Eli Lilly and Company Limited

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 to bring the Irish SPC version in line with the EU licence.No other information has changed.

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

Revision date remains unchanged.

10.          DATE OF REVISION OF THE TEXT

                01 July 2009

*SPC updated for Mix25 vial launch - to add Mix25 vial only, no other information has been changed.

Header updated:

HUMALOG MIX25                                                                                                                  SUMMARY OF PRODUCT

100U/ml suspension for injection in vial                                                                             CHARACTERISTICS

100U/ml suspension for injection in cartridge                                                                  

100U/ml Pen, suspension for injection

100U/ml KwikPen, suspension for injection

1.             NAME OF THE MEDICINAL PRODUCT

Added:

HUMALOG* Mix25 100U/ml suspension for injection in vial.

6.             Pharmaceutical Particulars

6.3          Shelf-life

Added:

Unopened vials

2 years

Added (bold):

After cartridge insertion, or after first use (vial and prefilled pen)

28 days

6.4          Special precautions for storage

Added:

Vials

Do not freeze.  Do not expose to excessive heat or direct sunlight.

Unopened vials

Store in a refrigerator (2°C - 8°C).

After first use (vials only)

Store in a refrigerator (2°C - 8°C) or below 30°C.

6.5          Nature and contents of container

Added:

HUMALOG Mix25 100U/ml suspension for injection in vial

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

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 Mix50 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 Mix50 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

1.             NAME OF THE MEDICINAL PRODUCT

Added:

Humalog Mix50 100U/ml suspension for injection in cartridge.

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.

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

2 x (5 x 3ml) Humalog Mix50 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

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

2 x (5 x 3ml) Humalog Mix50 cartridges for a 3ml pen:              EU/1/96/007/025

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 and new presentations added:

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

Humalog Mix50 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 Mix50 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