Consumer medicine information

Humulin Cartridges

Insulin neutral human; Insulin isophane human

BRAND INFORMATION

Brand name

Humulin Preparations

Active ingredient

Insulin neutral human; Insulin isophane human

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Humulin Cartridges.

What is in this leaflet

This leaflet answers some common questions about HUMULIN.

It does not contain all the available information. It does not take the place of talking with your doctor or pharmacist.

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 HUMULIN and its use that you should be aware of.

All medicines have risks and benefits.

Your doctor has weighed the risks of you taking HUMULIN against the benefits they expect it will have for you.

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

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

What HUMULIN is used for

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

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 juvenile onset diabetes.

Type 2 diabetes - also called maturity onset diabetes.

Patients with type 1 diabetes always require insulin to control their blood sugar levels.

Some patients with type 2 diabetes may also require insulin after initial treatment with diet, exercise and tablets.

HUMULIN is identical to the insulin produced by the pancreas.

There are 3 different types of HUMULIN cartridges:

  • HUMULIN R
  • HUMULIN NPH
  • HUMULIN 30/70.

Your doctor will tell you the type of HUMULIN that is best suited to you.

The duration of action of the insulin you inject will vary according to the type being used, the dose, injection site, blood flow, temperature and level of physical activity.

Your doctor may tell you to use a short acting human insulin such as HUMULIN R in combination with a longer acting human insulin such as HUMULIN NPH.

The abbreviation "rbe" indicates the method of genetic engineering used to manufacture the insulin.

This medicine is not addictive.

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

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

Before you use HUMULIN

When you must not use it

Do not use HUMULIN if:

  1. you have an allergy to:
  • any medicine containing insulin
  • any of the ingredients listed at the end of this leaflet.
Some of the symptoms of an allergic reaction may include:
- redness, swelling, rash and itching at the injection site
- rash, itching or hives on the skin
- shortness of breath
- wheezing or difficulty breathing
- swelling of the face, lips, tongue or other parts of the body.
The only time you would take this medicine if you have an allergy to it, is if your doctor has you on a desensitisation program to minimise allergic reactions.
  1. you are experiencing low blood sugar levels (a "hypo").
If you have a lot of hypos discuss appropriate treatment with your doctor.

Do not use this medicine after the expiry date on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

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

Before you start to use it

Tell your doctor if you have any allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • kidney problems
  • liver problems
  • overactive thyroid glands (hyperthyroidism)
  • overactive adrenal glands (Cushing's Syndrome)
  • enlargement of the face, hands and feet (acromegaly)
  • a tumour of the adrenal gland (phaeochromocytoma)
  • fluid retention especially in the hands, ankles or feet
  • heart disease.

Tell your doctor if you are pregnant or plan 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. Your doctor can discuss with you the risks and benefits involved.

Tell your doctor if you are breast-feeding or plan to breast-feed. Your doctor/pharmacist can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell them before you start using HUMULIN.

Taking other medicines

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

Some medicines may affect the way HUMULIN works.

These include:

  • oral hypoglycaemic medicines that are used to treat type 2 diabetes
  • medicines that affect your metabolism (corticosteroids such as prednisone, cortisone)
  • medicines used for oral contraception
  • medicines used in thyroid replacement therapy
  • certain medicines 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
  • some antibiotics
  • certain 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
  • alcohol
  • 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.

Tell your doctor about any other medicines that you are taking. This is very important. Your doctor will advise you if it is all right to keep taking them or if you should stop taking them.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while using this medicine.

How to use HUMULIN

Your doctor, diabetes education nurse or pharmacist will have shown you how to use HUMULIN.

Carefully follow all the directions. They may differ from the information contained in this leaflet.

Do not inject HUMULIN into a vein or muscle.

Any change in dose or type of insulin should be made cautiously and only under medical supervision. If you change the type of insulin that you use, you may have to use more or less than before. This may happen with the first dose or over a period of time.

If you do not understand the instructions, ask your doctor or pharmacist for help.

How much to use

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

It is very important that you manage your diabetes carefully. Too much or too little insulin can cause serious effects.

When to use it

Your doctor will tell you when to use HUMULIN.

How to use it

Checking your HUMULIN cartridge

Check the HUMULIN cartridge before each preparation and injection. Make sure you are using the correct cartridge.

HUMULIN 3.0 mL cartridges are only for use with the HumaPen. The manufacturer's instructions for the HumaPen injection delivery systems should be followed for loading the cartridge, attaching the needle and administering the insulin injection.

Do not use HUMULIN NPH or HUMULIN 30/70 suspension if it is no longer a cloudy white suspension after shaking or has solid pieces in it.

Do not use HUMULIN if the cartridge appears frosted. This can occur when solid white particles stick to the bottom and walls, after mixing. If this occurs, please return to the place of purchase for exchange.

Do not use HUMULIN R if it is thickened, coloured or has solid pieces in it.

Always check your insulin injection device for insulin flow (priming) before use. The priming procedure may highlight a malfunction with your insulin injection device. Priming also removes any air bubbles and helps indicate whether or not a needle is broken.

Preparing a dose

  1. Wash your hands.
  2. If your cartridge is already inside your pen, check the amount of insulin remaining. Stop using the cartridge if the leading edge of the plunger has gone to, or beyond, the left side of the gauge on the side of the cartridge. You can see how much HUMULIN is left by looking at the gauge on the side of the cartridge. The distance between each mark on the gauge is about 20 units. If there is not enough for your dose, change the cartridge.
  3. If you are using a cloudy insulin, just before use, roll the cartridge/pen between the palms 10 times and invert 10 times until the suspension appears uniformly cloudy or milky. Do not shake. Inspect the cartridge for uniform mixing and repeat the above steps if necessary.
  4. Put the cartridge into the pen.
  5. Attach a needle.

Checking for insulin flow (Priming)

  1. Remove the needle cap.
  2. Set the dose to 1 or 2 units.
  3. Hold the pen with the needle pointing up and tap the side of the pen so that any bubbles float to the top.
  4. With the pen still pointing up, press the injection button. Do this until a drop or stream of HUMULIN comes out of the needle. This is very important to help make sure you inject the correct dose.
  5. Repeat steps 2-4 until you see a drop of insulin at the needle tip. If a drop of insulin still does not appear hold the pen with the needle facing upwards and away from your face. Attach a new needle. Repeat steps 2-4 again. If you are still unable to get insulin flowing out of the needle, do not use the pen. Return the pen to your doctor, diabetes education nurse or pharmacist to obtain a replacement pen.
  6. Only dial up your required dose after you see a drop of insulin at the needle tip. There may still be some small air bubbles left in the cartridge. These are harmless.
  7. If the air bubble is too big, you should prime the cartridge again.
  8. If you need to put the pen down, make sure the needle does not touch anything.

Injecting a dose

Choose a site for injection.

Inject HUMULIN in the upper arms, thighs, buttocks or abdomen.

Change the injection site so that the same position is not used more often than once a month. This will reduce the chance of local skin reactions developing.

Pinch the skin between two fingers, push the needle into the raised skin and inject the full dose of insulin under the skin.

Slowly count to 5 or 6 before pulling the needle out.

Apply gentle pressure over the injection site for several seconds.

Do not rub the area.

After injecting

Using the outer needle cap, unscrew the needle and dispose of it safely into a yellow plastic sharps container.

Do not share needles, cartridges or pens.

Leave the cartridge in the pen until it needs to be replaced.

How long to use it

Do not stop using your insulin unless your doctor tells you to.

If you take too much (overdose) - Hypoglycaemia

Your blood sugar level may become too low (you may experience hypoglycaemia or a "hypo") if you:

  • accidentally use too much HUMULIN
  • have too much or unexpected exercise
  • delay eating meals or snacks
  • eat too little food
  • are ill.

The first symptoms of mild to moderate hypos can come on suddenly. They may include:

  • cold sweat, cool pale skin
  • fatigue, drowsiness, unusual tiredness and weakness
  • nervousness, anxious feeling, tremor, rapid heart beat
  • confusion, difficulty concentrating
  • excessive hunger
  • vision changes
  • headache, nausea.

Always carry some sugary food or fruit juice with you.

If you experience any of these symptoms of a hypo, immediately eat some sugary food or have a drink, e.g. lollies, biscuits or fruit juice.

Tell your relatives, friends, close workmates or carers that you have diabetes. It is important that they recognise the signs and symptoms of a hypo.

Make sure they know to give you some sugary food or fruit juice for mild to moderate symptoms of a hypo.

If you lose consciousness, make sure they know:

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

This is because you could choke.

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, eat some sugary food or have a drink as soon as you are conscious again.

If you do not feel better after this, contact your doctor, diabetes education nurse, or go Accident and Emergency at the nearest hospital. If you do not respond to glucagon treatment, you will have to be treated in a hospital.

See your doctor if you keep having hypo reactions, or if you have ever become unconscious after using insulin. Your insulin dose may need to be changed.

If a severe hypo is not treated, it can cause brain damage and death.

If you miss a dose - Hyperglycaemia

If you forget your insulin dose, test your blood sugar level as soon as possible.

If you are not sure what to do, talk to your doctor, diabetes education nurse or pharmacist.

Do not use a double dose of your insulin.

If it is almost time for your next dose, skip the dose you missed and use your next dose when you are meant to.

Otherwise, use it as soon as you remember, and then go back to using it as you would normally.

Your blood sugar levels may become high (hyperglycaemia) if you:

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

High blood sugar levels over a long period of time can lead to too much acid in the blood (diabetic ketoacidosis).

Contact your doctor immediately if your blood sugar level is high or you recognise any of the following symptoms.

Symptoms of mild to moderate hyperglycaemia include:

  • drowsy feeling
  • flushed face
  • thirst, loss of appetite
  • fruity odour on the breath
  • blurred vision
  • passing larger amounts of urine than usual
  • getting up at night more often than usual to pass urine
  • high levels of glucose and acetone in the urine.

Symptoms of severe hyperglycaemia include:

  • heavy breathing
  • fast pulse
  • nausea, vomiting
  • dehydration
  • loss of consciousness.

Severe hyperglycaemia can lead to unconsciousness and in extreme cases death if untreated.

Discuss any worries you may have about this with your doctor or pharmacist.

While you are using HUMULIN

Things you must do

Measure your blood sugar levels regularly.

Make sure all friends, relatives, workmates or carers know that you have diabetes.

It is important to keep using your medicine even if you feel well. This medicine helps to control your condition, but does not cure it.

Tell your doctor if you often have hypos (low blood sugar levels). Your doctor may need to adjust your insulin dose.

Always carry some sugary food or fruit juice with you. If you experience any of the symptoms of a hypo, immediately eat some sugary food or have a drink, e.g. lollies, biscuits or fruit juice.

Tell your doctor if you have trouble recognising the symptoms of hypos. Under certain conditions, the early warning signs of hypos can be different or less obvious. Your doctor may need to adjust your insulin dose.

Make sure that you tell every doctor, dentist, pharmacist or other health care professional who is treating you that you have diabetes and are using insulin.

Tell your doctor, diabetes education nurse or pharmacist if you are travelling. Ask your doctor for a letter explaining why you are taking injecting devices with you. Each country you visit will need to see this letter, so you should take several copies.

You may need to inject your insulin and eat your meals at different times because of time differences in and between countries.

You may not be able to get the same type of insulin in the country you are visiting.

Your doctor, diabetes education nurse or pharmacist can provide you with some helpful information.

Tell your doctor if you are having trouble/difficulty with your eyesight. Visual disturbances in uncontrolled diabetes are reversed during the early stages of treatment.

Once established on insulin, if your vision changes, see your doctor as soon as possible.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are using HUMULIN.

If you become pregnant while using this medicine, tell your doctor immediately.

If you are about to have any blood tests, tell your doctor that you are using this medicine.

Keep all of your doctor's appointments so that your progress can be checked. Your doctor may do some tests from time to time to make sure the medicine is working and to prevent unwanted side effects.

Always carry a supply of HUMULIN cartridges and your pen with you.

Always carry something to show you have diabetes.

Things you must not do

Do not stop using your medicine unless your doctor tells you to.

Do not use this medicine if you think it has been frozen or exposed to excessive heat. It will not work as well.

Do not use empty cartridges again.

Do not use HUMULIN to treat any other complaints unless your doctor tells you to.

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

Do not adjust the dosage of your medicine without checking with your doctor.

Things to be careful of

Be careful driving or operating machinery until you know how the insulin affects you.

Tell your doctor if you drink alcohol. Alcohol may mask the symptoms of hypos.

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.

Tell your doctor if you are feeling particularly excited or upset. Emotional disturbances may change your insulin needs.

Tell your doctor if you are exercising more than usual. Exercise may lower your need for HUMULIN. Exercise may also speed up the effect of a dose of HUMULIN, especially if the exercise involves the area of injection site (e.g. the leg should not be used for injection prior to jogging or running).

Tell your doctor if your diet changes. Changes in diet may cause your insulin needs to change.

Side effects

Tell your doctor, diabetes education nurse or pharmacist as soon as possible if you do not feel well while you are using HUMULIN. This medicine helps most people with type 1 or type 2 diabetes, but it may have unwanted side effects in a few people.

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

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor, diabetes nurse educator or pharmacist to answer any questions you may have.

The most common side effect when using insulin is low blood sugar levels (a hypo).

Tell your doctor or pharmacist if you notice any of the following:

  • hypos (mild to moderate)
  • redness, swelling or itching at the injection site (local allergy) Usually these symptoms disappear within a few weeks during continued use.
  • a depression or thickening of the skin around the injection site (lipodystrophy)
  • fluid retention, particularly in the ankles, feet and hands (oedema).

This list includes the more common side effects of your medicine.

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

More severe symptoms of low blood sugar levels, including:

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

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

If a severe hypo is not treated, it can cause brain damage and death.

Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if you notice any of the following:

  • skin rashes over a large part of the body
  • shortness of breath, wheezing
  • swelling of the face, lips or tongue
  • fast pulse
  • sweating.

This list includes very serious side effects. You may need urgent medical attention or hospitalisation.

Tell your doctor if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After using HUMULIN

Storage

HUMULIN cartridges should be kept in the refrigerator between 2°C and 8°C. Do not freeze.

While in the pen or carried as a spare, cartridges can be kept at room temperature (below 30°C) for up to 21 days.

Do not put the cartridge in the refrigerator while it is inserted in the pen. The cartridge-pen combination should not be refrigerated.

Dispose of unrefrigerated cartridges after 21 days, even if the cartridge still contains HUMULIN.

Do not store HUMULIN or any other medicine in the bathroom or near a sink. Do not put it near heat or in the sun.

Keep it where children cannot reach it. A locked cupboard or compartment at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

Dispose of your needles safely into a yellow plastic sharps container.

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

Product Description

What it looks like

The HUMULIN product range is differentiated by colour and by symbols on the carton and cartridge labels.

HUMULIN R (regular neutral soluble human insulin (rbe)) is a clear colourless solution, with a water-like appearance and consistency. It is available in 3 mL cartridges. The carton and label have a golden yellow band with a white diamond symbol.

HUMULIN NPH (isophane human insulin (rbe)) is a milky or cloudy white suspension. It is available in 3 mL cartridges. The carton and label have a lime green band with a white square symbol.

HUMULIN 30/70 (mixture of 30% R regular neutral soluble human insulin (rbe) and 70% NPH isophane human insulin (rbe)) is a milky or cloudy white suspension. It is available in 3 mL cartridges. The carton and label have a tan band with a symbol consisting of a square with triangles on three sides.

Ingredients

HUMULIN R contains 100 units of insulin per mL as the active ingredient.

It also contains:

  • metacresol
  • glycerol
  • water for injections.

HUMULIN NPH and HUMULIN 30/70 contain 100 units of insulin per mL as the active ingredient.

They also contain:

  • metacresol
  • glycerol
  • zinc oxide
  • dibasic sodium phosphate heptahydrate
  • protamine sulfate
  • phenol
  • water for injections.

Supplier

HUMULIN is supplied in Australia by:

Eli Lilly Australia Pty. Limited
112 Wharf Road
WEST RYDE NSW 2114
AUSTRALIA

HUMULIN is supplied in New Zealand by:

Eli Lilly and Company (NZ) Limited
PO Box 109 197
Newmarket
Auckland 1149
NEW ZEALAND

Australian Registration Numbers

HUMULIN R cartridges AUST R 39666

HUMULIN NPH cartridges AUST R 39662

HUMULIN 30/70 cartridges AUST R 39659

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

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

This leaflet was revised in January 2020.

®= Registered Trademark

Published by MIMS June 2020

BRAND INFORMATION

Brand name

Humulin Preparations

Active ingredient

Insulin neutral human; Insulin isophane human

Schedule

S4

 

1 Name of Medicine

Insulin.

6.7 Physicochemical Properties

Chemical structure.

The active ingredient in Humulin solutions and suspensions is human insulin (recombinant DNA origin). Human insulin is a polypeptide hormone consisting of a 21 amino acid A-chain and a 30 amino acid B-chain linked by two disulphide bonds. Its empirical formula is C257H383N65O77S6, which corresponds to a molecular weight of 5808.

CAS number.

The CAS number for human insulin is 11061-68-0.

2 Qualitative and Quantitative Composition

There are three different presentations in the Humulin range:

Humulin R (regular-neutral-soluble).

Neutral human insulin of recombinant DNA origin.

Humulin NPH (isophane).

Isophane human insulin of recombinant DNA origin.

Humulin 30/70.

A mixture consisting of 30% regular (neutral human insulin of recombinant DNA origin) and 70% NPH (isophane human insulin of recombinant DNA origin).
For the full list of excipients, see Section 6.1 List of Excipients.
Humulin is found to be chemically, physically, biologically and immunologically equivalent to pancreatic human insulin which differs slightly from porcine or bovine insulin in amino acid composition.

3 Pharmaceutical Form

Humulin R.

A sterile, clear colourless, aqueous solution of neutral human insulin (rbe) adjusted to pH 6.6 to 8.0.

Humulin NPH.

A sterile suspension of white, crystalline precipitate of isophane human insulin (rbe) in an isotonic phosphate buffer adjusted to pH 6.9 to 7.5.

Humulin 30/70.

A sterile mixture of 30% regular and 70% NPH human insulin (rbe) adjusted to pH 6.9 to 7.5.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The administration of suitable doses of insulin to patients with diabetes mellitus, along with controlled diet and exercise, temporarily restores their ability to metabolise carbohydrates, fats and proteins, to store glycogen in the liver and to convert glucose to fat. When given in suitable doses at regular intervals to a patient with diabetes mellitus, the blood glucose is maintained within a reasonable range, the urine remains relatively free of glucose and ketone bodies, and diabetic acidosis and coma are prevented.
Studies indicate that immunogenicity problems with biosynthetic human insulin produced by recombinant DNA technology are no more likely to occur than with insulin that is derived from animal origin. Biosynthetic human insulin is devoid of all protein contaminants of pancreatic origin normally present even in trace amounts in all insulins of pancreatic origin.
The rigid purification procedures used in the manufacture of biosynthetic human insulin remove E. coli proteins detectable by presently available methods. Even if E. coli proteins are present in trace amounts, clinical studies indicate the absence of any detectable E. coli protein antibodies ascribable to the use of biosynthetic human insulin. Biosynthetic human insulin did not elicit an antigenic response when administered to E. coli polypeptide sensitised rats and guinea pigs.
Although human insulins appear to produce less antigenicity than beef/pork insulins, they are not free of antigenicity.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Humulin R is a short acting preparation. Onset of action occurs at approximately 30 minutes, with a duration of activity of 6 to 8 hours and peak activity at 2 to 4 hours.
Humulin NPH is an intermediate acting preparation. Onset of action occurs at approximately 1 hour, with a duration of activity of 16 to 18 hours and peak activity at 4 to 10 hours.
Humulin 30/70 is an intermediate acting insulin with a more rapid onset of action than NPH alone. Humulin 30/70 has a duration of activity of 16 to 18 hours and a peak activity at 2 to 12 hours.

5.3 Preclinical Safety Data

Genotoxicity.

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

Carcinogenicity.

Carcinogenicity or fertility studies with Humulin have not been conducted.

4 Clinical Particulars

4.1 Therapeutic Indications

Humulin is indicated for the treatment of insulin dependent diabetic patients.

4.3 Contraindications

Humulin R, Humulin NPH and Humulin 30/70 are contraindicated in hypoglycaemia.
Human insulin is contraindicated in patients with hypersensitivity to human insulin or any of its excipients (unless used as part of a desensitisation program).

Vials.

Humulin NPH and 30/70 vials should not be administered by the intravenous route.

Cartridges.

Humulin R, NPH and 30/70 cartridges should not be administered by the intramuscular or intravenous route.

4.4 Special Warnings and Precautions for Use

Any change of insulin or human insulin analogue should be made cautiously and only under medical supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, etc.), species (animal, human, human insulin analogue) and/or method of manufacture (recombinant DNA versus animal source insulin) may result in the need for a change in dosage.
Prompt recognition and appropriate management of the complications of insulin therapy are essential for the safe and effective control of diabetes mellitus.
The number and size of daily doses and the time of administration, as well as diet and exercise, are problems that require direct and continuous medical supervision.
Under special circumstances (such as increased physical effort, insufficient food, etc.) the daily dose of insulin administered to the patient may represent an overdose. Patients should always carry some glucose with them. For symptoms, see Section 4.9 Overdose.
Insulin requirements may be increased during illness or emotional disturbances. In the event of infectious diseases such as colds, boils, etc., the insulin requirements increase, in which case the patient must consult his physician in time to prevent the development of dangerous complications.
Patients whose glycaemic control is greatly improved, e.g. by flexible insulin therapy, may lose some or all of the warning symptoms of hypoglycaemia and should be advised accordingly. Other conditions which may make the early warning symptoms of hypoglycaemia different or less pronounced include a long duration of diabetes, diabetic nerve disease or medications such as beta-blockers. Uncorrected hypoglycaemic or hyperglycaemic reactions can cause loss of consciousness, coma or death.
The presence of such diseases as acromegaly, Cushing's syndrome, hyperthyroidism and phaeochromocytoma complicate the control of diabetes.
Thiazolidinediones (TZDs) in combination with insulin are associated with an increased risk of oedema and heart failure; especially in patients with underlying cardiac disease.
Visual disturbances in uncontrolled diabetes due to refractive changes are reversed during the early phase of effective management. However, since alteration in osmotic equilibrium between the lens and ocular fluids may not stabilise for a few weeks after initiating therapy, it is wise to postpone prescribing new corrective lenses for 3 to 6 weeks.
Patients who are travelling overseas (or to destinations with substantially different time zones) should contact their doctor/ pharmacist/ diabetes educator for information.
Patients who receive insulin which contains protamine have an increased risk of severe reactions simulating anaphylaxis when protamine is used to reverse systemic heparinisation after cardiac catheterisation.

Use in hepatic impairment.

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

Use in renal impairment.

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

Use in the elderly.

No data available.

Paediatric use.

No data available.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The physician should be consulted when using other medication in addition to human insulin (see Section 4.4 Special Warnings and Precautions for Use).
Insulin requirements can increase, decrease or remain unchanged in patients receiving diuretics. Insulin requirements may be increased if the patient is receiving concurrent administration of drugs with hyperglycaemic activity, e.g. oral contraceptives, corticosteroids, thyroid replacement therapy, growth hormone, glucagon, adrenaline, isoniazid, phenothiazines or beta-2 stimulants (such as salbutamol, terbutaline). The hypoglycaemic action of insulin may also be antagonised by phenytoin.
Insulin requirements may be reduced if the patient is receiving concurrent administration of drugs with hypoglycaemic activity, e.g. anabolic steroids, MAO inhibitors, guanethidine, propranolol (masking effect), oral hypoglycaemics, salicylates (for example, aspirin), sulphonamides, antidepressants, angiotensin converting enzyme inhibitors (captopril and enalapril), angiotensin II receptor blockers, other beta-blockers, octreotide and alcohol.

Transferring from other insulins.

A small number of patients transferring from insulins of animal source to insulins of recombinant DNA origin may require a reduced dosage, especially if they are tightly controlled and bordering on hypoglycaemia. The dosage reduction may occur with the first dose or over a period of several weeks. There is a risk of hypoglycaemia if the insulin requirement is decreased, and both the physician and the patient should be aware of this possibility. The risk can be considered to be minimal if the daily dose is less than 40 units. Insulin resistant patients receiving more than 100 units daily should be hospitalised for transferring from other insulins.
Pharmacological studies suggest that these human insulins may have a quicker onset of action and a shorter duration of effect than their beef or pork counterparts in patients already stabilised on a mixture of neutral and isophane insulin. Some adjustment of the proportions may be needed after transfer to human insulin.
A few patients who experienced hypoglycaemic reactions after being transferred to Humulin have reported that these early warning symptoms were less pronounced than they were with animal source insulin.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Carcinogenicity or fertility studies with Humulin have not been conducted.
It is essential to maintain good control of the insulin dependent diabetic patient throughout pregnancy. Insulin requirements usually decrease 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.
Patients with diabetes who are lactating may require adjustments in insulin dose, diet or both.

4.8 Adverse Effects (Undesirable Effects)

The use of preparations of Humulin should minimise the incidence of side effects which have been associated with insulins of animal source. However, there have been rare reports of patients with hypersensitivity reactions to human insulins who have tolerated insulins of animal origin.
The following reactions have been reported.

Hypoglycaemia.

Hypoglycaemia is the most frequent undesirable effect of insulin therapy. Severe hypoglycaemia may lead to loss of consciousness and, in extreme cases, death.

Local allergy.

Including pruritus, rash, erythema, induration. 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.

Including anaphylactoid reaction, urticaria. 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.

Insulin resistance.


Spontaneous data.

Cases of oedema have been reported with insulin therapy, particularly if previous poor metabolic control is improved by intensified insulin therapy (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.

4.2 Dose and Method of Administration

The dosage should be determined by the physician, according to the requirements of the patient. Subcutaneous administration, preferably by the patient, should be in the upper arms, thighs, buttocks or abdomen. Use of injection sites should be rotated so that the same site is not used more frequently than once a month.
Care should be taken to ensure that a blood vessel has not been inadvertently entered. The injection site should not be massaged.

Vials.

Humulin R is a short acting insulin which may be administered by subcutaneous, intramuscular or intravenous injection. Humulin NPH and Humulin 30/70 should only be administered by subcutaneous or intramuscular injection.
Humulin R may be administered in combination with Humulin NPH, depending on individual metabolic requirements of the patients as determined by the physician. A mixture of Humulin R and NPH is usually administered as a twice daily regimen.
Humulin NPH may be given as a single daily dose before breakfast, usually the most satisfactory injection time.
The effects of mixing these products with insulins of animal source have not been studied, and this practice is not recommended.
Humulin NPH and Humulin 30/70 - the vial should be rotated in the palms of the hands before use in order to resuspend.

Mixing of insulins.

The shorter acting (Humulin R) insulin should be drawn into the syringe first to prevent contamination of the vial by the longer acting (Humulin NPH) preparation. It is advisable to inject immediately after mixing.

Cartridges.

Humulin R, NPH and 30/70 are supplied as 3.0 mL cartridges (100 units/mL) for use in HumaPen. Humulin 3.0 mL cartridges are not designed to allow any other insulin to be mixed in the cartridge.
Humulin NPH and 30/70 cartridges should be rotated in the palms of hands before use in order to resuspend.
Humulin R, NPH and 30/70 cartridges should be used only for subcutaneous administration.

Instructions for use/ handling.

To prevent the possible transmission of disease, each cartridge must be used by one patient only, even if the needle on the delivery device is changed.

4.7 Effects on Ability to Drive and Use Machines

The patient's ability to concentrate and to react may be impaired as a result of 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.

4.9 Overdose

Symptoms.

Hypoglycaemia can occur if the patient takes too much insulin, misses meals, exercises or works too hard just before a meal, or has an infection or becomes ill (especially with diarrhoea or vomiting) or if the body need for insulin changes for other reasons.
Symptoms include listlessness, confusion, palpitations, sweating, vomiting, hunger, faintness and dizziness. Patients also may experience headache, drowsiness, fatigue, anxiety, blurred vision, diplopia or numbness of the lips, nose or fingers.
Symptoms are likely to appear when the blood sugar concentration falls below 2.22 mmol/L but may occur with a sudden drop in blood glucose even when the value remains above 2.22 mmol/L.
The clinical manifestations of hypoglycaemia can be masked by the concomitant administration of propranolol or other beta-adrenergic blockers.

Treatment.

Mild hypoglycaemic episodes will respond to oral administration of glucose or sugar and rest.
Correction of moderately severe hypoglycaemia can be accomplished by the intramuscular or subcutaneous administration of glucagon, 1 unit every 20 minutes for 2 or 3 doses 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, intravenous administration of 10 to 20 g of dextrose in sterile solution is required.
For information on the management of overdose, contact the Poison Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Humulin R (regular-neutral-soluble).

Neutral human insulin of recombinant DNA origin. This product consists of zinc insulin crystals dissolved in a clear fluid.
It also contains glycerol, metacresol and water for injection.

Humulin NPH (isophane).

Isophane human insulin of recombinant DNA origin. Humulin NPH is a crystalline suspension of human insulin with protamine and zinc.
It also contains glycerol, dibasic sodium phosphate heptahydrate, metacresol, phenol and water for injection.

Humulin 30/70.

A mixture consisting of 30% regular (neutral human insulin of recombinant DNA origin) and 70% NPH (isophane human insulin of recombinant DNA origin).
It also contains metacresol, glycerol, phenol, protamine sulphate, dibasic sodium phosphate heptahydrate, zinc oxide and water for injection.

6.2 Incompatibilities

Humulin 3.0 mL cartridges are not designed to allow any other insulin to be mixed in the cartridge.

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.
For information on the in-use shelf life, see Section 6.4 Special Precautions for Storage.

6.4 Special Precautions for Storage

Vials.

Preparations of Humulin (unopened or new vials) should be stored in a refrigerator between 2 and 8°C. They should not be frozen or exposed to excessive heat or sunlight. Under these conditions, potency should be maintained for 24 months from the date of manufacture for Humulin R, Humulin NPH and Humulin 30/70.
Vials of Humulin preparations while in use may be kept at room temperature for up to 28 days without loss of potency. Insulin opened and stored at room temperature which has not been used for a month or more should be discarded. Insulin which is used only occasionally is best kept refrigerated.

Cartridges.

Cartridges of Humulin preparations should be stored in a refrigerator between 2°C and 8°C. Humulin cartridges have a 2 year shelf-life when stored between 2°C and 8°C. Do not allow the insulin to freeze.
When inserted in HumaPen or when carried as a spare, Humulin R, NPH and 30/70 cartridges need not be refrigerated but should be kept cool (below 30°C) and away from excessive heat and direct sunlight. Unrefrigerated Humulin R, NPH and 30/70 cartridges should be discarded after 21 days even if the cartridges still contain insulin.

6.5 Nature and Contents of Container

Humulin is supplied in vials, cartridges and a disposable Humulin Pen device containing 3.0 mL Humulin cartridges. For information on Humulin Pens, please refer to the separate Humulin Pen product information document.
Humulin R is supplied in 100 units/mL in 10 mL size rubber-stoppered vials (No. HI-210) and 100 units/mL in 3.0 mL size cartridges (No. HI-219) in packs of 5. The 3.0 mL size cartridges are to be used in the HumaPen.
Humulin NPH is supplied in 100 units/mL in 10 mL size rubber-stoppered vials (No. HI-310) and in 3.0 mL size cartridges (No. HI-319) in packs of 5. The 3.0 mL size cartridges are to be used in the HumaPen.
Humulin 30/70 is supplied in 100 units/mL in 10 mL size rubber-stoppered vials (No. HI-710) and in 3.0 mL size cartridges (HI-719) in packs of 5. The 3.0 mL size cartridges are to be used in the HumaPen.

6.6 Special Precautions for Disposal

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

Summary Table of Changes