Humalog Mix25 100 units/ml suspension for injection in cartridge

Changes

Added (underline) deleted (strikethrough)

4. Possible side effects

Reporting of Side effects

United Kingdom (Northern Ireland): Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

6. Contents of the pack and other information

…

For any information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

Ireland and United Kingdom (Northern Ireland)

Eli Lilly and Company (Ireland) Limited

Tel: + 353-(0) 1 661 4377

United Kingdom

Eli Lilly and Company Limited

Tel: + 44-(0) 1256 315000

This leaflet was revised in September 2020 September 2021

Changes

 Added (underline) deleted (strikethrough)

2.         What you need to know before you use Humalog  

Warnings and precautions

…..

Skin changes at the injection site

The injection site should be rotated to prevent skin changes such as lumps under the skin. The insulin may not work very well if you inject into a lumpy area (See How to use Humalog Mix25). Contact your doctor if you are currently injecting into a lumpy area before you start injecting 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.

4.         Possible side effects

…..

Lipodystrophy (thickening or pitting of the skin) is uncommon (³ 1/1,000 to <1/100). If you notice your skin thickening or pitting at the injection site, tell your doctor. If you inject insulin too often at the same place, the fatty tissue may either shrink (lipoatrophy) or thicken (lipohypertrophy). Lumps under the skin may also be caused by build-up of a protein called amyloid (cutaneous amyloidosis). The insulin may not work very well if you inject into a lumpy area. Change the injection site with each injection to help prevent these skin changes.

6.             Contents of the pack and other information

…..

This leaflet was last revised in September 2020.

Changes

Added (underline) deleted (strikethrough)

4.       CLINICAL PARTICULARS

4.2   Posology and method of administration

……….

Method of administration

………

Use of injection sites should be rotated so that the same site is not used more than approximately once a month, in order to reduce the risk of lipodystrophy and cutaneous amyloidosis (see section 4.4 and 4.8).

………

4.4   Special warnings and precautions for use

………

Injection technique

Patients must be instructed to perform continuous rotation of the injection site to reduce the risk of developing lipodystrophy and cutaneous amyloidosis. There is a potential risk of delayed insulin absorption and worsened glycaemic control following insulin injections at sites with these reactions. A sudden change in the injection site to an unaffected area has been reported to result in hypoglycaemia. Blood glucose monitoring is recommended after the change in the injection site, and dose adjustment of antidiabetic medications may be considered.

……….

4.8   Undesirable effects

………

Tabulated list of adverse reactions

The following related adverse reactions from clinical trials are listed below as MedDRA preferred term by system organ class and in order of decreasing incidence (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 form the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Description of selected adverse reactions

………

Skin and subcutaneous tissue disorders

Lipodystrophy 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).

Lipodystrophy

Lipodystrophy at the injection site is uncommon.

10.          DATE OF REVISION OF THE TEXT

23 July 2020 03 September 2020

                                                                                                     HGL81M, HGL82M, HGL83M, HLG84

Minor amendments to wording & formatting have been made throughout sections of the PIL.

Changes

 Minor formatting changes have been made throughout SmPC.  No new text/concepts with exception of below:

 Added (underline) deleted (strikethrough)

6.5   Nature and contents of container

Vial

The suspension is contained in type I flint glass vials, sealed with butyl or halobutyl stoppers and secured with aluminium seals.  Dimeticone or silicone emulsion may have been used to treat the vial stoppers.

10 ml Vial: Pack of 1 vial. Not all packs may be marketed

Cartridge

The suspension is contained in type I flint glass cartridges, sealed with butyl or halobutyl disc seals and plunger heads and secured with aluminium seals. Dimeticone or silicone emulsion may have been used to treat the cartridge plunger, and/or the glass cartridge.

 3 ml Cartridge: Packs of 5 or 10 cartridges. Not all packs may be marketed.

 KwikPen

The suspension is contained in type I flint glass cartridges, sealed with halobutyl disc seals and plunger heads and secured with aluminium seals.  Dimeticone or silicone emulsion may have been used to treat the cartridge plunger, and/or the glass cartridge. The 3 ml cartridges are sealed in a disposable pen injector, called the “KwikPen”.  Needles are not included.

3 ml KwikPen: Packs of 5 pre-filled pens or a multipack of 10 (2 packs of 5) pre-filled pens. Not all packs may be marketed.

10.          DATE OF REVISION OF THE TEXT

 13 January 2019 23 July 2020

HLG78M

4.4            Special warnings and precautions for use

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.

4.8            Undesirable effects

Ireland: HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, wWebsite: www.hpra.ie, e-mail: medsafety@hpra.ie, or United Kingdom: Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

10.      DATE OF REVISION OF THE TEXT

17 May  201816 January 2020

HLG70MHLG74M

Change to the alternative manufacturer only - PIL section 6.

No change of content.  SmPC Date of revision of the text:  17 May 2018.

A major change in this variation is the consolidation of the 10 individual SmPCs (1 per presentation) into 4 combined SmPCs, divided as follows:

• 100 u/ml cartridge, vial, KwikPen, Junior KwikPen
• Mix25 100 u/ml cartridge, vial, KwikPen
• Mix50 100 u/ml cartridge, KwikPen
• 200 u/ml KwikPen

New information in SmPCs

• All cartridges to be used in a Lilly reusable pen only
• Clarification that vials only to be used for intravenous administration
• 100 u/ml cartridges can be used in compatible pump systems for continuous subcutaneous insulin infusion (CSII)
• New vial text in section 6.6: ‘Patients using vials must never share needles or syringes. The patient should discard the needle after every injection.’
• Insulin requirements in Renal/Hepatic impairment text – moved from section 4.4 (Special warnings and precautions for use) to 4.2 (Posology and method of administration)

Changes

Added (underline) deleted (strikethrough)

4.2       Posology and method of administration

Paediatric population

Administration of Humalog Mix25 to children below 12 years of age should be considered only in case of an expected benefit when compared to soluble insulin.

4.4       Special warnings and precautions for use

Administration of insulin lispro to children below 12 years of age should be considered only in case of an expected benefit when compared to soluble insulin.

4.8          Undesirable effects

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 Ireland: HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, website: www.hpra.ie, e-mail: medsafety@hpra.ie, or United Kingdom: Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

10. DATE OF REVISION OF THE TEXT

19^th October 2017

                                                                                                                                                                                HLG61M

Changes

6.             Pharmaceutical Particulars

6.5          Nature and contents of container and special equipment for use, administration or implantation

………..

5 x 3ml HUMALOG Mix25 cartridges for a 3ml pen.

2 x (510 x 3ml) HUMALOG Mix25 cartridges for a 3ml pen.

5 x 3ml HUMALOG Mix50 cartridges for a 3ml pen.

2 x (510 x 3ml) HUMALOG Mix50 cartridges for a 3ml pen.

………..

8.             Marketing Authorisation NUMBERS

                ………..

5 x 3ml HUMALOG Mix25 cartridges for a 3ml pen:               EU/1/96/007/008

2 x (510 x 3ml) HUMALOG Mix25 cartridges for a 3ml pen:  EU/1/96/007/024

5 x 3ml HUMALOG Mix50 cartridges for a 3ml pen:                EU/1/96/007/006

2 x (510 x 3ml) HUMALOG Mix50 cartridges for a 3ml pen:  EU/1/96/007/025

                ………..

10.          DATE OF REVISION OF THE TEXT

10 November 2016     17 March 2017

(New text bold.  Text struck-through removed)

Changes

Throughout SPC, the abbreviated term for units, ‘U’, is replaced with the full spelling (i.e.- ‘units’). 

10.          DATE OF REVISION OF THE TEXT

01 January 2016   10 November 2016

(New text bold.  Text struck-through removed)

Changes

4.             CLINICAL PARTICULARS

4.4         Special warnings and precautions for use

……………

Combination of HUMALOG Mix25 or HUMALOG Mix50 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 HUMALOG Mix25 or HUMALOG Mix50 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.

Instructions for use and handling

Cartridges: 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.

KwikPens: To prevent the possible transmission of disease, each pen must be used by one patient only, even if the needle is changed.

4.8         Undesirable effects

                ……………..

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 UK: www.mhra.gov.uk/yellowcard, or Ireland: Pharmacovigilance Section, Irish Medicines Board, Kevin O’Malley House, Earlsfort Centre, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, www.imb.ie, imbpharmacovigilance@imb.ie.

Ireland: HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, website: www.hpra.ie, e-mail: medsafety@hpra.ie., or the UK: Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard.

6.             PHARMACEUTICAL PARTICULARS

6.6          Special precautions for disposal and other handling

                ……………..

HUMALOG Mix25 or HUMALOG Mix50 100U/ml suspension for injection in cartridges

Instructions for use and handling

Cartridges: 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.

                …………….

Humalog Mix25 or HUMALOG Mix50 100U/ml KwikPen, suspension for injection

a)       Instructions for use and handling

KwikPens: To prevent the possible transmission of disease, each pen must be used by one patient only, even if the needle is changed.

7.            MARKETING AUTHORISATION HOLDER

Eli Lilly Nederland B.V.

Papendorpseweg 83, 3528 BJ Utrecht Grootslag 1-5, NL-3991 RA, Houten
The Netherlands

10.          DATE OF REVISION OF THE TEXT

14 November 2013          01 January 2016

4.             CLINICAL PARTICULARS

4.8            Undesirable effects

Hypoglycaemia is the most frequent undesirable effect of insulin therapy that a patient with diabetes may suffer.  Severe hypoglycaemia may lead to loss of consciousness and in extreme cases, death. No specific frequency for hypoglycaemia is presented, since hypoglycaemia is a result of both the insulin dose and other factors, e.g., a patient’s level of diet and exercise.

Local allergy in patients is common (1/100 to <1/10). Redness, swelling, and itching can occur 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, which is rare (1/10,000 to <1/1,000) but potentially more serious, is a generalised allergy to insulin. It may cause a 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 at the injection site is uncommon (1/1,000 to <1/100).

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

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 UK: www.mhra.gov.uk/yellowcard, or Ireland: Pharmacovigilance Section, Irish Medicines Board, Kevin O’Malley House, Earlsfort Centre, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, www.imb.ie, imbpharmacovigilance@imb.ie.

10.          DATE OF REVISION OF THE TEXT

Revision date changed to:
14 November 2013

Changes

(Humalog Mix25 vials only)


6.             Pharmaceutical Particulars

6.3          Shelf-life

Unopened vials

2 years     3 years

10.          DATE OF REVISION OF THE TEXT

Revision date changed to:

13 April 2012

PLEASE NOTE:  the SPC has been updated throughout in order to reflect QRD template changes and the removal of Humalog Mix 25 & Mix50 Pen information.

Changes

4.             CLINICAL PARTICULARS

4.8          Undesirable effects

Added (new) text:

Changes

4.             CLINICAL PARTICULARS

4.4          Special warnings and precautions for use

SPC updated to add Mix25 vial & Mix50 Cartridge information only. No other information has changed.

Individual affiliate contact details deleted from SPC consistent with other European SPCs

This brings the Irish SPC version in line with EU licence.


Header updated (see underlined):

HUMALOG MIX25                                                                              
100U/ml suspension for injection in vial                                               
100U/ml suspension for injection in cartridge                                     
100U/ml Pen, suspension for injection
100U/ml KwikPen, suspension for injection

HUMALOG MIX50

100U/ml suspension for injection in cartridge

100U/ml Pen, suspension for injection

100U/ml KwikPen, suspension for injection

Revision date remains unchanged.

10.          DATE OF REVISION OF THE TEXT

                01 July 2009

4.             CLINICAL PARTICULARS

4.5          Interaction with other medicinal products and other forms of interaction

Added (bold):

Insulin requirements may be reduced in the presence of medicinal products with hypoglycaemic activity, such as oral hypoglycaemics, salicylates (for example, acetylsalicylic acid), sulpha antibiotics, certain antidepressants (monoamine oxidase inhibitors, selective serotonin reuptake inhibitors),

5.             PHARMACOLOGICAL PROPERTIES

5.1          Pharmacodynamic properties

Updated:

6.             PHARMACEUTICAL PARTICULARS

6.3          Shelflife

Added:

Unused cartridges & pre-filled pens

Added (bold) Deleted (strikethrough):

3 years 2 years

Added (bold) deleted (strikethrough):

After cartridge insertion, or after first use (prefilled pen) insertion of the cartridge in a pen, or the first use of the prefilled pen, the solution should be used within 28 days. when stored below 30°C.

6.4          Special precautions for storage

Added:

Unused cartridge and unused pre-filled pens

Store in a refrigerator (2°C-8°C).  Do not freeze.  Do not expose to excessive heat or direct sunlight.

Added:

After cartridge insertion or first use (pre-filled pen)

Store below 30°C. Do not refrigerate. The pen with the inserted cartridge and the pre-filled pen should not be stored with the needle attached.

6.6                Special precautions for disposal and other handling

Re-formatted to provide better clarity between the pen and Kwikpen instructions.

9.             DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Dates changed as per EMEA request:

Date of first authorisation:        30 April 1996

Date of last renewal:                   30 April 2006

10.          DATE OF REVISION OF THE TEXT

6.             PHARMACEUTICAL PARTICULARS

6.6          Special precautions for disposal and other handling

Deleted from section 4.2 and inserted into section 6.6:

Instructions for use and handling

The vial is to be used in conjunction with an appropriate syringe (100 U markings).

a)         Preparing a dose

Vials containing Humalog Mix25 should be rotated in the palms of the hands before use to resuspend the insulin until it appears uniformly cloudy or milky. Do not shake vigorously as this may cause frothing which may interfere with the correct measurement of the dose. The vials should be examined frequently and should not be used if clumps of material are present or if solid white particles stick to the bottom or wall of the vial, giving it a frosted appearance.

Humalog Mix25

1.         Wash your hands.

2.         If using a new vial, flip off the plastic protective cap, but do not remove the stopper.  

3.         Draw air into the syringe equal to the prescribed Humalog Mix25 dose.  Wipe the top of the vial with an alcohol swab.  Put the needle through rubber top of the Humalog Mix25 vial and inject the air into the vial.

4.         Turn the vial and syringe upside down. Hold the vial and syringe firmly in one hand.

5.         Making sure the tip of the needle is in the Humalog Mix25, withdraw the correct dose into the syringe.

6.         Before removing the needle from the vial, check the syringe for air bubbles that reduce the amount of Humalog Mix25 in it. If bubbles are present, hold the syringe straight up and tap its side until the bubbles float to the top. Push them out with the plunger and withdraw the correct dose.

7.         Remove the needle from the vial and lay the syringe down so that the needle does not touch anything.

b)         Injecting a dose

1.         Choose a site for injection.

2.         Clean the skin as instructed.

3.         Stabilise the skin by spreading it or pinching up a large area.  Insert the needle and inject as instructed.

4.         Pull the needle out and apply gentle pressure over the injection site for several seconds. Do not rub the area.

5.         Dispose of the syringe and needle safely.

6.         Use of the injection sites should be rotated so that the same is not used more than approximately once a month.

10.          DATE OF REVISION OF THE TEXT

31 January 2008

4.             CLINICAL PARTICULARS

4.5          Interaction with other medicinal products and other forms of interaction

Added text in bold

Insulin requirements may be reduced in the presence of medicinal products with hypoglycaemic activity, such as oral hypoglycaemics, salicylates (for example, acetylsalicylic acid), sulpha antibiotics, certain antidepressants (monoamine oxidase inhibitors), certain angiotensin converting enzyme inhibitors (captopril, enalapril), angiotensin II receptor blockers, beta-blockers, octreotide, or alcohol.

5.             PHARMACOLOGICAL PROPERTIES

Changes in bold text and deletions in strikethrough

5.1          Pharmacodynamic properties

10.          DATE OF REVISION OF THE TEXT

New date

3 May 2007

5.             PHARMACOLOGICAL PROPERTIES

5.1          Pharmacodynamic properties

Added:

In two 8-month open label crossover studies, Type 2 diabetes patients who were either new to insulin therapy or already using one or two injections of insulin received 4 months of treatment with Humalog Mix25 (used twice daily with metformin) and insulin glargine (used once daily with metformin) in a randomised sequence.  Detailed information can be found in the following table.

9.             Date of First Authorisation/Renewal of the Authorisation

Dates changed:

Date of first authorisation:                         Humalog Mix25 cartridge:           30 April 1996

                                                                        Humalog Mix25 Pen:                    30 April 1996

Humalog Mix50 Pen:                    30 April 1996

Date of renewal of the authorisation:       Humalog Mix25 cartridge:           30 April 2006

Humalog Mix25 Pen:                    30 April 2006

Humalog Mix50 Pen:                    30 April 2006

10.          DATE OF REVISION OF THE TEXT

New date:

1 September 2006

4.             CLINICAL PARTICULARS

4.2          Posology and method of administration

Added:

Instructions for use and handling for all presentations now under this section instead of section 6.6.

4.8          Undesirable effects

Added:

No specific frequency for hypoglycaemia is presented, since hypoglycaemia is a result of both the insulin dose and other factors, eg, a patient’s level of diet and exercise.

Re-worded:

Local allergy in patients is common (1/100 to <1/10).  Redness, swelling, and itching can occur 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, which is rare (1/10,000 to <1/1,000) but potentially more serious, is a generalised allergy to insulin.  It may cause a 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 at the injection site is uncommon (1/1,000 to <1/100).

6.             PHARMACEUTICAL PARTICULARS

6.5          Nature and contents of container

Added:

2 x (5 x 3ml) Humalog Mix25 cartridges for a 3ml pen.

2 x (5 x 3ml) Humalog Mix25 100U/ml Pens.

2 x (5 x 3ml) Humalog Mix50 100U/ml Pens.

Not all packs may be marketed.

8.             Marketing Authorisation NUMBERS

Added:

2 x (5 x 3ml) Humalog Mix25 cartridges for a 3ml pen:              EU/1/96/007/024

2 x (5 x 3ml) Humalog Mix25 100U/ml Pens:                               EU/1/96/007/027

2 x (5 x 3ml) Humalog Mix50 100U/ml Pens:                               EU/1/96/007/028

9.             Date of First Authorisation/Renewal of the Authorisation

Re-worded:

Date of first authorisation:                         Humalog Mix25 cartridge:           19 November 1998

Humalog Mix25 Pen:                    19 November 1998

Humalog Mix50 Pen:                    19 November 1998

Date of renewal of the authorisation:       Humalog Mix25 cartridge:           9 February 2006

Humalog Mix25 Pen:                    9 February 2006

Humalog Mix50 Pen:                    9 February 2006

10.          DATE OF REVISION OF THE TEXT

9 February 2006