Fiasp 100 units/mL Penfill solution for injection in cartridge

Addition of Norther Ireland to reporting side effects section.

Change of revision date.

Black Triangle removed

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions.

Section 2, Warnings and precautions

Updates to the following bullet points:

• Switching from other insulin medicinal products -- Your doctor may need to advise you on your insulin dose The insulin dose may need to be changed if you switch from another insulin.
• If your insulin treatment is being combined with pioglitazone (oral antidiabetic medicine used to treat type 2 diabetes) - Tell your doctor as soon as possible if you get signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling caused by fluid retention (oedema).Pioglitazone used together with insulin - This may increase the risk of heart failure, see under ‘Other medicines and Fiasp’ below.
• Eye disorder - Fast improvements in blood sugar control may lead to a temporary worsening of diabetic eye disorder such as diabetic retinopathy.
• Ensuring you use the right type of insulin – always check the insulin label before each injection to avoid accidental mix-ups between insulin products.
• Insulin treatment can cause the body to produce antibodies to insulin (substance that act against insulin). However, only very rarely, this will require a change to your insulin dose.

“Some conditions and activities can affect how much insulin you need. Talk to 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 talk to your doctor.
• if you are going abroad, travelling over time zones may affect your insulin needs and the timing of your injections.”

Section 2, Other medicines and Fiasp

Text changes:

“Your blood sugar level may fall (hypoglycaemia) if you take:

•              other medicines for diabetes (oral and injectable)

•              sulphonamide antibiotics (for used to treat infections)

•              anabolic steroids (such as testosterone)

•              beta-blockers - for e.g.,(used to treat high blood pressure or angina)

They may make it harder to recognise the warning signs of low blood sugar (see section 4 ‘Warning signs of low blood sugar’)

•              acetylsalicylic acid (and other salicylates) -  f(or used to relieve pain and mild lower fever)

•              monoamine oxidase inhibitors (MAOI) inhibitors  - (for used to treat depression)

•              angiotensin converting enzyme (ACE) inhibitors (for some heart problems or high blood pressure)

Your blood sugar level may rise (hyperglycaemia) if you take:

•              danazol - (medicine acting on ovulation)for endometriosis”

“Pioglitazone - oral antidiabetic medicine used to treat type 2 diabetes. Some patients with long-standing type 2 diabetes and heart disease or previous stroke who were treated with pioglitazone and insulin developed heart failure. Tell your doctor immediately if you have signs of heart failure such as unusual shortness of breath, rapid increase in weight or localised swelling (oedema).”

Section 2, 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. This medicine can be used during pregnancy; however your insulin dose may need to be changed during pregnancy and after delivery. The amount of insulin you need usually falls during the first 3 months of pregnancy and increases for the remaining 6 months. Careful control of your diabetes is needed in pregnancy. Avoiding low blood sugar (hypoglycaemia) is particularly important for the health of your baby. After you have had your baby your insulin requirements will likely return to how much you needed before your pregnancy.

There are no restrictions on treatment with Fiasp during breast-feeding.”

Section 2 – Excipients

“This medicine contains less than 1 mmol sodium (23 mg) per dose,. This means that this medicine is to say essentially ‘sodium-free’.”

Section 3, How to use Fiasp

“This medicine is only suitable for injection under the skin (subcutaneous injection) from a Novo Nordisk reusable insulin pen.”

Section 4 – Possible side effects

“If you have a serious allergic reaction (including an anaphylactic shock) to insulin or any of the ingredients in Fiasp (how often this occurs is not known), stop using this medicine and contact emergency medical service straight away.”

“Skin changes at the injection site: If you inject insulin at the same place, the fatty tissue may shrink (lipoatrophy) or thicken (lipohypertrophy) (these are uncommon and may affect up to 1 in 100 people).”

“High blood sugar (hyperglycaemia) frequency not known (cannot be estimated from the available data)”

Section 6

“Each One pre-filled pen contains…”

Revision date updated to: 08/2021

Black Triangle removed

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions.

Section 2

“Each One pre-filled pen contains…”

Section 4.2:

“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 dose adjusted on an individual basis (see section 5.2).

Hepatic impairment

Hepatic impairment may reduce the patient’s insulin requirements. In patients with hepatic impairment, glucose monitoring should be intensified and the dose adjusted on an individual basis (see section 5.2).”

Text updates in “Method of administration”:

“Fiasp 100 units/mL FlexTouch solution for injection in pre-filled pen

Administration with a pre-filled pen (FlexTouch)

The pre-filled pen (FlexTouch) is designed to be used with NovoFine Plus, NovoFine or NovoTwist injection needles. The pre-filled pen (FlexTouch) delivers 1–80 units in steps of 1 unit.

FlexTouch is colour-coded and accompanied by a package leaflet with detailed instructions for use to be followed. For instructions on administration, see “Instructions for Use” at the end of the package leaflet.”

“Fiasp 100 units/mL Penfill solution for injection in cartridge

Administration with a reusable insulin pen

The cartridge (Penfill) is designed to be used with Novo Nordisk reusable insulin pens and NovoFine Plus, NovoFine or NovoTwist injection needles for subcutaneous injection only.

If administration by syringe or intravenous injection is necessary, a vial should be used. If administration by infusion pump is necessary, a vial or a PumpCart cartridge should be used (see section 6.6).”

“Fiasp 100 units/mL solution for injection in vial

Administration with a syringe

The vial is to be used with insulin syringes with the corresponding unit scale (unitsU-100 or 100 unitsU/mL).

Continuous subcutaneous insulin infusion (CSII)

Fiasp solution for injection in vial can be used for CSII in pumps suitable for insulin infusion and will cover both the bolus insulin requirement (approximately 50%) and basal insulin. It can be administered in accordance with the instructions provided by the pump manufacturer, preferably in the abdomen. Infusion site should be rotated within the same region to reduce the risk of lipodystrophy. When used with an insulin infusion pump, it should not be diluted or mixed with any other insulin medicinal products.”

“Fiasp 100 units/mL PumpCart solution for injection in cartridge

Administration via Continuous Subcutaneous Insulin Infusion (CSII)

The cartridge (PumpCart) is only for use with an insulin infusion pump system designed to be used with this cartridge (see section 6.6), such as the Accu-Chek Insight and YpsoPump insulin pumps.

“Intravenous use

Fiasp 100 units/mL solution for injection in vial

If necessary, Fiasp can be administered intravenously by health care professionals.

For intravenous use, it should be used at concentrations from 0.5 unit/mL to 1.0 unit/mL insulin aspart in infusion systems – using polypropylene infusion bags. Fiasp has been shown to be stable at room temperature for 24 hours in the infusion fluids such as sodium chloride 9 mg/mL (0.9%) solution or 5% glucose solution.

Fiasp must not be mixed with any other insulin or any other medicinal product except those mentioned in section 6.6. For instructions on dilution of the medicinal product before administration, see section 6.6.

Monitoring of blood glucose is necessary during insulin infusion. Care should be taken to ensure that the insulin is injected into the infusion bag and not simply the entry port.”

Section 4.4:

“Hyperglycaemia and diabetic ketoacidosis

The use of inadequate doses or discontinuation of treatment, especially in patients requiring insulin, may lead to hyperglycaemia and diabetic ketoacidosis; conditions which are potentially lethal.”

“Fiasp 100 units/mL PumpCart solution for injection in cartridge

Misuse of PumpCart

The cartridge (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 the cartridge, as this may result in incorrect insulin dosing and subsequent hyper- or hypoglycaemia (see section 6.6).”

“Combination of thiazolidinediones pioglitazone and insulin medicinal products

Cases of congestive heart failure have been reported when thiazolidinediones pioglitazone were used in combination with insulin, especially in patients with risk factors for development of congestive heart failure. This should be kept in mind if treatment with the combination of thiazolidinediones pioglitazone and insulin medicinal products is considered. If the combination is used, patients should be observed for signs and symptoms of congestive heart failure, weight gain and oedema. Thiazolidinediones Pioglitazone should be discontinued if any deterioration in cardiac symptoms occurs.”

“Excipients

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say i.e. essentially ‘sodium-free’.”

Section 4.6:

“Breast-feeding

There are no restrictions on treatment with Fiasp during breast-feeding. Insulin treatment of the nursing breast-feeding mother presents no risk to the baby. However, the dosage may need to be adjusted.”

Section 5.1:

“Fiasp has an earlier onset of action compared to NovoRapid (see section 5.2), leading to a subsequent increased early glucose-lowering effect. This must be considered when prescribing Fiasp.”

Section 6.2:

“The medicinal product must not be diluted or mixed with any other medicinal products except infusion fluids as described in section 4.26.6.”

Section 6.3:

“Fiasp 100 units/mL PumpCart solution for injection in cartridge

After first opening or carried as a spare, the medicinal product may be stored for a maximum of 2 weeks below 30°C. Thereafter it can be used for up to 7 days below 37°C in an insulin infusion pump system designed to be used with this cartridge, such as the Accu-Chek Insight and YpsoPump insulin pumps (see section 6.6). Do not refrigerate. Do not freeze. If cartridge is carried as a spare and unused, the cartridge should be kept in the outer carton in order to protect from light.”

Section 6.4:

“After first opening or carried as a spare For storage conditions after first opening of the medicinal product or carried as a spare, see section 6.3.”

Section 6.6:

“Fiasp 100 units/mL FlexTouch solution for injection in pre-filled pen

The pre-filled pen (FlexTouch) is designed to be used with injection needles developed according to the pen needle ISO standard of a length between 4 mm to 8 mm and a gauge between 30G and 32G for subcutaneous injection only.

Needles and pre-filled pens must not be shared. The cartridge must not be refilled.

The patient should discard the needle after each injection.

Fiasp 100 units/mL Penfill solution for injection in cartridge

The cartridge (Penfill) is designed to be used with Novo Nordisk reusable insulin pens and injection needles developed according to the pen needle ISO standard of a length between 4 mm to 8 mm and a gauge between 30G and 32G for subcutaneous injection only.

Needles and cartridges must not be shared. The cartridge must not be refilled.

The patient should discard the needle after each injection.

Fiasp 100 units/mL solution for injection in vial

Needles and syringes must not be shared.

The patient should discard the needle after each injection.

Administration via CSII

When Fiasp is drawn from a vial, it can be used in an infusion pump (CSII) for a maximum of 6 days, as described in section 4.2 and in the package leaflet. Tubings in which the inner surface materials are made of polyethylene or polyolefin have been evaluated and found compatible with pump use.

Intravenous use

Fiasp has been shown to be stable at room temperature for 24 hours in the infusion fluids such as sodium chloride 9 mg/mL (0.9%) solution for injection or 5% glucose solution for injection.

For intravenous use, it should be used at concentrations from 0.5 unit/mL to 1 unit/mL insulin aspart in infusion systems – using polypropylene infusion bags.

Fiasp 100 units/mL PumpCart solution for injection in cartridge

The cartridge must not be shared or refilled.

The cartridge (PumpCart) is only for use with the followingan insulin infusion pump systems: 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.”

Section 9:

“Date of latest renewal: 18 August 2021”

Section 10:

Revision date updated to: 08/2021

Section 2 – what you need to know - warnings and precautions

New text:

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 Fiasp^®’). 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.

Section 4 – possible side effects

New text:

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 up to 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.

Deleted text:

Uncommon (may affect up to 1 in 100 people)

Changes under the skin where you use the injection (lipodystrophy): Fatty tissue under the skin may shrink (lipoatrophy) or get thicker (lipohypertrophy). Changing where you inject each time may reduce the risk of developing these skin changes. If you notice these skin changes, tell your doctor or nurse. If you keep injecting in the same place, these reactions can become more severe and affect the amount of medicine your body gets.

Section 4.2 - method of administration

Updated text:

Fiasp is recommended to be administered subcutaneously by injection in the abdominal wall or the upper arm (see section 5.2). 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).

Section 4.4

New text:

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.

Section 4.8

Addition to adverse reaction list, skin and subcutaneous tissue disorders:

Not known – cutaneous amyloidosis†

† ADR from postmarketing sources.

Skin and subcutaneous tissue disorders

Lipodystrophy (including lipohypertrophy, lipoatrophy) and cutaneous amyloidosis may occur at the injection site and delay local insulin absorption. Lipodystrophy was reported at the injection/infusion site in patients treated with Fiasp (0.5% vs. 0.2% in comparator). Continuous rotation of the injection site within the particular given injection area may help to reduce or prevent the risk of developing these reactions (see section 4.4).

Product name

'Penfill®' added to product name

Section 2, Warnings and precautions

New sentence added: When using Fiasp® it is strongly recommended that the name and batch number of each package is recorded in order to maintain a record of the batches used.

Sections 1, 2, 3:

The trademarked product descriptions ‘FlexTouch^®’ and ‘Penfill^®’ are introduced into the product names for the current pre-filled pen and cartridge presentations. This update is reflected throughout the SPC.

 The Fiasp^® PumpCart^® presentation is introduced. (Please note that this is not yet launched.)

 Section 4.2:

Information on the PumpCart is included in the section ‘Method of administration’

 Section 4.4:

Text added to warn on misuse of PumpCart^®

 Text added on the ‘Transfer from other insulin medicinal products’

 Text added on ‘Traceability’. This is new standard text being introduced into the SmPCs of biological medicines.

Section 6.3, Shelf life: text added for PumpCart^®

 Section 6.4, Special precautions for storage: text added for PumpCart^®

 Section 6.5, Nature and contents of container: text added for PumpCart^®

 Section 6.6, Special precautions for disposal and other handling: text added for PumpCart^®

 Section 8, Marketing Authorisation Numbers: license numbers for PumpCart^® added

Section 4.8

Addition of the following reactions

“Other side effects include: 

 Common (may affect up to 1 in 10 people)  

Reaction at administration site: Local reactions at the place you inject yourself may occur. The signs may include: rash, redness, inflammation, bruising, irritation, pain and itching. The reactions usually disappear after a few days.”

Section 4.8 – reporting of side effects

Updated to list shortened contact details for the HPRA

Section 6

revision date updated to “09/2019”

Section 4.8

Text updates as follows:

"Tabulated list of adverse reactions Adverse reactions listed below (Table 2) are based on data from 6 3 completed therapeutic confirmatory trials in adults.”

Description of selected adverse reactions

Allergic reactions

Allergic skin manifestations reported with Fiasp (1.8 1.5 % vs. 1.5 1.4 % for comparator) include eczema, rash, rash pruritic, urticaria and dermatitis.

 With Fiasp generalised hypersensitivity reactions (manifested by generalised skin rash and facial oedema) was reported uncommonly (0.2% vs. 0.3 0.1 % for comparator).

Lipodystrophy

Lipodystrophy (including lipohypertrophy, lipoatrophy) was reported at the injection/infusion site in patients treated with Fiasp (0.5 0.2 % vs. 0.2 0% in comparator). Continuous rotation of the injection site within the particular injection area may help to reduce the risk of developing these reactions.

Injection/infusion site reactions

Injection site reactions (including rash, redness, inflammation, pain and bruising and itching) were was  reported in patients treated with Fiasp (1.3 1.0 % vs. 1.0 0.7 % in comparator). In patients using CSII (N=261): Infusion site reactions (including redness, inflammation, irritation, pain, bruising and itching) were reported in patients treated with Fiasp (10.0% vs. 8.3% in comparator). These reactions are usually mild and transitory and they normally disappear during continued treatment.

 Section 4.8 – Undesirable effects – how to report a side effect

Updated to list shortened contact details for the HPRA

Section 10

Revision of text updated to "09/2019"

Section 1

Text update to expand indication:

“Fiasp® is a solution for injection containing insulin aspart and is used to treat diabetes mellitus in adults, adolescents and children aged 1 year and above. “

Section 2, children and adolescents

Text updated to reflect updated indication of use from 1 year as follows:

“This medicine is not recommended for use in children below the age of 1 year.”

Section 2, pregnancy and breast-feeding

Text updated:

“This medicine can be used during pregnancy; however your insulin dose may need to be changed during pregnancy and after delivery. Careful control of your diabetes is needed in pregnancy.

Section 3, How to use Fiasp®

Text udpated:

“Adults: Fiasp® should be injected right before (0-2 minutes) the start of the meal, with an option to inject up to 20 minutes after starting the meal.

Children: Fiasp® should be injected right before (0-2 minutes) the start of the meal, with the possibility to inject up to 20 minutes after starting the meal in situations, when there is uncertainty about how the child will eat. Ask your doctor for advice on these situations.”

Section 4

“Flushed” updated to “flushed skin”

Section 4.2:

Indication updated to include paediatrics as follows:

“Treatment of diabetes mellitus in adults, adolescents and children aged 1 year and above” 

“The individual total daily insulin requirement in adults, adolescents and children may vary and is usually between 0.5 and 1.0 unit/kg/day.

 “The early onset of action must be considered when prescribing Fiasp (see section 5.1).”

Paediatric population updated as follows:

“Fiasp can be used in adolescents and children from the age of 1 year (see section 5.1). There is no clinical experience with the use of Fiasp in children below the age of 2 year.

Fiasp is recommended to be administered prior to the meal (0-2 minutes), with the flexibility to administer up to 20 minutes after starting the meal in situations, when there is uncertainty about the meal intake.”

“The safety and efficacy of Fiasp in children and adolescents below 18 years of age have not been established. Currently available data are described in section 5.2, but no recommendation on a posology can be made.”

Section 4.4

Text added:

“Paediatric population

Close monitoring of blood glucose levels is recommended if administering this medicine after the start of the last meal of the day, in order to avoid nocturnal hypoglycaemia.”

Section 4.8:

Text added:

“Paediatric population

Safety and efficacy have been investigated in a therapeutic confirmatory trial in children with type 1 diabetes aged 2 to less than 18 years. In the trial, 519 patients were treated with Fiasp. Overall the frequency, type and severity of adverse reactions in the paediatric population do not indicate differences to the experience in the adult population. Lipodystrophy (including lipohypertrophy, lipoatrophy) at the injection site was reported more often in this study with paediatric patients compared to studies in adults (see above). In the paediatric population lipodystrophy was reported with a frequency of 2.1% for Fiasp vs. 1.6% for NovoRapid.“

Section 5.1:

Text added as follows:

 Pharmacodynamic effects:

“Fiasp has an earlier onset of action compared to NovoRapid (see section 5.2), leading to a subsequent increased glucose-lowering effect. This must be considered when prescribing Fiasp.”

 Clinical efficacy and safety:

“….Furthermore, Fiasp has been studied in 777 paediatric subjects with type 1 diabetes in a randomised efficacy and safety trial (26 weeks of treatment). No children below the age of 2 years were randomised in the trial.”

 “Paediatric population

The efficacy and safety of Fiasp have been studied in a 1:1:1 randomised active controlled clinical trial in children and adolescents with type 1 diabetes, aged 1 to 18 years, for a period of 26 weeks (N=777). In this trial the efficacy and safety of Fiasp administered at mealtime (0–2 minutes before meal) or postmeal (20 minutes after meal start) and NovoRapid administered at mealtime, both used in combination with insulin degludec, were compared.

Patients in the Fiasp mealtime arm included 16 children aged 2–5 years, 100 children aged 6–11 years and 144 adolescents aged 12–17 years. Patients in the Fiasp postmeal arm included 16 children aged 2–5 years, 100 children aged 6–11 years and 143 adolescents aged 12–17 years.

Fiasp administered at mealtime showed superior glycaemic control compared to NovoRapid mealtime with regards to change in HbA_1c (ETD: -0.17% [-0.30; -0.03]_{95% CI}). Fiasp administered postmeal showed non-inferior glycaemic control compared to NovoRapid mealtime (ETD: 0.13% [-0.01; 0.26]_{95% CI}).

Fiasp mealtime showed a statistically significant improvement in 1– hour postmeal glucose increment mean over all three main meals compared to NovoRapid (measured by SMPG). For Fiasp postmeal this comparison favoured NovoRapid mealtime.

No overall increased risk of severe or blood glucose confirmed hypoglycaemia was observed compared to NovoRapid.

The observed effects and the safety profiles were comparable between all age groups.”

Section 4.8:

- Addition of 'anaphylactic reactions' as frequency ‘Not known’ in table 2

- Deletion of "Anaphylactic reactions have not been reported with Fiasp. With insulin preparations in general, anaphylactic reactions may occur. Immediate-type allergic reactions to either insulin itself or the excipients may potentially be life‑threatening.

Section 6.3:

- Deletion of ‘At the end of this period the pen should be used or discarded’.

- Sentence update for Fiasp 100 units/mL solution for injection in vial as follows:
“After first opening, the medicinal product may be stored for a maximum of 4 weeks (including time in a pump reservoir, see section 6.6). At the end of this period the pen should be used or discarded’”

Section 6.6:
Shortening of the pump in-use time for the Fiasp vial from 9 to 6 days as follows:
“Fiasp 100 units/mL solution for injection in vial

Fiasp may be used in an infusion pump (CSII) for a maximum of 9 6 days, as described in section 4.2 and in the package leaflet.”