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.

What is in this leaflet

This leaflet is designed to provide you with answers to some common questions about this medicine. It does not contain all the available information and does not take the place of talking with your doctor.

The information in this leaflet was last updated on the date shown on the final page. More recent information on this medicine may be available. Make sure you speak to your pharmacist, nurse or doctor to obtain the most up to date information on this medicine. You can also download the most up to date leaflet from www.lilly.com.au. The updated leaflet may contain important information about HUMALOG U200 and its use that you should be aware of.

All medicines have risks and benefits. Your doctor has more information about this medicines than is contained in this leaflet. Also, your doctor has had the benefit of taking a full and detailed history from you and is in the best position to make an expert judgement to meet your individual needs.

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

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

What HUMALOG U200 is used for

HUMALOG U200 contains insulin lispro and is used to reduce high blood sugar (glucose) levels in insulin dependent diabetic patients. 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 mellitus:

Type 1 diabetes - also called Insulin Dependent Diabetes Mellitus (IDDM). Patients with type 1 diabetes always need insulin to control their blood sugar levels.

Type 2 diabetes - also called Non insulin dependent diabetes mellitus (NIDDM). Some patients with type 2 diabetes may also need insulin after initial treatment with diet, exercise and tablets.

The duration of effect of insulin lispro varies in each individual and also depends on dose, site of injection, blood supply, body temperature and physical activity.

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

Before using HUMALOG U200

Tell your doctor if you have any of the following conditions or if you have ever experienced any of these conditions.

When you must not use HUMALOG U200

Do not use/inject HUMALOG U200:

  • if you have had an allergic reaction to HUMALOG U200, or to any of the ingredients listed at the end of this leaflet (see 'Product Description').
    Signs of an allergic reaction include redness, swelling and itching at the injection site, rash, shortness of breath, fast pulse or sweating.
  • if the packaging is torn or shows signs of tampering.
  • if you are experiencing low blood sugar (hypoglycaemia).
  • if HUMALOG U200 solution is cloudy, thickened, coloured or has solid pieces in it.
  • if the expiry date (EXP) on the pack has passed.

If you are not sure whether you should start using HUMALOG U200, talk to your doctor or pharmacist.

Before you start using HUMALOG U200

You must tell your doctor:

  • if you have had an allergic reaction to any medicine which you have used previously to treat your current condition.
  • if you have or have had any medical conditions, especially kidney, liver or heart disease.
  • if you experience fluid retention especially in the hands, ankles or feet.
  • if you are pregnant or intend to become pregnant.
    Pregnancy may make managing your diabetes more difficult. Insulin needs usually decrease during the first three months of pregnancy and increase during the last six months.
  • if you are breast-feeding or plan to breast-feed.
    It is not known if insulin lsipro is excreted in significant amounts in breast milk.
  • if you often have hypoglycaemia (low blood sugar) or if you have trouble recognising the symptoms of hypoglycaemia.
    Under certain conditions the early warning signs of hypoglycaemia can be different or less pronounced.
  • if you drink alcohol.
  • 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 are exercising more than usual.
    Exercise may lower your need for insulin. Exercise may also speed up the effect of an insulin dose, especially if the exercise involves the area of injection site (e.g. the leg should not be used for injection just prior to running). Discuss with your doctor how much insulin you should use if you are exercising.
  • if your diet changes.
    Changes in diet may cause your insulin needs to change.

Tell your doctor about these things before you use HUMALOG U200.

Taking other medicines

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

Some medicines may affect the way your HUMALOG U200 works. These include:

  • oral antidiabetic medicines
  • medicines that affect your metabolism (corticosteroids such as prednisone, cortisone)
  • medicines used for oral contraception
  • medicines used in thyroid replacement therapy
  • certain antibiotics used to treat tuberculosis, such as isoniazid
  • medicines such as aspirin or other salicylates
  • certain medicines used to treat depression
  • certain medicines used to treat asthma, such as salbutamol or terbutaline
  • medicines used to treat high blood pressure or other heart conditions
  • certain medicines used to treat people with growth disorders and tumours, such as octreotide
  • medicines used to treat hormone-related disorders, such as danazol
  • thiazolidinediones (TZDs), also used to treat type 2 diabetes; when used with insulin there may be an increased risk of fluid retention and heart disease.

Your doctor or pharmacist has more information on medicines to be careful with or avoid while using HUMALOG U200.

Tell your doctor about these medicines before you use HUMALOG U200.

How to use HUMALOG U200

DO NOT TRANSFER THIS MEDICINE TO A SYRINGE. SEVERE OVERDOSE CAN RESULT.

Follow all directions given to you by your doctor or pharmacist carefully. These may differ from the information contained in this leaflet.

More frequent blood glucose monitoring is recommended when changing insulin dose or type.

HUMALOG U200 should not be mixed with any other insulin.

How much to use

Your doctor will tell you how much insulin you need to use each day.

Do not change your insulin unless your doctor tells you to. Be very careful if you do change insulin. If you change the type of insulin that you use (for example from human insulin to HUMALOG U200), you may have to take more or less than before. This may happen with the first injection or it may be a gradual change over several weeks or months.

How to use it

Inject HUMALOG U200 under the skin. Under no circumstances should HUMALOG U200 be given intravenously.

Follow the steps below.

Preparing a dose

  1. Remove Pen Cap and check the cartridge in your KwikPen. The solution of HUMALOG U200 should be clear and colourless.
Check your KwikPen before each injection.
  1. Wash your hands.

The manufacturer's instructions for the KwikPen insulin delivery system should be followed for preparing and priming the KwikPen, attaching the needle and administering the insulin injection.

Check for insulin flow (Priming)

  1. Set the dose to 2 units.
  2. Hold the KwikPen with the needle pointing up and tap the side of the pen so that any bubbles float to the top.
  3. With the KwikPen still pointing up, press the Dose Knob in until it stops and 0 is seen in the Dose Window. Hold Dose Knob in and count slowly for 5 seconds. Priming is complete when a stream of insulin comes out of the needle. This is very important to ensure the correct dose is injected.
  4. Only after seeing a stream of insulin at the needle tip can you proceed to dial up your required dose. 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 a dose

  1. Wash your hands.
  2. Choose a site for injection. Use of injection sites should be rotated so that the same site is not used more than approximately once a month
  3. Remove outer needle cap.
  4. Stabilise the skin by spreading it or pinching up a large area. Insert the needle as instructed by your doctor.
  5. Press the Dose Knob and push firmly until the Dose Knob stops moving. Count to 5 slowly before removing the needle from the skin.
  6. Pull the needle out and apply gentle pressure over the injection site for several seconds. Do not rub the area.
  7. Using the outer needle cap, unscrew the needle and dispose of it safely. Do not reuse the needle. NEEDLES and PENS MUST NOT BE SHARED.

Further injections

  1. Check your KwikPen before each injection
  2. Before every injection, check for insulin flow. Do this by dialling 2 units and pressing the Dose Knob with the pen pointing up. Do this until a stream of insulin comes out of the needle.
  3. Stop using the KwikPen if the correct dose can no longer be dialled. The KwikPen will not allow you to dial a dose greater than the number of insulin units remaining in the cartridge in the KwikPen.
  4. You can see how much insulin is left by looking at the gauge on the side of the cartridge in the KwikPen. The scale on the cartridge shows how many units you have left. If there is not enough for your dose, you may either:
    a. Give the partial dose and then give the remaining dose using a new KwikPen.
    Or
    b. Give the full dose with a new KwikPen.

Do not mix any other insulin in your pen. Once the pen is empty, do not use it again.

When to use it

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 soon after a meal. When HUMALOG U200 is given after a meal, it must be within 20 minutes of the start of the meal.

How long do I use it

Do not stop using HUMALOG U200 just because you feel better.

It is important that you do not stop using HUMALOG U200 unless your doctor tells you to.

If you inject too much

Low blood sugar (hypoglycaemia) is the most likely reaction if you have injected more insulin than you need.

Symptoms of mild to moderate hypoglycaemia can include:

  • sweating
  • hunger, headache
  • tremor, unsteady movement
  • lightheadedness
  • drowsiness, dizziness
  • depressive mood, anxiety
  • irritability, personality change
  • abnormal behaviour
  • inability to concentrate
  • sleep disturbance
  • blurred vision
  • increased heart rate or irregular heart beat
  • tingling in the hands/feet/lips or tongue
  • slurred speech.

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

Symptoms of severe hypoglycaemia can include:

  • disorientation
  • seizures
  • unconsciousness.

If you experience symptoms of low blood sugar, eat some sugary food or drink, such as jelly beans, orange 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.

While you are using HUMALOG U200

Things you must do

Tell all doctors, dentists and pharmacists who are treating you that you are using HUMALOG U200. While you are using HUMALOG U200, tell your doctor or pharmacist before you start any new medicine.

If you become pregnant while using HUMALOG U200 tell your doctor.

Always carry a supply of HUMALOG U200 KwikPens with you.

Always carry something to show you have diabetes.

Always carry glucose or sugary foods with you.

Always check for insulin flow before injecting a dose.

Immediately after an injection, remove the needle from the pen. This will ensure sterility and prevent leakage, re-entry of air and potential needle clogs.

Things you must not do

DO NOT TRANSFER THIS MEDICINE TO A SYRINGE. SEVERE OVERDOSE CAN RESULT.

Do not stop using HUMALOG U200 without first checking with your doctor.

Do not give your HUMALOG U200 KwikPen to anyone else, even if they have the same condition as you. Your doctor has prescribed HUMALOG U200 specifically for you.

Do not share needles or pens.

Do not reuse needles.

Do not inject HUMALOG U200 directly into a vein (intravenously).

Do not use HUMALOG U200 in a subcutaneous infusion pump.

Things to be careful of

  • if you become ill
  • if you are exercising more than usual
  • if your diet changes.

You should learn to recognise your own symptoms of hypoglycaemia (low blood sugar). You can then take the appropriate action, when necessary. If you are having problems recognising these symptoms, frequent monitoring of your blood sugar level is recommended.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using HUMALOG U200.

Like other medicines, HUMALOG U200 may cause some unwanted side effects. These are likely to vary from patient to patient. Some side effects may be related to the dose of your insulin so it is important that you never exceed the stated dose.

Tell your doctor as soon as possible about any unwanted effects. Your doctor may then decide to adjust the dose of insulin you are using.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

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

Tell your doctor if you experience any of the following side effects:

  1. Hypoglycaemia - The most common unwanted effect when using insulin, including HUMALOG U200, is low blood sugar (hypoglycaemia).
If untreated, severe hypoglycaemia may lead to unconsciousness and, in extreme cases, death.
If you experience symptoms of low blood sugar (hypoglycaemia), eat some sugary food or drink, such as jelly beans, orange 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.
  1. Local Allergy - Some patients occasionally experience redness, swelling and itching at the injection site. Sometimes this local allergy may be due to factors other than your insulin, such as irritants in the skin cleansing agent or poor injection technique.
If you have local allergic reactions while using HUMALOG U200 contact your doctor.
  1. Generalised Allergy - Generalised allergy is less common, but can be more serious than local allergies. Symptoms of generalised allergy include: 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.
If you think you are having a generalised allergic reaction to HUMALOG U200, tell a doctor immediately or go to the Emergency Department at your nearest hospital.
  1. Lipodystrophy - A depression in the skin or an enlargement or thickening of the tissue can develop at the injection site.
Tell your doctor if you notice these symptoms.
A change in the way you inject and rotating the injection site may help relieve these symptoms.
  1. Oedema - Fluid retention, particularly in the ankles, feet and hands.

Tell your doctor if you notice anything unusual or if you are concerned about any aspect of your health, even if you think the problems are not connected with this medicine and are not referred to in this leaflet.

After using HUMALOG U200

Storage

Keep your pens in a fridge between 2°- 8°C. Do not freeze HUMALOG U200.

You may keep the pens below 30°C for up to 28 days while you are using them. Do not put your pens near heat or in the sun. Do not keep the pre-filled pen that you are using in the fridge.

Do not use a pen after the expiry date (month, year) stamped on the label.

All medicines should be kept where young children cannot reach them.

Disposal

If your doctor tells you to stop using HUMALOG U200 or you find your pens have passed their expiry date, please return any leftover pens to your pharmacist.

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 or pharmacist where you can dispose of the container once it is full.

Product Description

What it looks like

HUMALOG U200 is available in 3 mL prefilled pens in a grey carton with a checkerboard design.

HUMALOG U200 is a clear colourless solution.

Ingredients

HUMALOG U200 contains 200 units of insulin lispro per mL.

HUMALOG U200 also contains metacresol, glycerol, trometamol, zinc oxide and water for injection.

Supplier

Supplied in Australia by:

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

Australian Registration Number:

HUMALOG U200 -AUST R 226893

Further Information

You can get more information about diabetes and insulin from:

Diabetes Australia

  • freecall helpline 1300 136 588
  • www.diabetesaustralia.com.au.

Diabetes New Zealand

  • toll free helpline 0800 DIABETES (0800 342 238)
  • www.diabetes.org.nz.

®= Registered Trademark

This leaflet was prepared in September 2023.

vA2

Published by MIMS November 2023

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