Tepezza

Patient Information Leaflet

TEPEZZA 500 mg powder for concentrate for solution for infusion

teprotumumab
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before receiving this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

1. What TEPEZZA is and what it is used for
2. What you need to know before you are given TEPEZZA
3. How TEPEZZA is administered
4. Possible side effects
5. How to store TEPEZZA
6. Contents of the pack and other information

1. What TEPEZZA is and what it is used for

TEPEZZA contains teprotumumab, a type of protein (monoclonal antibody).
This medicinal product is used in adults to treat moderate to severe thyroid eye disease (TED).
TED is an autoimmune disease in which the immune system (the body's natural defenses) attacks the muscles and fat around the eyes. A protein called IGF-1R is present in the muscles and fat around the eyes. In people with TED, the immune system activates the IGF-1R protein, causing inflammation and swelling that can push the eyes forward, making them bulge. It may also cause double vision and, in more severe cases, lead to irreversible vision damage.
The active substance in TEPEZZA, teprotumumab, blocks the IGF-1R protein, preventing the immune system from attacking the muscle and fat tissues around the eyes, thereby helping to reduce swelling, relieve pressure around the eyes, and improve disease symptoms.

2. What you should know before being given TEPEZZA

Do not use TEPEZZA

• if you are allergic to teprotumumab or to any of the other ingredients of this medicine (listed in section 6);
• if you are pregnant (see section “Pregnancy, breastfeeding and contraception”).

If in doubt, consult your doctor or nurse before being given TEPEZZA.
Warnings and precautions
Talk to your doctor or nurse before taking TEPEZZA if:

• you have had hearing problems or use hearing aids;
• you are sensitive to loud noises;
• you have diabetes or pre-diabetes;
• you have inflammatory bowel disease;
• you are pregnant or planning to have a baby;
• you smoke;
• you have ever had high blood pressure.

You must stop smoking before starting treatment; in addition, your doctor may need to monitor
your blood pressure before and during treatment.
Your doctor will explain the benefits and risks of TEPEZZA and will provide you with a “Patient Guide” to
help you understand the risk of developing hearing problems and the need for using an effective
contraceptive method during treatment.
Infusion-related reactions
You will be monitored during the infusion and for 90 minutes afterwards to check whether you develop an
infusion-related reaction. Inform your doctor or nurse if symptoms of an infusion-related reaction occur,
especially if this happens after the monitoring period. Symptoms of infusion-related reactions are listed in
section 4, “Possible side effects”.
High blood sugar (hyperglycaemia)
TEPEZZA may cause an increase in blood sugar levels, especially if you already have
diabetes or pre-diabetes (see section 4, “Possible side effects”).
Your doctor or nurse will check your blood sugar levels before starting treatment,
during treatment, and for up to 6 months after completion of treatment. If your current diabetes
medications fail to control your blood sugar, discuss this with your doctor. It is important
to ensure that blood sugar levels are properly managed before starting
treatment with TEPEZZA.
Hearing problems
TEPEZZA may cause hearing problems, including severe hearing loss which could be
permanent. Symptoms of hearing problems are listed in section 4, “Possible side
effects”. If you already have hearing problems, symptoms may worsen during or after
treatment. If you notice any change in your hearing at any time, consult your doctor as
soon as possible.
During treatment, you should avoid loud noises. Your hearing will be monitored through a
hearing test before starting treatment, during, and after completion of treatment.
Your doctor will decide whether additional hearing tests are needed and will monitor your
hearing for 6 months after completion of treatment. If hearing loss occurs that requires
medical treatment, interferes with your ability to perform daily activities, or worsens,
your doctor may discontinue treatment with TEPEZZA.
Inflammatory bowel disease
TEPEZZA may worsen existing inflammatory bowel disease (IBD), an inflammation
of the colon and rectum, including ulcerative colitis and Crohn’s disease. If during treatment you notice signs of
IBD flare-up (see section 4), inform your doctor or seek medical attention as soon
as possible.
Children and adolescents
TEPEZZA is not recommended for children and adolescents under 18 years of age. The safety and
benefits of this medicine have not been established in these patient populations.
Other medicines and TEPEZZA
Inform your doctor or nurse if you are taking, have recently taken, or might take
any other medicines. This includes non-prescription medicines and herbal
medicines.
It is important to inform your doctor if you are taking medicines that may affect hearing, such as:

• certain antibiotics (e.g., aminoglycosides or vancomycin);
• platinum-containing medicines used to treat cancer;
• diuretic tablets (loop diuretics) used to remove excess fluid.
  Concomitant use of these medicines with TEPEZZA may increase the risk of hearing problems.

Pregnancy, breastfeeding and contraception
Pregnancy
If you suspect you are pregnant or are planning a pregnancy, ask your doctor or nurse for advice before
using this medicine.
Do not use this medicine if you are pregnant. TEPEZZA may cause harm to the unborn baby.
Contraception
If you are of childbearing potential, you must use an effective contraceptive method during treatment with
TEPEZZA and for at least 6 months after the last dose.
Breastfeeding
Do not use this medicine if you are breastfeeding. It is not known whether this medicine passes into
breast milk, and the risk to the breastfed infant is unknown. If you plan to breastfeed, consult your
doctor or nurse before using this medicine.
Driving and using machines
During treatment with TEPEZZA, you may experience fatigue or headache, which could
impair your ability to drive or operate machinery. If you experience these symptoms, do not
drive or operate machinery.
TEPEZZA contains polysorbate
This medicine contains 1.05 mg of polysorbate 20 in each 10.5 mL volume. Polysorbates
may cause allergic reactions. Inform your doctor if you have known allergies.

3. How TEPEZZA is administered

This medicine is administered in a healthcare setting under the supervision of a healthcare professional.
You will receive eight infusions given once every three weeks. The dose of Tepezza depends on your body weight.
A doctor or nurse will administer the medicine to you as an intravenous infusion (into a vein). The doctor will determine the duration of the infusion.

If you are given too much TEPEZZA
TEPEZZA will be administered by healthcare personnel, so it is unlikely that you will receive an overdose. However, if this should happen, your doctor will monitor you for any signs or symptoms of adverse effects and will treat them as necessary.

If you miss a dose of TEPEZZA
If you miss a dose, contact your doctor immediately to schedule another appointment for TEPEZZA administration. Your doctor will decide when to administer your next dose.

If you stop treatment with TEPEZZA
Do not stop treatment with TEPEZZA without first talking to your doctor.
If you have any doubts about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Immediately inform your doctor or nurse if you experience any of the following symptoms
during or after the infusion:
Infusion-related reactions (common, may affect up to 1 in 10 people)
You may experience symptoms such as:

• difficulty breathing or chest pain
• skin redness or flushing, or skin rash
• chills or shivering
• feeling unwell
• dizziness
• rapid heartbeat
• loss of consciousness

Contact a doctor immediately or go to the nearest emergency room if you experience any of the
following symptoms:
Very high blood sugar (hyperglycaemia)
TEPEZZA may cause uncontrolled high blood sugar levels, especially if you already have diabetes or pre-diabetes. Inform your doctor, nurse, or go to the nearest emergency room immediately if you experience signs of very high blood sugar, including:

• diabetic ketoacidosis (uncommon, may affect up to 1 in 100 people): a potentially life-threatening condition in people with diabetes where lack of insulin causes increased blood sugar and ketone levels. Early symptoms include excessive thirst and increased need to urinate. You may also experience other symptoms such as nausea, vomiting, feeling tired or confused, stomach pain, rapid or deeper breathing, and fruity-smelling breath.
• hyperglycaemic hyperosmolar state (frequency not known, cannot be estimated from available data): a serious condition that occurs when blood sugar becomes extremely high over several days or weeks, leading to severe dehydration and confusion.

Contact a doctor as soon as possible if you experience any of the following symptoms:
Hearing problems
You may experience symptoms such as:
Common (may affect up to 1 in 10 people)

• sensation of blocked ears or pressure in the ear (ear discomfort)
• partial or complete hearing loss
• ringing or buzzing in the ears (tinnitus)
• hearing your own voice louder than normal
• muffled hearing

Uncommon (may affect up to 1 in 100 people)

• damage to the eardrum
• increased sensitivity to certain sounds

Worsening of inflammatory bowel disease (uncommon, may affect up to 1 in 100 people)
Symptoms may include an increase in watery stools with stomach pain or cramps, or blood in the stools.
See also section 2, "Warnings and precautions", for further information.
Other side effects:
most of the following side effects are mild to moderate in severity.
Very common (may affect more than 1 in 10 people)

• muscle cramps
• diarrhoea
• hair loss
• feeling extremely tired or lacking energy
• feeling unwell (nausea)
• headache

Common (may affect up to 1 in 10 people)

• dry skin
• change in taste sensation
• COVID-19
• high blood pressure
• weight loss
• diabetes mellitus
• nails breaking, splitting, or separating from the nail bed
• loss of eyebrows or eyelashes
• pre-diabetes
• change in nail colour
• absence of one or more menstrual periods
• irregular menstrual cycle
• heavy menstrual bleeding
• light menstrual bleeding
• pain or cramps during menstruation

Uncommon (may affect up to 1 in 100 people)

• ingrown nail

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store TEPEZZA

TEPEZZA will be stored by healthcare professionals at the hospital or clinic.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the outer carton and on the label of the vial after Exp. The expiry date refers to the last day of the month.
Unopened vials:
Store in a refrigerator (2 °C–8 °C).
Do not freeze.
Keep the vial in the outer packaging to protect the medicine from light.

6. Package contents and other information

What TEPEZZA contains

• The active substance is teprotumumab.
• Each vial contains 500 mg of teprotumumab.

The other components are histidine, monohydrochloride monohydrate of histidine, polysorbate 20 (E432), and trehalose dihydrate. See section 2, “TEPEZZA contains polysorbate”.

Description of the appearance of TEPEZZA and the contents of the pack

TEPEZZA is a powder for concentrate for solution for infusion, supplied in a glass vial with a rubber stopper containing 500 mg of teprotumumab. The powder is white to off-white, supplied in a single-dose vial. Each pack contains one vial.

Marketing Authorization Holder

Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands

Manufacturer

Horizon Therapeutics Ireland DAC
Pottery Road,
Dun Laoghaire
Dublin
A96 F2A8
Ireland

Manufacturer

Amgen NV
Telecomlaan 5-7
1831 Diegem
Belgium

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
s.a. Amgen n.v. Amgen Switzerland AG Vilniaus filialas
Tél/Tel: +32 (0)2 7752711 Tel: +370 5 219 7474

България Luxembourg/Luxemburg
Амджен България ЕООД s.a. Amgen
Тел.: +359 (0)2 424 7440 Belgique/Belgien
Tél/Tel: +32 (0)2 7752711

Česká republika Magyarország
Amgen s.r.o. Amgen Kft.
Tel: +420 221 773 500 Tel.: +36 1 35 44 700

Danmark Malta
Amgen, filial af Amgen AB, Sverige Amgen S.r.l.
Tlf.: +45 39617500 Italy
Tel: +39 02 6241121

Deutschland Nederland
Amgen GmbH Amgen B.V.
Tel.: +49 89 1490960 Tel: +31 (0)76 5732500

Eesti Norge
Amgen Switzerland AG Vilniaus filialas Amgen AB
Tel: +372 586 09553 Tlf: +47 23308000

Ελλάδα Österreich
Amgen Ελλάς Φαρμακευτικά Ε.Π.Ε. Amgen GmbH
Τηλ: +30 210 3447000 Tel: +43 (0)1 50 217

España Polska
Amgen S.A. Amgen Biotechnologia Sp. z o.o.
Tel: +34 93 600 18 60 Tel.: +48 22 581 3000

France Portugal
Amgen S.A.S. Amgen Biofarmacêutica, Lda.
Tél: +33 (0)9 69 363 363 Tel: +351 21 4220606

Hrvatska România
Amgen d.o.o. Amgen România SRL
Tel: +385 (0)1 562 57 20 Tel: +4021 527 3000

Ireland Slovenija
Amgen Ireland Limited AMGEN zdravila d.o.o.
Tel: +353 1 8527400 Tel: +386 (0)1 585 1767

Ísland Slovenská republika
Vistor Amgen Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2 321 114 49

Italia Suomi/Finland
Amgen S.r.l. Amgen AB, sivuliike Suomessa/Amgen AB, filial
Tel: +39 02 6241121 i Finland
Puh/Tel: +358 (0)9 54900500

Kύπρος Sverige
C.A. Papaellinas Ltd Amgen AB
Τηλ: +357 22741 741 Tel: +46 (0)8 6951100

Latvija
Amgen Switzerland AG Rīgas filiāle
Tel: +371 257 25888

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency, https://www.ema.europa.eu.

The following information is intended exclusively for healthcare professionals:

Dosage and administration

TEPEZZA must be prepared by a healthcare professional using an aseptic technique to ensure sterility of the prepared solution.

Preparation of the medicinal product prior to administration

Step 1: Calculate the dose (mg) and determine the number of vials required for the 10 or 20 mg/kg dose based on the patient's body weight. Each TEPEZZA vial contains 500 mg of teprotumumab.

Step 2: Using appropriate aseptic technique, reconstitute each vial with 10 mL of Water for Injections. Avoid directing the diluent stream onto the lyophilized powder, which has a tablet-like appearance. Do not shake. Gently swirl the vial until the lyophilized powder is completely dissolved. The reconstituted solution has a total volume of 10.5 mL. Withdraw 10.5 mL of reconstituted solution to obtain 500 mg. After reconstitution, the final concentration is 47.6 mg/mL.

Step 3: Prior to infusion, the reconstituted solution must be further diluted in 0.9% Sodium Chloride Solution for Infusion (9 mg/mL). To prepare the diluted solution, use 100 mL infusion bags for doses below 1,800 mg and 250 mL infusion bags for doses equal to or greater than 1,800 mg. To maintain a constant volume in the infusion bag, use a sterile syringe and needle to withdraw the volume equivalent to the amount of reconstituted solution to be added to the infusion bag. The withdrawn volume of 0.9% Sodium Chloride Solution (9 mg/mL) must be discarded.

Step 4: Withdraw the required volume from the reconstituted vial(s) based on the patient’s body weight (in kg) and transfer it into an intravenous infusion bag containing 0.9% Sodium Chloride Solution (9 mg/mL) for infusion. Gently invert the bag to mix the diluted solution. Do not shake. If refrigerated prior to administration, allow the diluted solution to reach room temperature before infusion. Care must be taken to ensure sterility of the prepared solution.

No incompatibilities have been observed between teprotumumab and polyethylene (PE), polyvinyl chloride (PVC), polyurethane (PUR), or polyolefin (PO) infusion bags, or intravenous administration sets.

Appearance upon reconstitution

After reconstitution, TEPEZZA is a solution ranging from clear to opalescent, almost colourless or slightly brown, and free of foreign particles. Prior to administration, the reconstituted solution should be inspected visually for particulate matter and discoloration. If particulates or discoloration are observed, the vial must be discarded.

Storage of reconstituted and diluted infusion solution

The chemical and physical in-use stability of the reconstituted solution in the vial has been demonstrated for up to 4 hours at room temperature (20 °C–25 °C) or up to 48 hours when stored at 2 °C–8 °C.

The chemical and physical in-use stability of the diluted solution in the infusion bag has been demonstrated for 24 hours when stored at 2 °C–8 °C, followed by 24 hours at room temperature (20 °C–25 °C).

From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage time and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2 °C–8 °C, unless reconstitution and dilution have been carried out under controlled, aseptic, and validated conditions. If refrigerated prior to administration, the diluted solution must be brought to room temperature before infusion.

Administration

• This medicinal product must be administered by intravenous infusion. It must not be administered by intravenous injection or bolus.
• Prior to infusion:
  • Reconstitute the powder with Water for Injections.
  • The reconstituted solution must be further diluted in 0.9% Sodium Chloride Solution for Infusion (9 mg/mL).
• TEPEZZA must not be administered simultaneously with other medicinal products through the same infusion line.
• For the first two infusions, the diluted solution must be administered intravenously over at least 90 minutes. If well tolerated, the minimum infusion time for subsequent infusions may be reduced to 60 minutes.
• If a 60-minute infusion is not well tolerated, the minimum duration for subsequent infusions must remain 90 minutes, the infusion rate should be reduced, and premedication is recommended for future infusions.

Special precautions for disposal and handling

Any unused medicinal product and waste materials derived from its use must be disposed of in accordance with local regulations.