Darzalex Dosage/Direction for Use

DARZALEX should be administered by a healthcare professional, with immediate access to emergency equipment and appropriate medical support to manage infusion-related reactions (IRRs) if they occur.
Pre- and post-infusion medications should be administered (see Recommended concomitant medications as follows).
Dosage - Adults (≥18 years): Recommended dose: The DARZALEX dosing schedule in Table 9 is for combination therapy with 4-week cycle regimens (e.g. lenalidomide) and for monotherapy as follows: combination therapy with lenalidomide and low-dose dexamethasone for patients with newly diagnosed multiple myeloma ineligible for autologous stem cell transplant (ASCT); combination therapy with lenalidomide and low-dose dexamethasone for patients with relapsed/refractory multiple myeloma; combination therapy with carfilzomib and low-dose dexamethasone for patients with relapsed/refractory multiple myeloma; monotherapy for patients with relapsed/refractory multiple myeloma.
The recommended dose is DARZALEX 16 mg/kg body weight administered as an intravenous infusion according to the following dosing schedule (infusion rates presented in Table 14): (See Table 9.)

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The recommended dose for DARZALEX when administered in combination with carfilzomib and dexamethasone (4-week cycle) for patients with relapsed/refractory multiple myeloma is provided in Table 10: (See Table 10.)

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For dosing instructions of medicinal products administered with DARZALEX, see Pharmacology: Pharmacodynamics: Clinical studies under Actions and manufacturer's prescribing information.
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 is DARZALEX 16 mg/kg body weight administered as an intravenous infusion according to the following dosing schedule (infusion rates presented in Table 14): (See Table 11.)

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Bortezomib is given twice weekly at Weeks 1, 2, 4 and 5 for the first 6-week cycle, followed by once weekly at Weeks 1, 2, 4 and 5 for eight more 6-week cycles. For information on the VMP dose and dosing schedule when administered with DARZALEX, see Pharmacology: Pharmacodynamics: Clinical studies under Actions.
The DARZALEX dosing schedule in Table 12 is for combination therapy with bortezomib, thalidomide and dexamethasone (4-week cycle regimens) for treatment of newly diagnosed patients eligible for ASCT.
The recommended dose is DARZALEX 16mg/kg body weight administered as an intravenous infusion according to the following dosing schedule (infusion rates presented in Table 14): (See Table 12.)

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For dosing instructions of medicinal products administered with DARZALEX, see Pharmacology: Pharmacodynamics: Clinical studies under Actions and manufacturer's prescribing information.
The DARZALEX dosing schedule in Table 13 is for combination therapy with bortezomib and dexamethasone (3-week cycle regimen) for patients with relapsed/refractory multiple myeloma.
The recommended dose is DARZALEX 16 mg/kg body weight administered as an intravenous infusion according to the following dosing schedule (infusion rates presented in Table 14): (See Table 13.)

Click on icon to see table/diagram/image

For dosing instructions for medicinal products administered with DARZALEX see Pharmacology: Pharmacodynamics: Clinical studies under Actions and manufacturer's prescribing information.
Missed dose(s): If a planned dose of DARZALEX is missed, administer the dose as soon as possible and adjust the dosing schedule accordingly, maintaining the treatment interval.
Dose modifications: No dose reductions of DARZALEX are recommended. Dose delay may be required to allow recovery of blood cell counts in the event of hematological toxicity (see Precautions). For information concerning medicinal products given in combination with DARZALEX, see manufacturer's prescribing information.
Recommended concomitant medications: Pre-infusion medication: Administer the following pre-infusion medications to reduce the risk of IRRs to all patients 1-3 hours prior to every infusion of DARZALEX: Corticosteroid (long-acting or intermediate-acting): Monotherapy: Methylprednisolone 100 mg, or equivalent, administered intravenously. Following the second infusion, the dose of corticosteroid may be reduced (oral or intravenous methylprednisolone 60 mg).
Combination therapy: Administer 20 mg dexamethasone (or equivalent) prior to every DARZALEX infusion. When dexamethasone is the background-regimen specific corticosteroid, the dexamethasone treatment dose will instead serve as pre-medication on DARZALEX infusion days (see Pharmacology: Pharmacodynamics: Clinical studies under Actions).
Dexamethasone is given intravenously prior to the first DARZALEX infusion and oral administration may be considered prior to subsequent infusions. Additional background-regimen specific corticosteroids (e.g. prednisone) should not be taken on DARZALEX infusion days when patients have received dexamethasone as a pre-medication.
Antipyretics (oral paracetamol/acetaminophen 650 to 1000 mg).
Antihistamine (oral or intravenous diphenhydramine 25 to 50 mg or equivalent).
Post-infusion medication: Administer post-infusion medication to reduce the risk of delayed infusion related reactions as follows: Monotherapy: Administer oral corticosteroid (20 mg methylprednisolone or equivalent dose of an intermediate acting or long acting corticosteroid in accordance with local standards) on each of the 2 days following all DARZALEX infusions (beginning the day after the infusion).
Combination therapy: Consider administering low-dose oral methylprednisolone (≤ 20 mg) or equivalent the day after the DARZALEX infusion.
However, if a background regimen-specific corticosteroid (e.g. dexamethasone, prednisone) is administered the day after the DARZALEX infusion, additional post-infusion medications may not be needed (see Pharmacology: Pharmacodynamics: Clinical studies under Actions).
Additionally, for patients with a history of chronic obstructive pulmonary disease, consider the use of post-infusion medications including short and long acting bronchodilators, and inhaled corticosteroids. Following the first four infusions, if the patient experiences no major IRRs, these inhaled post-infusion medications may be discontinued at the discretion of the physician.
Prophylaxis for herpes zoster virus reactivation: Anti-viral prophylaxis should be considered for the prevention of herpes zoster virus reactivation.
Special populations: Pediatrics (17 years of age and younger): The safety and efficacy of DARZALEX have not been established in pediatric patients.
Elderly (65 years of age and older): No dose adjustments are considered necessary in elderly patients (see Pharmacology: Pharmacokinetics under Actions and Adverse Reactions).
Renal impairment: No formal studies of daratumumab in patients with renal impairment have been conducted. Based on population pharmacokinetic (PK) analyses, no dosage adjustment is necessary for patients with renal impairment (see Pharmacology: Pharmacokinetics under Actions).
Hepatic impairment: No formal studies of daratumumab in patients with hepatic impairment have been conducted. Changes in hepatic function are unlikely to have any effect on the elimination of daratumumab since IgG1 molecules such as daratumumab are not metabolized through hepatic pathways. Based on population PK analyses, no dosage adjustments are necessary for patients with hepatic impairment (see Pharmacology: Pharmacokinetics under Actions).
Administration: DARZALEX is administered as an intravenous infusion following dilution with 0.9% Sodium Chloride. For instructions on dilution of the medicinal product before administration, see Instructions for Use and Handling and Disposal under Cautions for Usage.
Following dilution the DARZALEX infusion should be intravenously administered at the appropriate initial infusion rate presented in Table 14 as follows. Incremental escalation of the infusion rate should be considered only in the absence of infusion reactions.
To facilitate administration, the first prescribed 16 mg/kg dose at Week 1 may be split over two consecutive days i.e. 8 mg/kg on Day 1 and Day 2 respectively, see Table 14 as follows.
For patients receiving DARZALEX in combination with carfilzomib and dexamethasone (DKd), 16 mg/kg daratumumab dose at Week 1 should be split over two days to minimize risk of volume overload (see option 2 under Table 14). (See Table 14.)

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Management of infusion-related reactions: Administer pre-infusion medications to reduce the risk of IRRs prior to treatment with DARZALEX.
For IRRs of any grade/severity, immediately interrupt the DARZALEX infusion and manage symptoms.
Management of IRRs may further require reduction in the rate of infusion, or treatment discontinuation of DARZALEX as outlined as follows (see also Precautions).
Grade 1-2 (mild to moderate): Once reaction symptoms resolve, resume the infusion at no more than half the rate at which the IRR occurred. If the patient does not experience any further IRR symptoms, infusion rate escalation may resume at increments and intervals as clinically appropriate up to the maximum rate of 200 mL/hour (Table 14).
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 appropriate (Table 14). 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 reaction.
Grade 4 (life-threatening): Permanently discontinue DARZALEX treatment.