.

SUMMARY CMI

HUMALOG® U200 KwikPen®

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 HUMALOG U200?

HUMALOG U200 contains the active ingredient insulin lispro (rbe). HUMALOG U200 is used to reduce high blood sugar (glucose) levels in patients with diabetes. For more information, see Section 1. Why am I using HUMALOG U200? in the full CMI.

2. What should I know before I use HUMALOG U200?

Do not use if you have ever had an allergic reaction to insulin lispro or any of the ingredients listed at the end of the CMI or when you have low blood sugar.

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 HUMALOG U200? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with HUMALOG U200 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 HUMALOG U200 KwikPen?

  • Your doctor will tell you what dose of HUMALOG U200 you need to use each day.
  • Do not inject HUMALOG U200 directly into your veins (intravenously). Do not transfer the HUMALOG U200 solution from the KwikPen into an insulin infusion pump or syringe. Severe overdose can result.

More instructions can be found in Section 4. How do I use HUMALOG U200? in the full CMI.

5. What should I know while using HUMALOG U200?

Things you should do
  • Remind any doctor, dentist, pharmacist, and diabetes nurse educator you visit that you are using HUMALOG U200.
  • Monitor your blood sugar levels regularly. Always carry some glucose or sugary foods with you in case you get low blood sugar.
  • Tell your doctor if you become pregnant or start breastfeeding while using HUMALOG U200.
Things you should not do
  • Do not stop using or change your dose of HUMALOG U200 without first checking with your doctor.
  • Do not use HUMALOG U200 when you have low blood sugar as it will make it worse.
Driving or using machines
  • Low blood sugar may impair your ability to concentrate or react while driving. Do not drive if you feel like your blood sugar levels are low.
Drinking alcohol
  • Tell your doctor if you drink alcohol. Alcohol may mask the symptoms of low blood sugar.
Looking after your medicine
  • Keep your pens in a fridge between 2°C - 8°C. Do not freeze.
  • You may keep the pens below 30°C for up to 28 days while using them. Dispose after 28 days.
  • Do not keep the pen that you are using in the fridge.

For more information, see Section 5. What should I know while using HUMALOG U200? in the full CMI.

6. Are there any side effects?

The most common (and potentially the most severe) side effect of HUMALOG U200 is low blood sugar.

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

HUMALOG® U200 KwikPen®

Active ingredient: insulin lispro (rbe)

Consumer Medicine Information (CMI)

This leaflet provides important information about using HUMALOG U200. 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 HUMALOG U200.

Where to find information in this leaflet:

1. Why am I using HUMALOG U200?
2. What should I know before I use HUMALOG U200?
3. What if I am taking other medicine?
4. How do I use HUMALOG U200?
5. What should I know while using HUMALOG U200?
6. Are there any side effects?
7. Product details

1. Why am I using HUMALOG U200?

HUMALOG U200 contains the active ingredient insulin lispro (rbe).

HUMALOG U200 is used to reduce high blood sugar (glucose) levels in patients with diabetes.

Diabetes is a condition in which your pancreas does not produce enough insulin to control your blood sugar level. Extra insulin is therefore needed.

There are two types of diabetes:

Type 1 diabetes - patients with type 1 diabetes always need insulin to control their blood sugar levels.

Type 2 diabetes - some patients with type 2 diabetes may also need insulin after initial treatment with diet, exercise, and tablets.

2. What should I know before I use HUMALOG U200?

Warnings

Do not use HUMALOG U200:

  • if you are allergic to insulin lispro, or any of the ingredients listed at the end of this leaflet. Always check the ingredients to make sure you can use this medicine.
  • when you have hypoglycaemia (low blood sugar).

Check with your doctor if you:

  • have had an allergic reaction to any medicine which you have used previously to treat diabetes.
  • are using, or have used, another type or brand of insulin. This may affect the dose of HUMALOG U200 that you are prescribed.
  • have or have had kidney or liver disease. This may affect the dose of HUMALOG U200 that you are prescribed.
  • have or have had heart disease and are also taking thiazolidinediones, a type of medicine used to treat type 2 diabetes (such as pioglitazone, rosiglitazone). You may be more at risk to develop fluid retention (oedema) especially in the hands, ankles, or feet, or heart failure while using HUMALOG U200.
  • are taking any other medications.

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. Pregnancy may make managing diabetes more difficult. Insulin needs usually decrease during the first three months of pregnancy and increase during the last six months.

Talk to your doctor if you are breastfeeding or intend to breastfeed. It is not known if HUMALOG U200 is excreted in significant amounts in breast milk.

Children (under 18 years)

The use of HUMALOG U200 has not been studied in children under the age of 18.

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.

You may need a lower dose of HUMALOG U200 if you are also taking any of the following medicines:

  • other medicines that treat diabetes
  • aspirin or other salicylates
  • a group of antibiotics, known as sulfonamides, used to treat infections
  • certain medicines used to treat depression, such as monoamine oxidase inhibitors
  • certain medicines used to treat high blood pressure or other heart conditions such as captopril, enalapril, angiotensin II receptor blockers, and beta blockers
  • certain medicines used to treat people with growth disorders and tumours, such as octreotide.

You may need a higher dose of HUMALOG U200 if you are also taking any of the following medicines:

  • medicines used for oral contraception ('the pill')
  • medicines that affect your metabolism (corticosteroids such as prednisone and cortisone)
  • medicines used in thyroid replacement therapy
  • certain antibiotics used to treat tuberculosis, such as isoniazid
  • certain medicines used to treat asthma, such as salbutamol or terbutaline
  • certain medicines used to treat schizophrenia, bipolar disorder, or nausea and vomiting, such as phenothiazines
  • certain medicines used to treat hormone-related disorders, such as danazol.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins, or supplements you are taking and if these affect HUMALOG U200.

4. How do I use HUMALOG U200?

How much to use

Your doctor will tell you what dose of HUMALOG U200 you need to use each day.

When to use HUMALOG U200

  • Your doctor will tell you when to use HUMALOG U200.
  • You should normally use HUMALOG U200 immediately (or up to 15 minutes) before a meal.
  • When necessary, HUMALOG U200 can be used within 20 minutes after the start of a meal.

How to use HUMALOG U200

Read the instructions for use leaflet contained in the carton carefully before using the HUMALOG U200 KwikPen.

  • Check to make sure that you are using HUMALOG U200 KwikPen. This is especially important if you use more than one type of insulin.
  • HUMALOG U200 should look clear and colourless. Do not use if it is cloudy, coloured, or has particles or clumps in in.
  • Do not transfer HUMALOG U200 solution into a syringe. Severe overdose can result.
  • HUMALOG U200 is injected under the skin (subcutaneously) of your stomach area or upper legs. Use of injection sites should be rotated so that the same spot is not used more than approximately once a month.
  • Under no circumstances should HUMALOG U200 be injected directly into your veins (intravenously).

If you forget to use HUMALOG U200

Test your blood sugar level as soon as possible.

If you use less HUMALOG U200 than you need, a high blood sugar level (hyperglycaemia) may occur.

Use it as soon as you remember, and then go back to using it as you would normally. Do not use a double dose of HUMALOG U200.

If you are unsure, talk to your doctor, diabetes educator, or pharmacist.

If you use too much HUMALOG U200

Hypoglycaemia (low blood sugar) may occur if you have used more HUMALOG U200 than you need. Check your blood sugar.

If your blood sugar is low (mild hypoglycaemia) eat glucose tablets, sugar or drink a sugary drink. Then eat fruit, biscuits, or a sandwich. This will often resolve mild hypoglycaemia or a minor insulin overdose.

If you get worse and your breathing is shallow and your skin gets pale, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre (by calling 13 11 26), or
  • 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.

5. What should I know while using HUMALOG U200?

Things you should do

  • Remind any doctor, dentist, pharmacist, and diabetes educator you visit that you are using HUMALOG U200.
  • Monitor your blood sugar levels regularly to ensure that your dose of HUMALOG U200 is appropriate. More frequent monitoring is recommended when changing insulin dose or type, or when you start taking a new medicine.
  • Always carry a supply of HUMALOG U200 KwikPens.
  • Always carry something to show you have diabetes.
  • Always carry glucose or sugary foods in case you develop hypoglycaemia (low blood sugar).

Tell your doctor

  • if you become pregnant or start breastfeeding while using HUMALOG U200.
  • if you notice changes to your eyesight. This may be a sign that your diabetes is not being controlled appropriately.
  • Tell your doctor, pharmacist, or diabetes educator if you plan to travel. You may need to carry a letter explaining why you are taking injecting devices with you. Your doctor, pharmacist, or diabetes educator can provide you with some helpful information.

Things you should not do

  • Do not transfer HUMALOG U200 solution from the KwikPen into an insulin infusion pump or syringe. Severe overdose can result.
  • Do not use HUMALOG U200 when you have hypoglycaemia (low blood sugar) as it will make it worse.
  • Do not stop using HUMALOG U200 without first checking with your doctor.
  • Do not change your insulin (dose or type) without first checking with your doctor.
  • Do not give your HUMALOG U200 to anyone else, even if they have the same condition as you. Your doctor has prescribed HUMALOG U200 specifically for you.
  • Do not mix HUMALOG U200 with any other animal or human insulin preparations.
  • Do not share needles or pens.
  • Do not re-use needles.
  • Do not store your insulin pen with the needle attached. This will ensure that your insulin will not become contaminated, and prevent leakage, the re-entry of air, and potential needle clogs.
  • Do not use HUMALOG U200 if the packaging is torn or shows signs of tampering.
  • Do not use HUMALOG U200 if the solution is cloudy, thickened, coloured, or has solid pieces in it, as it may no longer be good to use.
  • Do not use HUMALOG U200 if the cartridge in the KwikPen appears frosted, as it may no longer be good to use.
  • Do not use HUMALOG U200 if you think it has been frozen or exposed to excessive heat. It will not work as well.

Hypoglycaemia (low blood sugar)

Your blood sugar level may become too low if you:

  • use too much HUMALOG U200
  • exercise too much or excessively
  • delay eating meals or snacks
  • eat too little food
  • are ill.

Symptoms of mild to moderate hypoglycaemia can come on suddenly, and may include:

  • weakness, trembling or shaking
  • sweating
  • light headedness/headache
  • lack of concentration
  • behaviour change
  • dizziness
  • tearfulness/crying
  • irritability
  • numbness around the lips/fingers
  • hunger

Tell your doctor if you have trouble recognising these symptoms, if you often have hypoglycaemia or if you have ever become unconscious after using insulin. More frequent monitoring of your blood sugar level may be recommended, or your dose of HUMALOG U200 may need to be changed.

Recognising these mild to moderate symptoms early may allow you to take the necessary steps to avoid more serious hypoglycaemia.

Always carry some sugary food or drink with you.

If you experience symptoms of mild to moderate hypoglycaemia, immediately eat some sugary food or drink, such as jelly beans, fruit juice or glucose tablets.

If you do not feel better after eating/drinking some sugary food or drink, contact your doctor or go to the Emergency department at your nearest hospital.

Tell your relatives, friends, close workmates, or carers that you have diabetes.

It is important that they also recognise the signs and symptoms of hypoglycaemia.

Make sure they know to give you some sugary food or drink for mild to moderate symptoms of hypoglycaemia.

Severe symptoms of hypoglycaemia may include:

  • disorientation
  • seizures, fits, or convulsions
  • loss of consciousness.

If you lose consciousness, make sure your relatives, friends, close workmates, or carers know:

  • to turn you on your side and get medical help immediately.
  • not to give you anything to eat or drink to avoid choking.

Severe hypoglycaemia can lead to unconsciousness and in extreme cases death if not treated.

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.

Hyperglycaemia (high blood sugar)

Your blood sugar levels may become too high if you:

  • miss doses of HUMALOG U200 or use less than you need
  • have uncontrolled diabetes
  • exercise less than usual
  • eat more carbohydrates than usual
  • are ill or stressed.

Contact your doctor if your blood sugar level is too high and you experience any of the following symptoms. High blood sugar levels over a long period of time can lead to too much acid in the blood (diabetic ketoacidosis).

Symptoms of mild to moderate hyperglycaemia may include:

  • drowsiness
  • 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
  • nausea and vomiting.

Contact your doctor or the Emergency Department immediately if your blood sugar level is too high and you experience any of the following severe symptoms. Severe hyperglycaemia can lead to unconsciousness and in extreme cases death (if left untreated).

Symptoms of severe hyperglycaemia:

  • heavy breathing
  • fast pulse
  • nausea, and vomiting where you cannot keep any fluids down (leading to severe dehydration)
  • loss of consciousness.

Illness

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.

Emotional disturbances

Tell your doctor if you are feeling particularly excited, upset, or stressed.

Emotional disturbances may impact your dose of HUMALOG U200.

Exercise

Exercise may lower your need for insulin. Exercise may also make insulin work more quickly, especially if the exercise involves the area around the injection site (e.g., the leg should not be used as an injection site prior to jogging or running).

Tell your doctor if you are exercising more than usual, as your dose of HUMALOG U200 may need to change.

Diet

Changes to your diet may cause your insulin needs to change.

Tell your doctor before making any significant changes to your diet (e.g., removing carbohydrates).

Injection site

If you inject HUMALOG U200 in the same place, the fatty tissue may shrink (lipoatrophy) or thicken (lipohypertrophy).

Lumps under the skin may also be caused by build-up of a protein called amyloid (cutaneous amyloidosis).

To help prevent these skin changes, do not use the same place for injection more often than once a month.

HUMALOG U200 may not work very well if you inject into a lumpy, shrunken, or thickened area. Avoid injecting into these areas.

Tell your doctor if you are currently injecting into these affected areas before you start injecting in a different area.

Your doctor may tell you to measure your blood sugar more frequently, and to adjust your dose of HUMALOG U200 or other antidiabetic medications.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how HUMALOG U200 affects you.

Do not drive if you feel like your blood sugar level is low.

Hypoglycaemia (low blood sugar) may impair your ability to concentrate or react while driving.

Drinking alcohol

Tell your doctor if you drink alcohol.

Alcohol may mask the symptoms of hypoglycaemia (low blood sugar) and make it more difficult to recognise them.

Alcohol may also affect the dose of HUMALOG U200 that you are prescribed.

Looking after your medicine

  • Keep your pens in a fridge between 2°C - 8°C. Do not freeze.
  • While in-use, do not keep the pens in the fridge. You may keep them at unrefrigerated (below 30°C) for up to 28 days.
  • Dispose of unrefrigerated pens after 28 days even if they still contain insulin.
  • Do not store the pens in the bathroom or near a sink.
  • Do not put the pens near heat or in the sun.
  • Keep it where young children cannot reach it.

When to discard your medicine

Discard pens after the expiry date (month, year) stamped on the label has passed.

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.

Empty pens and needles should be disposed of in a sharps container or similar puncture proof container composed of hard plastic or glass.

Ask your doctor, nurse, pharmacist or diabetes educator where you can dispose of the container once it is full.

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.

Less serious side effects

Less serious side effectsWhat to do
Blood sugar related:
  • Mild to moderate hypoglycaemia (low blood sugar), symptoms may include:
    - weakness, trembling or shaking
    - sweating
    - light headedness/headache
    - lack of concentration
    - behaviour change
    - dizziness
    - tearfulness/crying
    - irritability
    - numbness around the lips/fingers
    - hunger.
Immediately eat some sugary food or drink, such as jelly beans, fruit juice or glucose tablets.
If you do not feel better after eating/drinking some sugary food or drink, contact your doctor or go to the Emergency Department at your nearest hospital.
Allergy related:
  • Local allergy, symptoms may include redness, swelling and itching around the injection site. These symptoms generally resolve within days to a few weeks of continued use.
Skin related:
  • Lipodystrophy, symptoms may include a depression in the skin or an enlargement or thickening of the tissue around the injection site.
    - A change in injection technique may help resolve the problem.
General:
  • Oedema (fluid retention), particularly in the ankles, feet and hands.
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Blood sugar related:
  • Severe hypoglycaemia (low blood sugar), symptoms may include:
    - disorientation
    - seizures, fits, or convulsions
    - loss of consciousness.
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.
If you lose consciousness, caregivers should turn you on your side and get medical help immediately. They should not give you anything to eat or drink to avoid choking.
Allergy related:
  • Generalised allergy, symptoms may include:
    - rash over a large part of body
    - shortness of breath
    - wheezing
    - low blood pressure
    - 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.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. 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

HUMALOG U200 is only available with a doctor's prescription.

What HUMALOG U200 contains

Active ingredient
(main ingredient)		insulin lispro (200 units per mL)
Other ingredients
(inactive ingredients)
  • glycerol
  • hydrochloric acid
  • metacresol
  • sodium hydroxide
  • trometamol
  • water for injection
  • zinc oxide

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

What HUMALOG U200 looks like

HUMALOG U200 (AUST R 226893)

HUMALOG U200 is available in 3 mL prefilled KwikPens.

HUMALOG U200 is a clear colourless solution.

Who distributes HUMALOG insulins?

Supplied in Australia by:

Eli Lilly Australia Pty Ltd
Level 9, 60 Margaret Street
SYDNEY NSW 2000

This leaflet was prepared in October 2024.

vA10.0_Oct24

®= Registered Trademark

Published by MIMS December 2024

BRAND INFORMATION

Brand name

Humalog U200

Active ingredient

Insulin lispro

Schedule

S4

 

1 Name of Medicine

Insulin lispro (rbe).

2 Qualitative and Quantitative Composition

Insulin lispro solution [recombinant DNA origin] is an aqueous solution of insulin lispro ([Lys (B28), Pro (B29)] human insulin analogue, adjusted to pH 7.0 - 7.8. It also contains metacresol, glycerol, trometamol, zinc oxide and water for injection. Hydrochloric acid and sodium hydroxide may be used to adjust pH.
Humalog U200 is available as a clear, colourless solution for subcutaneous administration in a concentration of 200 units/mL in a 3 mL prefilled insulin delivery device (Humalog U200 KwikPen).
Humalog U200 is a Lilly human insulin analogue. It has a very quick onset of action and a short duration of activity.
Humalog U200 should be given immediately (up to 15 minutes) before a meal. When necessary, it can be given soon after meals (within 20 minutes of the start of a meal).

3 Pharmaceutical Form

See Section 2 Qualitative and Quantitative Composition.

4 Clinical Particulars

4.1 Therapeutic Indications

For the treatment of patients with Type 1 (IDDM) and Type 2 (NIDDM) diabetes mellitus who require insulin for the maintenance of normal glucose homeostasis.

4.2 Dose and Method of Administration

Adults.

In adults, Humalog U200 can be given immediately (up to 15 minutes before a meal). When necessary, it can be given soon after meals (within 20 minutes of the start of the meal). It is anticipated the same dose of Humalog U200 to Humalog 100 units/mL will be required.
In patients with Type 2 diabetes Humalog U200 may be administered in combination therapy with oral sulfonylurea agents.

Children.

In clinical studies involving children and adolescents (ages 3 - 19 years), Humalog 100 units/mL has been shown to be safe, effective and well-tolerated.
There have been no studies of Humalog U200 in children (see Section 4.4 Special Warnings and Precautions for Use).

General.

During changes to a patient's insulin regimen, increase the frequency of glucose monitoring. Humalog U200 should be given by subcutaneous injection.
Subcutaneous administration should be in the abdomen or thighs. The injection sites should be rotated so that the same site is not used more than approximately once a month, in order to reduce the risk of lipodystrophy and localised cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localised cutaneous amyloidosis.
The time course of action of any insulin may vary considerably in different individuals or at different times in the same individual. As with all insulin preparations, the duration of action of Humalog U200 is dependent on dose, site of injection, blood supply, temperature and physical activity.
As Humalog U200 is a rapid acting insulin and has a time activity profile that is different from other insulins, patients previously stabilised on other types-of-insulins should be titrated cautiously with Humalog U200, under medical supervision (see Section 4.4 Special Warnings and Precautions for Use).

Humalog U200 and Humalog (100 units/mL).

Humalog KwikPen is available in two strengths. For both, the needed dose is dialed in units. Both prefilled pens, the Humalog U200 KwikPen and the Humalog KwikPen deliver 1 - 60 units in steps of 1 unit in a single injection. The dose counter shows the number of units regardless of strength and no dose conversion should be done when transferring a patient to a new strength.
Humalog U200 should be reserved for the treatment of patients with diabetes requiring daily doses of more than 20 units of rapid-acting insulin. The Humalog U200 solution should not be withdrawn from the KwikPen, or mixed with any other insulin, or diluted (see Section 4.4 Special Warnings and Precautions for Use).
Do not use Humalog U200 solution for injection in an insulin infusion pump.
Do not use Humalog U200 solution for injection intravenously.
Only patients who have been trained in the correct administration technique, and were educated about the different posology of this product, should attempt self-administration.

4.3 Contraindications

Hypoglycaemia.
Hypersensitivity to insulin lispro or one of its excipients.

4.4 Special Warnings and Precautions for Use

Change in insulin.

Patients using Humalog U200 should be educated about the safe use of insulin. Humalog U200 is a "rapid acting" type-of-insulin (see Section 5 Pharmacological Properties; Section 4.2 Dose and Method of Administration; Section 4.9 Overdose).
Changing types-of-insulin (i.e. rapid acting, short acting, intermediate acting, long acting) should be done cautiously and under medical supervision. More frequent monitoring of blood glucose levels is recommended.
Within the "rapid acting" type-of-insulin category, changes to the molecular form of the insulin analogue (e.g. lispro, aspart, glulisine) should be done cautiously and under medical supervision. More frequent monitoring of blood glucose levels is recommended.

Injection technique.

Patients must be instructed to perform continuous rotation of the injection site to reduce the risk of developing lipodystrophy and 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.

Hypoglycaemia.

All insulins, including Humalog U200, lower blood glucose levels and may cause hypoglycaemia (see Section 4.9 Overdose). Patients should be educated about the symptoms of hypoglycaemia (e.g. hunger, anxiety, sweating, tachycardia, confusion, etc.); and the risk factors for hypoglycaemia (e.g. reduced carbohydrate intake, exercise, oral hypoglycaemic agents, alcohol). Following an episode of hypoglycaemia, more frequent blood glucose monitoring and dose adjustment may be required.
The ability to concentrate and to react may be impaired as a result of hypoglycaemia, in particular recurrent hypoglycaemia. This may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or operating machinery). Patients should be advised to take precautions to avoid hypoglycaemia while driving, this is particularly important in those who have reduced or absent awareness of the warning signs of hypoglycaemia or have frequent episodes of hypoglycaemia. The advisability of driving should be considered in these circumstances.
Conditions which may make the early warning symptoms of hypoglycaemia different or less pronounced include long duration of diabetes, intensified insulin therapy, diabetic nerve disease, or medical products such as beta blockers.

Hyperglycaemia.

Use of dosages which are inadequate or discontinuation of treatment, especially in insulin-dependent diabetics, may lead to hyperglycaemia and diabetic ketoacidosis; conditions which are potentially lethal.

Insulin requirements and dosage adjustment.

Insulin requirements may be increased during illness or emotional disturbances.
Adjustment of dosage may also be necessary if patients undertake increased physical activity or change their usual diet.

Combination of Humalog U200 with thiazolidinediones.

Thiazolidinediones (TZDs) in combination with insulin are associated with an increased risk of oedema and heart failure; especially in patients with underlying cardiac disease.

Medication error.

Humalog U200 solution for injection must not be transferred from the prefilled KwikPen to a syringe. The markings on the insulin syringe will not measure the dose correctly. Overdose can result causing severe hypoglycaemia. Humalog U200 solution for injection must not be transferred from the KwikPen to any other insulin delivery device, including insulin infusion pumps.

Renal or hepatic impairment.

Some studies with human insulin have shown increased levels of circulating insulin in patients with renal and/or hepatic dysfunction. However, some patients with chronic hepatic impairment may have increased insulin requirements. Careful glucose monitoring and dose adjustments of Humalog U200 may be necessary (see Section 4.2 Dose and Method of Administration).

Use in hepatic impairment.

Insulin requirements may be reduced in patients with hepatic impairment due to reduced capacity for gluconeogenesis and reduced insulin breakdown; however, in patients with chronic hepatic impairment, an increase in insulin resistance may lead to increased insulin requirements.

Use in renal impairment.

Insulin requirements may be reduced in the presence of renal impairment.

Use in the elderly.

No data available.

Paediatric use.

There have been no studies of Humalog U200 in children. Humalog U200 was shown to be bioequivalent to Humalog 100 units/mL in healthy adults (n = 73) (see Section 5 Pharmacological Properties). In clinical studies involving children and adolescents (ages 3-19 years), Humalog 100 units/mL has been shown to be safe, effective and well-tolerated.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The medical practitioner should be consulted when using other medication in addition to insulin lispro (see Section 4.4 Special Warnings and Precautions for Use).
Insulin requirements may be increased by drugs with hyperglycaemic activity, such as oral contraceptives, corticosteroids, thyroid replacement therapy, isoniazid, phenothiazines, danazol or beta-2 stimulants (such as salbutamol, terbutaline).
Insulin requirements may be reduced in the presence of drugs with hypoglycaemic activity, such as oral hypoglycaemics, salicylates (for example, aspirin), sulphonamides, certain antidepressants (monoamine oxidase inhibitors), certain angiotensin converting enzyme inhibitors (captopril and enalapril), angiotensin II receptor blockers, beta blockers, octreotide and alcohol.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No effects on male or female fertility have been observed in rats dosed subcutaneously with insulin lispro at dose levels up to 20 U/kg/day.
(Category A)
Humalog U200 can be used during pregnancy. There is a large body of data which suggests that the use of insulin lispro during pregnancy is beneficial, and as safe as other forms of insulin therapy.
In a retrospective cohort study, the medical records of 496 women with Type 1 or Type 2 diabetes treated with Humalog for at least 1 month before conception and during at least the first trimester of pregnancy were reviewed to determine the rate of major congenital anomalies in their offspring. Outcomes of 533 pregnancies (542 offspring) showed the incidence of major congenital anomalies in the offspring was 5.4% (95% CI: 3.45%, 7.44%), consistent with previously published results for the offspring of women with type 1 and type 2 pregestational diabetes.
It is essential to maintain good control of the insulin-treated patient (insulin-dependent or gestational diabetes) throughout pregnancy. Insulin requirements usually fall during the first trimester and increase during the second and third trimesters. Patients with diabetes should be advised to inform their doctor if they are pregnant or are contemplating pregnancy. Careful monitoring of the patient is required throughout pregnancy. During the perinatal period, careful monitoring of infants born to mothers with diabetes is warranted.
A reproductive study in rats showed no adverse effects on pregnancy or foetal development when insulin lispro was injected subcutaneously once daily at doses up to 20 U/kg. Teratogenic potential has not been adequately assessed in rabbits, although one study showed no embryotoxic or teratogenic activity at subcutaneous doses up to 0.75 U/kg/day.
 Patients with diabetes who are lactating may require adjustments in insulin dose, diet or both. It is not known if insulin lispro is excreted in significant amounts in human milk. Many drugs, including human insulin, are excreted in human breast milk.

4.7 Effects on Ability to Drive and Use Machines

The ability to concentrate to react may be impaired as a result of hypoglycaemia, in particular recurrent hypoglycaemia. This may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or operating machinery). Patients should be advised to take precautions to avoid hypoglycaemia while driving, this is particularly important in those who have reduced or absent awareness of the warning signs of hypoglycaemia or have frequent episodes of hypoglycaemia. The advisability of driving should be considered in these circumstances.

4.8 Adverse Effects (Undesirable Effects)

The preclinical safety profile indicates that insulin lispro (the active ingredient in Humalog U200 and Humalog) is safe in the chronic treatment of diabetes in humans. The safety profile of insulin lispro has been assessed in a series of preclinical studies. In in vitro tests, including binding to insulin receptor sites and effects on growing cells, insulin lispro behaved in a manner that closely resembled human insulin. Toxicology studies produced no significant toxicity findings. Most importantly, and like human insulin, insulin lispro did not produce proliferative effects or tumours in organs and tissues when given at very high subcutaneous doses in chronic toxicity tests.

Hypoglycaemia.

Hypoglycaemia is the most frequent undesirable effect of insulin therapy. Severe hypoglycaemia may lead to loss of consciousness and, in extreme cases, death. The clinical studies on Humalog 100 units/mL showed no difference between the frequency of symptomatic hypoglycaemia or the frequency of hypoglycaemic coma when compared to Humulin R; however, the studies did show a consistent, but not always significant, reduction of postprandial glycaemic excursion in patients using Humalog.

Allergic reactions.

Local allergy in patients occasionally occurs as redness, swelling and itching at the site of insulin injection. This condition usually resolves in a few days to a few weeks. In some instances, this condition may be related to factors other than insulin, such as irritants in the skin cleansing agent or poor injection technique. Systemic allergy, less common but potentially more serious, is a generalised allergy to insulin. It may cause rash over the whole body, shortness of breath, wheezing, reduction in blood pressure, fast pulse or sweating. Severe cases of generalised allergy may be life-threatening.

Lipodystrophy.

Rarely, administration of insulin subcutaneously can result in lipoatrophy or lipohypertrophy. A change in injection technique may help alleviate the problem.

Spontaneous data.

Cases of oedema have been reported with insulin therapy, particularly if previous poor metabolic control is improved by intensified insulin therapy.
Lipodystrophy and localised cutaneous amyloidosis at the injection site have occurred. Hyperglycaemia has been reported with repeated insulin injections into areas of lipodystrophy or localised cutaneous amyloidosis; hypoglycaemia has been reported with a sudden change to an unaffected injection site (see Section 4.4 Special Warnings and Precautions for Use).

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 http://www.tga.gov.au/reporting-problems.

4.9 Overdose

Insulins have no specific overdose definitions because serum glucose concentrations are a result of complex interactions between insulin levels, glucose availability and other metabolic processes. Hypoglycaemia may occur as a result of an excess of insulin or insulin analogue relative to food intake and energy expenditure.
Hypoglycaemia may be associated with listlessness, confusion, palpitations, headache, sweating and vomiting.
Mild hypoglycaemic episodes will respond to oral administration of glucose or other sugar or saccharated products.
Correction of moderately severe hypoglycaemia can be accomplished by intramuscular or subcutaneous administration of glucagon, followed by oral carbohydrate when the patient recovers sufficiently. Patients who fail to respond to glucagon must be given glucose solution intravenously.
If the patient is comatose, glucagon should be administered intramuscularly or subcutaneously. However, glucose solution must be given intravenously if glucagon is not available or if the patient fails to respond to glucagon. The patient should be given a meal as soon as consciousness is recovered.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The unique structure of Humalog U200 results in a fast rate of absorption from subcutaneous sites of injection, a rapid effect and a short duration of action, more closely mimicking the normal physiological response.
Humalog U200 has a very rapid onset of action, allowing it to be given immediately before a meal, compared to regular insulin, which should be given 30 minutes before a meal. Humalog U200 solution for injection was bioequivalent to Humalog 100 units/mL solution for injection after subcutaneous administration of a single 20 unit dose in healthy adults (n = 73). Time to maximum concentration was also similar between formulations. In initial clinical pharmacology studies, the onset of action of Humalog 100 units/mL was seen within 15 minutes of administration. Serum insulin levels peak earlier with insulin lispro (the active ingredient in Humalog U200 and Humalog) at 1 hour, corresponding to an earlier peak action of insulin lispro. Insulin lispro has a short duration of activity of 3.5 to 4.5 hours.
As with all insulin preparations, the time course of Humalog U200 action may vary in different individuals or at different times in the same individual and is dependent on site of injection, blood supply, body temperature and physical activity. The primary activity of Humalog U200 is the regulation of glucose metabolism.
In addition, insulins have several anabolic and anti-catabolic actions on a variety of different tissues. In muscle and other tissues (except the brain), insulin causes rapid transport of glucose and amino acids intracellularly, promotes anabolism, and inhibits protein catabolism. In the liver, insulin promotes the uptake and storage of glucose in the form of glycogen, inhibits gluconeogenesis, and promotes the conversion of excess glucose into fat.
The pharmacodynamics of a single 20 unit dose of Humalog U200 administered subcutaneously were compared to the pharmacodynamics of a single 20 unit dose of Humalog 100 units/mL administered subcutaneously in a euglycemic clamp study enrolling healthy subjects. In this study, the overall, maximum, and time to maximum glucose lowering effect were similar between Humalog U200 and Humalog 100 units/mL. The mean area under the glucose infusion rate curves (measure of overall pharmacodynamic effect) were 125 g and 126 g for Humalog U200 and Humalog 100 units/mL, respectively. The maximum glucose infusion rate was 534 mg/min and 559 mg/min and the corresponding median time (min, max) to maximum effect were 2.8 h (0.5 h - 6.3 h) and 2.4 h (0.5 h - 4.7 h) for Humalog U200 and Humalog 100 units/mL, respectively (see Figure 1).

Clinical trials.

Eight pivotal studies were designed to evaluate the use of Humalog 100 units/mL as a mealtime insulin using postprandial glucose control as the primary efficacy objective. These studies were designed to incorporate men and women of many racial/ethnic heritages and cultural dietary patterns aged 12 to 85 with new or previously treated Type 1 or Type 2 diabetes mellitus. In these trials, 2,247 patients received Humalog 100 units/mL.
Four global, multicentre, clinical studies of Humalog 100 units/mL (studies IOAA - IOAD) were designed to incorporate Type 1 and Type 2 patients who were already receiving insulin therapy and who had been treated with human insulin for at least 2 months prior to study entry. All four were 1-year, open-label, randomised, parallel studies using Humulin R in a multiple daily injection, basal-bolus therapeutic regimen as the active comparator (see Table 1).
Four global, multicentre, clinical studies of Humalog 100 units/mL (studies IOAE - IOAH) were conducted to incorporate Type 1 and Type 2 patients who had never received insulin, to evaluate antibody formation in patients not previously treated with insulin, and to have larger studies of both Type 1 and 2 patients previously treated with insulin (see Table 1).
The studies in new Type 1 and Type 2 patients, IOAE and IOAF, were 1-year, open-label, randomised, parallel, studies using Humulin R as the active comparator. The choice of basal insulin was at the discretion of the investigator, either Humulin NPH or Humulin UL, and once chosen was the basal insulin for the entire study. The study design was identical to the earlier studies, IOAA - IOAD.
Studies IOAG and IOAH were 6-month, open-label, randomised, crossover studies in Type 1 and Type 2 patients who were currently being treated with insulin and had been using human insulin for at least the previous 2 months. Humulin R was the active comparator. The choice of basal insulin was at the discretion of the investigator, either Humulin NPH or Humulin UL, and once chosen was the basal insulin for the entire study. The power of the crossover design, with each patient serving as his or her own control, and the large patient numbers allowed these two studies to provide the major conclusions (consistent with the conclusions of the first six studies) regarding the efficacy of Humalog 100 units/mL on reduction of the postprandial glucose excursion in patients with diabetes. In addition, study IOAG demonstrated a significant reduction in the rate of hypoglycaemia overall as well as demonstrating significant reduction in nocturnal hypoglycaemia in patients receiving Humalog 100 units/mL.
In all of the studies there were no clinically significant safety issues with Humalog 100 units/mL. There was no evidence of increased immunogenicity of Humalog 100 units/mL compared to Humulin R.
In the clinical trials of Humalog 100 units/mL, approximately one-half to two-thirds of Type 1 patients and approximately one-third of Type 2 patients had their basal insulin in the morning. More than 90% of the patients having a morning dose of basal insulin had it mixed with their breakfast dose of Humalog 100 units/mL.
Clinical studies have demonstrated significant improvement in postprandial glucose excursions without producing delayed postprandial hyperglycaemia and without an adverse effect on overall control as measured by haemoglobin A1c. Therapy with Humalog 100 units/mL was also associated with no adverse impact on hypoglycaemia, and, in fact, in the large studies with Type 1 patients (those most at risk of hypoglycaemia) there was a reduction in the rate of hypoglycaemia overall and a reduction in nocturnal hypoglycaemia. Across all of the studies there were no significant safety issues.
Humalog 100 units/mL is superior to regular human insulin in those measures that reflect rapid onset and shorter duration of action. Early studies showed no significant difference in overall glycaemic control, as measured by haemoglobin A1c, between Humalog 100 units/mL and regular human insulin, either in patients established on insulin or in newly diagnosed patients. Haemoglobin A1c is improved with Humalog 100 units/mL by varying the basal regimen, to compensate for preprandial hyperglycaemia and to make use of the reduced postprandial blood glucose levels provided by Humalog 100 units/mL.
In patients with Type 2 diabetes on maximum doses of sulfonylurea agents, the addition of Humalog 100 units/mL resulted in an improvement in haemoglobin A1c compared to patients continuing on sulfonylurea therapy alone. Study IOCE was a 2-month randomised, open-label comparative study of Humalog 100 units/mL, sulfonylurea and insulin NPH combinations. In this study, haemoglobin A1c levels were reduced by 1.6% with the combination of Humalog 100 units/mL and sulfonylurea, when compared to baseline, in patients with fasting hyperglycaemia despite maximal doses of sulfonylurea.

5.2 Pharmacokinetic Properties

See Section 5.1 Pharmacodynamic Properties.

5.3 Preclinical Safety Data

Genotoxicity.

There was no evidence of any genotoxic activity in a range of assays for gene mutations, chromosomal effects and DNA damage.

Carcinogenicity.

Carcinogenicity studies of insulin lispro have not been conducted.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition; Section 3 Pharmaceutical Form.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

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.

6.4 Special Precautions for Storage

Humalog U200 should be stored in a refrigerator between 2°C and 8°C. It should not be frozen or exposed to excessive heat or sunlight.
Humalog U200 KwikPen can be kept at ambient temperature below 30°C and away from direct heat and light for 28 days while in use.

6.5 Nature and Contents of Container

Humalog U200 [200 units/mL of insulin lispro (rbe)] is supplied in a KwikPen prefilled insulin delivery device containing a 3 mL cartridge (in packs of 2 and 5).

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.


CAS number.

133107-64-9.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription only medicine.

Summary Table of Changes