Tevimbra: detailed information

Patient Information Leaflet

Tevimbra 100 mg concentrate for solution for infusion

tislelizumab
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 you are given this medicine as it contains important information for you.

Keep this leaflet. You may need to read it again.
It is important to keep the Patient Card with you during treatment.
If you have any questions, consult your doctor.
If you experience any side effects, including those not listed in this leaflet, consult your doctor. See section 4.

Contents of this leaflet

What Tevimbra is and what it is used for
What you need to know before you are given Tevimbra
How Tevimbra is administered
Possible side effects
How to store Tevimbra
Contents of the pack and other information

1. What Tevimbra is and what it is used for

Tevimbra is a cancer medicine that contains the active substance tislelizumab. It is a monoclonal antibody, a type of protein designed to recognise and attack a specific target in the body called programmed death receptor (PD-1), which is 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 defences). When PD-1 is activated by tumour cells, it can inactivate T cells. By blocking PD-1, Tevimbra prevents the inactivation of T cells and helps the 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 extensive-stage small cell lung cancer
a type of stomach cancer called gastric adenocarcinoma or gastroesophageal junction adenocarcinoma
a type of oesophageal cancer called oesophageal squamous cell carcinoma
a type of head and neck cancer called nasopharyngeal carcinoma

Tevimbra is given to patients when the cancer has spread or cannot be removed by surgery.
Tevimbra is also given before surgery (neoadjuvant therapy) to treat non-small cell lung cancer, and treatment continues after surgery (adjuvant therapy) to help prevent the cancer from returning.

If you have any questions about how Tevimbra works or why this medicine has been prescribed for you, speak with your doctor.
Tevimbra may be given in combination with other anti-cancer medicines. It is important that you also read the package leaflet for these other medicines. If you have any questions about these medicines, speak with your doctor.

2. What you should know before being given Tevimbra

Do not be given Tevimbra

if you are allergic to tislelizumab or to any of the other ingredients of this medicine (listed in section 6). If in doubt, consult your doctor.

Warnings and precautions
Talk to your doctor before being given Tevimbra if you have or have had:

autoimmune disease (a condition in which the body's immune system attacks normal cells)
liver inflammation (hepatitis) or other liver problems
kidney inflammation (nephritis)
lung infection or lung inflammation (pneumonitis)
inflammation of the large intestine (colitis)
severe skin rash
problems with glands that produce hormones (including adrenal, pituitary, and thyroid glands)
type 1 diabetes mellitus
organ transplant
infusion-related reaction
a rare condition in which the immune system produces an excessive number of infection-fighting cells called histiocytes and lymphocytes. This may lead to enlargement of the liver and/or spleen, heart problems, and kidney abnormalities. Symptoms may include fever, rash, swollen lymph nodes, breathing difficulties, and easy bruising. Inform your doctor immediately if you experience these symptoms together (hemophagocytic lymphohistiocytosis).

Tevimbra acts on the immune system. It may cause inflammation in certain parts of the body. The risk of these side effects may be higher if you already have an autoimmune disease (a condition in which the body attacks its own cells). Recurrent flare-ups of autoimmune disease may also occur, which are usually mild in most cases.
If you fall into any of the above categories or have any doubts, speak with your doctor before being given Tevimbra.

Be aware of serious side effects
Tevimbra can cause serious side effects, which sometimes may be life-threatening and can lead to death. Inform your doctor immediately if you experience any of the following serious side effects during treatment with Tevimbra:

liver inflammation (hepatitis) or other liver problems
kidney inflammation (nephritis)
lung inflammation (pneumonitis)
inflammation of the large intestine (colitis)
severe skin reactions (including Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN)): symptoms may include fever, flu-like symptoms, rash, itching, blistering of the skin, or mouth ulcers or ulcers on other moist surfaces
problems with hormone-producing glands (especially adrenal, pituitary, and thyroid glands): symptoms may include rapid heartbeat, extreme fatigue, weight gain or weight loss, dizziness or fainting, hair loss, feeling cold, constipation, persistent headache or unusual headaches
type 1 diabetes mellitus
infusion-related reaction
muscle inflammation (myositis)
heart muscle inflammation (myocarditis)
inflammation of the membrane surrounding the heart (pericarditis)
joint inflammation (arthritis)
inflammatory disorder causing muscle pain and stiffness, especially in shoulders and hips (polymyalgia rheumatica): symptoms may include pain in shoulders, neck, upper arms, buttocks, hips, or thighs; stiffness in affected areas; pain or stiffness in wrists, elbows, or knees
nerve inflammation: symptoms may include pain, weakness, and paralysis in extremities (Guillain-Barré syndrome)

For more information on symptoms of any of the above effects, read section 4 ("Possible side effects"). Speak with your doctor if you have any questions or concerns.

Patient Card
You will find the key information from this leaflet also in the Patient Card you received from your doctor. It is important that you always carry the Patient Card with you and show it to a healthcare professional if you develop signs and symptoms that may indicate immune-mediated adverse reactions (listed above under "Be aware of serious side effects"), so that timely diagnosis and appropriate treatment can be provided.

Monitoring during treatment with Tevimbra
Your doctor will perform regular tests (liver function tests, kidney function tests, imaging tests) before and during treatment.
Your doctor will also perform regular blood tests before and during treatment with Tevimbra to monitor your blood sugar levels and hormone levels. This is because blood sugar and hormone levels may be affected by Tevimbra.

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

Other medicines and Tevimbra
Inform your doctor if you are taking, have recently taken, or might take any other medicines. This includes herbal medicines and over-the-counter drugs.
In particular, inform your doctor if you are taking any medicines that reduce the activity of 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 prescribe corticosteroids to reduce any side effects you may experience.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor before being given this medicine.
You must not be given Tevimbra if you are pregnant unless specifically prescribed by your doctor. The effects of Tevimbra in pregnant women are unknown, but the active substance, tislelizumab, may harm the unborn baby.

If you are a woman who could become pregnant, you must use an effective method of contraception during treatment with Tevimbra and for at least 4 months after the last dose of Tevimbra.
If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, inform your doctor.

It is not known whether Tevimbra is excreted in breast milk. The risk to the breastfed infant cannot be excluded. If you are breastfeeding, inform your doctor. You must 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 influence on the ability to drive and use machines.
Feeling tired or weak are possible side effects of Tevimbra. Do not drive or operate machinery after receiving Tevimbra unless you are sure you feel well.

Tevimbra contains sodium
Inform your doctor if you are on a low-sodium (low-salt) diet before taking Tevimbra. This medicine contains 1.6 mg of sodium (the main component of table salt) in each mL of concentrate, or 16 mg of sodium per 10 mL vial. A single infusion of Tevimbra contains 32 mg of sodium in two 10 mL vials before dilution. This corresponds to 1.6% of the maximum daily recommended dietary intake for an adult. Tevimbra must be diluted in a sodium chloride-based infusion solution. This should be taken into account for patients on a low-sodium diet.

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

3. How Tevimbra is administered

Tevimbra will be administered to you in a hospital or clinic under the supervision of an experienced doctor.

The dose of Tevimbra is 200 mg once every 3 weeks or 400 mg once every 6 weeks, given as an intravenous infusion (intravenous drip).
For the 200 mg dose of Tevimbra, the first dose will be administered by infusion over 60 minutes. If you tolerate the first dose well, the next infusion may be given over 30 minutes.
The infusion of an initial 400 mg dose of Tevimbra must be administered over 120 minutes (or over 90 minutes if used as subsequent treatment following the 200 mg dose). If well tolerated, the second infusion may be administered over 60 minutes. If the second infusion is well tolerated, subsequent infusions may be administered over 30 minutes.
When Tevimbra is administered in combination with chemotherapy, Tevimbra will be given to you first, followed by chemotherapy.
Refer to the package leaflet of the other anticancer medicines for information on their use. If you have any doubts, consult your doctor.
Your doctor will determine the number of treatments you need.

If you miss a dose of Tevimbra

Contact your doctor immediately to schedule a new 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 without first discussing it with your doctor.
If you have any questions about your treatment or the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Some side effects of Tevimbra may be serious (see the list under “Be aware of serious side effects” in section 2 of this leaflet). If you experience any of these serious side effects, inform your doctor immediately.
The following side effects have been reported with Tevimbra when given alone:
Very common (may affect more than 1 in 10 people)

Weakness, rapid heartbeat, shortness of breath (anaemia)
Spontaneous bleeding or bruising (thrombocytopenia)
Underactive thyroid gland which may cause tiredness, weight gain, changes in skin and hair (hypothyroidism)
Cough
Nausea
Diarrhoea
Rash
Itching
Tiredness (fatigue)
Fever
Decreased appetite
Increased blood levels of the liver enzyme aspartate aminotransferase
Increased blood levels of the liver enzyme alanine aminotransferase
Increased blood levels of bilirubin, a breakdown product of red blood cells, which may 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 may cause hyperactivity, sweating, weight loss and thirst (hyperthyroidism)
Tiredness, swelling at the base of the neck, pain in front of the throat – possible symptoms of thyroid gland problems (thyroiditis)
Increased blood sugar levels, thirst, dry mouth, need to urinate more frequently, tiredness, increased appetite with weight loss, confusion, nausea, vomiting, fruity breath, difficulty breathing, dry or red skin – possible symptoms of hyperglycaemia
Tiredness, confusion, muscle cramps, seizures (hyponatraemia)
Muscle weakness, muscle spasms, irregular heartbeat (hypokalaemia)
Increased blood pressure (hypertension)
Difficulty breathing (dyspnoea)
Shortness of breath, cough or chest pain – possible symptoms of lung problems (pneumonia)
Mouth pain or ulcers with inflammation of the gums (stomatitis)
Feeling unwell (nausea), vomiting, loss of appetite, pain on the right side of the stomach, yellowing of the skin or whites of the eyes, drowsiness, dark-coloured urine, bleeding or bruising more easily than usual – possible symptoms of liver problems (hepatitis)
Joint pain (arthralgia)
Muscle pain (myalgia)
Increased blood levels of the liver enzyme alkaline phosphatase
Increased blood levels of creatinine
Chills or trembling, itching or rash, flushing, shortness of breath or wheezing, dizziness or fever that may occur during or up to 24 hours after infusion – possible symptoms of infusion-related reaction
Low haemoglobin levels 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 aminotransferase, aspartate aminotransferase and creatine kinase
High levels of alkaline phosphatase in the blood
High levels of bilirubin in the blood
High levels of creatinine in the blood
High levels of glucose in the blood
Low levels of potassium and sodium in the blood

Uncommon (may affect up to 1 in 100 people)

A disorder in which the adrenal glands do not produce enough hormones (adrenal insufficiency)
Frequent headaches, changes in vision (both blurred vision and double vision), tiredness and/or weakness, confusion, low blood pressure, dizziness – possible symptoms of pituitary gland problems (hypophysitis)
High blood sugar levels, feeling unusually hungry or thirsty, urinating more often than normal – possible symptoms of diabetes mellitus
Red eyes, eye pain and swelling – possible symptoms of problems affecting the uvea, the layer beneath the white of the eye (uveitis)
Chest pain, rapid or irregular heartbeat, shortness of breath at rest or during activity, fluid accumulation with swelling in legs, ankles and feet, tiredness – 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, abdominal tenderness – possible symptoms of pancreas problems (pancreatitis)
Diarrhoea or more frequent bowel movements than normal, black tarry sticky stools, blood or mucus in stools, severe abdominal pain or tenderness – possible symptoms of intestinal problems (colitis)
Skin discolouration (vitiligo)
Itching or peeling of the skin, skin ulcers – possible symptoms of serious skin reactions
Muscle pain, stiffness, weakness, chest pain or extreme tiredness – possible symptoms of muscle problems (myositis)
Joint pain, stiffness, swelling or redness, reduced joint mobility – possible symptoms of joint problems (arthritis)
Changes in amount or colour of urine, pain during urination, pain in the kidney area – possible symptoms of kidney problems (nephritis)
High levels of haemoglobin in the blood
Low white blood cell count in the blood
High lymphocyte count in the blood
Low albumin levels in the blood
Low blood glucose levels
High levels of potassium and sodium in the blood

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

Serious nerve problems, which may cause difficulty breathing, tingling or numbness in fingers of hands, feet, ankles or wrists, leg weakness spreading to the upper body, unsteady walking or inability to walk or climb stairs, difficulty with facial movements including speaking, chewing or swallowing, double vision or inability to move eyes, difficulty controlling bladder or bowel function, rapid heartbeat and paralysis – possible symptoms of Guillain-Barré syndrome
Coeliac disease (characterised by symptoms such as stomach pain, diarrhoea and abdominal swelling after consuming foods containing gluten)
Severe rash and redness of the skin on the upper body spreading rapidly to other parts of the body, blistering of lips, eyes or mouth, skin peeling, sometimes accompanied by 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, urgency to urinate, blood in the urine, pain or pressure in the lower abdomen (non-infectious cystitis)

Other side effects reported (frequency not known):

A rare condition in which the immune system produces an excessive number of infection-fighting cells called histiocytes and lymphocytes. Symptoms may include fever, rash, swollen lymph nodes, breathing problems, easy bruising (haemophagocytic lymphohistiocytosis)
Absence or reduction of digestive enzymes produced by the pancreas (pancreatic exocrine insufficiency)

The following side effects have been reported with Tevimbra when administered together with other anticancer medicines
Please note that it is important for you to also read the package leaflet of the other anticancer medicines you are receiving, as these may also cause side effects.
Very common (may affect more than 1 in 10 people)

Pneumonia
Weakness, rapid heartbeat, shortness of breath (anaemia)
Spontaneous bleeding or bruising (thrombocytopenia)
Frequent infections, fever, chills, sore throat or mouth ulcers due to infections (neutropenia or lymphopenia)
Underactive thyroid gland which may cause tiredness, weight gain, changes in skin and hair (hypothyroidism)
Increased blood sugar levels, thirst, dry mouth, need to urinate more frequently, tiredness, increased appetite with weight loss, confusion, nausea, vomiting, fruity breath, difficulty breathing, dry or red skin – possible symptoms of hyperglycaemia
Tiredness, confusion, muscle cramps, seizures (hyponatraemia)
Muscle weakness, muscle spasms, irregular heartbeat (hypokalaemia)
Cough
Nausea
Diarrhoea
Rash
Itching sensation (pruritus)
Joint pain (arthralgia)
Tiredness (fatigue)
Fever
Reduced appetite
Increased blood levels of the liver enzyme aspartate aminotransferase
Increased blood levels of the liver enzyme alanine aminotransferase
Increased blood levels of bilirubin, a breakdown product of red blood cells, which may cause yellowing of the skin and eyes, indicating liver problems
Increased blood levels of creatinine, a substance normally eliminated by the kidneys in urine. This may indicate impaired kidney function
Low haemoglobin levels in the blood
Low blood levels of the following blood cells: white blood cells, neutrophils and platelets
Low sodium levels in the blood

Common (may affect up to 1 in 10 people)

Overactive thyroid gland, which may cause hyperactivity, sweating, weight loss and thirst (hyperthyroidism)
High blood sugar levels, feeling unusually hungry or thirsty, urinating more often than normal – possible symptoms of diabetes mellitus
Chest pain, rapid or irregular heartbeat, shortness of breath at rest or during activity, fluid accumulation with swelling in legs, ankles and feet, tiredness – possible symptoms of heart muscle problems (myocarditis)
Increased blood pressure (hypertension)
Difficulty breathing (dyspnoea)
Shortness of breath, cough or chest pain – possible symptoms of lung problems (pneumonia)
Severe pain in the upper abdomen, nausea, vomiting, abdominal tenderness – possible symptoms of pancreas problems (pancreatitis)
Sores or ulcers in the mouth with inflammation of the gums (stomatitis)
Diarrhoea or more frequent bowel movements than normal, black tarry sticky stools, blood or mucus in stools, severe abdominal pain or tenderness – possible symptoms of intestinal problems (colitis)
Feeling unwell (nausea), vomiting, loss of appetite, pain on the right side of the abdomen, yellowing of the skin and whites of the eyes, drowsiness, dark-coloured urine, bleeding or bruising more easily than usual – possible symptoms of liver problems (hepatitis)
Muscle pain (myalgia)
Joint pain, stiffness, swelling or redness, reduced joint mobility – possible symptoms of joint problems (arthritis)
Increased blood levels of the liver enzyme alkaline phosphatase
Chills or trembling, itching or rash, flushing, shortness of breath or wheezing, dizziness or fever that may occur during 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 bilirubin levels in the blood
High levels of creatine kinase and creatinine in the blood
High blood glucose levels
High potassium levels in the blood
Low potassium levels in the blood

Uncommon (may affect up to 1 in 100 people)

A disease in which the immune system attacks glands that produce moisture for the body, such as tears and saliva (Sjögren's syndrome)
Tiredness, swelling at the base of the neck, pain in the front of the throat – possible symptoms of thyroid gland problems (thyroiditis)
Adrenal insufficiency (a disorder in which the adrenal glands do not produce enough hormones)
Frequent headaches, changes in vision (blurred vision or double vision), tiredness and/or weakness, confusion, low blood pressure, dizziness – possible symptoms of pituitary gland problems (hypophysitis)
Red eyes, eye pain and swelling – possible symptoms of problems affecting the uvea, the layer beneath the white of the eye (uveitis)
Changes in amount and colour of urine, pain during urination, pain in the kidney area – possible symptoms of kidney problems (nephritis)
Muscle pain, stiffness, weakness, chest pain or extreme tiredness – possible symptoms of muscle problems (myositis)
Skin discolouration (vitiligo)
High lymphocyte count in the blood
Low albumin levels in the blood
High alkaline phosphatase levels in the blood
High sodium levels in the blood
High sodium levels in the blood

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

A rare condition in which the immune system produces an excessive number of infection-fighting cells called histiocytes and lymphocytes. Symptoms may include fever, rash, swollen lymph nodes, breathing problems, easy bruising (haemophagocytic lymphohistiocytosis)
Brain inflammation, which may cause confusion, fever, memory problems or seizures (encephalitis)
Serious nerve problems, which may cause difficulty breathing, tingling or numbness in fingers of hands, feet, ankles or wrists, leg weakness spreading to the upper body, unsteady walking or inability to walk or climb stairs, difficulty with facial movements including speaking, chewing or swallowing, double vision or inability to move eyes, difficulty controlling bladder or bowel function, rapid heartbeat and paralysis – possible symptoms of Guillain-Barré syndrome
Muscle weakness and tiredness (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 ulcers – possible symptoms of serious skin reactions. Inform your doctor immediately if you experience any of the serious side effects listed above.

Te vimbra treatment must be stopped and immediate medical help sought if any of the following symptoms occur:
Not known (frequency cannot be estimated from available data)

Reddish, flat, circular or target-like spots on the trunk, often with central blisters, skin peeling, mouth, throat, nose, genital or eye ulcers. These severe skin rashes may be preceded by fever and flu-like symptoms (NET)

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

5. How to store Tevimbra

Your doctor, pharmacist, or nurse is responsible for the storage of this medicine and the proper disposal of any unused product. The following information is intended for healthcare professionals.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the vial label after "Exp". The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C).
Do not freeze.
Keep vials in the outer packaging to protect the medicine from light.
Tevimbra does not contain a preservative. Chemical and physical in-use stability has been demonstrated for 10 days (240 hours) at 2°C to 8°C. The 10 days (240 hours) include storage of the diluted solution under refrigeration (2°C to 8°C), the time required to return to room temperature (25°C or less), and the time needed to complete the infusion within 4 hours.
From a microbiological standpoint, once diluted, the product should be used immediately.
If not used immediately, the duration and conditions of in-use storage are the responsibility of the user. The diluted solution must not be frozen.
Do not store unused portions of the infusion solution for later reuse. Unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations.

6. Package contents and other information

What Tevimbra contains

The active substance 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 ingredients are sodium dihydrogen citrate dihydrate (see section 2 "Tevimbra contains sodium"), monohydrate citric acid, L-histidine hydrochloride monohydrate, L-histidine, trehalose dihydrate, polysorbate 20 and water for injections.

Description of the appearance of Tevimbra and contents of the pack
Tevimbra concentrate for solution for infusion (sterile concentrate) is a solution ranging from transparent to slightly opalescent, from colourless to slightly yellowish.
Tevimbra is available in packs containing 1 vial and multiple packs containing 2 (2 packs of 1) vials.

Marketing Authorisation Holder
BeOne Medicines Ireland Limited
10 Earlsfort Terrace
Dublin 2
D02 T380
Ireland
Tel. +353 1 566 7660
E-mail: [email protected]

Manufacturer
BeOne Medicines I GmbH, Dutch Branch
Evert Van De Beekstraat 1/104
Schiphol
1118 CL
The Netherlands

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

The following information is intended exclusively for healthcare professionals:

Tevimbra vials are for single use only. Each vial contains 100 mg of tislelizumab.
The diluted solution for infusion must be prepared by a healthcare professional using aseptic technique.

Preparation of infusion solution

Remove the required number of vials from the refrigerator, taking care not to shake them.
Visually inspect each vial for particulate matter and discoloration prior to administration. The concentrate is a clear or slightly opalescent solution, colorless to pale yellow. Do not use a vial if the solution is cloudy, or if visible particles or discoloration are observed.
Gently invert the vials without shaking. Withdraw the required volume from the vial (or vials) into a syringe and transfer it into an intravenous infusion bag containing sodium chloride 9 mg/mL (0.9%) injection solution to prepare a diluted solution with a final concentration between 2 and 5 mg/mL. Mix the diluted solution by gentle inversion to avoid foaming or excessive viscosity.

Administration

Administer the diluted Tevimbra solution by intravenous infusion through an intravenous administration line with an in-line or add-on sterile, pyrogen-free, low protein-binding 0.2 or 0.22 micron filter with a surface area of approximately 10 cm².
For the 200 mg dose administered every 3 weeks, the first infusion should be given over 60 minutes. If well tolerated, subsequent infusions may be administered over 30 minutes.

The infusion of an initial dose of Tevimbra 400 mg should be administered over 120 minutes (over 90 minutes if used as subsequent treatment following the 200 mg dose once every 3 weeks). If well tolerated, the second infusion may be administered over 60 minutes. If the second infusion is well tolerated, subsequent infusions may be administered over 30 minutes.

Other medicinal products must not be co-administered through the same infusion line.
Tevimbra must not be administered by intravenous injection or as a single intravenous bolus.
Tevimbra does not contain a preservative. Chemical and physical in-use stability has been demonstrated for 10 days (240 hours) at 2°C to 8°C. The 10 days (240 hours) include refrigerated storage of the diluted solution (2°C to 8°C), the time required to return to room temperature (25°C or less), and the time to complete the infusion within 4 hours. From a microbiological standpoint, the product should be used immediately after dilution. If not used immediately, the duration and conditions of in-use storage are the responsibility of the user.
The diluted solution must not be frozen.
Discard any unused portion remaining in the vial.
The intravenous line must be flushed at the end of the infusion.
Tevimbra vials are for single use only.