Darzalex

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Other drugs may interact with daratumumab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

IV Preparation

Each vial is for single use only (does not contain preservatives)

Calculate the dose in mg and total volume in mL of daratumumab solution required and the number vials needed based on patient actual body weight

Check that the solution is colorless to pale yellow; do not use if opaque particles, discoloration, or other foreign particles are present

Using aseptic technique, remove a volume of 0.9% NaCl from the infusion bag/container that is equal to the required volume of daratumumab solution

Withdraw the daratumumab dose from the vial(s) and dilute to the appropriate volume by adding to the infusion bag/container containing 0.9% NaCl (first infusion 1000 mL; second and subsequent infusions 500 mL)

Infusion bags/containers must be made of polyvinylchloride (PVC), polypropylene (PP), polyethylene (PE), or polyolefin blend (PP+PE)

Dilute under appropriate aseptic conditions

Discard any unused portion left in the vial

Gently invert the bag/container to mix the solution

Do not shake

Following dilution, the infusion bag/container may be stored for up to 24 hr in a refrigerator at 2-8ºC (36-46ºF); protect from light and do not freeze

After allowing the bag/container to come to room temperature, use immediately since the solution does not contain a preservative

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit

The diluted solution may develop very small, translucent-to-white proteinaceous particles, as daratumumab is a protein

Do not use if visibly opaque particles, discoloration, or foreign particles are observed

IV Administration

Should be administered by a healthcare professional, with immediate access to emergency equipment and appropriate medical support to manage infusion reactions if they occur

Administer the diluted solution by IV infusion using an infusion set fitted with a flow regulator and with an in-line, sterile, nonpyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometer)

Polyurethane (PU), polybutadiene (PBD), PVC, PP, or PE administration sets must be used

Infusion should be completed within 15 hr

Do not store any unused portion of the infusion solution for reuse

Any unused product or waste material should be disposed of in accordance with local requirements

Do not infuse concomitantly in the same IV line with other agents

Concomitant medications

• Preinfusion medications
  • Premedicate patients with antihistamines, antipyretics, and corticosteroids 1 hr before every infusion
  • PO antipyretics (acetaminophen 650-1000 mg), plus
  • PO or IV antihistamine (diphenhydramine 25-50 mg or equivalent), plus
  • Monotherapy: IV corticosteroid (methylprednisolone 100 mg, or equivalent dose of an intermediate-acting or long-acting corticosteroid); following the second infusion, the dose of corticosteroid may be reduced (methylprednisolone 60 mg IV), OR
  • Combination therapy: Dexamethasone 20 mg before every daratumumab infusion; given IV before first daratumumab infusion and oral administration may be considered prior to subsequent infusion
• Postinfusion medications (monotherapy)
  • To reduce the risk of delayed infusion reactions, administer oral corticosteroids to all patients the first and second day after all infusions
  • PO corticosteroid (20 mg methylprednisolone or equivalent dose of a corticosteroid in accordance with local standards) on the first and second day after all infusions
  • History of COPD: Consider prescribing postinfusion medications (eg, short- and long-acting bronchodilators, and inhaled corticosteroids); after the first 4 infusions, if the patient experiences no major infusion reactions, these additional inhaled postinfusion medications may be discontinued
• Postinfusion medications (combination therapy)
  • Consider administering low-dose oral methylprednisolone (≤20 mg) or equivalent, the day after daratumumab infusion
  • However, if a background regimen-specific corticosteroid (eg, dexamethasone) is administered the day after, additional postinfusion medications may not be needed
• Herpes zoster reactivation prophylaxis
  • Initiate antiviral prophylaxis to prevent herpes zoster reactivation within 1 week of starting daratumumab and continue for 3 months following treatment

Infusion rate

• Consider incremental escalation only in the absence of infusion reactions with the previous infusion
• First infusion (1000 mL dilution): 50 mL/hr for first hour; may increase by 50 mL/hr every hour, not to exceed 200 mL/hr
• Second infusion (500 mL dilution): 50 mL/hr for first hour; may increase by 50 mL/hr every hour, not to exceed 200 mL/hr
• Subsequent infusions (500 mL dilution): 100 mL/hr for first hour; may increase by 50 mL/hr every hour, not to exceed 200 mL/hr

Infusion reactions

• For infusion reactions of any grade/severity, immediately interrupt the infusion, and manage symptoms
• Management of infusion reactions may further require reduction in the rate of infusion, or treatment discontinuation
• Grade 1-2 (mild-to-moderate)
  • Once reaction symptoms resolve, resume the infusion at no more than half the rate at which the reaction occurred
  • If no further reaction symptoms experienced, infusion rate escalation may resume at increments and intervals as clinically appropriate up to a maximum of 200 mL/hr
• Grade 3 (severe)
  • Once reaction symptoms resolve, resume the infusion at no more than half the rate at which the reaction occurred
  • If no further reaction symptoms experienced, infusion rate escalation may resume at increments and intervals outlined in Administration section
  • Repeat the procedure above in the event of recurrence of additional episodes
  • Permanently discontinue upon the third occurrence of a ≥grade 3 infusion reaction
• Grade 4 (life threatening)
  • Permanently discontinue treatment

Missed dose

• If a planned dose is missed, administer the dose as soon as possible and adjust the dosing schedule accordingly, maintaining the treatment interval

Storage

Unopened vials

• Does not contain a preservative
• Refrigerate at 2-8ºC (36-46ºF)
• Protect from light
• Do not freeze
• Do not shake

Diluted solution

• Since drug does not contain a preservative, administer the diluted solution immediately at room temperature 15-25°C (59-77°F) and in room light
• Diluted solution may be kept at room temperature for a maximum of 15 hr (including infusion time)
• If not used immediately
  • May store for up to 24 hr in a refrigerator at 2-8ºC (36-46ºF)
  • Protect from light
  • Do not freeze

Darzalex is a prescription medication used to treat multiple myeloma in those who have been given at least one prior therapy.

Darzalex can be given in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone. 

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

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

• Janssen Biotech, Inc.

Daratumumab is a monoclonal antibody that blocks a certain protein in the body that can affect tumor cell growth. Monoclonal antibodies are made to target and destroy only certain cells in the body. This may help to protect healthy cells from damage.

Daratumumab is used to treat multiple myeloma (bone marrow cancer). Daratumumab is usually given after other cancer medicines have been tried without success.

Daratumumab is used alone when given to a person who has been treated with at least 3 prior cancer medicines.

For a person treated with only 1 prior cancer medicine, daratumumab may be given in combination with another cancer medicine (either lenalidomide or bortezomib) plus a steroid medicine called dexamethasone.

For a person treated with 2 prior cancer medicines, daratumumab may be given in combination with pomalidomide plus a steroid medicine called dexamethasone.

Daratumumab may also be used for purposes not listed in this medication guide.

In the U.S.

• Darzalex

Available Dosage Forms:

• Solution

Therapeutic Class: Antineoplastic Agent

Pharmacologic Class: Monoclonal Antibody

It is very important that your doctor check you at regular visits while you are receiving this medicine to make sure that the medicine is working properly. Blood tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant during treatment and for at least 3 months after your last dose. If you think you have become pregnant while using the medicine, tell your doctor right away.

This medicine may cause an infusion reaction, which can be life-threatening and requires immediate medical attention. Tell your doctor right away if you have chills, cough, dizziness or lightheadedness, headache, itching, nausea or vomiting, runny or stuffy nose, a rash or hives, shortness of breath or trouble breathing, or sore throat while you are receiving this medicine.

Daratumumab can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor immediately if you notice any unusual bleeding or bruising, black, tarry stools, blood in the urine or stools, or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
• Avoid contact sports or other situations where bruising or injury could occur.

Make sure any doctor who treats you knows that you are using daratumumab. This medicine may affect the results of certain medical tests including tests to determine your blood type. These effects may last up to 6 months after your last dose. Tell all of your healthcare providers that you are receiving this medicine before you receive a blood transfusion.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time after being added to fluids.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

Infusion Reactions

Darzalex can cause severe infusion reactions. Approximately half of all patients experienced a reaction, most during the first infusion.

Infusion reactions can also occur with subsequent infusions. Nearly all reactions occurred during infusion or within 4 hours of completing Darzalex. Prior to the introduction of post-infusion medication in clinical trials, infusion reactions occurred up to 48 hours after infusion.

Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, laryngeal edema and pulmonary edema. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting and nausea. Less common symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, and hypotension [see Adverse Reactions (6.1)].

Pre-medicate patients with antihistamines, antipyretics and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt Darzalex infusion for reactions of any severity and institute medical management as needed. Permanently discontinue Darzalex therapy for life-threatening (Grade 4) reactions. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion [see Dosage and Administration (2.1)].

To reduce the risk of delayed infusion reactions, administer oral corticosteroids to all patients following Darzalex infusions [see Dosage and Administration (2.2)]. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.

Interference with Serological Testing

Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive Indirect Antiglobulin Test (Indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient's serum1 [see References (15)]. The determination of a patient's ABO and Rh blood type are not impacted [see Drug Interactions (7.1)].

Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received Darzalex. Type and screen patients prior to starting Darzalex.

Neutropenia

Darzalex may increase neutropenia induced by background therapy [see Adverse Reactions (6.1)].

Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Darzalex dose delay may be required to allow recovery of neutrophils. No dose reduction of Darzalex is recommended. Consider supportive care with growth factors.

Thrombocytopenia

Darzalex may increase thrombocytopenia induced by background therapy [see Adverse Reactions (6.1)].

Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Darzalex dose delay may be required to allow recovery of platelets. No dose reduction of Darzalex is recommended. Consider supportive care with transfusions.

Interference with Determination of Complete Response

Daratumumab is a human IgG kappa monoclonal antibody that can be detected on both, the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein [see Drug Interactions (7.1)]. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Infusion Reactions

Advise patients to seek immediate medical attention for any of the following signs and symptoms of infusion reactions:

• itchy, runny or blocked nose; chills, nausea, throat irritation, cough, headache, shortness of breath or difficulty breathing [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)].

Neutropenia

• Advise patients that if they have a fever, they should contact their healthcare professional [see Warnings and Precautions (5.3) and Adverse Reactions (6.1)].

Thrombocytopenia

• Advise patients to inform their healthcare professional if they notice signs of bruising or bleeding [see Warnings and Precautions (5.4) and Adverse Reactions (6.1)].

Interference with Laboratory Tests

Advise patients to inform healthcare providers including blood transfusion centers/personnel that they are taking Darzalex, in the event of a planned transfusion [see Warnings and Precautions (5.2) and Drug Interactions (7.1)].

Advise patients that Darzalex can affect the results of some tests used to determine complete response in some patients and additional tests may be needed to evaluate response [see Warnings and Precautions (5.5) and Drug Interactions (7.1)].

Manufactured by:
Janssen Biotech, Inc.
Horsham, PA 19044
U.S. License Number 1864

© Janssen Biotech, Inc., 2015

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Other drugs may interact with daratumumab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.