DARZALEX 20 mg/mL concentrate for infusion solution

2. What you need to know before you receive DARZALEX

You must not receive DARZALEX

• if you are allergic to daratumumab or any of the other ingredients of this medicine (listed in section 6).

You must not receive DARZALEX if you meet the above criterion. If you are not sure, consult your doctor or nurse before receiving DARZALEX.

Warnings and precautions

Consult your doctor or nurse before receiving DARZALEX.

Infusion-related reactions

DARZALEX is given as an infusion (drip) into a vein. Before and after each DARZALEX infusion, you will be given medicines that help reduce the chances of you experiencing infusion-related reactions (see the section “Medicines given during treatment with DARZALEX” in section 3). These reactions can occur during the infusion or in the 3 days after the infusion.

In some cases, you may experience a severe allergic reaction that can include swelling of the face, lips, mouth, tongue, or throat, difficulty swallowing or breathing, or an itchy rash (urticaria). Some severe allergic reactions and other severe infusion-related reactions have resulted in death.

Tell your doctor or nurse immediately if you experience any of the infusion-related reactions or symptoms indicated at the beginning of section 4.

If you experience infusion-related reactions, you may need other medicines or the infusion may need to be slowed down or stopped. The infusion can be restarted when these reactions disappear or improve.

These reactions occur mainly with the first infusion. If you have already experienced an infusion-related reaction, it is less likely that you will experience it again. If you experience a severe infusion-related reaction, your doctor may decide not to use DARZALEX.

Decrease in blood cell count

DARZALEX may reduce the number of white blood cells, which help fight infections, and other blood cells called platelets, which help blood to clot. Tell your healthcare professional if you experience any symptoms of infection such as fever or any symptoms of low platelet count such as bruising or bleeding.

Blood transfusions

If you need a blood transfusion, you will first have a blood test to determine your blood group. DARZALEX may affect the results of this blood test. Tell the person performing the test that you are using DARZALEX.

Hepatitis B

Tell your doctor if you have ever had or may currently be infected with the Hepatitis B virus. This is because DARZALEX could cause the Hepatitis B virus to become active again. Your doctor will examine you for signs of this infection before, during, and for some time after treatment with DARZALEX. Tell your doctor immediately if you experience worsening fatigue, or if you experience yellowing of the skin or the white part of the eyes.

Children and adolescents

Do not give DARZALEX to children and adolescents under 18 years of age, as it is not known how they will be affected by the medicine.

Other medicines and DARZALEX

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

Pregnancy

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before receiving this medicine.

If you become pregnant during treatment with this medicine, tell your doctor or nurse immediately. You and your doctor will decide if the benefit of receiving the medicine is greater than the risk to the fetus.

Contraception

Women receiving DARZALEX must use an effective method of contraception during treatment and for 3 months after treatment.

Breast-feeding

You and your doctor will decide if the benefit of breast-feeding is greater than the risk to your baby, as this medicine may pass into breast milk and it is not known how it may affect your baby.

Driving and using machines

You may feel tired after using DARZALEX, which may affect your ability to drive or use machines.

DARZALEX contains sorbitol

Sorbitol is a source of fructose. If you have hereditary fructose intolerance (HFI), a rare genetic disorder, do not receive this medicine. Patients with HFI cannot break down fructose, which can cause serious side effects.

Consult your doctor before receiving this medicine if you have HFI.

3. How DARZALEX is administered

Dose administered

Your doctor will calculate the dose and dosing schedule of DARZALEX. The dose of DARZALEX will depend on your body weight.

The usual initial dose of DARZALEX is 16 mg per kg of body weight. DARZALEX can be administered alone or with other medicines used to treat multiple myeloma.

When administered alone, DARZALEX is administered as follows:

• once a week for the first 8 weeks
• then once every 2 weeks for 16 weeks
• after this, once every 4 weeks while the disease does not worsen.

When DARZALEX is administered with other medicines, your doctor may modify the time between doses and the number of treatments you receive.

In the first week, your doctor may administer the dose of DARZALEX divided over two consecutive days.

How the medicine is administered

A doctor or nurse will administer DARZALEX to you. It is given as a drip into a vein (“intravenous infusion”) over several hours.

Medicines given during treatment with DARZALEX

You may be given medicines to reduce the chances of you getting herpes zoster.

Before each DARZALEX infusion, you will be given medicines that help reduce the chances of you experiencing infusion-related reactions. These may include:

• medicines to treat allergic reactions (antihistamines)
• medicines to treat inflammation (corticosteroids)
• medicines to treat fever (such as paracetamol).

After each DARZALEX infusion, you will be given medicines (such as corticosteroids) to reduce the chances of you experiencing infusion-related reactions.

People with respiratory problems

If you have respiratory problems, such as asthma or Chronic Obstructive Pulmonary Disease (COPD), you will be given inhaled medicines that help treat respiratory problems:

• medicines to keep the airways in the lungs open (bronchodilators)
• medicines to reduce inflammation and irritation of the lungs (corticosteroids).

If you receive more DARZALEX than you should

Your doctor or nurse will administer this medicine to you. In the unlikely event that you are given too much (overdose), your doctor will check for side effects.

If you miss your appointment to receive DARZALEX

It is very important that you attend all your appointments to ensure that the treatment works. If you miss an appointment, make another one as soon as possible.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Infusion-related reactions

Tell your doctor or nurse immediately if you experience any of the signs of an infusion-related reaction listed below during or in the 3 days after the infusion. You may need other medicines, or the infusion may need to be slowed down or stopped.

These reactions include the following symptoms:

Very common (may affect more than 1 in 10 people):

• chills
• sore throat, cough
• feeling sick (nausea)
• vomiting
• itching, runny or stuffy nose
• difficulty breathing or other breathing problems.

Common (may affect up to 1 in 10 people):

• chest pain
• dizziness or lightheadedness (hypotension)
• itching
• wheezing.

Rare (may affect up to 1 in 1000 people):

• severe allergic reaction, which can include swelling of the face, lips, mouth, tongue, or throat, difficulty swallowing or breathing, or an itchy rash (urticaria). See section 2.
• eye pain
• blurred vision.

If you experience any of the above infusion-related reactions, tell your doctor or nurse immediately.

Other side effects

Very common(may affect more than 1 in 10 people):

• fever
• feeling very tired
• diarrhea
• constipation
• loss of appetite
• headache
• nerve damage that can cause tingling, numbness, or pain
• high blood pressure
• muscle spasms
• swelling of hands, ankles, or feet
• weakness
• back pain
• chills
• lung infection (pneumonia)
• bronchitis
• infection of the respiratory tract, such as the nose, sinuses, or throat
• low number of red blood cells, which carry oxygen in the blood (anemia)
• low number of white blood cells, which help fight infections (neutropenia, lymphopenia, leucopenia)
• low number of platelets, which help blood to clot (thrombocytopenia)
• strange sensation in the skin (such as tingling or prickling).

Common(may affect up to 1 in 10 people):

• irregular heartbeat (atrial fibrillation)
• fluid build-up in the lungs, which can cause difficulty breathing
• flu
• urinary tract infection
• severe infection throughout the body (sepsis)
• dehydration
• fainting
• high blood sugar
• low calcium levels in the blood
• low levels of antibodies called ‘immunoglobulins’ in the blood, which help fight infections (hypogammaglobulinemia)
• inflammation of the pancreas
• infection with a type of herpes virus (cytomegalovirus infection)
• COVID-19.

Uncommon(may affect up to 1 in 100 people):

• inflammation of the liver (hepatitis).

Reporting of side effects

If you experience any side effects, consult your doctor or nurse, even if they are not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of DARZALEX

DARZALEX will be stored in the hospital or clinic.

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 carton and on the label of the vial after “EXP”. The expiry date is the last day of the month stated.

Store in a refrigerator (between 2°C and 8°C). Do not freeze.

Store in the original package to protect from light.

Medicines should not be disposed of via wastewater or household waste. Your healthcare professional will dispose of any unused medicines. This will help protect the environment.

6. Container Contents and Additional Information

DARZALEX Composition

• The active substance is daratumumab. One ml of concentrate contains 20 mg of daratumumab. Each 5 ml vial of concentrate contains 100 mg of daratumumab. Each 20 ml vial of concentrate contains 400 mg of daratumumab.
• The other ingredients are L-histidine, L-histidine hydrochloride monohydrate, L-methionine, polysorbate 20, sorbitol (E420), and water for injectable preparations (see the section "DARZALEX contains sorbitol" in section 2).

Product Appearance and Container Contents

DARZALEX is a concentrate for solution for infusion and is a colorless to yellow liquid.

DARZALEX is supplied in a carton containing 1 glass vial.

DARZALEX is also available as a starter pack containing 11 vials: (6 vials of 5 ml + 5 vials of 20 ml).

Marketing Authorization Holder

Janssen-Cilag International NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Manufacturer

Janssen Biologics B.V.

Einsteinweg 101

NL-2333 CB Leiden

Netherlands

For further information on this medicinal product, please contact the local representative of the marketing authorization holder:

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: http://www.ema.europa.eu.

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This information is intended for healthcare professionals only:

This medicinal product is for single use only.

Prepare the infusion solution using aseptic technique as follows:

• Calculate the dose (mg) and total volume (ml) of DARZALEX solution required and the number of DARZALEX vials needed based on the patient's weight.
• Check that the DARZALEX solution is colorless to yellow. Do not use if it contains opaque particles, color changes, or other foreign particles.
• Using aseptic technique, withdraw a volume of sodium chloride 9 mg/ml (0.9%) for injectable preparations from the infusion bag/container equivalent to the required volume of the DARZALEX solution.
• Withdraw the required amount of DARZALEX solution and dilute to the appropriate volume by adding it to an infusion bag/container containing sodium chloride 9 mg/ml (0.9%) for injectable preparations. The infusion bags/containers must be made of polyvinyl chloride (PVC), polypropylene (PP), polyethylene (PE), or a polyolefin mixture (PP + PE). Dilute under appropriate aseptic conditions. Discard any unused remaining portion in the vial.
• Gently invert the bag/container to mix the solution. Do not shake.
• Before administration, perform a visual inspection of the parenteral medicinal product to detect any presence of solid particles and color changes. The diluted solution may contain very small, translucent to white, proteinaceous particles, as daratumumab is a protein. Do not use if visible opaque particles, color changes, or other foreign particles are observed.
• Since DARZALEX does not contain any preservative, the diluted solution should be administered within 15 hours (including infusion time) at room temperature (between 15°C and 25°C) and under ambient light.
• If not used immediately, the diluted solution may be stored for up to 24 hours before administration under refrigerated conditions (between 2°C and 8°C) and protected from light. Do not freeze.
• Administer the diluted solution by intravenous infusion using a infusion set with a flow regulator and a sterile, apyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 μm). Administration sets made of polyurethane (PU), polybutadiene (PBD), PVC, PP, or PE should be used.
• DARZALEX should not be administered with other medicinal products through the same intravenous line.
• Do not store and reuse any unused portion of the infusion solution. Disposal of the unused medicinal product and all materials that have come into contact with it should be done in accordance with local regulations.

Traceability

In order to improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly recorded.