Pharmacy Guide
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
Pharmacy Guide
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
NovoRapid FlexPen
⚠ This medicine appears to have been discontinued
The electronic medicines compendium (emc) no longer publishes a Summary of Product Characteristics for this product, which usually means it is no longer marketed in the UK. The patient leaflet below is kept for reference, but the product may not be available.
If you were prescribed this medicine, other products containing Insulin aspart may still be available. Do not stop your treatment — ask your pharmacist or GP what to use instead.
What it is and what it is used for
for
NovoRapid® is a modern insulin (insulin analogue) with a rapid-acting effect. Modern insulin products are improved versions of human insulin. NovoRapid® is used to reduce the high blood sugar level in adults, adolescents and children aged 1 year and above with diabetes mellitus (diabetes). Diabetes is a disease where your body does not produce enough insulin to control the level of your blood sugar. Treatment with NovoRapid® helps to prevent complications from your diabetes. NovoRapid® will start to lower your blood sugar 10-20 minutes after you inject it, a maximum effect occurs between 1 and 3 hours after the injection and the effect lasts for 3-5 hours. Due to this short action NovoRapid® should normally be taken in combination with intermediate-acting or long-acting insulin preparations. 2.
What you need to know before you take it
e NovoRapid®
Do not use NovoRapid® ► ► ► ► ►
If you are allergic to insulin aspart, or any of the other ingredients in this medicine (see section 6, Contents of the pack and other information). If you suspect hypoglycaemia (low blood sugar) is starting (see a) Summary of serious and very common side effects in section 4). If FlexPen® is dropped, damaged or crushed. If it has not been stored correctly or been frozen (see section 5, How to store NovoRapid®). If the insulin does not appear clear and colourless.
If any of these applies, do not use NovoRapid®. Talk with your doctor, nurse or pharmacist for advice. Before using NovoRapid® ►
Check the label to make sure it is the right type of insulin.
► ► ►
Always use a new needle for each injection to prevent contamination. Needles and NovoRapid® FlexPen® must not be shared. NovoRapid® FlexPen® is only suitable for injecting under the skin. Speak to your doctor if you need to inject your insulin by another method.
Warnings and precautions Some conditions and activities can affect your need for insulin. Consult your doctor: ► If you have trouble with your kidneys or liver, or with your adrenal, pituitary or thyroid glands. ► If you exercise more than usual or if you want to change your usual diet, as this may affect your blood sugar level. ► If you are ill, carry on taking your insulin and consult your doctor. ► If you are going abroad, travelling over time zones may affect your insulin needs and the timing of your injections. Skin changes at the injection site The injection site should be rotated to help prevent changes to the fatty tissue under the skin, such as skin thickening, skin shrinking or lumps under the skin. The insulin may not work very well if you inject into a lumpy, shrunken or thickened area (see section 3, How to use NovoRapid®). Tell your doctor if you notice any skin changes at the injection site. 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 check your blood sugar more closely, and to adjust your insulin or your other antidiabetic medications dose. Children and adolescents Do not give this medicine to children below 1 year of age since no clinical studies have been carried out in children below the age of 1 year. Other medicines and NovoRapid® Tell your doctor, nurse or pharmacist if you are taking, have recently taken or might take any other medicines. Some medicines affect your blood sugar level and this may mean that your insulin dose has to change. Listed below are the most common medicines which may affect your insulin treatment. Your blood sugar level may fall (hypoglycaemia) if you take: • Other medicines for the treatment of diabetes • Monoamine oxidase inhibitors (MAOI) (used to treat depression) • Beta-blockers (used to treat high blood pressure) • Angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure) • Salicylates (used to relieve pain and lower fever) • Anabolic steroids (such as testosterone) • Sulphonamides (used to treat infections). Your blood sugar level may rise (hyperglycaemia) if you take: • Oral contraceptives (birth control pills) • Thiazides (used to treat high blood pressure or excessive fluid retention) • Glucocorticoids (such as 'cortisone' used to treat inflammation) • Thyroid hormones (used to treat thyroid gland disorders) • Sympathomimetics (such as epinephrine [adrenaline], or salbutamol, terbutaline used to treat asthma) • Growth hormone (medicine for stimulation of skeletal and somatic growth and pronounced influence on the body's metabolic processes) • Danazol (medicine acting on ovulation).
Octreotide and lanreotide (used for treatment of acromegaly, a rare hormonal disorder that usually occurs in middle-aged adults, caused by the pituitary gland producing excess growth hormone) may either increase or decrease your blood sugar level. Beta-blockers (used to treat high blood pressure) may weaken or suppress entirely the first warning symptoms which help you to recognise low blood sugar. Pioglitazone (tablets used for the treatment of type 2 diabetes) Some patients with long-standing type 2 diabetes and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema). If you have taken any of the medicines listed here, tell your doctor, nurse or pharmacist. Drinking alcohol and taking NovoRapid® ►
If you drink alcohol, your need for insulin may change as your blood sugar level may either rise or fall. Careful monitoring is recommended.
Pregnancy and breast-feeding ►
►
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. NovoRapid® can be used during pregnancy. Your insulin dose may need to be changed during pregnancy and after delivery. Careful control of your diabetes, particularly prevention of hypoglycaemia, is important for the health of your baby. There are no restrictions on treatment with NovoRapid® during breast-feeding.
Ask your doctor, nurse or pharmacist for advice before taking this medicine while pregnant or breastfeeding. Driving and using machines ► • •
Please ask your doctor whether you can drive a car or operate a machine: If you have frequent hypoglycaemia. If you find it hard to recognise hypoglycaemia.
If your blood sugar is low or high, your concentration and ability to react might be affected and therefore also your ability to drive or operate a machine. Bear in mind that you could endanger yourself or others. NovoRapid® has a rapid onset of effect therefore if hypoglycaemia occurs, you may experience it earlier after an injection when compared to soluble human insulin. Important information about some of the ingredients of NovoRapid® NovoRapid® contains less than 1 mmol sodium (23 mg) per dose, i.e. NovoRapid® is essentially 'sodiumfree'. 3.
How to take it
NovoRapid®
Dose and when to take your insulin Always use your insulin and adjust your dose exactly as your doctor has told you. Check with your doctor, nurse or pharmacist if you are not sure. NovoRapid® is generally taken immediately before a meal. Eat a meal or snack within 10 minutes of the injection to avoid low blood sugar. When necessary, NovoRapid® can be given soon after a meal. See How and where to inject below for information.
Do not change your insulin unless your doctor tells you to. If your doctor has switched you from one type or brand of insulin to another, your dose may have to be adjusted by your doctor. Use in children and adolescents NovoRapid® can be used in adolescents and children aged 1 year and above instead of soluble human insulin when a rapid onset of effect is preferred. For example, when it is difficult to dose the child in relation to meals. Use in special patient groups If you have reduced kidney or liver function, or if you are above 65 years of age, you need to check your blood sugar more regularly and discuss changes in your insulin dose with your doctor. How and where to inject NovoRapid® is for injection under the skin (subcutaneously). You must never inject yourself directly into a vein (intravenously) or muscle (intramuscularly). NovoRapid® FlexPen® is only suitable for injecting under the skin. Speak to your doctor if you need to inject your insulin by another method. With each injection, change the injection site within the particular area of skin that you use. This may reduce the risk of developing lumps or skin pitting (see section 4, Possible side effects). The best places to give yourself an injection are: the front of your waist (abdomen), the upper arm or the front of your thighs. The insulin will work more quickly if injected into the front of your waist. You should always measure your blood sugar regularly. How to handle NovoRapid® FlexPen® NovoRapid® FlexPen® is a pre-filled, colour-coded, disposable pen containing insulin aspart. Read carefully the instructions on how to use NovoRapid® FlexPen® included in this package leaflet. You must use the pen as described in the instructions on how to use NovoRapid® FlexPen®. Always ensure you use the correct pen before you inject your insulin. If you take more insulin than you should If you take too much insulin your blood sugar gets too low (hypoglycaemia). See a) Summary of serious and very common side effects in section 4. If you forget to take your insulin If you forget to take your insulin your blood sugar may get too high (hyperglycaemia). See c) Effects from diabetes in section 4. If you stop taking your insulin Do not stop taking your insulin without speaking with a doctor, who will tell you what needs to be done. This could lead to very high blood sugar (severe hyperglycaemia) and ketoacidosis. See c) Effects from diabetes in section 4. If you have any further questions on the use of this medicine, ask your doctor, nurse or pharmacist. 4.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
a)
Summary of serious and very common side effects
Low blood sugar (hypoglycaemia) is a very common side effect. It may affect more than 1 in 10 people. Low blood sugar may occur if you: • Inject too much insulin. • Eat too little or miss a meal. • Exercise more than usual. • Drink alcohol (see Drinking alcohol and taking NovoRapid® in section 2). Signs of low blood sugar: Cold sweat; cool pale skin; headache; rapid heartbeat; feeling sick; feeling very hungry; temporary changes in vision; drowsiness; unusual tiredness and weakness; nervousness or tremor; feeling anxious; feeling confused; difficulty in concentrating. Severe low blood sugar can lead to unconsciousness. If prolonged severe low blood sugar is not treated, it can cause brain damage (temporary or permanent) and even death. You may recover more quickly from unconsciousness with an injection of the hormone glucagon by someone who knows how to use it. If you are given glucagon, you will need glucose or a sugar snack as soon as you are conscious. If you do not respond to glucagon treatment, you will have to be treated in a hospital. What to do if you experience low blood sugar: ► If you experience low blood sugar, eat glucose tablets or another high sugar snack (e.g. sweets, biscuits, fruit juice). Measure your blood sugar if possible and rest. Always carry glucose tablets or high sugar snacks with you, just in case. ► When symptoms of low blood sugar have disappeared or when blood sugar level is stabilised, continue insulin treatment as usual. ► If you have such a low blood sugar that it makes you pass out, if you have had need for injection of glucagon, or if you have experienced many incidents of low blood sugar, talk with a doctor. The amount or timing of insulin, food or exercise may need to be adjusted. Tell relevant people that you have diabetes and what the consequences may be, including the risk of passing out (become unconscious) due to low blood sugar. Let them know that if you pass out, they must turn you on your side and get medical help straight away. They must not give you any food or drink due to risk of suffocation. Serious allergic reactions to NovoRapid® or one of its ingredients (called a systemic allergic reaction) is a very rare side effect but can potentially be life threatening. It may affect less than 1 in 10,000 people. Seek medical advice immediately: • If signs of allergy spread to other parts of your body. • If you suddenly feel unwell, and you: start sweating; start being sick (vomiting); have difficulty in breathing; have a rapid heartbeat; feel dizzy. ► If you notice any of these signs, seek medical advice immediately. Skin changes at the injection site: If you inject insulin at the same place, the fatty tissue may shrink (lipoatrophy) or thicken (lipohypertrophy) (may affect less than 1 in 100 people). Lumps under the skin may also be caused by build-up of a protein called amyloid (cutaneous amyloidosis; how often this occurs is not known). The insulin may not work very well if you inject into a lumpy, shrunken or thickened area. Change the injection site with each injection to help prevent these skin changes. b)
List of other side effects
Uncommon side effects May affect less than 1 in 100 people.
Signs of allergy: Local allergic reactions (pain, redness, hives, inflammation, bruising, swelling and itching) at the injection site may occur. These usually disappear after a few weeks of taking your insulin. If they do not disappear, or if they spread throughout your body, talk to your doctor immediately. See also Serious allergic reactions above. Vision problems: When you first start your insulin treatment, it may disturb your vision, but the disturbance is usually temporary. Swollen joints: When you start taking insulin, water retention may cause swelling around your ankles and other joints. Normally this soon disappears. If not, talk to your doctor. Diabetic retinopathy (an eye disease related to diabetes which can lead to loss of vision): If you have diabetic retinopathy and your blood sugar level improves very fast, the retinopathy may get worse. Ask your doctor about this. Rare side effects May affect less than 1 in 1,000 people. Painful neuropathy (pain due to nerve damage): If your blood sugar level improves very fast, you may get nerve related pain. This is called acute painful neuropathy and is usually transient. Reporting of side effects If you get any side effects, talk with your doctor, nurse or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Great Britain Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine. c)
Effects from diabetes
High blood sugar (hyperglycaemia) High blood sugar may occur if you: • Have not injected enough insulin. • Forget to inject your insulin or stop taking insulin. • Repeatedly inject less insulin than you need. • Get an infection and/or a fever. • Eat more than usual. • Exercise less than usual. Warning signs of high blood sugar: The warning signs appear gradually. They include: increased urination; feeling thirsty; losing your appetite; feeling sick (nausea or vomiting); feeling drowsy or tired; flushed; dry skin; dry mouth and a fruity (acetone) smell of the breath. What to do if you experience high blood sugar: ► If you get any of the above signs: test your blood sugar level, test your urine for ketones if you can, then seek medical advice immediately. ► These may be signs of a very serious condition called diabetic ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). If you do not treat it, this could lead to diabetic coma and eventually death.
5.
How to store it
NovoRapid®
Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the FlexPen® label and carton, after 'EXP'. The expiry date refers to the last day of that month. Always keep the pen cap on your FlexPen® when you are not using it in order to protect it from light. NovoRapid® must be protected from excessive heat and light. Before opening: NovoRapid® FlexPen® that is not being used is to be stored in the refrigerator at 2°C to 8°C, away from the cooling element. Do not freeze. During use or when carried as a spare: You can carry your NovoRapid® FlexPen® with you and keep it at a temperature below 30°C or in a refrigerator (2 ̊C to 8 ̊C) for up to 4 weeks. If refrigerated, keep away from the cooling element. Do not freeze. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment. 6.
Contents of the pack and other information
What NovoRapid® contains • •
The active substance is insulin aspart. Each ml contains 100 units of insulin aspart. Each pre-filled pen contains 300 units of insulin aspart in 3 ml solution for injection. The other ingredients are glycerol, phenol, metacresol, zinc chloride, disodium phosphate dihydrate, sodium chloride, hydrochloric acid, sodium hydroxide and water for injections.
What NovoRapid® looks like and contents of the pack NovoRapid® is presented as a solution for injection. Pack sizes of 1 (with or without needles), 5 (without needles) and 10 (without needles) pre-filled pens of 3 ml. Not all pack sizes may be marketed. The solution is clear and colourless. Marketing Authorisation Holder and Manufacturer Marketing Authorisation Holder Novo Nordisk A/S, Novo Allé, DK-2880 Bagsværd, Denmark Manufacturer The manufacturer can be identified by the batch number printed on the slip of the carton and on the label: •
If the second and third characters are S6, P5, K7, R7, VG, FG or ZF, the manufacturer is Novo Nordisk A/S, Novo Allé, DK-2880 Bagsværd, Denmark.
•
If the second and third characters are H7 or T6, the manufacturer is Novo Nordisk Production SAS, 45 Avenue d'Orléans F-28000 Chartres, France.
Now turn over for information on how to use your FlexPen®. This leaflet was last revised in 10/2022
NovoRapid®, FlexPen®, NovoFine® and NovoTwist® are trademarks owned by Novo Nordisk A/S, Denmark © 2022 Novo Nordisk A/S
Instructions on how to use NovoRapid® solution for injection in FlexPen®. Read the following instructions carefully before using your FlexPen®. If you do not follow the instructions carefully, you may get too little or too much insulin, which can lead to too high or too low blood sugar level. Your FlexPen® is a pre-filled dial-a-dose insulin pen. You can select doses from 1 to 60 units in increments of 1 unit. FlexPen® is designed to be used with NovoFine® or NovoTwist® disposable needles up to a length of 8 mm. As a precautionary measure, always carry a spare insulin delivery device in case your FlexPen® is lost or damaged. NovoRapid® FlexPen® Pen cap
Cartridge
Residual scale
Pointer
Dose selector Pushbutton
Needle (example) Big outer needle cap
Inner needle cap
Needle
Paper tab
Caring for your pen Your FlexPen® must be handled with care. If it is dropped, damaged or crushed, there is a risk of insulin leakage. This may cause inaccurate dosing, which can lead to too high or too low blood sugar level. You can clean the exterior of your FlexPen® by wiping it with a medicinal swab. Do not soak it, wash or lubricate it as it may damage the pen. Do not refill your FlexPen®. Once empty, it must be disposed of. Preparing your NovoRapid® FlexPen® Check the name and coloured label of your pen to make sure that it contains the correct type of insulin. This is especially important if you take more than one type of insulin. If you take the wrong type of insulin, your blood sugar level may get too high or too low. A Pull off the pen cap.
B Remove the paper tab from a new disposable needle. Screw the needle straight and tightly onto your FlexPen®.
C Pull off the big outer needle cap and keep it for later.
D Pull off the inner needle cap and dispose of it. Never try to put the inner needle cap back on the needle. You may stick yourself with the needle.
Always use a new needle for each injection. This reduces the risk of contamination, infection, leakage of insulin, blocked needles and inaccurate dosing. Be careful not to bend or damage the needle before use. Checking the insulin flow Prior to each injection small amounts of air may collect in the cartridge during normal use. To avoid injection of air and ensure proper dosing: E Turn the dose selector to select 2 units. E
2 units selected
F Hold your FlexPen® with the needle pointing upwards and tap the cartridge gently with your finger a few times to make any air bubbles collect at the top of the cartridge. F
G Keeping the needle upwards, press the push-button all the way in. The dose selector returns to 0. A drop of insulin should appear at the needle tip. If not, change the needle and repeat the procedure no more than 6 times. If a drop of insulin still does not appear, the pen is defective, and you must use a new one.
G
Always make sure that a drop appears at the needle tip before you inject. This makes sure that the insulin flows. If no drop appears, you will not inject any insulin, even though the dose selector may move. This may indicate a blocked or damaged needle. Always check the flow before you inject. If you do not check the flow, you may get too little insulin or no insulin at all. This may lead to too high blood sugar level. Selecting your dose Check that the dose selector is set at 0. H Turn the dose selector to select the number of units you need to inject. The dose can be corrected either up or down by turning the dose selector in either direction until the correct dose lines up with the pointer. When turning the dose selector, be careful not to push the push-button as insulin will come out. You cannot select a dose larger than the number of units left in the cartridge.
Always use the dose selector and the pointer to see how many units you have selected before injecting the insulin. Do not count the pen clicks. If you select and inject the wrong dose, your blood sugar level may get too high or too low. Do not use the residual scale, it only shows approximately how much insulin is left in your pen. Making the injection Insert the needle into your skin. Use the injection technique shown by your doctor or nurse. I Inject the dose by pressing the push-button all the way in until 0 lines up with the pointer. Be careful only to push the push-button when injecting. Turning the dose selector will not inject insulin.
J Keep the push-button fully depressed and let the needle remain under the skin for at least 6 seconds. This will make sure you get the full dose. Withdraw the needle from the skin, then release the pressure on the push-button. Always make sure that the dose selector returns to 0 after the injection. If the dose selector stops before it returns to 0, the full dose has not been delivered, which may result in too high blood sugar level. J
K Lead the needle into the big outer needle cap without touching it. When the needle is covered, carefully push the big outer needle cap completely on and then unscrew the needle. Dispose of it carefully and put the pen cap back on.
Always remove the needle after each injection and store your FlexPen® without the needle attached. This reduces the risk of contamination, infection, leakage of insulin, blocked needles and inaccurate dosing. Further important information Caregivers must be very careful when handling used needles – to reduce the risk of needle sticks and cross-infection. Dispose of your used FlexPen® carefully without the needle attached. Never share your pen or your needles with other people. It might lead to cross-infection. Never share your pen with other people. Your medicine might be harmful to their health. Always keep your pen and needles out of sight and reach of others, especially children.
Frequently asked questions about NovoRapid FlexPen
What is the active substance in NovoRapid FlexPen?
The active substance in NovoRapid FlexPen is insulin aspart.
Are there equivalent medicines to NovoRapid FlexPen?
Medicines with the same active substance, strength and form include: NovoRapid PumpCart, NovoRapid Vial. They are interchangeable only if your prescriber or pharmacist says so.
Where does this information come from?
This leaflet reproduces the patient information leaflet approved for NovoRapid FlexPen, as published on the electronic medicines compendium (emc). The version printed inside your medicine’s packaging is the one that applies to you.
Can I get NovoRapid FlexPen without a prescription?
Whether a medicine is available over the counter or on prescription only depends on its licence. Check the leaflet, or ask your pharmacist — they can tell you straight away.
About this leaflet
The text above reproduces the patient information leaflet approved for this medicine, restructured for easier reading.
- Source: electronic medicines compendium (emc), Datapharm
- Active substance: insulin aspart
- Official document: view the original leaflet on emc →
⚕For healthcare professionals — Summary of Product Characteristics (SmPC)Full SmPC: dosage, interactions, contraindications, warnings+
1. Name of the medicinal product
NovoRapid FlexPen 100 units/ml solution for injection in pre-filled pen
2. Qualitative and quantitative composition
1 pre-filled pen contains 3 ml equivalent to 300 units.1 ml solution contains 100 units insulin aspart* (equivalent to 3.5 mg).
*Insulin aspart is produced in Saccharomyces cerevisiae by recombinant DNA technology.
For the full list of excipients, see section 6.1.
3. Pharmaceutical form
Solution for injection.
The solution is clear, colourless and aqueous.
4. Clinical particulars
4.1. Therapeutic indications
NovoRapid is indicated for treatment of diabetes mellitus in adults, adolescents and children aged 1 year and above.
4.2. Posology and method of administration
The potency of insulin analogues, including insulin aspart, is expressed in units, whereas the potency of human insulin is expressed in international units.
NovoRapid dosing is individual and determined in accordance with the needs of the patient. It should normally be used in combination with intermediate-acting or longacting insulin.
Moreover NovoRapid vial and NovoRapid PumpCart can be used for continuous subcutaneous insulin infusion (CSII) in pump systems.
NovoRapid vial can also be used if intravenous administration of insulin aspart, by physicians or other healthcare staff, is applicable.
Blood glucose monitoring and insulin dose adjustments are recommended to achieve optimal glycaemic control.
The individual insulin requirement in adults and children is usually between 0.5 and 1.0 unit/kg/day. In a basal-bolus treatment regimen 50–70% of this requirement may be provided by NovoRapid and the remainder by intermediate-acting or long-acting insulin.
Adjustment of dose may be necessary if patients undertake increased physical activity, change their usual diet or during concomitant illness.
Special populations
Elderly (≥ 65 years old)
NovoRapid can be used in elderly patients.
In elderly patients, glucose monitoring should be intensified and the insulin aspart dose adjusted on an individual basis.
Renal and hepatic impairment
Renal or hepatic impairment may reduce the patient's insulin requirements.
In patients with renal or hepatic impairment, glucose monitoring should be intensified and the insulin aspart dose adjusted on an individual basis.
Paediatric population
NovoRapid can be used in children and adolescents aged 1 year and above in preference to soluble human insulin when a rapid onset of action might be beneficial, for example, in the timing of the injections in relation to meals (see sections 5.1 and 5.2).
The safety and efficacy of NovoRapid in children below 1 year of age have not been established.
No data are available.
Transfer from other insulin medicinal products
When transferring from other insulin medicinal products, adjustment of the NovoRapid dose and the dose of the basal insulin may be necessary. NovoRapid has a faster onset and a shorter duration of action than soluble human insulin. When injected subcutaneously into the abdominal wall, the onset of action will occur within 10–20 minutes of injection. The maximum effect is exerted between 1 and 3 hours after the injection. The duration of action is 3 to 5 hours.
Close glucose monitoring is recommended during the transfer and in the initial weeks thereafter (see section 4.4).
Method of administration
NovoRapid is a rapid-acting insulin analogue.
NovoRapid is administered subcutaneously by injection in the abdominal wall, the thigh, the upper arm, the deltoid region or the gluteal region. Injection sites should always be rotated within the same region in order to reduce the risk of lipodystrophy and cutaneous amyloidosis (see sections 4.4 and 4.8). Subcutaneous injection in the abdominal wall ensures a faster absorption than other injection sites. Compared to soluble human insulin the faster onset of action of NovoRapid is maintained regardless of the injection site. The duration of action will vary according to the dose, injection site, blood flow, temperature and level of physical activity.
Due to the faster onset of action, NovoRapid should generally be given immediately before a meal. When necessary NovoRapid can be given soon after a meal.
NovoRapid FlexPen
Administration with FlexPen
NovoRapid FlexPen is a pre-filled pen (colour-coded) designed to be used with NovoFine or NovoTwist disposable needles up to a length of 8 mm. FlexPen delivers 1–60 units in increments of 1 unit. NovoRapid FlexPen is only suitable for subcutaneous injections. If administration by syringe or intravenous injection is necessary, a vial should be used. If administration by infusion pump is necessary, a vial or NovoRapid PumpCart should be used.
For detailed user instructions, please refer to the package leaflet.
4.3. Contraindications
Hypersensitivity to the active substance or to any of the excipients (see section 6.1).
4.4. Special warnings and precautions for use
Before travelling between different time zones, the patient should seek the doctor's advice since this may mean that the patient has to take the insulin and meals at different times.
NovoRapid PumpCart
Misuse of NovoRapid PumpCart
NovoRapid PumpCart is only for use with an insulin infusion pump system designed to be used with this cartridge, such as the Accu-Chek Insight and YpsoPump insulin pumps. It must not be used with other devices not designed for NovoRapid PumpCart, as this may result in incorrect insulin dosing and subsequent hyper- or hypoglycaemia.
Hyperglycaemia
Inadequate dosing or discontinuation of treatment, especially in type 1 diabetes, may lead to hyperglycaemia and diabetic ketoacidosis. Usually the first symptoms of hyperglycaemia develop gradually over a period of hours or days. They include thirst, increased frequency of urination, nausea, vomiting, drowsiness, flushed dry skin, dry mouth, loss of appetite as well as acetone odour of breath. In type 1 diabetes, untreated hyperglycaemic events eventually lead to diabetic ketoacidosis, which is potentially lethal.
Hypoglycaemia
Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia.
Especially in children, care should be taken to match insulin doses (especially in basal-bolus regimens) with food intake, physical activities and current blood glucose level in order to minimise the risk of hypoglycaemia.
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. In case of hypoglycaemia or if hypoglycaemia is suspected NovoRapid must not be injected. After stabilisation of patient's blood glucose adjustment of the dose should be considered (see sections 4.8 and 4.9).
Patients whose blood glucose control is greatly improved, e.g. by intensified insulin therapy, may experience a change in their usual warning symptoms of hypoglycaemia, and should be advised accordingly. Usual warning symptoms may disappear in patients with longstanding diabetes.
A consequence of the pharmacodynamics of rapid-acting insulin analogues is that if hypoglycaemia occurs, it may occur earlier after an injection when compared with soluble human insulin.
Since NovoRapid should be administered in immediate relation to a meal, the rapid onset of action should be considered in patients with concomitant diseases or treatment where a delayed absorption of food might be expected.
Concomitant illness, especially infections and feverish conditions, usually increases the patient's insulin requirements. Concomitant diseases in the kidney, liver or affecting the adrenal, pituitary or thyroid gland can require changes in the insulin dose.
When patients are transferred between different types of insulin medicinal products, the early warning symptoms of hypoglycaemia may change or become less pronounced than those experienced with their previous insulin.
Transfer from other insulin medicinal products
Transferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type, origin (animal, human insulin or human insulin analogue) and/or method of manufacture (recombinant DNA versus animal source insulin) may result in the need for a change in dose. Patients transferred to NovoRapid from another type of insulin may require an increased number of daily injections or a change in dose from that used with their usual insulin medicinal products. If an adjustment is needed, it may occur with the first dose or during the first few weeks or months.
Injection site reactions
As with any insulin therapy, injection site reactions may occur and include pain, redness, hives, inflammation, bruising, swelling and itching. Continuous rotation of the injection site within a given area reduces the risk of developing these reactions. Reactions usually resolve in a few days to a few weeks. On rare occasions, injection site reactions may require discontinuation of NovoRapid.
Skin and subcutaneous tissue disorders
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 from an affected to an unaffected area, and dose adjustment of antidiabetic medications may be considered.
Combination of NovoRapid with pioglitazone
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, especially in patients with risk factors for development of cardiac heart failure. This should be kept in mind if treatment with the combination of pioglitazone and NovoRapid is considered. If the combination is used, patients should be observed for signs and symptoms of heart failure, weight gain and oedema.
Pioglitazone should be discontinued if any deterioration in cardiac symptoms occurs.
Avoidance of accidental mix-ups/medication errors
Patients must be instructed to always check the insulin label before each injection to avoid accidental mix-ups between NovoRapid and other insulin products.
Insulin antibodies
Insulin administration may cause insulin antibodies to form. In rare cases, the presence of such insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to hyper- or hypoglycaemia.
Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
4.5. Interaction with other medicinal products and other forms of interaction
A number of medicinal products are known to interact with the glucose metabolism.
The following substances may reduce the patient's insulin requirements:
Oral antidiabetic medicinal products, monoamine oxidase inhibitors (MAOI), betablockers, angiotensin converting enzyme (ACE) inhibitors, salicylates, anabolic steroids and sulphonamides.
The following substances may increase the patient's insulin requirements:
Oral contraceptives, thiazides, glucocorticoids, thyroid hormones, sympathomimetics, growth hormone and danazol.
Beta-blockers may mask the symptoms of hypoglycaemia.
Octreotide/lanreotide may either increase or decrease the insulin requirement.
Alcohol may intensify or reduce the hypoglycaemic effect of insulin.
4.6. Fertility, pregnancy and lactation
Pregnancy
NovoRapid (insulin aspart) can be used in pregnancy. Data from two randomised controlled clinical trials (322 and 27 exposed pregnancies) do not indicate any adverse effect of insulin aspart on pregnancy or on the health of the foetus/newborn when compared to human insulin (see section 5.1).
Intensified blood glucose control and monitoring of pregnant women with diabetes (type 1 diabetes, type 2 diabetes or gestational diabetes) are recommended throughout pregnancy and when contemplating pregnancy. Insulin requirements usually fall in the first trimester and increase subsequently during the second and third trimester.
After delivery, insulin requirements normally return rapidly to pre-pregnancy values.
Breast-feeding
There are no restrictions on treatment with NovoRapid during breast-feeding. Insulin treatment of the nursing mother presents no risk to the baby. However, the NovoRapid dose may need to be adjusted.
Fertility
Animal reproduction studies have not revealed any differences between insulin aspart and human insulin regarding fertility.
4.7. Effects on ability to drive and use machines
The patient's ability to concentrate and 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.
4.8. Undesirable effects
Adverse reactions observed in patients using NovoRapid are mainly due to the pharmacologic effect of insulin.
The most frequently reported adverse reaction during treatment is hypoglycaemia. The frequencies of hypoglycaemia vary with patient population, dose regimens and level of glycaemic control (see section 4.8, Description of selected adverse reactions).
At the beginning of the insulin treatment, refraction anomalies, oedema and injection site reactions (pain, redness, hives, inflammation, bruising, swelling and itching at the injection site) may occur. These reactions are usually of transitory nature. Fast improvement in blood glucose control may be associated with acute painful neuropathy, which is usually reversible. Intensification of insulin therapy with abrupt improvement in glycaemic control may be associated with temporary worsening of diabetic retinopathy, while long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy.
Tabulated list of adverse reactions
Adverse reactions listed below are based on clinical trial data and classified according to MedDRA frequency and System Organ Class. Frequency categories are defined according to the following convention: Very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data).
| Immune system disorders | Uncommon – Urticaria, rash, eruptions |
| Very rare – Anaphylactic reactions* | |
| Metabolism and nutrition disorders | Very common – Hypoglycaemia* |
| Nervous system disorders | Rare – Peripheral neuropathy (painful neuropathy) |
| Eye disorders | Uncommon – Refraction disorders |
| Uncommon – Diabetic retinopathy | |
| Skin and subcutaneous tissue disorders | Uncommon – Lipodystrophy* |
| Not known – Cutaneous amyloidosis*† | |
| General disorders and administration site conditions | Uncommon – Injection site reactions |
| Uncommon – Oedema |
* see section 4.8, Description of selected adverse reactions.
† ADR from postmarketing sources.
Description of selected adverse reactions
Anaphylactic reactions:
The occurrence of generalised hypersensitivity reactions (including generalised skin rash, itching, sweating, gastrointestinal upset, angioneurotic oedema, difficulties in breathing, palpitation and reduction in blood pressure) is very rare but can potentially be life threatening.
Hypoglycaemia:
The most frequently reported adverse reaction is hypoglycaemia. It may occur if the insulin dose is too high in relation to the insulin requirement. Severe hypoglycaemia may lead to unconsciousness and/or convulsions and may result in temporary or permanent impairment of brain function or even death. The symptoms of hypoglycaemia usually occur suddenly. They may include cold sweats, cool pale skin, fatigue, nervousness or tremor, anxiousness, unusual tiredness or weakness, confusion, difficulty in concentration, drowsiness, excessive hunger, vision changes, headache, nausea and palpitation.
In clinical trials, the frequency of hypoglycaemia varied with patient population, dose regimens and level of glycaemic control. During clinical trials the overall rates of hypoglycaemia did not differ between patients treated with insulin aspart compared to human insulin.
Skin and subcutaneous tissue disorders:
Lipodystrophy (including lipohypertrophy, lipoatrophy) and cutaneous amyloidosis may occur at the injection site and delay local insulin absorption. Continuous rotation of the injection site within the given injection area may help to reduce or prevent these reactions (see section 4.4).
Paediatric population
Based on post-marketing sources and clinical trials, the frequency, type and severity of adverse reactions observed in the paediatric population do not indicate any differences to the broader experience in the general population.
Other special populations
Based on post-marketing sources and clinical trials, the frequency, type and severity of adverse reactions observed in the elderly patients and in patients with renal or hepatic impairment do not indicate any differences to the broader experience in the general population.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation 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 via:
Great Britain
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple store
4.9. Overdose
A specific overdose for insulin cannot be defined, however, hypoglycaemia may develop over sequential stages if too high doses relative to the patient's requirement are administered:
• Mild hypoglycaemic episodes can be treated by oral administration of glucose or sugary products. It is therefore recommended that the diabetic patient always carries sugar-containing products.
• Severe hypoglycaemic episodes, where the patient has become unconscious, can be treated with glucagon (0.5 to 1 mg) given intramuscularly or subcutaneously by a trained person, or with glucose given intravenously by physicians or other healthcare staff. Glucose must be given intravenously, if the patient does not respond to glucagon within 10 to 15 minutes. Upon regaining consciousness, administration of oral carbohydrates is recommended for the patient in order to prevent a relapse.
5. Pharmacological properties
5.1. Pharmacodynamic properties
Pharmacotherapeutic group: Drugs used in diabetes. Insulins and analogues for injection, fast-acting. ATC code: A10AB05.
Mechanism of action and pharmacodynamic effects
The blood glucose lowering effect of insulin aspart is due to the facilitated uptake of glucose following binding of insulin to receptors on muscle and fat cells and to the simultaneous inhibition of glucose output from the liver.
NovoRapid produces a more rapid onset of action compared to soluble human insulin, together with a lower glucose concentration, as assessed within the first four hours after a meal. NovoRapid has a shorter duration of action compared to soluble human insulin after subcutaneous injection.
Fig. I. Blood glucose concentrations following a single pre-meal dose of NovoRapid injected immediately before a meal (solid curve) or soluble human insulin administered 30 minutes before a meal (hatched curve) in patients with type 1 diabetes mellitus.
When NovoRapid is injected subcutaneously, the onset of action will occur within 10 to 20 minutes of injection. The maximum effect is exerted between 1 and 3 hours after injection. The duration of action is 3 to 5 hours.
Clinical efficacy
Clinical trials in patients with type 1 diabetes have demonstrated a lower postprandial blood glucose with NovoRapid compared to soluble human insulin (Fig. I). In two long-term open label trials in patients with type 1 diabetes comprising 1070 and 884 patients, respectively, NovoRapid reduced glycated haemoglobin by 0.12 [95% C.I. 0.03; 0.22] percentage points and by 0.15 [95% C.I. 0.05; 0.26] percentage points compared to human insulin; a difference of limited clinical significance.
Clinical trials in patients with type 1 diabetes have demonstrated a reduced risk of nocturnal hypoglycaemia with insulin aspart compared with soluble human insulin. The risk of daytime hypoglycaemia was not significantly increased.
Insulin aspart is equipotent to soluble human insulin on a molar basis.
Special populations
Elderly ( ≥ 65 years old)
A randomised, double-blind cross-over PK/PD trial comparing insulin aspart with soluble human insulin was performed in elderly patients with type 2 diabetes (19 patients aged 65–83 years, mean age 70 years). The relative differences in the pharmacodynamic properties (GIRmax,AUCGIR, 0–120 min) between insulin aspart and soluble human insulin in the elderly were similar to those seen in healthy subjects and in younger patients with diabetes.
Paediatric population
A clinical trial comparing preprandial soluble human insulin with postprandial insulin aspart was performed in small children (20 patients aged 2 to less than 6 years, studied for 12 weeks, among those four were younger than 4 years old) and a single dose PK/PD trial was performed in children (6–12 years) and adolescents (13– 17 years). The pharmacodynamic profile of insulin aspart in children was similar to that seen in adults.
The efficacy and safety of NovoRapid given as bolus insulin in combination with either insulin detemir or insulin degludec as basal insulin has been studied for up to 12 months, in two randomised controlled clinical trials in adolescents and children aged 1 to less than 18 years (n=712). The trials included 167 children aged 1–5 years, 260 aged 6–11 and 285 aged 12–17. The observed improvements in HbA1c and the safety profiles were comparable between all age groups.
Pregnancy
A clinical trial comparing safety and efficacy of insulin aspart vs. human insulin in the treatment of pregnant women with type 1 diabetes (322 exposed pregnancies (insulin aspart: 157; human insulin: 165)) did not indicate any adverse effect of insulin aspart on pregnancy or on the health of the foetus/newborn.
In addition the data from a clinical trial including 27 women with gestational diabetes randomised to treatment with insulin aspart vs. human insulin (insulin aspart: 14; human insulin: 13) showed similar safety profiles between treatments.
5.2. Pharmacokinetic properties
Absorption, distribution and elimination
In NovoRapid substitution of amino acid proline with aspartic acid at position B28 reduces the tendency to form hexamers as observed with soluble human insulin. NovoRapid is therefore more rapidly absorbed from the subcutaneous layer compared to soluble human insulin.
The time to maximum concentration is, on average, half of that for soluble human insulin. A mean maximum plasma concentration of 492±256 pmol/l was reached 40 (interquartile range: 30–40) minutes after a subcutaneous dose of 0.15 unit/kg bodyweight in type 1 diabetic patients. The insulin concentrations returned to baseline about 4 to 6 hours after dose. The absorption rate was somewhat slower in type 2 diabetic patients, resulting in a lower Cmax (352±240 pmol/l) and later tmax (60 (interquartile range: 50–90) minutes). The intra-individual variability in time to maximum concentration is significantly less for NovoRapid than for soluble human insulin, whereas the intra-individual variability in Cmax for NovoRapid is larger.
Special populations
Elderly (≥ 65 years old)
The relative differences in pharmacokinetic properties between insulin aspart and soluble human insulin in elderly patients (65–83 years, mean age 70 years) with type 2 diabetes were similar to those observed in healthy subjects and in younger patients with diabetes. A decreased absorption rate was observed in elderly patients, resulting in a later tmax (82 (interquartile range: 60–120) minutes), whereas Cmax was similar to that observed in younger patients with type 2 diabetes and slightly lower than in patients with type 1 diabetes.
Hepatic impairment
A single dose pharmacokinetic study of insulin aspart was performed in 24 subjects with hepatic function ranging from normal to severely impaired. In patients with hepatic impairment, absorption rate was decreased and more variable, resulting in delayed tmax from about 50 min in subjects with normal hepatic function to about 85 min in patients with moderate and severe hepatic impairment. AUC, Cmax and CL/F were similar in patients with reduced hepatic function compared with subjects with normal hepatic function.
Renal impairment
A single dose pharmacokinetic study of insulin aspart in 18 subjects with renal function ranging from normal to severely impaired was performed. No apparent effect of creatinine clearance values on AUC, Cmax, CL/F and tmax of insulin aspart was found. Data were limited in patients with moderate and severe renal impairment. Patients with renal failure necessitating dialysis treatment were not investigated.
Paediatric population
The pharmacokinetic and pharmacodynamic properties of NovoRapid were investigated in children (6–12 years) and adolescents (13–17 years) with type 1 diabetes. Insulin aspart was rapidly absorbed in both age groups, with similar tmax as in adults. However, Cmax differed between the age groups, stressing the importance of the individual titration of NovoRapid.
5.3. Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction and development.
In in vitro tests, including binding to insulin and IGF-1 receptor sites and effects on cell growth, insulin aspart behaved in a manner that closely resembled human insulin. Studies also demonstrate that the dissociation of binding to the insulin receptor of insulin aspart is equivalent to human insulin.
6. Pharmaceutical particulars
6.1. List of excipients
Glycerol
Phenol
Metacresol
Zinc chloride
Disodium phosphate dihydrate
Sodium chloride
Hydrochloric acid (for pH adjustment)
Sodium hydroxide (for pH adjustment)
Water for injections
6.2. Incompatibilities
Substances added to NovoRapid may cause degradation of insulin aspart.
This medicinal product must not be diluted or mixed with other medicinal products except for mixing with NPH (Neutral Protamine Hagedorn) insulin in a syringe for subcutaneous use, or with infusion fluids as described in section 4.2.
6.3. Shelf life
Before opening: 30 months.
During use or when carried as a spare: The product must be stored for a maximum of 4 weeks. Store below 30°C.
6.4. Special precautions for storage
For storage conditions of the medicinal product, see section 6.3.
Before opening: Store in a refrigerator (2°C – 8°C). Do not freeze.
During use or when carried as a spare: Store below 30°C. Can be stored in a refrigerator (2°C – 8°C). Do not freeze.
Keep the pen cap on the pen in order to protect from light.
6.5. Nature and contents of container
3 ml solution in cartridge (type 1 glass) with a plunger (bromobutyl) and a rubber closure (bromobutyl/polyisoprene) contained in a pre-filled multidose disposable pen made of polypropylene.
Pack sizes of 1 (with or without needles), 5 (without needles) and 10 (without needles) pre-filled pens. Not all pack sizes may be marketed.
6.6. Special precautions for disposal and other handling
Do not use this medicinal product if you notice that the solution is not clear, colourless and aqueous.
NovoRapid which has been frozen must not be used.
The patient should be advised to discard the needle after each injection.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Needles, syringes, cartridges, pre-filled pens and infusion sets must not be shared.
The cartridge must not be refilled.
NovoRapid vial
NovoRapid may be used in an infusion pump system (CSII) as described in section 4.2. Tubings in which the inner surface materials are made of polyethylene or polyolefin have been evaluated and found compatible with pump use.
NovoRapid PumpCart
NovoRapid PumpCart is a pre-filled cartridge ready for use directly in the pump.
Please refer to the package leaflet where detailed instructions for use are provided.
To ensure correct dosing, NovoRapid PumpCart must not be used in an insulin pen.
NovoRapid PumpCart is only for use with an insulin infusion pump system designed to be used with this cartridge, such as the Accu-Chek Insight and YpsoPump insulin pumps, as described in section 4.2. Tubings in which the inner surface materials are made of polyethylene or polyolefin have been evaluated and found compatible with pump use.
7. Marketing authorisation holder
Novo Nordisk A/S, Novo Allé, DK-2880 Bagsværd, Denmark
8. Marketing authorisation number(s)
PLGB 04668/0388
9. Date of first authorisation/renewal of the authorisation
01/01/2021
10. Date of revision of the text
01/01/2021
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Ask anything about NovoRapid FlexPen. The assistant answers only from this leaflet — if the leaflet does not cover it, it will say so. It does not give medical advice.
Answers come from the patient leaflet published on the electronic medicines compendium (emc). They are not medical advice. Ask a pharmacist or your GP if you are unsure. For urgent help call NHS 111, or 999 in an emergency.
Medicines containing Insulin aspart
- Fiasp 100 units/mL Penfill solution for injection in cartridge
- Fiasp 100 units/mL solution for injection in vial
- NovoMix 30 FlexPen 100 units/ml
- NovoMix 30 Penfill 100 units/ml
- NovoRapid FlexTouch 100 units/ml
- NovoRapid Penfill 100 units/ml
- NovoRapid PumpCart
- NovoRapid Vial
- Trurapi 100 units/ml solution for injection in cartridge
- Trurapi 100 units/ml solution for injection in pre-filled pen
- Trurapi 100 units/ml solution for injection in vial