Humalog 100 units/ml, solution for injection in vial

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)

Section 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). 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 changes have been made throughout sections of the PIL.

Changes

The SmPC for Humalog 100 units/mL vial, cartridge, KwikPen, Junior KwikPen, Tempo Pen now includes new text relating to the non-marketed Tempo pen.

In addition, other minor formatting changes have been made throughout SmPC sections.

 Added (underline) deleted (strikethrough)

1.       NAME OF THE MEDICINAL PRODUCT

 Humalog 100 units/ml solution for injection in vial

Humalog 100 units/ml solution for injection in cartridge

Humalog 100 units/ml KwikPen solution for injection in a pre-filled pen

Humalog 100 units/ml Junior KwikPen solution for injection in a pre-filled pen

Humalog 100 units/ml Tempo Pen solution for injection in a pre-filled pen

2.       QUALITATIVE AND QUANTITATIVE COMPOSITION

………

 KwikPen and Tempo Pen

Each pre-filled pen contains 300 units of insulin lispro in 3 ml solution.

Each pre-filled pen KwikPen delivers 1-60 units in steps of 1 unit.

……… 

4.       CLINICAL PARTICULARS

 4.2   Posology and method of administration

Posology

The dosage dose should be determined by the physician, according to the requirement of the patient.

………

Humalog KwikPens

Humalog KwikPen is available in two strengths. The Humalog 100 units/ml KwikPen (and Humalog 200 units/ml KwikPen, see separate SmPC) delivers 1 – 60 units in steps of 1 unit in a single injection. The Humalog 100 units/ml Junior KwikPen delivers 0.5 – 30 units in steps of 0.5 units in a single injection. The number of insulin units is shown in the dose window of the pen regardless of strength and no dose conversion should be done when transferring a patient to a new strength or to a pen with a different dose step.

Humalog Tempo Pen

The Humalog 100 units/ml Tempo Pen delivers 1 – 60 units in steps of 1 unit in a single injection. The number of insulin units is shown in the dose window of the pen regardless of strength and no dose conversion should be done when transferring a patient to a new strength or to a pen with a different dose step. The Tempo Pen can be used with the optional transfer module Tempo Smart Button (see section 6.6).

As with any insulin injection, when using the Tempo Pen, Smart Button and the mobile application, the patient should be instructed to check their blood sugar levels when considering or making decisions about another injection if they are unsure how much they have injected.

………

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 medicinal product should be clearly recorded.

……….

Tempo Pen

The Tempo Pen contains a magnet (see section 6.5) that may interfere with the functions of an implantable electronic medical device, such as a pacemaker. The magnetic field extends to approximately 1.5 cm.

……….

6.             PHARMACEUTICAL PARTICULARS

6.2       Incompatibilities

Vial

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

Cartridge, KwikPen, and Junior KwikPen and Tempo Pen

These medicinal products should not be mixed with any other insulin or any other medicinal product.

Vial

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

6.4       Special precautions for storage

……….

KwikPen, and Junior KwikPen and Tempo Pen

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

……….

6.5   Nature and contents of container

……….

Junior KwikPen

Type I glass cartridges, sealed with halobutyl disc seals secured with aluminium seals and bromobutyl plunger heads. Dimeticone or silicone emulsion may be used to treat the cartridge plunger. The 3 ml cartridges are sealed in a disposable pen injector, called the “Junior KwikPen”. Needles are not included.

3 ml Junior KwikPen: Packs of 1 pre-filled pen, 5 pre-filled pens or a multipack of 10 (2 packs of 5) pre-filled pens. Not all packs may be marketed.

Tempo Pen

Type I glass cartridges, sealed with halobutyl disc seals secured with aluminium seals and bromobutyl plunger heads. Dimeticone or silicone emulsion may be used to treat the cartridge plunger. The 3 ml cartridges are sealed in a disposable pen injector, called the “Tempo Pen”. The Tempo Pen contains a magnet (see section 4.4). Needles are not included.

3 ml Tempo Pen: Packs of 5 prefilled pens or a multipack of 10 (2 packs of 5) prefilled pens. Not all packs may be marketed.

6.6   Special precautions for disposal and other handling

……….

Humalog Tempo Pen

The Tempo Pen is designed to work with the Tempo Smart Button. The Tempo Smart Button is an optional product that can be attached to the Tempo Pen dose knob and aids in transmitting Humalog dose information from the Tempo Pen to a compatible mobile application. The Tempo Pen injects insulin with or without the Tempo Smart Button attached. To transmit data to the mobile application, follow the instructions provided with the Tempo Smart Button and the instructions with the mobile application.

 8.             MARKETING AUTHORISATION NUMBER(S)

……….

EU/1/96/007/046

EU/1/96/007/047

10.          DATE OF REVISION OF THE TEXT

13 January 2019 23 July 2020

HLG77M

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

HLG69MHLG73M

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

Humalog can be used in adolescents and children (see section 5.1).

4.4          Special warnings and precautions for use

Humalog should only be used in children in preference to soluble insulin when a fast action of insulin might be beneficial. For example, in the timing of the injections in relation to meals.

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

HLG58M

Changes

6.             PHARMACEUTICAL PARTICULARS

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

                ………..

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

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

                ………..

8.             MARKETING AUTHORISATION NUMBERS

                ………..

                HUMALOG cartridges

              5 x 3ml HUMALOG cartridges for a 3ml pen:               EU/1/96/007/004

              2 x (510 x 3ml) HUMALOG cartridges for a 3ml pen:   EU/1/96/007/023

                …………

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 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 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

Cartridge: 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.

KwikPen: 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: IMB Pharmacovigilance, 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 cartridges

Instructions for use and handling

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 KwikPen

Instructions for use and handling

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

4.2                   Posology and method of administration

                         . . . .

HUMALOG can be used in conjunction with a longer-acting human insulin or oral sulphonylurea agents, on the advice of a physician.

Use of HUMALOG in an insulin infusion pump:

Only certain CE-marked insulin infusion pumps may be used to infuse insulin lispro. Before infusing insulin lispro, the manufacturer’s instructions should be studied to ascertain the suitability or otherwise for the particular pump. Read and follow the instructions that accompany the infusion pump. Use the correct reservoir and catheter for the pump. The infusion set (tubing and cannula) should be changed in accordance with the instructions in the product information supplied with the infusion set. Change the infusion set every 48 hours. Use aseptic technique when inserting the infusion set. In the event of a hypoglycaemic episode, the infusion should be stopped until the episode is resolved. If repeated or severe low blood glucose levels occur, notify your health care professional and consider the need to reduce or stop your insulin infusion. A pump malfunction or obstruction of the infusion set can result in a rapid rise in glucose levels. If an interruption to insulin flow is suspected, follow the instructions in the product literature and if appropriate, notify your health care professional. When used with an insulin infusion pump, HUMALOG should not be mixed with any other 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 UK: www.mhra.gov.uk/yellowcard, or Ireland: IMB 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:
            23 April 2014

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

6.             PHARMACEUTICAL PARTICULARS

PLEASE NOTE:  the SPC has been updated throughout in order to reflect QRD template changes and the removal of Humalog 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

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),

6.             PHARMACEUTICAL PARTICULARS

6.3          Shelflife

Added:

Unopened vials

2 years

Unused cartridges and unused pre-filled pens

Added (bold) Deleted (strikethrough):

3 years 2 years

Added:

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

Added (bold) deleted (strikethrough):

After cartridge insertion, or after first use (vial and prefilled pen) insertion of the cartridge in a pen, or the first use of the vial or 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:

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.

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

Section 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

01 July 2009

4.       CLINICAL PARTICULARS

4.2          Posology and method of administration

Re-Formatted:

Use of HUMALOG in an insulin infusion pump:

Only certain CE-marked insulin infusion pumps may be used to infuse insulin lispro. Before infusing insulin lispro, the manufacturers instructions should be studied to ascertain the suitability or otherwise for the particular pump. Read and follow the instructions that accompany the infusion pump. Use the correct reservoir and catheter for the pump. Change the infusion set every 48 hours. Use aseptic technique when inserting the infusion set. In the event of a hypoglycaemic episode, the infusion should be stopped until the episode is resolved. If repeated or severe low blood glucose levels occur, notify your health care professional and consider the need to reduce or stop your insulin infusion. A pump malfunction or obstruction of the infusion set can result in a rapid rise in glucose levels. If an interruption to insulin flow is suspected, follow the instructions in the product literature and if appropriate, notify your health care professional. When used with an insulin infusion pump, HUMALOG should not be mixed with any other insulin.

Intravenous administration of insulin:

Intravenous injection of insulin lispro should be carried out following normal clinical practise for intravenous injections, for example by an intravenous bolus or by an infusion system. Frequent monitoring of the blood glucose levels is required.

Infusion systems at concentrations from 0.1U/ml to 1.0U/ml insulin lispro in 0.9% sodium chloride or 5% dextrose are stable at room temperature for 48 hours. It is recommended that the system is primed before starting the infusion to the patient.

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

Humalog vials

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

a)            Preparing a dose

Inspect the Humalog solution.  It should be clear and colourless.  Do not use Humalog if it appears cloudy, thickened, or slightly coloured, or if solid particles are visible.

i)             Humalog

1.             Wash your hands.

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

3.             If the therapeutic regimen requires the injection of basal insulin and Humalog at the same time, the two can be mixed in the syringe.  If mixing insulins, refer to the instructions for mixing that follow in section ii) and 6.2.

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

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

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

7.             Before removing the needle from the vial, check the syringe for air bubbles that reduce the amount of Humalog 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.

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

ii)            Mixing Humalog with longer-acting human insulins (see section 6.2)

1.                   Humalog should be mixed with longer-acting human insulins only on the advice of a doctor.

2.             Draw air into the syringe equal to the amount of longer-acting insulin being taken.  Insert the needle into the longer-acting insulin vial and inject the air.  Withdraw the needle.

3.             Now inject air into the Humalog vial in the same manner, but do not withdraw the needle.

4.             Turn the vial and syringe upside down.

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

6.             Before removing the needle from the vial, check the syringe for air bubbles that reduce the amount of Humalog 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 of Humalog and insert it into the vial of the longer-acting insulin.  Turn the vial and syringe upside down.  Hold the vial and syringe firmly in one hand and shake gently.  Making sure the tip of the needle is in the insulin, withdraw the dose of longer-acting insulin.

8.             Withdraw the needle 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.

c)             Mixing insulins

Do not mix insulin in vials with insulin in cartridges.  See section 6.2.

Humalog cartridges

Humalog cartridges are to be used with a CE marked pen as recommended in the information provided by the device manufacturer.

a)            Preparing a dose

Inspect the Humalog solution.  It should be clear and colourless.  Do not use Humalog if it appears cloudy, thickened, or slightly coloured, or if solid particles are visible.

The following is a general description.  The manufacturer’s instructions with each individual pen must be followed for loading the cartridge, attaching the needle, and administering the insulin injection.

b)            Injecting a dose

1.             Wash your hands.

2.                   Choose a site for injection.

3.             Clean the skin as instructed.

4.             Remove outer needle cap.

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

6.             Press the knob.

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

8.             Using the outer needle cap, unscrew the needle and dispose of it safely.

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

c)             Mixing insulins

Do not mix insulin in vials with insulin in cartridges.  See section 6.2.

Humalog Pens

a)            Preparing a dose

1.             Inspect the Humalog Pen solution.

It should be clear and colourless.  Do not use Humalog Pen if it appears cloudy, thickened, or slightly coloured, or if solid particles are visible.

2.             Put on the needle.

Wipe the rubber seal with alcohol.  Remove the paper tab from the capped needle.  Screw the capped needle clockwise onto the pen until it is tight.  Hold the pen with needle pointing up and remove the outer needle cap and inner needle cover.

3.             Priming the pen (check insulin flow).

(a)           The arrow should be visible in the dose window.  If the arrow is not present, turn the dose knob clockwise until the arrow appears and notch is felt or visually aligned.

(b)           Pull dose knob out (in direction of the arrow) until a ‘0’ appears in the dose window.  A dose cannot be dialled until the dose knob is pulled out.

(c)           Turn dose knob clockwise until a ‘2’ appears in the dose window.

(d)           Hold the pen with needle pointing up and tap the clear cartridge holder gently with your finger so any air bubbles collect near the top.  Depress the injection button fully until you feel or hear a click.  You should see a drop of insulin at the tip of the needle.  If insulin does not appear, repeat the procedure until insulin appears.

(e)           Always prime the pen (check the insulin flow) before each injection.  Failure to prime the pen may result in an inaccurate dose.

4.             Setting the dose.

(a)           Turn the dose knob clockwise until the arrow appears in the dose window and a notch is felt or visually aligned.

(b)           Pull the dose knob out (in the direction of the arrow) until a ‘0’ appears in the dose window.  A dose cannot be dialled until the dose knob is pulled out.

(c)           Turn the dose knob clockwise until the dose appears in the dose window.  If too high a dose is dialled, turn the dose knob backward (anti-clockwise) until the correct dose appears in the window.  A dose greater than the number of units remaining in the cartridge cannot be dialled.

b)            Injecting a dose

1.             Wash your hands.

2.             Choose a site for injection.

3.             Clean the skin as instructed.

4.             Remove outer needle cap.

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

6.             Press the injection button down with the thumb (until you hear or feel a click); wait 5 seconds.

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

8.             Immediately after an injection, use the outer needle cap to unscrew the needle.  Remove the needle from the pen.  This will ensure sterility, and prevent leakage, re-entry of air, and potential needle clogs.  Do not reuse the needle.  Dispose of the needle in a responsible manner.  Needles and pens must not be shared.

The prefilled pen can be used until it is empty.  Please properly discard or recycle.

9.             Replace the cap on the pen.

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

11.          The injection button should be fully depressed before using the pen again.

c)             Mixing insulins

Do not mix insulin in vials with insulin in cartridges.  See section 6.2.

10.          DATE OF REVISION OF THE TEXT

31 January 2008

4.             CLINICAL PARTICULARS

4.4          Special warnings and precautions for use

Added text in bold

Transferring a patient to another type or brand of insulin should be done under strict medical supervision.  Changes in strength, brand (manufacturer), type (soluble, isophane, lente, etc), species (animal, human, human insulin analogue), and/or method of manufacture (recombinant DNA versus animal-source insulin) may result in the need for a change in dosage.  For fast-acting insulins, any patient also on basal insulin must optimise dosage of both insulins to obtain glucose control across the whole day, particularly nocturnal/fasting glucose control.

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

5.1          Pharmacodynamic properties

Deletions in strikethrough text

Clinical trials in patients with Type 1 and Type 2 diabetes have demonstrated reduced postprandial hyperglycaemia with insulin lispro compared to soluble human insulin.  For fast-acting insulins, any patient also on a basal insulin must optimise dosage of both insulins to obtain improved glucose control across the whole day.

10.          DATE OF REVISION OF THE TEXT

New date

3 May 2007

4.             CLINICAL PARTICULARS

4.2                Posology and method of administration

Text previously under the heading ‘Instructions for use, handling and disposal’ (section 6.6), now appears unchanged here.

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.

Reworded:

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 10ml Humalog vials.

5 x (1 x 10ml) Humalog vials.

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

2 x (5 x 3ml) Humalog Pens.

6.6          Special precautions for disposal

Added:

Any unused product or waste material should be disposed of in accordance with local requirements.

8.             MARKETING AUTHORISATION NUMBERS

Added:

Humalog vials

2 x 10ml Humalog vials:                   EU/1/96/007/020

5 x (1 x 10ml) Humalog vials:           EU/1/96/007/021

Humalog cartridges

2 x (5 x 3ml) Humalog cartridges for a 3ml pen:     EU/1/96/007/023

Humalog Pens

2 x (5 x 3ml) Humalog Pens:     EU/1/96/007/026

9.             DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation:                         Vial:                                30 April 1996

                                                                        3ml cartridge:                30 April 1996

                                                                        Humalog Pen 3ml:        30 April 1996

Date of renewal of the authorisation:       Vial:                                30 April 2006

                                                                        3ml cartridge:                30 April 2006

                                                                        Humalog Pen 3ml:        30 April 2006

10.          DATE OF REVISION OF THE TEXT

9 February 2006