Darzalex Dosage/Direction for Use

Important Dosing Information: Administer pre-infusion and post-infusion medications [see Recommended Concomitant Medications as follows].
Administer only as an intravenous infusion after dilution in 0.9% Sodium Chloride Injection, USP [see Preparation and Administration as follows].
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 Infusion-Related Reactions under Precautions].
Type and screen patients prior to starting DARZALEX [see Interference with Serological Testing under Precautions].
Recommended Dosage: Monotherapy and In Combination with Lenalidomide (D-Rd) or Pomalidomide (D-Pd) and Dexamethasone: The DARZALEX dosing schedule in Table 10 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: See Table 10.

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For dosing instructions of combination agents administered with DARZALEX, see Pharmacology: Pharmacodynamics: Clinical Studies under Actions and manufacturer's prescribing information.
In Combination with Bortezomib, Melphalan and Prednisone (D-VMP): The DARZALEX dosing schedule in Table 11 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: See Table 11.

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For dosing instructions of combination agents administered with DARZALEX, see Pharmacology: Pharmacodynamics: Clinical Studies: Newly Diagnosed Multiple Myeloma under Actions.
In Combination with Bortezomib, Thalidomide and Dexamethasone (D-VTd): The DARZALEX dosing schedule in Table 12 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: See Table 12.

Click on icon to see table/diagram/image

For dosing instructions of combination agents administered with DARZALEX, see Pharmacology: Pharmacodynamics: Clinical Studies: Newly Diagnosed Multiple Myeloma under Actions and the manufacturer's prescribing information.
In Combination with Bortezomib and Dexamethasone (D-Vd): The DARZALEX dosing schedule in Table 13 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: See Table 13.

Click on icon to see table/diagram/image

For dosing instructions of combination agents administered with DARZALEX, see Pharmacology: Pharmacodynamics: Clinical Studies: Relapsed/Refractory Multiple Myeloma under Actions 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 14. (See Table 14.)

Click on icon to see table/diagram/image

For dosing instructions of combination agents administered with DARZALEX, see Pharmacology: Pharmacodynamics: Clinical Studies: Newly Diagnosed Multiple Myeloma under Actions and manufacturer's prescribing information.
Infusion Rates: Administer DARZALEX intravenously at the infusion rate described as follows in Table 15. 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. (See Table 15.)

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Missed DARZALEX Doses: If a dose of DARZALEX is missed, administer the dose as soon as possible and adjust the dosing schedule to maintain the dosing interval.
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 Pharmacology: Pharmacodynamics: Clinical Studies under Actions].
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.
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 Pharmacology: Pharmacodynamics: Clinical Studies under Actions].
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.
Prophylaxis for Herpes Zoster Reactivation: Initiate antiviral prophylaxis to prevent herpes zoster reactivation within 1 week after starting DARZALEX and continue for 3 months following the end of treatment [see Clinical Trials Experience under Adverse Reactions].
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 Neutropenia and Thrombocytopenia under Precautions].
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 in the following text [see Infusion-Related Reactions under Precautions].
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 15).
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 15. Repeat the procedure as previously mentioned 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.
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 15 [see Recommended Dosage as previously mentioned]. 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.
Since DARZALEX does not contain a preservative, administer the diluted solution immediately at room temperature 15°C to 25°C (59°F to 77°F) and in room light. Diluted solution may be kept at room temperature for a maximum of 15 hours (including infusion time).
If not used immediately, the diluted solution can be stored prior to administration for up to 24 hours at refrigerated conditions 2°C to 8°C (36°F to 46°F) and protected from light. 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.
Use in Specific Populations: Pediatric Use: Safety and effectiveness of DARZALEX in pediatric patients have not been established.
Geriatric Use: Of the 2,459 patients who received DARZALEX at the recommended dose, 38% were 65 to 74 years of age, and 15% were 75 years of age or older. No overall differences in effectiveness were observed between these patients and younger patients. The incidence of serious adverse reactions was higher in older than in younger patients [see Clinical Trials Experience under Adverse Reactions]. Among patients with relapsed and refractory multiple myeloma (n=1,213), the serious adverse reactions that occurred more frequently in patients 65 years and older were pneumonia and sepsis. Within the DKd group in CANDOR, fatal adverse reactions occurred in 14% of patients 65 years and older compared to 6% of patients less than 65 years. Among patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (n=710), the serious adverse reaction that occurred more frequently in patients 75 years and older was pneumonia.