TEVIMBRA 100 MG CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the Patient

Tevimbra 100 mg concentrate for solution for infusion

tislelizumab

This medicinal product is subject to additional monitoring, which will allow for the quick identification of new safety information. You can help by reporting any side effects you may get. The last section of the leaflet contains information on how to report side effects.

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• It is important that you keep the Patient Information Card during treatment.
• If you have any further questions, ask your doctor.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Tevimbra and what is it used for

Tevimbra is a cancer medicine that contains the active substance tislelizumab. It is a monoclonal antibody, a type of protein designed to recognize and bind to a specific target in the body called programmed death receptor-1 (PD-1) found on the surface of T and B cells (types of white blood cells that are part of the immune system, the body's natural defenses). When PD-1 is activated by cancer cells, it can disconnect the activity of T cells. By blocking PD-1, Tevimbra prevents T cells from being disconnected, helping your immune system fight cancer.

Tevimbra is used in adults to treat:

• a type of lung cancer called non-small cell lung cancer.
• a type of lung cancer called small cell lung cancer in extensive stage.
• a type of stomach cancer called gastric or gastroesophageal junction adenocarcinoma.
• a type of esophageal cancer called esophageal squamous cell carcinoma.

If you have any questions about how Tevimbra works or why you have been prescribed this medicine, ask your doctor.

Tevimbra may be given in combination with other medicines to treat cancer. It is important that you also read the package leaflet for the patient for these other medicines. If you have any questions about these medicines, ask your doctor.

2. What you need to know before you are given Tevimbra

You should not be given Tevimbra

• if you are allergic to tislelizumab or any of the other ingredients of this medicine (listed in section 6). Tell your doctor if you are not sure.

Warnings and precautions

Tell your doctor before you are given Tevimbra if you have or have had:

• an autoimmune disease (a disease in which the body's defense system attacks normal cells)
• liver inflammation (hepatitis) or other liver problems
• kidney inflammation (nephritis)
• pneumonia or lung inflammation (pneumonitis)
• intestinal inflammation (colitis)
• severe rash
• problems with hormone-producing glands (including adrenal, pituitary, or thyroid glands)
• type 1 diabetes mellitus
• solid organ transplant
• infusion-related reaction

a rare condition in which the immune system produces an excessive number of cells that fight infections, called histiocytes and lymphocytes, which are otherwise normal. It can cause liver and/or spleen enlargement, heart problems, and kidney abnormalities. Symptoms may include fever, rash, swollen lymph nodes, breathing problems, and easy bruising. Tell your doctor immediately if you experience these symptoms at the same time (hemophagocytic lymphohistiocytosis)

If you are in any of these situations, or if you are not sure, talk to your doctor before you are given Tevimbra.

Severe side effects

Tevimbra may cause severe side effects, which can be life-threatening and may cause death. Tell your doctor immediately if you experience any of these severe side effects during treatment with Tevimbra:

• liver inflammation (hepatitis) or other liver problems
• kidney inflammation (nephritis)
• lung inflammation (pneumonitis)
• intestinal inflammation (colitis)
• severe skin reactions (such as Stevens-Johnson syndrome [SJS] or toxic epidermal necrolysis [TEN]): symptoms may include fever, flu-like symptoms, rash, itching, blisters on the skin, or ulcers on the mouth or other moist surfaces
• problems with hormone-producing glands (especially adrenal, pituitary, or thyroid glands): symptoms may include increased heart rate, extreme tiredness, weight gain or loss, dizziness or fainting, hair loss, feeling cold, constipation, or persistent headache
• type 1 diabetes mellitus
• infusion-related reaction
• muscle inflammation (myositis)
• heart muscle inflammation (myocarditis)
• inflammation of the membrane around the heart (pericarditis)
• joint inflammation (arthritis)
• inflammatory disorders that cause muscle pain and stiffness, especially in the shoulders and hips (polymyalgia rheumatica): symptoms may include pain in the shoulders, neck, upper arms, buttocks, hips, or thighs, stiffness in the affected areas, pain or numbness in the wrists, elbows, or knees
• nerve inflammation: symptoms may include pain, weakness, and paralysis in the limbs (Guillain-Barré syndrome)

• For more information on the symptoms of any of the above cases, see section 4 ("Possible side effects"). Talk to your doctor if you have any questions or concerns.

Patient Information Card

You will also find important information from this package leaflet in the Patient Information Card, which your doctor has given you. It is important that you carry the Patient Information Card with you at all times and show it to a healthcare professional if you experience signs or symptoms that may indicate an immune-related adverse reaction (described above in the "Severe side effects" section) so that you can receive a quick diagnosis and appropriate treatment.

Checks during treatment with Tevimbra

Your doctor will perform regular checks (liver function test, kidney function test, X-rays) before and during treatment.

Your doctor will also perform regular blood tests before and during treatment with Tevimbra to check your blood sugar and hormone levels. This is because Tevimbra may affect your blood sugar and hormone levels.

Children and adolescents

Tevimbra should not be used in children and adolescents under 18 years of age.

Other medicines and Tevimbra

Tell your doctor if you are taking, have recently taken, or might take any other medicines. This includes herbal medicines and medicines without a prescription.

In particular, tell your doctor if you are taking any medicine that suppresses the immune system, including corticosteroids (such as prednisone), as these medicines may interfere with the effect of Tevimbra. However, once you have started treatment with Tevimbra, your doctor may give you corticosteroids to reduce any side effect you may experience.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before you are given this medicine.

You should not be given Tevimbra if you are pregnant, unless your doctor prescribes it. The effects of Tevimbra on pregnant women are not known, but it is possible that the active substance, tislelizumab, may harm the fetus.

• If you are a woman who could become pregnant, you must use effective contraceptive methods while you are being treated with Tevimbra and for at least 4 months after the last dose of Tevimbra.
• If you are pregnant, think you may be pregnant, or are planning to have a baby, talk to your doctor.

It is not known whether Tevimbra passes into breast milk. A risk to the breastfed child cannot be excluded. If you are breastfeeding, tell your doctor. You should not breastfeed during treatment with Tevimbra and for at least 4 months after the last dose of Tevimbra.

Driving and using machines

Tevimbra has a minor effect on the ability to drive or use machines.

Some possible side effects of Tevimbra are feeling tired or weak. Do not drive or use machines after you have been given Tevimbra unless you are sure you feel well.

Tevimbra contains sodium

Tell your doctor if you are on a low-sodium diet (low-salt diet) before you are given Tevimbra. This medicine contains 1.6 mg of sodium (main component of cooking/table salt) in each ml of concentrate. A single infusion of Tevimbra contains 32 mg of sodium in two 10 ml vials before dilution. This is equivalent to 1.6% of the maximum daily intake of sodium recommended by the WHO for an adult. Tevimbra should be diluted in sodium chloride solution for infusion. This should be taken into account in patients with sodium-controlled diet.

Tevimbra contains polysorbate

This medicine contains 0.2 mg of polysorbate 20 in each ml of concentrate, which is equivalent to 4.0 mg in two 10 ml vials of a single infusion of Tevimbra. Polysorbates may cause allergic reactions. Tell your doctor if you have known allergies.

3. How Tevimbra is given

You will be given Tevimbra in a hospital or clinic under the supervision of an experienced doctor.

• The usual dose of Tevimbra is 200 mg, given as an intravenous infusion (by drip into a vein) every 3 weeks.
• The first dose of Tevimbra will be given over a period of 60 minutes. If you tolerate the first dose well, the next infusion will be given over 30 minutes.
• When Tevimbra is given in combination with chemotherapy, Tevimbra will be given first, followed by chemotherapy.
• Read the package leaflet for the other cancer medicines to understand their use. If you have any questions, ask your doctor.
• Your doctor will decide how many infusions you need.

If you miss a dose of Tevimbra

• Call your doctor immediately to schedule another appointment.
• It is very important that you do not miss a dose of this medicine.

If you stop treatment with Tevimbra

Stopping treatment may interrupt the effect of the medicine. Do not stop treatment with Tevimbra unless you have discussed it with your doctor.

If you have any other questions about your treatment or the use of this medicine, ask your doctor.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Some adverse effects of Tevimbra can be serious (see the list in “Serious Adverse Effects” in section 2 of this prospectus). If you experience any of these serious adverse effects, inform your doctor immediately.

The following adverse effects have been reported with Tevimbra alone:

Very Common(may affect more than 1 in 10 people)

• Weakness, rapid heart rate, difficulty breathing (anemia)
• Spontaneous bleeding or bruising (thrombocytopenia)
• Underactive thyroid gland, which can cause fatigue, weight gain, skin and hair changes (hypothyroidism)
• Cough
• Nausea
• Diarrhea
• Rash
• Itching (pruritus)
• Fatigue (fatigue)
• Fever
• Decreased appetite
• Increased level of liver enzyme aspartate aminotransferase in the blood
• Increased level of liver enzyme alanine aminotransferase in the blood
• Increased level of bilirubin in the blood, a breakdown product of red blood cells, which can cause yellowing of the skin and eyes, indicating liver problems

Common(may affect up to 1 in 10 people)

• Pneumonia
• Frequent infections, fever, chills, sore throat or mouth ulcers due to infections (neutropenia or lymphopenia)
• Overactive thyroid gland, which can cause hyperactivity, sweating, weight loss, and thirst (hyperthyroidism)
• Fatigue, swelling at the base of the neck, pain in the front of the throat - possible symptoms of thyroid gland problems (thyroiditis)
• Increased blood sugar level, thirst, dry mouth, need to urinate more frequently, fatigue, increased appetite with weight loss, confusion, nausea, vomiting, fruity breath odor, difficulty breathing, and dry or reddened skin - possible symptoms of hyperglycemia
• Weakness, confusion, muscle contractions, convulsions (hyponatremia)
• Muscle weakness, muscle spasms, abnormal heart rate (hypokalemia)
• Increased blood pressure (hypertension)
• Difficulty breathing (dyspnea)
• Difficulty breathing, cough, or chest pain - possible symptoms of lung problems (pneumonitis)
• Sores or ulcers in the mouth with gum inflammation (stomatitis)
• Nausea, vomiting, loss of appetite, pain in the right upper abdomen, yellowing of the skin or whites of the eyes, drowsiness, dark urine, bleeding or bruising more easily than normal - possible symptoms of liver problems (hepatitis)
• Joint pain (arthralgia)
• Muscle pain (myalgia)
• Increased level of liver enzyme phosphatase in the blood
• Increased level of creatinine in the blood
• Chills or shaking, itching or rash, flushing, difficulty breathing or wheezing, dizziness or fever, which can occur during infusion or up to 24 hours after infusion - possible symptoms of infusion-related reaction
• Low hemoglobin level in the blood
• Low levels of the following blood cells: lymphocytes, neutrophils, and platelets
• High levels of the following enzymes in the blood: alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, and creatine kinase
• High level of alkaline phosphatase in the blood
• High level of bilirubin in the blood
• High level of creatinine in the blood
• High level of glucose in the blood
• Low levels of potassium and sodium in the blood

Uncommon(may affect up to 1 in 100 people)

• Disorder in which the adrenal glands do not produce enough of certain hormones (adrenal insufficiency)
• Frequent headaches, changes in vision (either blurred vision or double vision), fatigue or weakness, confusion, decreased blood pressure - possible symptoms of pituitary gland problems (hypophysitis)
• High blood sugar level, increased hunger or thirst, frequent urination - possible symptoms of diabetes mellitus
• Eye redness, pain, and swelling - possible symptoms of problems affecting the uvea, the layer under the white of the eye (uveitis)
• Chest pain, rapid or abnormal heart rate, difficulty breathing at rest or during activity, fluid retention with swelling in the legs, ankles, and feet, fatigue - possible symptoms of heart muscle problems (myocarditis)
• Chest pain, fever, cough, palpitations - possible symptoms of problems affecting the membrane surrounding the heart (pericarditis)
• Severe pain in the upper abdomen, nausea, vomiting, fever, sensitivity in the abdomen - possible symptoms of pancreas problems (pancreatitis)
• Diarrhea or more bowel movements than normal, black, tarry stools, presence of blood or mucus in stools, severe pain or sensitivity in the stomach - possible symptoms of intestine problems (colitis)
• Change in skin color (vitiligo)
• Itching or peeling of the skin, skin sores - possible symptoms of severe skin reactions
• Muscle pain, stiffness, weakness, chest pain, or severe fatigue - possible symptoms of muscle problems (myositis)
• Joint pain, stiffness, swelling, or redness, decreased range of motion in the joints - possible symptoms of joint problems (arthritis)
• Change in urine color or amount, pain while urinating, pain in the kidney area - possible symptoms of kidney problems (nephritis)
• High level of hemoglobin in the blood
• Low level of white blood cells in the blood
• High level of lymphocytes in the blood
• Low level of albumin in the blood
• Low level of glucose in the blood
• High levels of potassium and sodium in the blood

Rare(may affect up to 1 in 1,000 people)

• Severe nerve problems, which can cause difficulty breathing, tingling sensation in the fingers, toes, ankles, or wrists, weakness in the legs that spreads to the upper body, unsteady gait or inability to walk or climb stairs, difficulty moving the face, including speaking, chewing, or swallowing, double vision or inability to move the eyes, difficulty controlling the bladder or bowels, rapid heart rate, and paralysis - possible symptoms of Guillain-Barré syndrome
• Celiac disease (characterized by symptoms such as stomach pain, diarrhea, and bloating after consuming gluten-containing foods)
• Severe skin rash and redness on the upper body, spreading rapidly to other parts of the body, blistering of the lips, eyes, or mouth, skin peeling, sometimes with pseudo-flu-like symptoms, such as fever, sore throat, cough, and joint pain (Stevens-Johnson syndrome)
• Bladder inflammation. Signs and symptoms may include frequent and/or painful urination, urgent need to urinate, blood in the urine, pain or pressure in the lower abdomen (non-infectious cystitis)

Other adverse effects that have been reported (frequency not known):

• A condition in which the immune system produces an excessive amount of cells that fight infections, called histiocytes and lymphocytes, which are otherwise normal. Symptoms may include fever, skin rash, swollen lymph nodes, breathing problems, and easy bruising (hemophagocytic lymphohistiocytosis)
• Absence or reduction of digestive enzymes produced by the pancreas (exocrine pancreatic insufficiency)

The following adverse effects have been observed when Tevimbra is administered with other cancer medications

Note that it is important to also read the prospectuses of the other cancer medications you are receiving, as they may also cause adverse effects.

Very Common(may affect more than 1 in 10 patients)

• Pneumonia
• Weakness, rapid heart rate, difficulty breathing (anemia)
• Spontaneous bleeding or bruising (thrombocytopenia)
• Frequent infections, fever, chills, sore throat or mouth ulcers due to infections (neutropenia or lymphopenia)
• Underactive thyroid gland, which can cause fatigue, weight gain, skin and hair changes (hypothyroidism)
• Increased blood sugar level, thirst, dry mouth, need to urinate more frequently, fatigue, increased appetite with weight loss, confusion, nausea, vomiting, fruity breath odor, difficulty breathing, and dry or reddened skin - possible symptoms of hyperglycemia
• Weakness, confusion, muscle contractions, convulsions (hyponatremia)
• Muscle weakness, muscle spasms, abnormal heart rate (hypokalemia)
• Cough
• Nausea
• Diarrhea
• Rash
• Itching (pruritus)
• Joint pain (arthralgia)
• Fatigue (fatigue)
• Fever
• Decreased appetite
• Increased level of liver enzyme aspartate aminotransferase in the blood
• Increased level of liver enzyme alanine aminotransferase in the blood
• Increased level of bilirubin in the blood, a breakdown product of red blood cells, which can cause yellowing of the skin and eyes, indicating liver problems
• Increased level of creatinine in the blood, a substance that is normally eliminated by the kidneys in the urine, which may indicate that the kidneys are not functioning properly
• Low hemoglobin level in the blood
• Low levels of the following blood cells: white blood cells, lymphocytes, neutrophils, and platelets
• Low level of sodium in the blood

Common(may affect up to 1 in 10 people)

• Overactive thyroid gland, which can cause hyperactivity, sweating, weight loss, and thirst (hyperthyroidism)
• High blood sugar level, increased hunger and thirst, frequent urination - possible symptoms of diabetes mellitus
• Chest pain, rapid or abnormal heart rate, difficulty breathing at rest or during activity, fluid retention with swelling in the legs, ankles, and feet, fatigue - possible symptoms of heart muscle problems (myocarditis)
• Increased blood pressure (hypertension)
• Difficulty breathing (dyspnea)
• Difficulty breathing, cough, or chest pain - possible symptoms of lung problems (pneumonitis)
• Severe pain in the upper abdomen, nausea, vomiting, fever, sensitivity in the abdomen - possible symptoms of pancreas problems (pancreatitis)
• Sores or ulcers in the mouth with gum inflammation (stomatitis)
• Diarrhea or more bowel movements than normal, black, tarry stools, presence of blood or mucus in stools, severe pain or sensitivity in the stomach - possible symptoms of intestine problems (colitis)
• Nausea, vomiting, loss of appetite, pain in the right upper abdomen, yellowing of the skin or whites of the eyes, drowsiness, dark urine, bleeding or bruising more easily than normal - possible symptoms of liver problems (hepatitis)
• Muscle pain (myalgia)
• Joint pain, stiffness, swelling, or redness, decreased range of motion in the joints - possible symptoms of joint problems (arthritis)
• Increased level of liver enzyme phosphatase in the blood
• Chills or shaking, itching or rash, flushing, difficulty breathing or wheezing, dizziness or fever, which can occur during infusion or up to 24 hours after infusion - possible symptoms of infusion-related reaction
• High levels of the following enzymes in the blood: alanine aminotransferase and aspartate aminotransferase
• High level of bilirubin in the blood
• High levels of creatine kinase and creatinine in the blood
• High level of glucose in the blood
• High level of potassium in the blood
• Low level of potassium in the blood

Uncommon(may affect up to 1 in 100 people)

• Disease in which the immune system attacks the cells that produce moisture for the body, such as tears and saliva (Sjögren's syndrome)
• Fatigue, swelling at the base of the neck, pain in the front of the throat - possible symptoms of thyroid gland problems (thyroiditis)
• Adrenal insufficiency (a condition in which the adrenal glands do not produce enough of certain hormones)
• Frequent headaches, changes in vision (either blurred vision or double vision), fatigue or weakness, confusion, decreased blood pressure - possible symptoms of pituitary gland problems (hypophysitis)
• Eye redness, pain, and swelling - possible symptoms of problems affecting the uvea, the layer under the white of the eye (uveitis)
• Change in urine color or amount, pain while urinating, pain in the kidney area - possible symptoms of kidney problems (nephritis)
• Muscle pain, stiffness, weakness, chest pain, or severe fatigue - possible symptoms of muscle problems (myositis)
• Change in skin color (vitiligo)
• High level of lymphocytes in the blood
• Low level of albumin in the blood
• High level of alkaline phosphatase in the blood
• Low level of glucose in the blood
• High level of sodium in the blood

Rare(may affect up to 1 in 1,000 people)

• A condition in which the immune system produces an excessive amount of cells that fight infections, called histiocytes and lymphocytes, which are otherwise normal. Symptoms may include fever, skin rash, swollen lymph nodes, breathing problems, and easy bruising (hemophagocytic lymphohistiocytosis)
• Inflammation of the brain, which can cause confusion, fever, memory problems, or convulsions (encephalitis)
• Severe nerve problems, which can cause difficulty breathing, tingling sensation in the fingers, toes, ankles, or wrists, weakness in the legs that spreads to the upper body, unsteady gait or inability to walk or climb stairs, difficulty moving the face, including speaking, chewing, or swallowing, double vision or inability to move the eyes, difficulty controlling the bladder or bowels, rapid heart rate, and paralysis - possible symptoms of Guillain-Barré syndrome
• Muscle weakness and fatigue (myasthenia gravis)
• Chest pain, fever, cough, palpitations - possible symptoms of problems affecting the membrane surrounding the heart (pericarditis)
• Itching or peeling of the skin, skin sores - possible symptoms of severe skin reactions

Inform your doctor immediately if you experience any of the aforementioned adverse effects.

You must discontinue the use of Tevimbra and seek immediate medical attention if you notice any of the following symptoms:

Frequency not known (cannot be estimated from the available data)

• Red, non-raised, target-like or circular patches on the trunk, often with central blisters, skin peeling, mouth, throat, nose, genitals, and eye ulcers. These severe skin rashes can be preceded by fever and flu-like symptoms (Toxic Epidermal Necrolysis, TEN).

Reporting Adverse Effects

If you experience any adverse effects, consult your doctor, even if they are possible adverse effects that are not listed in this prospectus. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Tevimbra

Your doctor, pharmacist, or nurse is responsible for storing this medication and disposing of any unused portion correctly. The following information is intended for healthcare professionals.

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date shown on the carton and vial after CAD and EXP. The expiration date is the last day of the month indicated.

Store in a refrigerator (between 2°C and 8°C).

Do not freeze.

Keep the vial in the outer packaging to protect it from light.

Tevimbra does not contain a preservative. Chemical and physical stability has been demonstrated during use for 24 hours at 2°C to 8°C. The 24 hours include storage of the diluted solution in refrigeration (2°C to 8°C) for no more than 20 hours, the time required to reach room temperature (25°C or less), and the time to complete the infusion within 4 hours.

From a microbiological point of view, once diluted, the product must be used immediately.

If not used immediately, the in-use storage time and conditions are the responsibility of the user. The diluted solution must not be frozen.

Do not retain any part of the solution for reuse. Any unused medication or waste material must be disposed of according to local requirements.

6. Container Contents and Additional Information

Tevimbra Composition

• The active ingredient is tislelizumab. Each ml of concentrate for solution for infusion contains 10 mg of tislelizumab.
• Each vial contains 100 mg of tislelizumab in 10 ml of concentrate.

The other components are sodium dihydrate citrate (see section 2, "Tevimbra contains sodium"), citric acid monohydrate, L-histidine hydrochloride monohydrate, L-histidine, trehalose dihydrate, polysorbate 20, and water for injectable preparations.

Appearance of Tevimbra and Container Contents

Tevimbra concentrate for solution for infusion (sterile concentrate) is a clear to slightly opalescent, colorless to slightly yellowish solution.

Tevimbra is available in containers containing 1 vial and multiple containers containing 2 vials (2 packs of 1).

Marketing Authorization Holder

BeOne Medicines Ireland Limited

10 Earlsfort Terrace

Dublin 2

D02 T380

Ireland

Tel. +353 1 566 7660

Email: bg.ireland@beigene.com

Manufacturer

BeiGene Switzerland GmbH Dutch Branch

Evert Van De Beekstraat 1/104

Schiphol

1118 CL

Netherlands

Date of Last Revision of this Leaflet:

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu

This Information is Intended Only for Healthcare Professionals:

The vials of Tevimbra are for single use. Each vial contains 100 mg of tislelizumab.

The diluted solution for infusion must be prepared by a healthcare professional using an aseptic technique.

Preparation of the Solution for Infusion

• Two vials of Tevimbra are required for each dose.

• Remove the vials from the refrigerator, taking care not to shake them.

• Visually inspect each vial for particles or discoloration before administration. The concentrate is a clear to slightly opalescent, colorless to slightly yellowish solution. Do not use the vial if the solution is cloudy, or if visible particles or discoloration are observed.

• Gently invert the vials without shaking. Withdraw the solution from the two vials (a total of 200 mg in 20 ml) into a syringe and transfer it to an intravenous infusion bag containing a 9 mg/ml (0.9%) sodium chloride injectable solution, to prepare a diluted solution with a final concentration of 2 to 5 mg/ml. Mix the diluted solution by gentle inversion to avoid foam formation or excessive cutting of the solution.

Administration

• Administer the diluted Tevimbra solution through an intravenous administration line with a sterile, non-pyrogenic, 0.2-micron low-protein-binding filter, or a 0.22-micron in-line filter or an additional filter with a surface area of approximately 10 cm².

• The first infusion should be administered over 60 minutes. If well tolerated, subsequent infusions may be administered over 30 minutes.

• No other medications should be administered through the same infusion line.

• Tevimbra should not be administered as a rapid infusion or as a single bolus injection.

• Tevimbra does not contain preservatives. Chemical and physical stability has been demonstrated during use for 24 hours between 2 °C and 8 °C. The 24 hours include storage of the diluted solution in the refrigerator (2 °C to 8 °C) for no more than 20 hours, the time needed to return to room temperature (25 °C or below), and the time to complete the infusion in 4 hours. From a microbiological point of view, once diluted, the product must be used immediately. If not used immediately, storage times and conditions are the responsibility of the user.

• The diluted solution should not be frozen.

• Discard any unused portion remaining in the vial.

• The intravenous line should be flushed at the end of the infusion.

• The Tevimbra vials are for single use.