Practical help and advice when prescribing DARZALEX®

This page provides information on dosing and practicalities for DARZALEX® SC.
Daratumumab SC handling and administration

DARZALEX® is now available as a solution for injection.

Dosing schedules

DVTd dosing schedule: 4-week cycle regimen
DVTd dosing schedule: 4-week cycle regimen[1]
Treatment
Dose
Dosing schedule

DARZALEX® (daratumumab) SC

1800 mg SC

Cycles 1–2: Weekly

Cycles 3–4: Every 2 weeks

During ASCT: None

Cycles 5–6: Every 2 weeks

Velcade® (bortezomib)

1.3 mg/m2 SC​

Cycles 1­–6: Twice weekly during Weeks 1 and 2

Thalidomide

100 mg PO

Cycle 1–6: Once daily

Dexamethasone

40 mg PO

Cycle 1–2: Twice weekly during Weeks 1–3

Cycles 3–4: Day 1 and 2 of each cycle

Dexamethasone

20 mg PO

Cycle 3–4: Twice weekly during Weeks 2 and 3

Cycles 5–6: Twice weekly during Weeks 1–3

DRd dosing schedule: 4-week cycle regimen
DRd dosing schedule: 4-week cycle regimen[1]
Treatment
Dose
Dosing schedule

DARZALEX® (daratumumab) SC

1800 mg SC

Cycles 1–2: Weekly

Cycles 3–6: Every 2 weeks

Cycles 7+: Every 4 weeks until disease progression

Lenalidomide

25 mg PO

Once daily on Days 1–21 of each cycle until disease progression

Dexamethasone

40 mg PO/IV

Every week until disease progression

DVMP dosing schedule: 6-week cycle regimen
DVMP dosing schedule: 6-week cycle regimen[1]
Treatment
Dose
Dosing schedule

DARZALEX® (daratumumab) SC

1800 mg SC

Cycles 1: Weekly

Cycles 2–9: Every 3 weeks

Cycles 10+: Every 4 weeks until disease progression

Velcade® (bortezomib)

1.3 mg/m2 SC

Cycle 1: Twice weekly on Weeks 1, 2, 4 and 5

Cycles 2–9: Once weekly on Weeks 1, 2, 4 and 5

Melphalan

9 mg/m2 PO

Once daily on Days 1–4 of each cycle until disease progression

Prednisone*

60 mg/m2 PO

Once daily on Days 1–4 of each cycle until disease progression

* Dexamethasone at a dose of 20 mg was substituted for prednisone on Day 1 of each cycle.

DRd dosing schedule: 4-week cycle regimen
DRd dosing schedule: 4-week cycle regimen[1]
Treatment
Dose
Dosing schedule

DARZALEX® (daratumumab) SC

1800 mg SC

Cycles 1–2: Weekly

Cycles 3–6: Every 2 weeks

Cycles 7+: Every 4 weeks until disease progression

Lenalidomide

25 mg PO

Once daily on days 1–21 of each cycle until disease progression

Dexamethasone

40 mg PO/IV*

Every week until disease progression

* On DARZALEX® infusion days, 20 mg of the dexamethasone dose was given as a pre-infusion medication and the remainder given the day after the infusion.

DVd dosing schedule: 3-week cycle regimen
DVd dosing schedule: 3-week cycle regimen[1]
Treatment
Dose
Dosing schedule

DARZALEX® (daratumumab) SC

1800 mg SC

Cycles 1–3: Weekly

Cycles 4–8: Every 3 weeks

Cycles 9+: Every 4 weeks until disease progression


Velcade® (bortezomib)

1.3 mg/m2 SC/IV

Cycles 1–8: Days 1, 4, 8 and 11

Dexamethasone

20 mg PO*

Cycle 1–8: Days 1, 2, 4, 5, 8, 9, 11 and 12

* On DARZALEX® dosing days, the pre-administration medication replaces the daily dose of dexamethasone.

DARZALEX® dosing schedule: 4-week cycle regimen
DARZALEX® dosing schedule: 4-week cycle regimen[1]
Treatment
Dose
Dosing schedule

DARZALEX® (daratumumab) SC

1800 mg SC

Cycles 1–2: Weekly (total of 8 doses)

Cycles 3–6: Every 2 weeks (total of 8 doses)

Cycles 7+: Every 4 weeks until disease progression


Recommended concomitant medications & missed dose information

Medications should be administered to reduce the risk of IRRs to all patients 1–3 hours prior to every infusion of DARZALEX® as follows:

  • Corticosteroid (long-acting or intermediate-acting) – dexamethasone 20 mg or equivalent administered before every DARZALEX® injection. When dexamethasone is the background regimen-specific corticosteroid, the dexamethasone treatment dose will instead serve as pre-injection medicinal product on DARZALEX® administration days. Additional background regimen–specific corticosteroids (e.g., prednisone) should not be taken on DARZALEX® administration days when patients have received dexamethasone (or equivalent) as a pre-injection medication
  • Antipyretic – paracetamol 650–1000 mg
  • Antihistamine – diphenhydramine 25–50 mg PO/IV or equivalent

Medications should be administered to reduce the risk of delayed infusion-related reactions as follows:

  • Consider administering low-dose methylprednisolone PO (≤20 mg) or equivalent the day after the DARZALEX® injection. However, if a background regimen–specific corticosteroid (e.g., dexamethasone, prednisone) is administered the day after the DARZALEX® injection, additional post-injection medications may not be needed
  • If the patient experiences no major IRRs after the first three injections, post-injection corticosteroids (excluding any background regimen corticosteroids) may be discontinued
Patients with a history of COPD[1]
  • For patients with a history of chronic obstructive pulmonary disease, the use of post-injection medications, including short- and long-acting bronchodilators, and inhaled corticosteroids, should be considered. Following the first four injections, if the patient experiences no major IRRs, these inhaled post-injection medications may be discontinued at the discretion of the physician
Herpes zoster prophylaxis[1]
  • Anti-viral prophylaxis should be considered for the prevention of herpes zoster virus reactivation

If a planned dose of DARZALEX® is missed, the dose should be administered as soon as possible, and the dosing schedule should be adjusted accordingly, maintaining the treatment interval

No dose reductions of DARZALEX® are recommended. Dose delay may be required to allow recovery of blood cell counts in the event of haematological toxicity.[1]

IRR management

Infusion-related reactions (IRRs)

As is the case for all monoclonal antibodies, DARZALEX® is associated with IRRs, although not everybody will experience one[2]

Rate of IRRs[1]

In clinical trials with DARZALEX® SC formulation (monotherapy and combination treatments; N=639), the incidence of any grade IRRs was 8.2% with the first injection of DARZALEX® (1,800 mg, Week 1), 0.4% with the Week 2 injection, and 1.1% with subsequent injections. Grade 3 IRRs were seen in 0.8% of patients. No patients had Grade 4 IRRs.[1]

First infusion 8.8%
Second infusion 0.2%
Subsequent infusions 1.0%

Adapted from DARZALEX® (daratumumab) EU SmPC[1]

Patients should receive appropriate pre-injection and post-injection medications to reduce the risk of IRRs (see treatment schedules).[1]

In clinical trials, no modification to rate or dose of DARZALEX® SC was required to manage IRRs. The median time to onset of IRRs following DARZALEX® injection was 3.7 hours (range: 00.15–83.00 hours). Most IRRs occurred on the day of treatment. Delayed IRRs have occurred in 1% of patients.[1]

The most common IRRs include:[1]

  • Nasal congestion
  • Cough
  • Throat irritation
  • Allergic rhinitis
  • Wheezing
  • Pyrexia
  • Chest pain
  • Pruritis
  • Chills
  • Vomiting
  • Nausea
  • Hypotension

Severe IRRs include:[1]

  • Bronchospasm
  • Hypoxia
  • Dyspnoea
  • Hypertension
  • Tachycardia

Administration

DARZALEX® solution for subcutaneous injection is for subcutanous use, and the recommended dose is 1800 mg administered over approximately 3–5 minutes.[1]

DARZALEX® should be administered by a healthcare professional, and the first dose should be administered in an environment where resuscitation facilities are available.[1]

Pre- and post-injection medications should be administered to reduce the risk of infusion-related IRRs (see treatment schedules).[1]

Supplies you will need:[1]
  • Vial of DARZALEX® SC (1800 mg/15 ml)
  • Syringe – 20 mL recommended
  • Transfer needle – 18G x 38 mm recommended
  • Alcohol swabs
  • Cotton ball or gauze pad
  • Adhesive bandage
  • Sharps bin

Either an injection needle

  • 23G x 38 mm recommended

OR

a winged/butterfly infusion set

  • 23G x 19 mm recommended
Inspect the solution

1. Inspect the solution

  • Remove one DARZALEX® SC vial from the refrigerator and warm to room temperature
  • Check that the DARZALEX® SC solution is clear to opalescent and colourless-to-yellow
  • Do not use if opaque particles, discolouration or other foreign particles are present
Fill syringe

2. Attach transfer needle and fill syringe

  • Prepare the dosing syringe in controlled and validated aseptic conditions
  • Attach the transfer needle to the syringe. Withdraw the full contents of the vial into the syringe using the transfer needle*
  • Administer DARZALEX® SC within 4 hours of puncturing the vial or drawing the dose into the syringe
  • If not used immediately, label the syringe with the date and time
Attach needle

3. Attach injection needle and set dose

  • Remove the transfer needle and attach the injection needle to the syringe
  • Prime the syringe and set the dose to 15 ml
Choose site

4. Choose the injection site

  • Choose a site on the abdomen, about 7,5 cm to the right or left of the navel
  • Do not inject into skin that is tender, bruised, red, hard, or has scars
  • Wipe your chosen injection site with an alcohol swab and allow it to dry
  • Rotate injection sites for each successive injection – note down which side was used each time
Insert needle

5. Insert needle

  • Pinch skin at the injection site. It is important to pinch enough skin to inject under the skin and not into the muscle
  • Inject at a 45° angle
  • Release pinched skin
  • Check no blood vessel has been punctured
5 mins

6. Inject dose

  • Press the plunger with a constant rate of delivery for about 3–5 minutes
  • Try to limit needle and syringe movement during injection through a two-handed syringe grip
  • If the patient feels pain, pause or slow down the rate of delivery. If the patient still feels pain, consider using a different injection site on the opposite side of the abdomen to deliver the remainder of the dose
After injection

7. After injection

  • Gently remove the needle
  • Place a gauze pad or a cotton ball over the entrance site of the needle
Dispose used syringe

8. Dispose of used syringe

  • Put the used syringe in a sharps disposal container right away after use


Check injection site

9. Check injection site

  • There may be a small amount of blood or liquid at the injection site.
  • Hold pressure over skin with a cotton ball or gauze pad until any bleeding stops
  • Do not rub the injection site. If needed, cover the injection site with a bandage
Inspect the solution

1. Inspect the solution

  • Remove one DARZALEX® SC vial from the refrigerator and warm to room temperature
  • Check that the DARZALEX® SC solution is clear to opalescent and colourless-to-yellow
  • Do not use if opaque particles, discolouration or other foreign particles are present
Choose the injection site

2. Choose the injection site

  • Choose a site on the abdomen, about 7,5 cm to the right or left of the navel
  • Do not inject into skin that is tender, bruised, red, hard, or has scars
  • Wipe your chosen injection site with an alcohol swab and allow it to dry
  • Rotate injection sites for each successive injection – note down which side was used each time
    Prime infusion set

    3. Prime infusion set

    • Flush the tubing of the infusion set with a small volume of saline solution or with the product itself
    • Follow the instructions from your infusion set manufacturer
    Fill syringe

    4. Attach transfer needle and fill syringe

  • Prepare the dosing syringe in controlled and validated aseptic conditions
  • Attach the transfer needle to the syringe. Withdraw the full contents of the vial into the syringe using the transfer needle*
  • Administer DARZALEX® SC within 4 hours of puncturing the vial or drawing the dose into the syringe

    • * Vials are overfilled to allow for infusion set administration

    Insert needle

    5. Attach infusion set and set dose

    • Remove the transfer needle and attach the injection needle to the syringe
    • Set the dose to 15 ml
    • Follow the instructions from your infusion set manufacturer
    insert needle

    6. Insert needle

    • Remove needle safety cap
    • Pinch skin at the injection site. It is important to pinch enough skin to inject under the skin and not into the muscle
    • Inject at a 45° angle
    • Release pinched skin. If needed, secure site as per your institutional protocol (e.g., surgical tape)
    Inject dose

    7. Inject dose

    • Press the plunger with a constant rate of delivery for about 3–5 minutes (use phone/watch to track time)
    • If the patient feels pain, pause or slow down the rate of delivery. If the patient still feels pain, consider using a different injection site on the opposite side of the abdomen to deliver the remainder of the dose

    Optional: After completion of administration, flush the syringe with saline to ensure the patient receives the full dose.

    After injection

    8. After injection

    • Remove the surgical tape, if used
    • Gently remove the needle
    • Place a gauze pad or a cotton ball over the entrance site of the needle
    • Put the used syringe in a sharps disposal container right away after use
    Check injection site

    9. Check injection site

    • There may be a small amount of blood or liquid at the injection site. Hold pressure over skin with a cotton ball or gauze pad until any bleeding stops
    • Do not rub the injection site. If needed, cover the injection site with a bandage

    Unopened vials have a shelf life of 18 months. Do not use this medicine after the expiry date, which is stated on the carton after “EXP”.[1]

    DARZALEX® should be stored in a refrigerator (2°C–8°C) and never frozen. It should be stored in the original package in order to protect from light.[1]

    Before use, remove the vial from refrigerated storage (2°C–8°C) and equilibrate to ambient temperature (15°C–30°C).[1]

    The unpunctured vial may be stored at ambient temperature and ambient light for a maximum of 24 hours out of direct sunlight and must not be shaken.[1]

    Once transferred from the vial into the syringe, DARZALEX® solution for injection can be stored for a maximum of 12 hours at ambient temperature (15ºC-25ºC) and ambient light.[1]

    Quick downloads

    SC Checklist beginning of treatment

    Includes a first use checklist of Darzalex® SC.

    Darzalex® SC Practical Guide

    Includes DARZALEX® SC handling and administration info, pre and post-injection medications, and more

    ASCT: autologous stem cell transplant

    COPD: chronic obstructive pulmonary disease

    DRd: DARZALEX®, lenalidomide, dexamethasone

    DVd: DARZALEX®, Velcade®, dexamethasone

    DVMP: DARZALEX®, Velcade®, melphalan, prednisone

    DVTd: DARZALEX®, Velcade®, thalidomide, dexamethasone

    IV: intravenous

    IRR: infusion-related reaction

    NDMM: newly-diagnosed multiple myeloma

    PO: oral

    RRMM: relapsed/refractory multiple myeloma

    SC: subcutaneous

    Titular da Autorização de Introdução no Mercado: Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Bélgica.
    Para mais informações deverá contactar o Representante do Titular da Autorização de Introdução no Mercado: Janssen-Cilag Farmacêutica, Lda.

    Medicamento de receita médica restrita, de utilização reservada a certos meios especializados.

    Antes de prescrever consulte o RCM completo.

    RCM de Darzalex®, veja aqui