Darzalex

Generic name: daratumumab
Drug class: CD38 monoclonal antibodies

Medically reviewed by  A Ras MD.

What is Darzalex?

Darzalex is a prescription medicine used to treat adults with multiple myeloma in combination with the medicines lenalidomide and dexamethasone in people with newly diagnosed multiple myeloma who cannot receive a type of stem cell transplant that uses their own stem cells (autologous stem cell transplant) and in people who have received at least one prior medicine to treat multiple myeloma, in combination with the medicines bortezomib, melphalan and prednisone, in people with newly diagnosed multiple myeloma who cannot receive a type of stem cell transplant that uses their own stem cells (autologous stem cell transplant).

it is also used to in the treatment of multiple myeloma in combination with the medicines bortezomib, thalidomide, and dexamethasone in newly diagnosed people who are eligible to receive a type of stem cell transplant that uses their own stem cells (autologous stem cell transplant), in combination with the medicines bortezomib and dexamethasone, in people who have received at least one prior medicine to treat multiple myeloma, in combination with the medicines pomalidomide and dexamethasone in people who have received at least two prior medicines to treat multiple myeloma, including lenalidomide and a proteasome inhibitor.

It is not known if Darzalex is safe and effective in children.

Description

Daratumumab is an immunoglobulin G1 kappa (IgG1κ) human monoclonal antibody that binds to CD38 antigen. It is produced in Chinese Hamster Ovary (CHO) cells using recombinant DNA technology. The molecular weight of daratumumab is approximately 148 kDa.

DARZALEX® (daratumumab) injection is supplied as a colorless to pale yellow preservative-free solution for intravenous use in a single-dose vial. The pH is 5.5.

Each DARZALEX 20 mL single-dose vial contains (NDC 57894-502-20) 400 mg daratumumab, glacial acetic acid (3.7 mg), mannitol (510 mg), polysorbate 20 (8 mg), sodium acetate trihydrate (59.3 mg), sodium chloride (70.1 mg), and Water for Injection, USP.

Each DARZALEX 5 mL single-dose vial contains (NDC 57894-502-05) 100 mg daratumumab, glacial acetic acid (0.9 mg), mannitol (127.5 mg), polysorbate 20 (2 mg), sodium acetate trihydrate (14.8 mg), sodium chloride (17.5 mg), and Water for Injection, USP.

Each DARZALEX 20 mL single-dose vial contains (NDC 57894-505-20) 400 mg daratumumab, L-histidine (7 mg), L-histidine hydrochloride monohydrate (32.6 mg), L-methionine (20 mg), polysorbate 20 (8 mg), sorbitol (1093 mg), and Water for Injection, USP.

Each DARZALEX 5 mL single-dose vial contains (NDC 57894-505-05) 100 mg daratumumab, L-histidine (1.8 mg), L-histidine hydrochloride monohydrate (8.2 mg), L-methionine (5 mg), polysorbate 20 (2 mg), sorbitol (273.3 mg), and Water for Injection, USP.

Mechanism of Action

CD38 is a transmembrane glycoprotein (48 kDa) expressed on the surface of hematopoietic cells, including multiple myeloma and other cell types and tissues and has multiple functions, such as receptor mediated adhesion, signaling, and modulation of cyclase and hydrolase activity. Daratumumab is an IgG1κ human monoclonal antibody (mAb) that binds to CD38 and inhibits the growth of CD38 expressing tumor cells by inducing apoptosis directly through Fc mediated cross linking as well as by immune-mediated tumor cell lysis through complement dependent cytotoxicity (CDC), antibody dependent cell mediated cytotoxicity (ADCC) and antibody dependent cellular phagocytosis (ADCP). A subset of myeloid derived suppressor cells (CD38+MDSCs), regulatory T cells (CD38+Tregs) and B cells (CD38+Bregs) are decreased by daratumumab.

Who should not take Darzalex?

Do not receive Darzalex:

• if you have a history of a severe allergic reaction to daratumumab or any of the ingredients in Darzalex. See the end of this leaflet for a complete list of ingredients in Darzalex.

What should I tell my healthcare provider before taking Darzalex?

Before you receive Darzalex, tell your healthcare provider about all of your medical conditions, including if you:

• have a history of breathing problems
• have had shingles (herpes zoster)
• have ever had or might now have a hepatitis B infection as Darzalex could cause hepatitis B virus to become active again. Your healthcare provider will check you for signs of this infection before, during and for some time after treatment with Darzalex. Tell your healthcare provider right away if you get worsening tiredness or yellowing of your skin or white part of your eyes.
• are pregnant or plan to become pregnant. Darzalex may harm your unborn baby. ell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with Darzalex.
  • Females who are able to become pregnant should use an effective method of birth control during treatment and for at least 3 months after your final dose of Darzalex. Talk to your healthcare provider about birth control methods that you can use during this time.
  • Before starting Darzalex in combination with lenalidomide, pomalidomide, or thalidomide, females and males must agree to the instructions in the lenalidomide, pomalidomide, or thalidomide REMS program.
    • The lenalidomide, pomalidomide, and thalidomide REMS has more information about effective methods of birth control, pregnancy testing, and blood donation for females who can become pregnant.
    • For males who have female partners who can become pregnant, there is information in the lenalidomide, pomalidomide, and thalidomide REMS about sperm donation and how lenalidomide, pomalidomide, and thalidomide can pass into human semen.
• are breastfeeding or plan to breastfeed. It is not known if Darzalex passes into your breast milk.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How should I take Darzalex?

• Darzalex may be given alone or together with other medicines used to treat multiple myeloma.
• Darzalex will be given to you by your healthcare provider by intravenous (IV) infusion into your vein.
• Your healthcare provider will decide the time between doses as well as how many treatments you will receive.
• Your healthcare provider will give you medicines before each dose of Darzalex and after each dose of Darzalex to help reduce the risk of infusion reactions.
• If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.

What are the possible side effects of Darzalex?

Darzalex may cause serious reactions, including:

• Infusion reactions. Infusion reactions are common with Darzalex and can be severe or serious. Your healthcare provider may temporarily stop your infusion or completely stop treatment with Darzalex if you have infusion reactions. Get medical help right away if you get any of the following symptoms:
  • shortness of breath or trouble breathing
  • dizziness or lightheadedness (hypotension)
  • cough
  • wheezing
  • throat tightness
  • runny or stuffy nose
  • headache
  • itching
  • nausea
  • vomiting
  • chills
  • fever
• Changes in blood tests. Darzalex can affect the results of blood tests to match your blood type. These changes can last for up to 6 months after your final dose of Darzalex. Your healthcare provider will do blood tests to match your blood type before you start treatment with Darzalex. Tell all of your healthcare providers that you are being treated with Darzalex before receiving blood transfusions.
• Decreases in blood cell counts. Darzalex can decrease white blood cell counts which help fight infections and blood cells called platelets which help to clot blood. Your healthcare provider will check your blood cell counts during treatment with Darzalex. Tell your healthcare provider if you develop fever or have signs of bruising or bleeding.

The most common side effects of Darzalex include:

• tiredness
• nausea
• diarrhea
• shortness of breath
• trouble sleeping
• feeling weak
• decreased appetite
• fever
• cough
• muscle spasms
• back pain
• joint pain
• vomiting
• bronchitis
• cold-like symptoms (upper respiratory infection)
• nerve damage causing tingling, numbness or pain
• swollen hands ankles or feet
• constipation
• chills
• dizziness
• lung infection (pneumonia)

Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Darzalex. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of Darzalex

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your healthcare provider or pharmacist for information about Darzalex that is written for health professionals.

How should I store Darzalex?

Store in a refrigerator at 2°C to 8°C (36°F to 46°F).

Do not freeze or shake. Protect from light. This product contains no preservative.

What are the ingredients in Darzalex?

Active ingredient: daratumumab
Inactive ingredients: glacial acetic acid, mannitol, polysorbate 20, sodium acetate trihydrate, sodium chloride, and water for injection

Label

PRINCIPAL DISPLAY PANEL – 100 MG/5 ML VIAL CARTON