Drug Detail:Darzalex (Daratumumab [ dar-a-toom-ue-mab ])
Generic Name: DARATUMUMAB 100mg in 5mL
Dosage Form: injection, solution, concentrate
Drug Class: CD38 monoclonal antibodies
Important Dosing Information
- Administer pre-infusion and post-infusion medications [see Dosage and Administration (2.3)] .
- Administer only as an intravenous infusion after dilution in 0.9% Sodium Chloride Injection, USP [see Dosage and Administration (2.5)].
- DARZALEX should be administered by a healthcare provider, with immediate access to emergency equipment and appropriate medical support to manage infusion-related reactions if they occur [see Warnings and Precautions (5.1)].
- Type and screen patients prior to starting DARZALEX [see Warnings and Precautions (5.2)] .
Recommended Dosage
Monotherapy and In Combination with Lenalidomide (D-Rd) or Pomalidomide (D-Pd) and Dexamethasone
The DARZALEX dosing schedule in Table 1 is for combination therapy (4-week cycle regimens) and monotherapy as follows:
- combination therapy with lenalidomide and low-dose dexamethasone for newly diagnosed patients ineligible for autologous stem cell transplant (ASCT) and in patients with relapsed/refractory multiple myeloma
- combination therapy with pomalidomide and low-dose dexamethasone for patients with relapsed/refractory multiple myeloma
- monotherapy for patients with relapsed/refractory multiple myeloma.
The recommended dose of DARZALEX is 16 mg/kg actual body weight administered as an intravenous infusion according to the following dosing schedule:
| Weeks | Schedule |
|---|---|
|
|
| Weeks 1 to 8 | weekly (total of 8 doses) |
| Weeks 9 to 24 * | every two weeks (total of 8 doses) |
| Week 25 onwards until disease progression † | every four weeks |
For dosing instructions of combination agents administered with DARZALEX, see Clinical Studies (14) and manufacturer's prescribing information.
In Combination with Bortezomib, Melphalan and Prednisone (D-VMP)
The DARZALEX dosing schedule in Table 2 is for combination therapy with bortezomib, melphalan and prednisone (6-week cycle regimen) for patients with newly diagnosed multiple myeloma ineligible for ASCT.
The recommended dose of DARZALEX is 16 mg/kg actual body weight administered as an intravenous infusion according to the following dosing schedule:
| Weeks | Schedule |
|---|---|
|
|
| Weeks 1 to 6 | weekly (total of 6 doses) |
| Weeks 7 to 54 * | every three weeks (total of 16 doses) |
| Week 55 onwards until disease progression † | every four weeks |
For dosing instructions of combination agents administered with DARZALEX see Clinical Studies (14.1).
In Combination with Bortezomib, Thalidomide and Dexamethasone (D-VTd)
The DARZALEX dosing schedule in Table 3 is for combination therapy with bortezomib, thalidomide, and dexamethasone (4-week cycle regimen) for patients with newly diagnosed multiple myeloma eligible for ASCT.
The recommended dose of DARZALEX is 16 mg/kg actual body weight administered as an intravenous infusion according to the following dosing schedule:
| Treatment phase | Weeks | Schedule |
|---|---|---|
|
||
| Induction | Weeks 1 to 8 | weekly (total of 8 doses) |
| Weeks 9 to 16 * | every two weeks (total of 4 doses) | |
| Stop for high dose chemotherapy and ASCT | ||
| Consolidation | Weeks 1 to 8 † | every two weeks (total of 4 doses) |
For dosing instructions of combination agents administered with DARZALEX, see Clinical Studies (14.1) and the manufacturer's prescribing information.
In Combination with Bortezomib and Dexamethasone (D-Vd)
The DARZALEX dosing schedule in Table 4 is for combination therapy with bortezomib and dexamethasone (3-week cycle) for patients with relapsed/refractory multiple myeloma.
The recommended dose of DARZALEX is 16 mg/kg actual body weight administered as an intravenous infusion according to the following dosing schedule:
| Weeks | Schedule |
|---|---|
|
|
| Weeks 1 to 9 | weekly (total of 9 doses) |
| Weeks 10 to 24 * | every three weeks (total of 5 doses) |
| Week 25 onwards until disease progression † | every four weeks |
For dosing instructions of combination agents administered with DARZALEX see Clinical Studies (14.2) and manufacturer's prescribing information .
In Combination with Carfilzomib and Dexamethasone (DKd)
The recommended dosage for DARZALEX when administered in combination with carfilzomib and dexamethasone (4-week cycle) for patients with relapsed/refractory multiple myeloma is provided in Table 5.
| Weeks | DARZALEX Dose * | Schedule |
|---|---|---|
|
||
| Week 1 | 8 mg/kg | days 1 and 2 (total 2 doses) |
| Weeks 2 to 8 | 16 mg/kg | weekly (total of 7 doses) |
| Weeks 9 to 24 † | 16 mg/kg | every two weeks (total of 8 doses) |
| Week 25 onwards until disease progression ‡ | 16 mg/kg | every four weeks |
For dosing instructions of combination agents administered with DARZALEX see Clinical Studies (14.1) and manufacturer's prescribing information .
Infusion Rates
Administer DARZALEX intravenously at the infusion rate described below in Table 6. Consider incremental escalation of the infusion rate only in the absence of infusion-related reactions.
The recommended dose of 16 mg/kg to be administered on Day 1 when DARZALEX is administered as monotherapy or in combination may be split over two consecutive days, such that an 8 mg/kg dose is administered on Day 1 and Day 2, respectively.
| Dilution volume | Initial rate (first hour) | Rate increment * | Maximum rate | |
|---|---|---|---|---|
|
||||
| Week 1 Infusion | ||||
| Option 1 (Single dose infusion) | ||||
| Week 1 Day 1 (16 mg/kg) | 1,000 mL | 50 mL/hour | 50 mL/hour every hour | 200 mL/hour |
| Option 2 (Split dose infusion) | ||||
| Week 1 Day 1 (8 mg/kg) | 500 mL | 50 mL/hour | 50 mL/hour every hour | 200 mL/hour |
| Week 1 Day 2 (8 mg/kg) | 500 mL | 50 mL/hour | 50 mL/hour every hour | 200 mL/hour |
| Week 2 (16 mg/kg)† | 500 mL | 50 mL/hour | 50 mL/hour every hour | 200 mL/hour |
| Week 3 onwards (16 mg/kg)‡ | 500 mL | 100 mL/hour | 50 mL/hour every hour | 200 mL/hour |
Recommended Concomitant Medications
Pre-infusion Medication
Administer the following pre-infusion medications 1 hour to 3 hours before every DARZALEX infusion:
- Corticosteroid (long- or intermediate-acting)
- Monotherapy:
Administer methylprednisolone 100 mg (or equivalent) intravenously. Following the second infusion, consider reducing the dose to 60 mg (or equivalent) administered either orally or intravenously.
In Combination:
Administer dexamethasone 20 mg (or equivalent) orally or intravenously.
When dexamethasone is the background regimen-specific corticosteroid, the dexamethasone dose that is part of the background regimen will serve as pre-medication on DARZALEX infusion days [see Clinical Studies (14)].
Do not administer background regimen-specific corticosteroids (e.g. prednisone) on DARZALEX infusion days when patients have received dexamethasone (or equivalent) as a pre-medication.
- Monotherapy:
- Acetaminophen 650 mg to 1,000 mg orally
- Diphenhydramine 25 mg to 50 mg (or equivalent) orally or intravenously.
Post-infusion Medication
Administer the following post-infusion medications:
- Monotherapy:
Administer methylprednisolone 20 mg (or an equivalent dose of an intermediate- or long-acting corticosteroid) orally for 2 days starting the day after the administration of DARZALEX.
In Combination:
Consider administering oral methylprednisolone at a dose of less than or equal to 20 mg (or an equivalent dose of an intermediate- or long-acting corticosteroid) beginning the day after the administration of a DARZALEX infusion.
If a background regimen-specific corticosteroid (e.g. dexamethasone, prednisone) is administered the day after the DARZALEX infusion, additional corticosteroids may not be needed [see Clinical Studies (14)].
For patients with a history of chronic obstructive pulmonary disease, consider prescribing short and long-acting bronchodilators and inhaled corticosteroids. Following the first 4 DARZALEX infusions, consider discontinuing these additional post-infusion medications, if the patient does not experience a major infusion-related reaction.
Dosage Modifications for Adverse Reactions
No dose reductions of DARZALEX are recommended. Consider withholding DARZALEX to allow recovery of blood cell counts in the event of myelosuppression [see Warnings and Precautions (5.3, 5.4)] .
For information concerning drugs given in combination with DARZALEX, see manufacturer's prescribing information.
Infusion-Related Reactions
For infusion-related reactions of any grade/severity, immediately interrupt the DARZALEX infusion and manage symptoms. Management of infusion-related reactions may further require reduction in the rate of infusion, or treatment discontinuation of DARZALEX as outlined below [see Warnings and Precautions (5.1)] .
- 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 the patient does not experience any further reaction symptoms, infusion rate escalation may resume at increments and intervals as clinically appropriate up to the maximum rate of 200 mL/hour (Table 6).
- Grade 3 (severe): Once reaction symptoms resolve, consider restarting the infusion at no more than half the rate at which the reaction occurred. If the patient does not experience additional symptoms, resume infusion rate escalation at increments and intervals as outlined in Table 6. Repeat the procedure above in the event of recurrence of Grade 3 symptoms. Permanently discontinue DARZALEX upon the third occurrence of a Grade 3 or greater infusion-related reaction.
- Grade 4 (life-threatening): Permanently discontinue DARZALEX.
Preparation and Administration
Preparation
DARZALEX is for single dose only.
Prepare the solution for infusion using aseptic technique as follows:
- Calculate the dose (mg), total volume (mL) of DARZALEX solution required and the number of DARZALEX vials needed based on patient actual body weight.
- DARZALEX vials of the same strength with different NDCs are available and can be admixed in the same infusion bag [see Description (11), How Supplied/Storage and Handling (16)] .
- Check that the DARZALEX solution is colorless to pale yellow. Do not use if opaque particles, discoloration or other foreign particles are present.
- Remove a volume of 0.9% Sodium Chloride Injection, USP from the infusion bag/container that is equal to the required volume of DARZALEX solution.
- Withdraw the necessary amount of DARZALEX solution and dilute to the appropriate volume by adding to the infusion bag/container containing 0.9% Sodium Chloride Injection, USP as specified in Table 6 [see Dosage and Administration (2.2)] . Infusion bags/containers must be made of either 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.
- 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.
- If not used immediately, store the diluted solution refrigerated for up to 24 hours at 2°C to 8°C (36°F to 46°F) and/or at room temperature up to 15 hours at 15°C to 25°C (59°F to 77°F). The room temperature storage includes infusion time. Protect from light during storage. Do not freeze.
Administration
- If stored in the refrigerator, allow the solution to come to room temperature. Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an in-line, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 micrometer or 0.2 micrometer). Administration sets must be made of either polyurethane (PU), polybutadiene (PBD), PVC, PP or PE.
- 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 DARZALEX concomitantly in the same intravenous line with other agents.
