Xultophy 100 units/ml + 3.6 mg/ml solution for injection

• Section 4.8: Addition of 'Intestinal obstruction' as an adverse reaction, with a frequency of 'unknown'
• Minor formatting changes throughout

Section 4: Addition of 'Bowel obstruction' as a possible side effect, with a frequency of 'not known'

Minor formatting changes throughout

Addition of a paragraph on Aspiration in association with general anaesthesia or deep sedation to Section 4.4.

-Addition of the following sentence to Section 2, Warnings and precautions:

If you know that you are due to have surgery where you will be under anesthesia (sleeping), please tell your doctor that you are taking Xultophy.

Added to possible side effects: Dizziness under common and delayed gastric emptying under Not Known. Revision Date updated to 12/2023

Added to section 4.8 undesirable effects: Dizziness added under common and Delayed gastric emptying added under unknown. In addition minor formatting changes made throughout document (spaces, remove underlining, italics)

Added to side effects: Change in how things taste.

Reference to glucagon injection changed to remove the word injection.

Dysgeusia added to section 4.8 undesirable effects.

text amended in section 4.9 in yellow highlight:

Severe hypoglycaemic episodes, where the patient is not able to treat himself, can be treated with glucagon (0.5 to 1 mg)  given intramuscularly, subcutaneously or intranasally by a trained person, or with glucose given intravenously by a healthcare professional. Glucose must be given intravenously if the patient does not respond to glucagon within 10 to 15 minutes. Upon regaining consciousness, administration of oral carbohydrates is recommended for the patient in order to prevent a relapse.

United Kingdom updated to United Kingdom (Northern Ireland)

Date of revision updated to 09/2022

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

New text:

Skin changes at the injection site

The injection site should be rotated to help prevent changes to the fatty tissue under the skin, such as skin thickening, skin shrinking or lumps under the skin. The insulin may not work very well if you inject into a lumpy, shrunken or thickened area (see section 3 ‘How to use Xultophy^®’). Tell your doctor if you notice any skin changes at the injection site. Tell your doctor if you are currently injecting into these affected areas before you start injecting in a different area. Your doctor may tell you to check your blood sugar more closely, and to adjust your insulin or your other antidiabetic medications dose.

Section 4 – possible side effects

New text:

Skin changes at the injection site:

If you inject insulin at the same place, the fatty tissue may shrink (lipoatrophy) or thicken (lipohypertrophy) (may affect up to 1 in 100 people). Lumps under the skin may also be caused by build-up of a protein called amyloid (cutaneous amyloidosis; how often this occurs is not known). The insulin may not work very well if you inject into a lumpy, shrunken or thickened area. Change the injection site with each injection to help prevent these skin changes.

Deleted text from ‘Uncommon (may affect up to 1 in 100 people)’:

Skin changes where you give the injection  (‘lipodystrophy’) the fatty tissue under the skin may shrink (‘lipoatrophy’) or get thicker (‘lipohypertrophy’). Changing the place where you inject each time may reduce the risk of these skin changes. If you notice these skin changes, tell your doctor or nurse. If you keep injecting in the same place, these changes can become more severe and affect the amount of medicine your body gets from the pen.

Section 4.2 - method of administration

Updated text:

Injection sites should are always to be rotated within the same region in order to reduce the risk of lipodystrophy and cutaneous amyloidosis (see sections 4.4 and 4.8).

Section 4.4

New text:

Skin and subcutaneous tissue disorders

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

Section 4.8

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

Not known – cutaneous amyloidosis†

† ADR from postmarketing sources.

Skin and subcutaneous tissue disorders

Lipodystrophy (including lipohypertrophy, lipoatrophy) and cutaneous amyloidosis may occur at the injection site and delay local insulin absorption. Continuous rotation of the injection site within the particular given injection area may help to reduce or prevent the risk of developing these reactions (see section 4.4).

Section 1

Subsection updated as follows:

"If you use basal insulin

You should stop your basal insulin treatment prior to starting on Xultophy."

Section 4

HPRA reporting details shortened to 'HPRA Pharmacovigilance, Website: www.hpra.ie"

Section 4.2:

Transfer from any basal insulin regimen that includes a basal insulin component

Therapy with other basal insulin regimens should be discontinued prior to initiation of Xultophy. When transferring from basal any other insulin therapy that includes a basal insulin component, the recommended starting dose of Xultophy is 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) (see section 4.4 and 5.1). The recommended starting dose should not be exceeded, but may be reduced to avoid hypoglycaemia in selected cases. Close glucose monitoring is recommended during the transfer and in the following weeks.

Section 4.8, how to report a side effect

Reporting details for the HPRA reduces as per QRD Appendix V.

Section 5.1

Figure 7 replaced to correct minor change

Black triangle removed

Section 9 updated to include "Date of latest renewal: 08 July 2019"

Black triangle removed

Section 4.4:

Sentence update: "In case of discontinuation of Xultophy, ensure that instruction for initiation of alternative antidiabetic medication treatment is followed"

Section 4.8:

Text update in Table 1. 'Adverse Drug Reaction' updated to 'Adverse reaction'

Reporting of side effects: reporting of adverse event to the MHRA deleted. Reporting to the HPRA remains.

Section 6.3:

Text updates: "After first opening, the medicinal product can be stored for 21 days at a maximum temperature of 30°C. The medicinal product should be discarded 21 days after first opening"