100 mg powder for concentrate for infusion solution
Infliximab
1. What Flixabi is and what it is used for
Flixabi contains the active substance infliximab. Infliximab is a monoclonal antibody – a type of protein that binds to a specific target in the body called TNF alpha ( tumor necrosis factor-alpha).
Flixabi belongs to a group of medicines called “TNF inhibitors”. It is used in adults for the following inflammatory diseases:
- rheumatoid arthritis
- psoriatic arthritis
- ankylosing spondylitis (Bechterew’s disease)
- psoriasis.
Flixabi is also used in adults and children, 6 years and older, in:
- Crohn’s disease
- ulcerative colitis.
Flixabi works by specifically binding to TNF alpha and blocking its function. TNF alpha participates in inflammatory processes in the body and by blocking them, inflammation in your body can be reduced.
Rheumatoid arthritis
Rheumatoid arthritis is an inflammatory disease that affects the joints. If you have active rheumatoid arthritis you will first be given other medicines. If these medicines do not work well enough on these medicines, you will be given Flixabi to take in combination with another medicine called methotrexate to:
- reduce the signs and symptoms of the disease
- reduce the damage to the joints
- improve your physical function.
Psoriatic arthritis
Psoriatic arthritis is an inflammatory disease of the joints, usually associated with psoriasis. If you have active psoriatic arthritis, you will first be given other medicines. If these medicines do not work well enough, you will be given Flixabi to:
- reduce the signs and symptoms of the disease
- reduce the damage to the joints
- improve your physical function.
Ankylosing spondylitis (Bechterew’s disease)
Ankylosing spondylitis is an inflammatory disease of the spine. If you have ankylosing spondylitis, you will first be given other medicines. If these medicines do not work well enough, you will be given Flixabi to:
- reduce the signs and symptoms of the disease
- improve your physical function.
Psoriasis
Psoriasis is an inflammatory disease of the skin. If you have moderate or severe plaque psoriasis, you will first be given other medicines or treatments such as light therapy. If these medicines or treatments do not work well enough, you will be given Flixabi to reduce the signs and symptoms of the disease.
Ulcerative colitis
Ulcerative colitis is an inflammatory disease of the intestine. If you have ulcerative colitis, you will first be given other medicines. If these medicines do not work well enough, you will be given Flixabi to treat the disease.
Crohn’s disease
Crohn’s disease is an inflammatory disease of the intestine. If you have Crohn’s disease, you will first be given other medicines. If these medicines do not work well enough, you will be given Flixabi to:
- treat active Crohn’s disease
- reduce the number of abnormal passages ( fistulas ) through the skin from the intestine that has not been controlled with other drugs or surgery
2. What you need to know before using Flixabi
You will not receive Flixabi if:
- you are allergic to infliximab or any of the other ingredients of this medicine (listed in section 6)
- you are allergic (hypersensitive) to protein you get from mice
- you have tuberculosis (TBC) or any other serious infection such as pneumonia or sepsis
- you have heart failure that is moderate or severe.
Do not use Flixabi if any of the above apply to you. If you are not sure, talk to your doctor before taking Flixabi.
Warnings and cautions
Talk to your doctor before or during treatment with Flixabi if you have:
Have been treated with any medicine containing infliximab before
- Tell your doctor if you have previously been treated with medicines containing infliximab and are now starting treatment with Flixabi again.
If you have had a break in your infliximab treatment for more than 16 weeks, there is an increased risk of allergic reactions when you start treatment again.
Infection is
- Tell your doctor before you get Flixabi if you have an infection, even if it is a very mild one before you get Flixabi.
- Tell your doctor before receiving Flixabi if you have ever lived in or traveled to areas where infection called histoplasmosis, coccidioidomycosis or blastomycosis is common. These infections are caused by a special type of fungus that can affect the lungs or other parts of the body.
- You can more easily get your infection when you are treated with Flixabi. If you are 65 years or older, the risk is higher.
- These infections can be serious and include tuberculosis, infections caused by viruses, fungi, bacteria, or other organisms in the environment, and blood poisoning that can be life-threatening.
Tell your doctor immediately if you get any signs of infection during treatment with Flixabi. Such signs include fever, cough, flu-like signs, general malaise, red or hot skin, sores, or dental problems. Your doctor may recommend that Flixabi treatment be stopped temporarily.
Tuberculosis (TBC)
- You must tell your doctor if you have ever had TB or if you have been in close contact with someone who has had or has TB.
- Your doctor will check if you have TB. Cases of TB have been reported in patients treated with Flixabi, including in patients already treated with anti-TB drugs. Your doctor will note the examinations on your Patient Card.
- If your doctor thinks you are at risk of getting TB, you can get TB medicine before you are given Flixabi.
Tell your doctor immediately if you get any signs of TB during treatment with Flixabi. Such signs include persistent cough, weight loss, feeling tired, fever, night sweats.
Hepatitis B virus
- Tell your doctor before receiving Flixabi if you are a hepatitis B carrier or if you have ever had it.
- Tell your doctor if you think you are at risk of getting hepatitis B.
- Your doctor will test you for the hepatitis B virus.
- Treatment with TNF- antagonists such as Flixabi may reactivate the hepatitis B virus in patients carrying this virus, which in some cases may be life-threatening.
Heart problems
- Tell your doctor if you have heart problems such as mild heart failure.
- Your doctor will closely monitor your heart. Tell your doctor immediately if you get new or worsening signs of heart failure during treatment with Flixabi. Such signs include shortness of breath or swollen feet.
Cancer and lymphoma
- Tell your doctor before receiving Flixabi if you have or have ever had lymphoma (a type of blood cancer) or any other cancer.
- Patients with severe rheumatoid arthritis who have had the disease for a long time may have a higher risk of developing lymphoma.
- Children and adults treated with Flixabi may be at increased risk of developing lymphoma or any other cancer.
- Some patients who have received TNF inhibitors, including Flixabi, have developed a rare type of cancer called T-cell lymphoma of the liver and spleen. Of these patients, most were teenage boys or younger men, and most had either Crohn’s disease or ulcerative colitis. This type of cancer usually leads to death. In addition to TNF inhibitors, almost all patients had also received medicines containing azathioprine or 6-mercaptopurine.
- Some patients treated with infliximab have developed certain types of skin cancer. Tell your doctor if there are any changes in the skin or growths on the skin during or after the treatment.
- Some women treated for rheumatoid arthritis with infliximab have developed cervical cancer. For women taking infliximab, even those over 60 years of age: Your doctor may recommend regular examination for cervical cancer.
Lung disease or heavy smoking
- Tell your doctor before taking Flixabi if you have a lung disease called chronic obstructive pulmonary disease (COPD), or if you are a heavy smoker.
- Patients who have COPD or patients who are heavy smokers may have a higher risk of developing cancer during treatment with Flixabi.
Diseases of the nervous system
- Tell your doctor if you have or have had problems affecting your nervous system before receiving Flixabi. These include multiple sclerosis, Guillain-Barré syndrome if you have a seizure or have been diagnosed with “optic neuritis”.
Tell your doctor immediately if you experience symptoms of nerve disease during treatment with Flixabi. Such signs include altered vision, weakness in the arms or legs, numbness or tingling in any part of the body.
Fistulas
- Tell your doctor if you have any abnormal skin opening ( fistula ) before receiving Flixabi.
Vaccinations
- Tell your doctor if you have recently had or are planning to get vaccinated.
- You should receive recommended vaccinations before starting treatment with Flixabi. You can get certain vaccinations during treatment with Flixabi but you should not get live vaccines (vaccines that contain a live but attenuated infectious agent) as they can cause you an infection.
- If you received Flixabi while you were pregnant, your baby may also be at a higher risk of getting an infection with live vaccines up to six months after birth. You must tell your child’s doctor and other healthcare professionals if you have been treated with Flixabi so that they can decide when your child should receive a vaccine, including live vaccines such as BCG (used to prevent tuberculosis ). For more information, see the section on pregnancy and breastfeeding.
Antimicrobial agents
- Tell your doctor if you have recently received or are planning to receive treatment with an antimicrobial agent (such as BCG installation which is used to treat cancer).
Operations or dental treatments
- Tell your doctor if you are going to have any surgery or dental treatment.
- Tell your doctor or dentist that you are being treated with Flixabi by showing your Patient Card.
Liver problem
- Some patients receiving infliximab have developed severe liver problems.
- Tell your doctor immediately if you experience symptoms of liver problems during treatment with Flixabi. Such signs include yellowing of the skin and eyes, dark brown urine, pain or swelling in the upper right side of the abdomen, joint pain, rash, or fever.
Low blood levels
- In some patients receiving infliximab, the body may not be able to produce enough blood cells to help fight infection or to stop bleeding.
- Tell your doctor immediately if you experience symptoms of low blood pressure during treatment with Flixabi. Such signs include persistent fever, easy bleeding or bruising, small red or purple spots caused by bleeding under the skin, or pallor.
Problems with the immune system
- Some patients receiving infliximab have developed symptoms of an immune disorder called lupus.
Tell your doctor immediately if you develop symptoms of lupus during treatment with Flixabi. Such signs include joint pain or rash on the cheeks or arms that are sensitive to the sun.
Children and young people
The above information also applies to children and young people. Also:
- Some children and teens who have received TNF inhibitors, such as Flixabi, have developed cancer, even rare types, which have sometimes led to death.
- More children taking Flixabi to get an infection compared to adults.
- Children should receive recommended vaccinations before starting treatment with Flixabi. Children may receive certain vaccines during treatment with Flixabi but should not receive live vaccines while using Flixabi.
If you are not sure if any of the above applies to you, talk to your doctor before taking Flixabi.
Other medicines and Flixabi
Tell your doctor if you are taking, have recently taken, or might take any other medicines.
Patients with inflammatory diseases are already taking medication to treat their problems. These drugs can cause side effects. Your doctor will tell you what other medicines you must continue to use when you receive Flixabi.
In particular, tell your doctor if you are taking any of the following medicines:
- Drugs that affect the immune system.
- Kineret (containing anakinra). Flixabi and Kineret should not be used together.
- Orencia (which contains abatacept). Flixabi and Orencia should not be used together.
You should not receive live vaccines (eg BCG vaccine) when using Flixabi. If you have been pregnant and used Flixabi at the same time, tell your child’s doctor and other healthcare professionals who have contact with your child that you have been treated with Flixabi before the child receives any vaccine.
If you are not sure if any of the above applies to you, talk to your doctor or pharmacist before taking Flixabi.
Pregnancy, breastfeeding, and fertility
- If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before using this medicine. Flixabi should only be used during pregnancy if your doctor thinks it is necessary.
- You should avoid becoming pregnant when you are being treated with Flixabi and for 6 months after stopping treatment. Discuss the use of appropriate contraceptives during this time with your doctor.
- Do not breast-feed when you are being treated with Flixabi or for 6 months after stopping Flixabi treatment.
- If you received Flixabi during your pregnancy, your baby may be at higher risk of getting an infection.
- You must tell your child’s doctor and other healthcare professionals if you have been treated with Flixabi before children are given any vaccine. If you received Flixabi during pregnancy and your baby is given the BCG vaccine (used to prevent tuberculosis ) within 6 months of birth, it can lead to infection with serious complications, even fatal. Live vaccines such as BCG should not be given to your baby within 6 months of birth. For more information, see the section on vaccinations.
- Significantly decreased white blood cell counts have been reported in infants born to women treated with Flixabi during pregnancy. If your child has a constant fever or infection, contact your child’s doctor immediately.
Driving and using machines
Flixabi has less effect on the ability to drive and use machines, e.g. dizziness and vertigo.
Flixabi contains excipients
This medicine contains less than 1 mmol sodium (23 mg) per dose, ie essentially ‘sodium-free’. Flixabi is prepared with a solution containing sodium before it is given to you. Talk to your doctor if you have been prescribed a low-salt (sodium-poor) diet.
How Flexabi is given
Rheumatoid arthritis
The usual dose is 3 mg per kg body weight.
Psoriatic Arthritis, Ankylosing Spondylitis (Bechterew’s Disease), Psoriasis, Ulcerative Colitis, and Crohn’s Disease
The usual dose is 5 mg per kg body weight.
How Flixabi is given
- Flixabi will be given to you by a doctor or nurse.
- Your doctor or nurse will prepare the medicine for infusion.
- The drug will be given as an infusion (drip) (over 2 hours) into a vein, usually in your arm. After the third treatment, your doctor may decide to give you your dose of Flixabi for 1 hour.
- You will be monitored while receiving Flixabi and also 1-2 hours afterward.
Amount of Flixabi given
- Your doctor will decide on your dose and how often you should receive Flixabi. It depends on your illness, weight, and how well you respond to Flixabi.
- The table below shows how you will usually receive this medicine after your first dose.
| 2nd dos en | 2 weeks after 1st dose one |
| 3rd dos en | 6 weeks after 1st dose one |
| Additional dose er | Every 6 to 8 weeks depending on the disease |
Use for children and adolescents
Flixabi should only be given to children and adolescents being treated for Crohn’s disease or ulcerative colitis. These children must be 6 years or older.
If you take more Flixabi than you should
As this medicine is given by a doctor or nurse, it is unlikely that you will receive too much. There are no known side effects after taking too much Flixabi.
If you forget or miss your Flixabi infusion
If you have forgotten or missed a visit to get Flixabi, book a new visit as soon as possible.
If you have any further questions on the use of this product, ask your doctor.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side effects are mild to moderate. However, some patients may experience serious side effects that may require treatment. Side effects may also occur after stopping treatment with Flixabi.
Tell your doctor immediately if you notice any of the following:
- Signs of an allergic reaction such as swelling of the face, lips, mouth, or throat, which can cause difficulty swallowing or breathing, skin rash, hives, swollen hands, feet, or ankles. Some of these reactions can be serious or life-threatening. An allergic reaction can occur within 2 hours after injection one or later. Several signs of an allergic reaction that can occur up to 12 days after injection include muscle pain, fever, joint or jaw pain, sore throat, or headache.
- Signs of heart problems such as chest discomfort or pain, pain in the arm, abdominal pain, shortness of breath, anxiety, dizziness, dizziness, fainting, sweating, nausea, vomiting, fluttering or throbbing beats in the chest, rapid or slow heartbeat, and/or swelling feet.
- Signs of infection (includes TB) such as fever, tiredness, cough which may be persistent, shortness of breath, flu-like symptoms, weight loss, night sweats, diarrhea, ulcers, accumulation of var in the intestine or around the anus (abscess), dental problems or burning sensation when urinating.
- Signs of lung problems such as cough, difficulty breathing, or tightness in the chest.
- Signs of nervous system problems (including eye problems) such as signs of stroke (sudden numbness or weakness in the face, arms, or legs, especially on one side of the body; sudden confusion, difficulty speaking or understanding; difficulty seeing with one or both eyes, difficulty walking, dizziness, loss of balance or coordination, or severe headache), seizures, tingling/numbness in any part of the body, or weakness in the arms or legs, altered vision such as double vision or other eye problems.
- Signs of liver problems (including hepatitis B infection if you have previously had hepatitis B) such as yellowing of the skin or eyes, dark brown urine, pain or swelling in the upper right side of the abdomen, joint pain, rash, or fever.
- Signs of an immune disease such as joint pain or rash on the cheeks or arms that are sensitive to the sun (lupus) or cough, shortness of breath, fever, or rash ( sarcoidosis ).
- Signs of low blood levels such as persistent fever, easy bleeding or bruising, small red or purple spots caused by bleeding under the skin, or pallor.
- Signs of serious skin problems such as reddish spots, or round spots often with blisters in the middle, localized on the upper body, large areas of scaly and tender skin (exfoliation), cold sores, sores in the throat, nose, genitals, and eyes, or small lumps that are can spread throughout the body. These skin reactions may be accompanied by fever.
Tell your doctor immediately if you notice any of the above.
The following side effects have been observed with infliximab:
Very common (may affect more than 1 user in 10)
- Abdominal pain, nausea
- Viral infections such as herpes or flu
- Upper respiratory tract infection such as sinusitis
- Headache
- A side effect is of an infusion
- Pain
Common (may affect up to 1 in 10 people )
- Changes in how the liver works, increase in liver enzyme values (shown by blood tests)
- Infection is in the lungs or breasts such as bronchitis or pneumonia
- Severe or painful breathing, chest pain
- Bleeding in the stomach or intestines, diarrhea, indigestion, heartburn, constipation
- Hives ( urticaria ), itchy rash, or dry skin
- Balance problems or dizziness
- Fever, increased sweating
- Circulatory problems such as low or high blood pressure
- Bruising, hot flashes or nosebleeds, hot, red skin ( redness )
- Feeling tired or weak
- Bacterial infections such as sepsis, abscess, or skin infection ( cellulite )
- Blood problems such as anemia or low white blood cell count
- Swollen lymph nodes
- Depression, sleep problems
- Eye problems involving redness and infection s
- Rapid heartbeat ( tachycardia ) or palpitations
- Pain in joints, muscles, or back
- Urinary tract infection
- Psoriasis, skin problems such as eczema and hair loss
- Injection site reactions such as pain, swelling, redness, or itching
- Chills, accumulation of fluid under the skin that causes swelling
- Numbness or a stinging sensation
Uncommon (may affect up to 1 in 100 people )
- Poor blood supply, swelling in a blood vessel
- Accumulation of blood outside the blood vessels (hematoma) or bruising
- Skin problems such as blisters, warts, abnormal skin color or pigmentation or swollen lips, or thickening of the skin, or red, scaly, and flaky skin
- Severe allergic reactions (eg anaphylaxis ), an immune disorder called lupus, allergic reactions to foreign protein s
- Impaired wound healing
- Swollen liver ( hepatitis ) or gallbladder, liver damage
- Feeling forgetful, annoyed, confused, nervous
- Eye problems that include blurred vision or impaired vision, swollen eyes, or vagal
- New onset or worsening of existing heart failure, slow heartbeat
- Fainting
- Cramps, nerve problems
- Intestinal perforation or obstruction in the intestine, abdominal pain, or cramps
- Swollen pancreas ( pancreatitis )
- Fungal infections such as infection of yeast or fungal infection of the nails
- Lung problems (such as edema )
- Fluid around the lungs (alveolar discharge)
- Narrowing of the airways in the lungs that causes difficulty breathing
- Pneumonia, which causes sharp chest pain that worsens with breathing
- Tuberculosis
- Kidney infections
- Low platelet count, too many white blood cells
- Infection is in the vagina
- Blood tests that show antibodies are against your own body.
Rare (may affect up to 1 in 1,000 people )
- A type of blood cancer ( lymphoma )
- The blood does not supply enough oxygen to the body, circulatory problems such as narrowing of a blood vessel
- Meningitis ( meningitis )
- Infection is caused by a weakened immune system
- Hepatitis B infection if you have had hepatitis B before
- Inflammation of the liver caused by problems with the immune system ( autoimmune hepatitis )
- Liver problems that cause yellowing of the skin or eyes (jaundice)
- Abnormal swelling or growth of tissue
- The severe allergic reaction that may cause unconsciousness and may be life-threatening (anaphylactic shock )
- Swelling of small blood vessels ( vasculitis )
- Immune disorders that may affect the lungs, skin, and lymph nodes (such as sarcoidosis )
- Accumulation of immune cells resulting from an inflammatory response (granulomatous changes)
- Lack of interest or feelings
- Severe skin problems such as toxic epidermal necrolysis, Stevens-Johnson syndrome, and acute generalized exanthematous pustulosis
- Other skin problems such as erythema multiforme, lichenoid reactions (itchy red-purple rash and/or thread-like white-gray lines on mucous membranes), blisters and scaly skin, or boils ( furunculosis )
- Severe nervous system disorders such as transverse myelitis, multiple sclerosis-like diseases, optic neuritis, and Guillain-Barré syndrome
- Fluid around the pericardium (ejection into the pericardium)
- Severe lung problems (such as interstitial lung disease)
- Melanoma (a type of skin cancer)
- Cervical cancer
- Low blood levels, even greatly reduced white blood cell, count.
- Small red or purple spots caused by bleeding under the skin
- Abnormal levels of a protein in the blood are called a “complement factor” that is part of the immune system.
Has been reported (occurs in an unknown number of users )
- Cancer in children and adults
- An unusual blood cancer that mostly affects teenage boys and young men (T-cell lymphoma in the liver and spleen )
- Liver failure
- Merkel cell carcinoma (a type of skin cancer
- Kaposi’s sarcoma, rare cancer associated with infection with human herpesvirus 8 Kaposi sarcoma occurs most often as purple spots on the skin.
- Exacerbation of a condition called dermatomyositis (seen as a skin rash with muscle weakness)
- Heart attack
- Stroke
- Temporary loss of vision during or within 2 hours after infusion
- Infection caused by a “live” vaccine, due to a weakened immune system.
Additional side effects in children and adolescents
Children and adolescents taking infliximab for Crohn’s disease had some differences in side effects compared with adults taking infliximab for Crohn’s disease. The most common side effects in children were: low red blood cell count ( anemia ), bloody stools, low white blood cell counts ( leukopenia ), red skin or redness (swelling), viral infections, low levels of white blood cells fighting infection ( neutropenia ), bone fractures, bacterial infection and allergic reactions of the respiratory tract.
5. How to store Flixabi
Flixabi is stored by healthcare professionals in a hospital or health center. The storage instructions are as follows if you need to know them:
- Keep this medicine out of the sight and reach of children.
- Do not use this medicine after the expiry date which is stated on the label after “EXP” and the carton after “EXP”. The expiration date is the last day of the specified month.
- Store in a refrigerator (2 ° C ‑ 8 ° C).
- It can also be stored in the original carton without refrigerated storage, for a maximum of 25 ° C, for a single period of up to six months, provided that the original expiry date is not exceeded. In this case, do not put the medicine back in the cold storage. Write the new expiration date on the box. Enter year-month-day.
Discard the medicine if it has not been used before the new expiry date or the expiry date which is stated on the carton, whichever comes first. - When Flixabi is ready for infusion, it is recommended that it be used as soon as possible (within 3 hours). However, if the solution is prepared under germ-free conditions, it can be stored in a refrigerator for up to 34 days at 2 ° C ‑ 8 ° C and for a further 24 hours at 25 ° C after removal from the refrigerator.
- Do not use this medicine if it is discolored or contains particles.
6. Contents of the packaging and other information
Content declaration
- The active substance is infliximab. Each vial contains 100 mg infliximab. After reconstitution, each ml contains 10 mg infliximab.
- The other ingredients are sucrose, polysorbate 80, monobasic sodium phosphate monohydrate, and dibasic sodium phosphate heptahydrate.
What the medicine looks like and the contents of the pack
Flixabi is supplied in a glass vial containing a powder for concentrate for solution for infusion. The powder is white.
Flixabi is manufactured in packs of 1, 2, 3, 4, and 5 vials. Not all pack sizes may be marketed
Marketing Authorization Holder and Manufacturer
Samsung Bioepis NL BV
Olof Palmestraat 10
2616 LR Delft
Netherlands
Manufacturer
Biogen (Denmark) Manufacturing ApS
Biogen Allé 1
3400 Hillerød
Denmark