DARZALEX 1.800 mg INJECTABLE SOLUTION

2. What you need to know before you receive DARZALEX

Do not receive DARZALEX

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

Do 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 administered as a subcutaneous injection using a small needle to inject the medicine under your skin. Before and after each injection, you will be given medicines that help reduce the likelihood of you experiencing infusion-related reactions (see the section “Medicines administered during treatment with DARZALEX” in section 3). These reactions occur mainly with the first injection and most occur on the day of injection. If you have already experienced an infusion-related reaction, it is less likely to happen again. However, delayed reactions can occur up to 3-4 days after injection. If you have a severe reaction after injection, your doctor may decide not to use DARZALEX.

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). See section 4.

Inform 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 to treat your symptoms, or it may be necessary to interrupt or stop the injections. When these reactions disappear or improve, the injection can be administered again.

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 clot. Inform your healthcare professional if you experience any symptoms of infection, such as fever, or any symptoms of a low platelet count, such as bruising or bleeding.

Blood transfusions

If you need a blood transfusion, a blood test will be performed to determine your blood type. DARZALEX may affect the results of this blood test. Inform the person performing the test that you are using DARZALEX.

Hepatitis B

Inform your doctor if you have ever been or may currently be infected with the hepatitis B virus. This is because DARZALEX could cause the hepatitis B virus to reactivate. Your doctor will examine you for signs of this infection before, during, and sometime after treatment with DARZALEX. Inform 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 administer DARZALEX to children or adolescents under 18 years of age, as it is not known how the medicine will affect them.

Other medicines and DARZALEX

Inform your doctor or nurse if you are taking, have recently taken, or may need to 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, inform 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 contraceptive method 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 solution for injection subcutaneously contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per 15 ml, which is essentially “sodium-free”.

DARZALEX solution for injection subcutaneously contains sorbitol

Sorbitol is a source of fructose. If your doctor has told you that you have an intolerance to some sugars or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which you cannot break down fructose, consult your doctor before you receive this medicine.

3. How DARZALEX is administered

Dose administered

The dose of DARZALEX solution for injection subcutaneously is 1800 mg.

DARZALEX can be administered alone or with other medicines used to treat multiple myeloma or with other medicines used to treat AL amyloidosis. DARZALEX is usually 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 as well as the number of treatments you receive.

How the medicine is administered

A doctor or nurse will administer DARZALEX as an injection under the skin (subcutaneous injection) over approximately 3-5 minutes. It is administered in the stomach area (abdomen), not in other areas of the body, and not in areas of the abdomen where the skin is red, bruised, sensitive, hardened, or scarred.

If you experience pain during the injection, the doctor or nurse may interrupt the injection and administer the rest of the injection in another area of your abdomen.

Medicines administered during treatment with DARZALEX

You may be given medicines to reduce the likelihood of you contracting herpes zoster.

Before each DARZALEX injection, you will be given medicines that help reduce the likelihood 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 injection, you will be given medicines (such as corticosteroids) to reduce the likelihood 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. In the unlikely event that you are given too much (overdose), your doctor will check if you experience any 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

Inform your doctor or nurse immediately if you experience any of the following symptoms during the 3-4 days after injection. You may need other medicines, or it may be necessary to interrupt or stop the injections.

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, inform your doctor or nurse immediately.

Reactions at the injection site

Reactions can occur on the skin at the injection site or nearby (local reactions), including injection site reactions, with DARZALEX solution for injection subcutaneously. These reactions are common (may affect up to 1 in 10 people). Injection site symptoms can include redness of the skin, itching, swelling, pain, bruising, rash, bleeding.

Other side effects

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

• fever
• feeling very tired
• diarrhea
• constipation
• decreased appetite
• difficulty sleeping
• headache
• nerve damage that can cause tingling, numbness, or pain
• rash
• muscle spasms
• joint pain
• swelling of the hands, ankles, or feet
• weakness
• back pain
• 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 a type of blood cell called platelets, which help blood clot (thrombocytopenia).

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

• irregular heartbeat (atrial fibrillation)
• fluid accumulation in the lungs, which can cause difficulty breathing
• urinary tract infection
• severe infection throughout the body (sepsis)
• dehydration
• high blood sugar levels
• low calcium levels in the blood
• low levels of antibodies called ‘immunoglobulins’ in the blood, which help fight infections (hypogammaglobulinemia)
• feeling dizzy
• fainting
• chest muscle pain
• flu
• chills
• itching
• strange sensations in the skin (such as tingling or numbness)
• pancreatitis
• high blood pressure
• COVID-19.

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

• inflammation of the liver (hepatitis)
• infection with a type of herpes virus (cytomegalovirus infection).

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. You can also report side effects directly through 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 solution for injection subcutaneously 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 packaging 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 solution contains 120 mg of daratumumab. Each 15 ml vial of injectable solution contains 1800 mg of daratumumab.
• The other components are recombinant human hyaluronidase (rHuPH20), L-histidine, L-histidine hydrochloride monohydrate, L-methionine, polysorbate 20, sorbitol (E420), and water for injectable preparations (see the section "DARZALEX contains sodium and sorbitol" in section 2).

Product Appearance and Container Contents

DARZALEX subcutaneous injectable solution is a colorless to yellow liquid.

DARZALEX subcutaneous injectable solution is supplied in a box containing 1 single-dose glass vial.

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, 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 only for healthcare professionals:

DARZALEX subcutaneous injectable solution should be administered by a healthcare professional.

To avoid medication errors, it is essential to check the vial labels to ensure that the correct formulation (intravenous or subcutaneous formulation) is administered and that the dose is administered to the patient as prescribed. DARZALEX injectable solution should only be administered by subcutaneous injection at the specified dose. DARZALEX subcutaneous formulation is not intended for intravenous administration.

DARZALEX subcutaneous injectable solution is for single use and is presented ready to use.

• DARZALEX subcutaneous injectable solution is compatible with polypropylene or polyethylene syringes; subcutaneous infusion sets made of polypropylene, polyethylene, or polyvinyl chloride (PVC); and stainless steel injection and transfer needles.
• DARZALEX subcutaneous injectable solution should be a clear to opalescent, colorless to yellow solution. Do not use if it contains opaque particles, color changes, or foreign particles.
• Remove the DARZALEX subcutaneous injectable solution vial from the refrigerator (2 °C – 8 °C) and equilibrate to room temperature (15 °C–30 °C). The unopened vial can be stored at room temperature and light for up to 24 hours in the original packaging to protect it from light. Protect from direct sunlight. Do not shake.
• Prepare the administration syringe under aseptic, controlled, and validated conditions.
• To avoid clogging the needle, attach the hypodermic needle or subcutaneous infusion set to the syringe immediately before injection.

Storage of the Prepared Syringe

• If the DARZALEX syringe is not used immediately, store the DARZALEX solution for up to 24 hours in refrigerated conditions followed by up to 12 hours at 15 °C-25 °C and room light. If stored in the refrigerator, allow the solution to reach room temperature before administration.

Administration

• Inject 15 ml of DARZALEX subcutaneous injectable solution into the subcutaneous tissue of the abdomen, approximately 7.5 cm to the right or left of the navel, over approximately 3-5 minutes. Do not inject DARZALEX subcutaneous injectable solution into other areas of the body, as there are no available data.
• Alternate injection sites for subsequent injections.
• DARZALEX subcutaneous injectable solution should never be injected into areas of the skin that show redness, bruising, sensitivity, induration, or scarring.
• Pause or reduce the administration rate if the patient experiences pain. If the pain does not resolve with a reduced injection rate, consider administering the remaining dose in a second injection site on the opposite side of the abdomen.
• During treatment with DARZALEX subcutaneous injectable solution, do not administer other medications by subcutaneous injection at the same site as DARZALEX.
• Disposal of unused medicinal products and all materials that have come into contact with them 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.