50 mg powder for concentrate for infusion solution
brentuximab vedotin
1. What Adcetris is and what it is used for
Adcetris contains the active substance brentuximab vedotin , an anti-cancer agent consisting of monoclonal antibodies bound to a substance which is intended to kill cancer cells. This substance is delivered to cancer cells by the monoclonal antibody . A monoclonal antibody is a protein that recognizes certain cancer cells.
Hodgkin’s lymphoma, systemic large cell anaplastic lymphoma, and cutaneous T cell lymphoma are types of cancers in the white blood cells.
Classical Hodgkin’s lymphoma has specific proteins on the cell surface that are different from non-classical Hodgkin’s lymphoma .
Adcetris is used to treat advanced classic Hodgkin’s lymphoma that has not been treated before. Adcetris is co-administered with doxorubicin, vinblastine, and dacarbazine, other chemotherapy drugs used to treat Hodgkin’s lymphoma.
Adcetris is also used as the only drug to reduce the likelihood of classic Hodgkin’s lymphoma returning after an infusion of your own healthy stem cells into your body ( autologous stem cell transplantation ) in patients with certain risk factors.
Adcetris is also used as the sole drug to treat classic Hodgkin’s lymphoma which has:
- returned after, or did not respond to, an autologous stem cell transplant or
- come back after, or never responded to, at least two previous treatments and you cannot receive additional combination treatments or an autologous stem cell transplant.
Systemic large-cell anaplastic lymphoma is a type of non‑ Hodgkin’s lymphoma found in the lymph nodes and / or other parts of the body.
Adcetris is used to treat systemic large-cell anaplastic lymphoma that has not been previously treated. Adcetris is given together with cyclophosphamide, doxorubicin, and prednisone, which are other chemotherapy drugs used to treat these conditions.
Adcetris is also used to treat large-cell anaplastic lymphoma such as:
- have not responded to other types of cancer treatments or
- has returned after previous cancer treatment.
Cutaneous T cell lymphoma is a cancer of a certain type of white blood cell called T cell that mainly affects the skin. Adcetris is used to treat cutaneous T cell lymphoma when a specific type of protein is present on the cell surface.
Adcetris is used to treat cutaneous T-cell lymphoma in patients who have previously been treated with at least one blood cancer drug.
2. What you need to know before you receive Adcetris
Do not use Adcetris
- if you are allergic to brentuximab vedotin or any of the other ingredients of this medicine (listed in section 6).
- if you are currently using bleomycin, an anticancer medicine.
Warnings and cautions
When you first receive this medicine or during treatment, tell your doctor about:
- you become confused, have difficulty thinking, memory loss, blurred or impaired vision, decreased strength, decreased control or loss of sensation in one arm or leg, a change in the way you walk or balance disorders as these can be symptoms of a serious and potentially life-threatening condition in the brain which is called progressive multifocal leukoencephalopathy (PML). If you have these symptoms before treatment with this medicine, tell your doctor immediately about any changes in these symptoms. You should also inform your partner or healthcare provider about your treatment as they may notice symptoms that you are not aware of.
- you have severe and persistent abdominal pain, with or without nausea and vomiting, as this may be a symptom of a serious and possibly fatal condition called pancreatitis ( inflammation of the pancreas).
- you have new-onset or worsening shortness of breath or cough as these can be symptoms of a serious and potentially fatal lung complication ( pulmonary toxicity)
- you are taking or have previously taken medicines that may affect the immune system, e.g. cytotoxic drugs or immunosuppressive agents.
- you have or think you have an infection. Some infections can be serious and can be due to viruses, bacteria, or other causes that can be life-threatening.
- there is a beeping (wheezing) sound when you breathe / shortness of breath, hives, itching, or swelling (signs of an infusion reaction). For more detailed information, see “Infusion reactions” in section 4.
- you have some problems with altered sensation in the skin, especially in the hands or feet, e.g. numbness, stinging or burning sensation, pain, discomfort, or weakness ( neuropathy )
- you have a headache, feel tired, dizzy, pale ( anemia ) or have unusual bleeding or bruising, bleed longer than usual after leaving a blood sample or bleed from the gums ( thrombocytopenia )
- you get chills or tremors or feel hot. You should check if you have a fever. Fever with low white blood cell count can be a sign of a serious infection
- you may experience dizziness, decreased urination, confusion, vomiting, nausea, swelling, shortness of breath, or arrhythmias (this can be a potentially life-threatening complication called tumor lysis syndrome)
- you experience flu-like symptoms followed by painful red or purple rashes that spread and form blisters and extensive skin discharge that can be life-threatening (this can be a serious skin reaction called Stevens-Johnson syndrome and toxic epidermal necrolysis )
- you have new or worsening stomach pain, nausea, vomiting, constipation as they may be symptoms of a serious and potentially fatal gastrointestinal complication (gastrointestinal complications)
- you have abnormal results when examining your liver function as it may be caused by serious and potentially fatal liver damage (liver toxicity). The risk of liver damage when you start treatment with Adcetris may increase if you already have pre-existing liver disease or other pre-existing conditions and of certain medicines.
- you feel tired, need to urinate frequently, have increased thirst, increased appetite with unintentional weight loss or irritability ( hyperglycemia )
- you have kidney or liver problems.
To check that it is safe for you to receive this medicine, your doctor will take regular blood tests on you.
Other medicines and Adcetris
Tell your doctor if you are taking, have recently taken, or might take any other medicines. This also applies to herbal preparations and other over-the-counter medicines.
Pregnancy, breastfeeding, and fertility
You and your partner must use two effective methods of contraception during your treatment with this medicine. Women must continue to use contraception for 6 months after the last dose of Adcetris.
You should not use this medicine if you are pregnant unless you and your doctor decide that the benefit to you outweighs the potential risk to the unborn baby.
It is important to tell your doctor before and during treatment, if you are pregnant, think you may be pregnant or are planning to have a baby.
If you are breast-feeding, you should discuss with your doctor whether you should receive this medicine.
Men treated with this medicine are advised to freeze semen samples for storage before treatment. Men are advised not to become fathers during treatment with this medicine or for the following six months after the last dose.
Driving and using machines
Your treatment may affect your ability to drive or use machines. If you do not feel well during the treatment, do not drive or use machines.
Adcetris contains sodium
This medicine contains 13.2 mg of sodium (the main component of common table salt) in each vial. This corresponds to 0.7% of the recommended maximum daily intake of sodium via the diet of an adult.
How Adcetris will be given
If you have any further questions on the use of this product, ask your doctor or nurse who is giving you an infusion.
Dose and frequency
The dose of this medicine depends on your body weight.
- The usual dose of Adcetris when given in combination with doxorubicin, vinblastine, and dacarbazine is 1.2 mg/kg given every two weeks for 6 months.
- The usual dose of Adcetris when given in combination with cyclophosphamide, doxorubicin and prednisone is 1.8 mg/kg given every 3 weeks for approximately 4-6 months.
See the package leaflet for these medicines given in combination with Adcetris for more information on their use and efficacy. After the first dose of Adcetris in combination with chemotherapy, your doctor may also give you a medicine to prevent or alleviate neutropenia (reduced white blood cell count ), as neutropenia may increase the risk of infection. Tell your doctor if you have kidney or liver problems as your doctor may reduce your starting dose or may not recommend Adcetris
The usual dose of Adcetris when given as a single drug is 1.8 mg / kg once every 3 weeks for a maximum of one year. If you have liver or kidney problems, your doctor may reduce the starting dose to 1.2 mg / kg.
Adcetris should only be given to adults. It is not intended for use in children.
How Adcetris is given
This medicine is given to you in a vein ( intravenously ) as an infusion. It is given by your doctor or nurse for 30 minutes. Your doctor or nurse will also monitor you during and after the infusion.
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.
Infusion reactions
Drugs of this type (monoclonal antibodies ) can lead to infusion reactions such as:
- rash
- respiratory distress
- hard to breathe
- cough
- pressure over the chest
- fever
- back pain
- frostbite
- headache
- malaise (nausea) or nausea (vomiting).
Infusion reactions of this medicine may occur in more than 1 in 10 people.
In general, these types of reactions occur within minutes to several hours after the infusion is completed. However, they may develop more than several hours after infusion one, but this is unusual. These infusion reactions can be severe or even fatal (so-called anaphylactic reaction ). The extent to which infusion-related reactions of this drug are severe or fatal is not known.
You can get other medicines, e.g.
- antihistamine is, a corticosteroid is or paracetamol
to alleviate some of the above reactions if you have already experienced them when you received this type of medicine.
If you think you may have had a similar reaction in the past, tell your doctor BEFORE you receive this medicine.
If you develop infusion reactions (as above), your doctor may stop giving you this medicine and start supportive treatment.
If infusion is started again, your doctor may increase the time during which your infusion is given so that you can tolerate it better.
Tell your doctor immediately if you notice any of the following symptoms as some of them may be signs of a serious or potentially fatal condition:
- progressive multifocal leukoencephalopathy (PML) has symptoms such as confusion, difficulty thinking, memory loss, blurred or impaired vision, decreased strength, decreased control or loss of sensation in one arm or leg, a change in gait or balance disorders (for more detailed information, see section 2) (may affect up to 1 in 100 people).
- symptoms of inflammation of the pancreas ( pancreatitis ) as serious and persistent stomach pain, with or without nausea and vomiting (may affect up to 1 in 100)
- shortness of breath and cough (may affect more than 1 in 10 people)
- flu-like symptoms followed by painful red or purple rashes that spread and form blisters and extensive skin discharge (may affect up to 1 in 100 people)
- altered sensation, especially in the skin, numbness, stinging sensation, discomfort, burning sensation, weakness, or pain in the hands or feet ( neuropathy, may occur in more than 1 in 10 people)
- feeling weak (may affect more than 1 in 10 people)
- constipation (may affect more than 1 in 10 people)
- diarrhea, vomiting (may affect more than 1 in 10 people)
- chills or tremors (may affect up to 1 in 10 people)
- feeling tired, need to urinate frequently, increased thirst, increased appetite with accidental weight loss, and irritability (this may be a sign of hyperglycemia, which may occur in up to 1 in 10 people)
- unusual bleeding or bruising, bleeding longer than usual after leaving a blood sample or bleeding from the gums (this may be a sign of thrombocytopenia, which may occur in up to 1 in 10 people)
- headache, dizziness, looks pale (this may be a sign of anemia , which may occur in more than 1 in 10 people)
You may experience the following side effects:
The following side effects have been reported when Adcetris is the only drug:
A very common side effect is (can occur in more than 1 in 10)
- decreased white blood cell count
- infection of the upper airways
- weight loss
- infection
- nausea
- abdominal pain
- itching
- muscle pain
- joint pain or painful swollen joints
Common side effects are (may affect up to 1 in 10 people)
- pneumonia
- tender creamy yellow rash in the mouth (mouth cod)
- decreased platelet count
- dizziness
- blisters that can form scabs
- elevated blood sugar levels
- elevated liver values
- unusual hair loss or thinning
Less common side effects are (may affect up to 1 in 100 people)
- tumor lysis syndrome – a potentially life-threatening condition; you may experience dizziness, decreased urination, confusion, vomiting, nausea, swelling, shortness of breath, or heart rhythm disturbances.
- new or recurrent infection with cytomegalovirus ( CMV )
- infection of the blood ( sepsis ) and/or septic shock (a life-threatening form of sepsis )
- Stevens-Johnson syndrome and toxic epidermal necrolysis – a rare, serious disorder in which you may experience flu-like symptoms followed by painful and red or purple rashes that spread and form blisters and extensive skin rash.
- decreased white blood cell count with concomitant fever
- damage to the nerves and nerve sheaths (demyelinating polyneuropathy ).
The following side effects have been reported when Adcetris is given in combination with chemotherapy:
Very common side effects (may affect more than 1 in 10 people)
- decreased white blood cell count
- decreased platelet count
- decreased white blood cell count at the same time as fever
- infection of the upper airways
- weight loss
- infection
- nausea
- abdominal pain
- abnormal hair loss or thinner hair
- muscle aches
- joint pain or painful swollen joints
- dizziness
- reduced appetite
- difficulty sleeping
- skeletal pain
- blisters that can form scabs.
Common side effects are (may affect up to 1 in 10 people)
- infection of the blood ( sepsis or sepsis ) and/or septic shock (a life-threatening form of sepsis ); pneumonia
- sores or inflammation in the mouth
- sore, yellowish, raised spots in the mouth (cod)
- itching
- elevated blood sugar
- elevated liver values.
Less common side effects are (may affect up to 1 in 100 people)
- Tumor light syndrome – a potentially life-threatening condition with symptoms such as dizziness, decreased urine output, confusion, vomiting, nausea, swelling, shortness of breath, and disturbed heart rhythm
- Stevens-Johnson syndrome – a rare and serious disease with flu-like symptoms followed by painful red or purple rash that spreads, as well as blisters and large areas of detached skin
- new or recurrent infection with cytomegalovirus ( CMV ).
If you are an elderly patient (65 years or older), you may be more likely to have serious side effects .
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to the Medical Products Agency, www.lakemedelsverket.se. By reporting side effects, you can help increase drug safety information
5. How to store Adcetris
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 vial label and outer carton after EXP. The expiration date is the last day of the specified month.
Unopened vial: Store in a refrigerator (2 ° C – 8 ° C). Do not freeze.
Keep the vial in the outer carton. Sensitive to light.
Reconstituted/diluted solution: Use immediately or refrigerate (2 ° C-8 ° C) and use within 24 hours.
Do not use this medicine if you notice any particles or discoloration before administering one.
Medicines should not be disposed of via wastewater or household waste. Your doctor or nurse will discard this medicine. These measures will help to protect the environment.
6. Contents of the packaging and other information
Content declaration
- The active substance is brentuximab vedotin. Each vial contains 50 mg of brentuximab vedotin. After reconstitution, each ml of solution contains 5 mg of Adcetris.
- The other ingredients are citric acid monohydrate, sodium citrate dihydrate, α, α-trehalose dihydrate, and polysorbate 80. See section 2 for more information on sodium.
What the medicine looks like and the contents of the pack
Adcetris is a white to off-white cake or powder for concentrate for solution for infusion, supplied in a glass vial.
Each pack of Adcetris contains one vial.
Marketing Authorization Holder and Manufacturer
Takeda Pharma A / S
Delta Park 45
2665 Vallensbaek Strand
Denmark
Manufacturer
Takeda Austria GmbH
St. Peter-Straβe 25
A4020 Linz
Austria
Delpharm Novara Srl
Via Crosa, 86
28065 Cerano (NO)
Italy
Contact the representative of the marketing authorization holder to find out more about this medicine:
| Belgium / Belgique / BelgienTakeda BelgiumTel / Tel: +32 2 464 06 11takeda‑belgium@takeda.com | LithuaniaTakeda, UABTel: +370 521 09 070lt‑info@takeda.com |
| BulgariaTakade BulgariaTel .: + 359 2 958 27 36 | Luxembourg / LuxemburgTakeda BelgiumTel / Tel: +32 2 464 06 11takeda‑belgium@takeda.com |
| Czech RepublicTakeda PharmaceuticalsCzech Republic sroTel: + 420 234722722 | HungaryTakeda Pharma Kft.Tel: +361 2707030 |
| DenmarkTakeda Pharma A / STel: +45 46 77 11 11 | MaltaTakeda Italia SpATel: +39 06 502601 |
| GermanyTakeda GmbHTel: +49 (0) 800 825 3325medinfoEMEA@takeda.com | The NetherlandsTakeda Nederland bvTel: +31 23 56 68 777nl.medical.info@takeda.com |
| EestiTakeda Pharma ASTel: +372 6177 669 | NorwayTakeda Nycomed ASTel: +47 6676 3030infonorge@takeda.com |
| GreeceTAKEDA ΕΛΛΑΣ Α.ΕTηλ: +30 210 6387800gr.info@takeda.com | AustriaTakeda Pharma Ges.mbHTel: +43 (0) 800‑20 80 50 |
| SpainTakeda Pharmacéutica España SATel: +34 917 90 42 22spain@takeda.com | PolandTakeda Pharma sp. z ooTel .: + 48 22 608 13 00 |
| FranceTakeda France SASTel .: + 33 1 40 67 33 00medinfoEMEA@takeda.com | PortugalTakeda Pharmaceuticals Portugal, Lda.Tel: + 351 21 120 1457 |
| CroatiaTakeda Pharmaceuticals Croatia dooTel: +385 1 377 88 96 | RomaniaTakeda Pharmaceuticals SRLTel: +40 21 335 03 91 |
| IrelandTakeda Products Ireland LimitedTel: +44 (0) 1628 537 900 | SloveniaTakeda GmbH, Podružnica SlovenijaTel: + 386 (0) 59 082 480 |
| IcelandVistor hf.Phone: +354 535 7000vistor@vistor.is | Slovak RepublicTakeda Pharmaceuticals Slovakia sroTel: +421 (2) 20 602 600 |
| ItalyTakeda Italia SpATel: +39 06 502601 | Finland / FinlandTakeda OyPuh / Tel: +358 20 746 5000infoposti@takeda.com |
| ΚύπροςA. POTAMITIS MEDICARE LTDTηλ: +357 22583333info@potamitismedicare.com | SwedenTakeda Pharma ABTel: +46 8 731 28 00infosweden@takeda.com |
| LatviaTakeda Latvia SIATel: +371 67840082 | United KingdomTakeda UK LtdTel: +44 (0) 1628 537 900 |
This leaflet was last modified on 15/09/2020
Other sources of information
This medicine has received a “conditional marketing authorization”. This means that more information about the drug is expected.
The European Medicines Agency reviews new information on this medicine at least every year and updates this leaflet as needed.
Further information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/.
The following information is intended for healthcare professionals only:
Traceability
To facilitate the traceability of biological drugs, the name and manufacturing batch number of the drug must be documented.
Disposal
Adcetris is for single use only.
Any unused product or waste material should be disposed of in accordance with local requirements.
Instructions for reconstitution
Each single-use vial must be reconstituted with 10.5 ml of water for injections to a final concentration of 5 mg / ml. Each vial contains 10% overfill, which means 55 mg of Adcetris per vial and a total volume after reconstitution of 11 ml.
- Aim the jet at the wall of the vial and not directly at the cake or powder.
- Gently swirl the vial to facilitate dissolution. DO NOT SHAKE.
- The reconstituted solution in the vial is clear to the slightly opalescent colorless solution with a final pH of 6.6.
- The reconstituted solution should be inspected visually for foreign matter and/or discoloration. If either is observed, the drug should be discarded.
Completion of infusion solution
Appropriate reconstituted Adcetris must be withdrawn from the vial (s) and injected into an infusion bag containing sodium chloride 9 mg/ml (0.9%) solution for injection to achieve a final concentration of 0.4-1.2 mg/ml Adcetris.
The recommended dilution volume is 150 ml.
Reconstituted Adcetris can also be diluted in glucose 50 mg/ml (5%) solution for injection or Ringer-lactate solution for injection.
Carefully turn the bag upside down to mix the solution containing Adcetris. DO NOT SHAKE.
Any remaining solution in the vial, after the solution has been withdrawn for dilution, must be discarded in accordance with local regulations.
Do not add any other medicines to the reconstituted Adcetris infusion solution or the intravenous infusion set. The infusion line should be flushed after administration with sodium chloride 9 mg/ml (0.9%) solution for injection, glucose 50 mg/ml (5%) solution for injection, or Ringer-lactate solution for injection.
After dilution, the Adcetris solution is infused immediately at the recommended infusion rate.
The total storage time of the solution from reconstitution to infusion should not exceed 24 hours.