Humulin I KwikPen 100 IU/ml suspension for injection

Change to United Kingdom (Great Britain & Northern Ireland) information only.

Joint UK/IE Leaflet:  UK MA Holder updated.  No change to Irish MA Holder.

Images updated in step 10 and step 11. Date of revision updated.

Changes

Added (underline) deleted (strikethrough)

2. What you need to know before you use Humulin I KwikPen

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 well if you inject into a lumpy area (See How to use Humulin I KwikPen). Contact your doctor if you are currently injecting into a lumpy area before you start injecting into 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

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Skin changes at the injection site:

If you inject insulin too often 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 area. Change the injection site with each injection to help prevent these skin changes.

Lipodystrophy (thickening or pitting of the skin) is uncommon (affects less than 1 person in 100). If you notice your skin thickening or pitting at the injection site, change your injection site and tell your doctor.

……..

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly 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. 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. By reporting side effects you can help provide more information on the safety of this medicine.

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6. Contents of the pack and other information

This leaflet was last revised in June 2020.

Changes

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4.       CLINICAL PARTICULARS

4.2   Posology and method of administration

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Method of administration

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

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4.4   Special warnings and precautions for use

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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.

……….

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.

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4.8   Undesirable effects

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Skin and subcutaneous tissue disorders: Frequency “unknown”: Cutaneous amyloidosis

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).

………

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.

…………

10.          DATE OF REVISION OF THE TEXT

09 November 2020

10. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION

Date of first authorisation: 13 March 2015

Date of last renewal: 11 March 2019

10. DATE OF REVISION OF THE TEXT

11 March 201919 October 2018

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10. DATE OF REVISION OF THE TEXT

17 August19 October 2018

Added (underline) deleted (strikethrough)

7.         MARKETING AUTHORISATION HOLDER

Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands. Eli Lilly and Company Limited, Lilly House, Priestley Road, Basingstoke, Hampshire, RG24 9NL, United Kingdom
 

8.         MARKETING AUTHORISATION NUMBER(S)

PA0047/088/002PA2276/005/002

10. DATE OF REVISION OF THE TEXT

17 August 2018

Changes

Added (underline) deleted (strikethrough)

4. CLINICAL PARTICULARS

4.2 Posology and method of administration

KwikPens (I)

Humulin I in pre-filled pen is only suitable for subcutaneous injections. should be given by subcutaneous injection but may although not recommended, also be given by intramuscular injection. This formulation should not be administered intravenously.

10. DATE OF REVISION OF THE TEXT

10 July 2018

4. CLINICAL PARTICULARS

4.4 Special warnings and precautions for use

…..

Excipients

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e., essentially

“sodium-free”.

4.8 Undesirable effects

…..

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, local reactions may be related to factors other than insulin, such as

irritants in the skin cleansing agent or poor injection technique.

…..

Lipodystrophy at the injection site is uncommon (≥1/1,000 to < 1/100).

(Introduction of a greater & equals symbol)

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Insulins and analogues for injection, intermediate-acting, Humulin I

ATC code: A10A C01.                              (Humulin I KwikPen)

…..

10. DATE OF REVISION OF THE TEXT

26 April 2018

New individual SmPC (previously included in a combined SmPC)

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, local reactions may be related to factors other than insulin, such as irritants in the skin cleansing agent or poor injection technique.

Systemic allergy, which is very rare (<1/10,000) but potentially more serious, is a generalised allergy to insulin.  It may cause rash over the whole body, shortness of breath, wheezing, reduction in blood pressure, fast pulse, or sweating.  Severe cases of generalised allergy may be life-threatening.  In the rare event of a severe allergy to HUMULIN, treatment is required immediately.  A change of insulin or desensitisation may be required.

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 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

6.          PHARMACEUTICAL PARTICULARS
6.1        List of excipients 

 . . . . . . . . . . . .
For HUMULIN I and HUMULIN M3 preparations:

m-cresol
Glycerol
Phenol
Protamine sulphfate
Dibasic sodium phosphate 7H₂O
Zinc oxide
Water for injections

The following may be used to adjust pH:
Hydrochloric acid and/or Sodium hydroxide

10.        DATE OF REVISION OF THE TEXT
Revision date changed to
31.3.2015

6.             PHARMACEUTICAL PARTICULARS
6.3          Shelf life

Vials

Unopened vials:   2  3 years.    

After first use: 28 days.

10.          DATE OF REVISION OF THE TEXT

Revision date changed to:

18 September 2012

Changes

6.             PHARMACEUTICAL PARTICULARS

6.3          Shelf life

Vials: The shelf life for HUMULIN S, HUMULIN I and HUMULIN M3 presentations is two years.

Once in use the vials may be used for up to 28 days.  Do not use beyond this period.  When in use the vials should not be stored above 30°C.

Cartridges: The shelf life for the HUMULIN S presentation is two years.  The shelf life for HUMULIN I and HUMULIN M3 presentations is 3 years.

After insertion of the cartridge in the pen, the solution or suspension should be used in 28 days.  Do not use beyond this period.  When in use the cartridges should not be stored above 30°C.

Pre-filled pen: The shelf life for HUMULIN I Pen is 3 years.

Once in use HUMULIN I Pen may be used for up to 28 days.  Do not use beyond this period.  When in use HUMULIN I Pen should not be stored above 30°C.

The shelf-life for HUMULIN S, HUMULIN I, and HUMULIN M3 presentations is two years.

Vials and pre-filled pens: Once in use the vials or HUMULIN I- and M3 Pen may be used for up to 28 days.  Do not use beyond this period.  When in use the vials or HUMULIN I- and M3 Pen should not be stored above 30°C.

Cartridges: After insertion of the cartridge in the pen, the solution or suspension should be used in 28 days.  Do not use beyond this period.  When in use the cartridges should not be stored above 30°C.

6.6          Special precautions for disposal and other handling

                Change to the 6.6 sub-heading title

6.6          Special precautions for disposal and other handling of a used medicinal product or waste materials derived from such medicinal product and other handling of the product

                Also inclusion of sub-heading   Instructions for use and handling

                The phase ‘…diabetic nurse.’ amended to ‘…diabetes specialist nurse’.

8.             MARKETING AUTHORISATION NUMBER(S)

Minor change of format of PA numbers, i.e.- from PA 47/58/3 to PA 0047/058/003

HUMULIN S vial:               PA 0047/058/003

HUMULIN I vial:                PA 0047/059/003

HUMULIN M3 vial:           PA 0047/069/002

HUMULIN S cartridge:      PA 0047/058/005

HUMULIN I cartridge:       PA 0047/059/006

HUMULIN M3 cartridge:  PA 0047/069/004

HUMULIN I Pen:                PA 0047/088/001

10.          DATE OF REVISION OF THE TEXT

New date

16 December 2009

3.             PHARMACEUTICAL FORM

Deleted (strikethrough):

Humulin I is a sterile suspension of a white, crystalline precipitate of isophane human insulin in an isotonic phosphate buffer. adjusted to a pH range of 6.9 to 7.5.

4.             CLINICAL PARTICULARS

4.1          Therapeutic indications

Deleted:

Humulin is also indicated for the initial control of diabetes mellitus and diabetes mellitus in pregnancy.

4.2                Posology and method of administration

Deleted:

Instructions for use and handling

A             Vials

A solution or suspension for injection in a 10ml vial to be used in conjunction with an appropriate syringe (100IU/ml markings).

B             Cartridges

A solution or suspension for injection in a 3ml cartridge to be used with a CE marked pen as recommended in the information provided by the device manufacturer.

C             Pre-filled pens

A suspension for injection in a pre-filled/disposable pen injector containing a 3ml cartridge.  HUMULIN I Pen delivers up to 60 units per dose in single unit increments.

a)             Preparing a dose

Vials or cartridges containing HUMULIN S formulation do not require resuspension and should only be used if it is clear, colourless, with no solid particles visible and if it is of water-like appearance.

Vials containing HUMULIN I or the HUMULIN M3 formulations should be rotated several times in the palms of the hands before use to completely resuspend the insulin, until it appears uniformly cloudy or milky.  Cartridges and pre-filled pens containing HUMULIN I and cartridges containing HUMULIN M3 formulations should be rolled in the palms of the hands ten times and inverted 180 ten times immediately before use to resuspend the insulin until it appears uniformly cloudy or milky.  If not, repeat the above procedure until contents are mixed.  Cartridges contain a small glass bead to assist mixing.  Do not shake vigorously as this may cause frothing, which may interfere with the correct measurement of the dose.

The vials and cartridges 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 or cartridge, giving a frosted appearance.

HUMULIN S and I Vials: Mixing of insulins - The shorter acting insulin should be drawn into the syringe first, to prevent contamination of the vial by the longer acting preparation.  It is advisable to inject directly after mixing.  However, if a delay is necessary, a consistent routine must be followed.

Alternatively, a separate syringe or, separate cartridges of HUMULIN S and I, can be used for administration of the correct amount of each formulation.

Vials:

Prepare your syringe prior to injection, as directed by your doctor or diabetic nurse.

Use an insulin syringe marked for the strength of insulin being administered.

Cartridges and pre-filled pens:

The cartridges are not designed to allow any other insulin to be mixed in the cartridge.  Cartridges are not designed to be refilled.

The manufacturer's instructions with each individual pen must be followed for loading the cartridge, attaching the needle and administering the insulin injection.

Follow the instructions with HUMULIN I Pen for attaching the needle and administering the insulin injection.

For HUMULIN I Pen, a needle must always be attached before priming, dialling, and injecting an insulin dose.  HUMULIN I Pen should always be primed before each injection.  Failure to prime HUMULIN I Pen may result in an inaccurate dose.

b)             Injecting a dose

Inject the correct dose of insulin, as directed by your doctor or diabetic nurse.

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

4.5           Interaction with other medicinal products and other forms of interaction

Added (bold):

Insulin requirements may be reduced in the presence of substances with hypoglycaemic activity, such as oral hypoglycaemics (OHA), salicylates (for example, acetylsalicylic acid), certain antidepressants (monoamine oxidase inhibitors), certain angiotensin converting enzyme (ACE) inhibitors (captopril, enalapril), angiotensin II receptor blockers, non-selective beta-blocking agents and alcohol.

Deleted (strikethrough) Added (bold):

Somatostatin analogues (octreotide, lanreotide) may both decrease and or increase insulin dose requirements.

6.             PHARMACEUTICAL PARTICULARS

6.1          List of excipients

Deleted (strikethrough) Added (bold):

disodium phosphate anhydrous dibasic sodium phosphate 7H₂0      

6.6          Special precautions for disposal and other handling

Instructions for use and handling

A             Vials

A solution or suspension for injection in a 10ml vial to be used in conjunction with an appropriate syringe (100IU/ml markings).

B             Cartridges

A solution or suspension for injection in a 3ml cartridge to be used with a CE marked pen as recommended in the information provided by the device manufacturer.

C             Pre-filled pens

A suspension for injection in a pre-filled/disposable pen injector containing a 3ml cartridge.  HUMULIN I Pen delivers up to 60 units per dose in single unit increments.

a)             Preparing a dose

Vials or cartridges containing HUMULIN S formulation do not require resuspension and should only be used if it is clear, colourless, with no solid particles visible and if it is of water-like appearance.

Vials containing HUMULIN I or the HUMULIN M3 formulations should be rotated several times in the palms of the hands before use to completely resuspend the insulin, until it appears uniformly cloudy or milky.  Cartridges and pre-filled pens containing HUMULIN I and cartridges containing HUMULIN M3 formulations should be rolled in the palms of the hands ten times and inverted 180 ten times immediately before use to resuspend the insulin until it appears uniformly cloudy or milky.  If not, repeat the above procedure until contents are mixed.  Cartridges contain a small glass bead to assist mixing.  Do not shake vigorously as this may cause frothing, which may interfere with the correct measurement of the dose.

The vials and cartridges 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 or cartridge, giving a frosted appearance.

HUMULIN S and I Vials: Mixing of insulins - The shorter acting insulin should be drawn into the syringe first, to prevent contamination of the vial by the longer acting preparation.  It is advisable to inject directly after mixing.  However, if a delay is necessary, a consistent routine must be followed.

Alternatively, a separate syringe or, separate cartridges of HUMULIN S and I, can be used for administration of the correct amount of each formulation.

Vials:

Prepare your syringe prior to injection, as directed by your doctor or diabetic nurse.

Use an insulin syringe marked for the strength of insulin being administered.

Cartridges and pre-filled pens:

The cartridges are not designed to allow any other insulin to be mixed in the cartridge.  Cartridges are not designed to be refilled.

The manufacturer's instructions with each individual pen must be followed for loading the cartridge, attaching the needle and administering the insulin injection.

Follow the instructions with HUMULIN I Pen for attaching the needle and administering the insulin injection.

For HUMULIN I Pen, a needle must always be attached before priming, dialling, and injecting an insulin dose.  HUMULIN I Pen should always be primed before each injection.  Failure to prime HUMULIN I Pen may result in an inaccurate dose.

b)             Injecting a dose

Inject the correct dose of insulin, as directed by your doctor or diabetic nurse.

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

Each pack contains a patient information leaflet with instructions on how to inject insulin.

10.          DATE OF REVISION OF THE TEXT

17 December 2008

7.             MARKETING AUTHORISATION HOLDER

Changed:

Eli Lilly and Company Limited

Lilly House

Priestley Road

Basingstoke

Hampshire, RG24 9NL

England.

10.          DATE OF REVISION OF THE TEXT

New date:

Humulin S vial:                    28 November 2007

Humulin I vial:                    28 November 2007

Humulin M3 vial:                28 November 2007

Humulin S cartridge:           28 November 2007

Humulin I cartridge:           28 November 2007

Humulin M3 cartridge:       28 November 2007

Humulin I Pen:                    28 November 2007

1.             NAME OF THE MEDICINAL PRODUCT

Deletions in strikethrough text

2.             QUALITATIVE AND QUANTITATIVE COMPOSITION

Changes shown in bold text

1ml contains 100IU human insulin (produced in E. coli by recombinant DNA technology).

Humulin S:           One vial contains 10ml equivalent to 1000IU of soluble insulin.

One cartridge contains 3ml equivalent to 300IU of soluble insulin.

Humulin I:            One vial contains 10ml equivalent to 1000IU of isophane insulin.

One cartridge contains 3ml equivalent to 300IU of isophane insulin

Humulin I Pen:    One pre-filled pen contains 3ml equivalent to 300IU of isophane insulin.

Humulin M3:       One vial contains 10ml equivalent to 1000IU of biphasic isophane insulin - 30% soluble insulin/70% isophane insulin.

One cartridge contains 3ml equivalent to 300IU of biphasic isophane insulin in - 30% soluble insulin/70% isophane insulin

For a full list of excipients, see section 6.1.

3.             PHARMACEUTICAL FORM

                Reformatted section and moved the following statements to section 5.1.

Humulin S is a rapidly acting insulin preparation.

Humulin I is an intermediate acting insulin preparation

Humulin M3 is an intermediate acting insulin preparation.

4.             CLINICAL PARTICULARS

4.2          Posology and method of administration

Deletions in strikethrough text and additions in bold

Humulin I and Humulin M3 in vials, and Humulin I and Humulin M3 in cartridge presentations should be given by subcutaneous injection but may, although not recommended, also be given by intramuscular injection.  These formulations should not be administered intravenously.

Humulin I (Isophane) may be administered in combination with Humulin S (Soluble).  (See section 6.6 ‘Instructions for use and handling’ for ‘Mixing of insulins’.)

The Humulin Mixture formulation is a ready-made defined mixture of Humulin S soluble and Humulin I isophane insulin designed to avoid the need for the patient to mix insulin preparations.  A patient’s treatment regimen should be based on their individual metabolic requirements.

                The entire section on ‘Instructions for use and handling’ brought forward from section 6.6 to section 4.2 with reformatting and slight rewording.

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.

Frequency categories added for the AEs; local allergy, systemic allergy and lipodystrophy.

4.9          Overdose

Added:

Sustained carbohydrate intake and observation may be necessary because hypoglycaemia may occur after apparent clinical recovery.

5.             PHARMACOLOGICAL PROPERTIES

5.1          Pharmacodynamic properties

The following statements moved from section 3 to this section.

Humulin S is a rapidly acting insulin preparation.

Humulin I is an intermediate acting insulin preparation.

Humulin M3 (Mixture 3) is an intermediate acting insulin preparation

6.             PHARMACEUTICAL PARTICULARS

6.1          List of excipients

Deleted the following statements:

Each vial or cartridge will contain human insulin (recombinant DNA origin) and the following excipients.

Each vial, cartridge, or pre-filled pen will contain human insulin (recombinant DNA origin) and the following excipients:

The name of the excipient ‘dibasic sodium phosphate’ changed to ‘disodium phosphate anhydrous’ for the Humulin I and M3 preparations.

6.3          Shelf-life

Deletions in strikethrough text and additions in bold.

The in-use shelf-life for all Humulin vials and all Humulin 3ml cartridges (including the Humulin I Pen) is 28 days.

Vials and pre-filled pens: Once in use the vials or Humulin I Pen may be used for up to 28 days.  Do not use beyond this period.  When in use the vials or Humulin I Pen should not be stored above 30 C.

Cartridges: After insertion of the cartridge in the pen, the solution or suspension should be used in 28 days.  Do not use beyond this period.  When in use the cartridges should not be stored above 30°C.

6.4          Special precautions for storage

Changed ‘Store at 2°C-8°C (in a refrigerator).’ to ‘Store in a refrigerator (2°C-8°C).’

Deleted following statements:

Once in use, the vials, cartridges, and pre-filled pens may be used for up to 28 days.  Do not use beyond this period.

When in use, the vials, cartridges, and pre-filled pens should not be stored above 30°C.

6.5          Nature and contents of container

Deletions in strikethrough text and additions in bold.

Humulin vials: The product is filled in vials that comply with the requirements of the PhEur for Type I flint glass, stoppered with rubber closures, and sealed with aluminium seals combined with a plastic 'flip top'.

1 x 10ml vial

Vials: 10ml of solution or suspension in a vial (Type I glass) with a stopper (rubber) sealed with a seal (aluminium) combined with a flip top (plastic).

Pack size 1 or 2.

Humulin cartridges and prefilled pens: The product is filled in cartridges that comply with the requirements of the PhEur for Type I flint glass, and sealed with rubber closures consisting of a plunger head at the bottom and a disk seal at the top of the cartridge.

5 x 3ml cartridges

5 x 3ml pens

Cartridges: 3ml solution or suspension in a cartridge (Type I glass) with a plunger head at the bottom (rubber) and disc seal at the top (rubber).

Pack size of 5.

Pre-filled pens: 3ml suspension in a cartridge (Type I glass) with a plunger head at the bottom (rubber) and disc seal at the top (rubber) in a pre-filled pen.

Pack size of 5

6.6          Instructions for use and handling Special precautions for disposal and other handling

The entire section on ‘Instructions for use and handling’ moved from this section to section 4.2.

Subheading, ‘c) Disposal of used containers and needles’ deleted.

Changes to the following paragraph shown in bolded text below:

Do not reuse needles.  Dispose of the needle in a responsible manner.  Needles and pens must not be shared.  Vials, cartridges and Humulin I Pen can be used until empty, then properly discard. Any unused product or waste material should be disposed of in accordance with local requirements.

9.             DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of last renewal for all presentations changed to 24 April 2006.

10.          DATE OF REVISION OF THE TEXT

New date

20 November 2006