Darzalex Dosage/Direction for Use

Daratumumab (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 Daratumumab (Darzalex) dosing schedule in Table 7 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; monotherapy for patients with relapsed/refractory multiple myeloma.
The recommended dose is Daratumumab (Darzalex) 16 mg/kg body weight administered as an intravenous infusion according to the following dosing schedule (infusion rates presented in Table 11): (see Table 7.)

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For dosing instructions of medicinal products administered with Daratumumab (Darzalex), see Pharmacology: Pharmacodynamics: Clinical Studies under Actions and manufacturer's prescribing information.
The Daratumumab (Darzalex) dosing schedule in Table 8 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 Daratumumab (Darzalex) 16 mg/kg body weight administered as an intravenous infusion according to the following dosing schedule (infusion rates presented in Table 11): see Table 8.

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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 Daratumumab (Darzalex), see Pharmacology: Pharmacodynamics: Clinical Studies under Actions.
The Daratumumab (Darzalex) dosing schedule in Table 9 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 Daratumumab (Darzalex) 16 mg/kg body weight administered as an intravenous infusion according to the following dosing schedule (infusion rates presented in Table 11): see Table 9.

Click on icon to see table/diagram/image

For dosing instructions of medicinal products administered with Daratumumab (Darzalex), see Pharmacology: Pharmacodynamics: Clinical Studies under Actions and manufacturer's prescribing information.
The Daratumumab (Darzalex) dosing schedule in Table 10 is for combination therapy with 3-week cycle regimens (e.g. bortezomib) for patients with relapsed/refractory multiple myeloma.
The recommended dose is Daratumumab (Darzalex) 16 mg/kg body weight administered as an intravenous infusion according to the following dosing schedule (infusion rates presented in Table 11): see Table 10.

Click on icon to see table/diagram/image

For dosing instructions for medicinal products administered with Daratumumab (Darzalex) see Pharmacology: Pharmacodynamics: Clinical Studies under Actions and manufacturer's prescribing information.
Missed dose(s): If a planned dose of Daratumumab (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 Daratumumab (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 Daratumumab (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 approximately 1-3 hours prior to every infusion of Daratumumab (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 Daratumumab (Darzalex) infusion. When dexamethasone is the background-regimen specific corticosteroid, the dexamethasone treatment dose will instead serve as pre-medication on Daratumumab (Darzalex) infusion days (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
Dexamethasone is given intravenously prior to the first Daratumumab (Darzalex) infusion and oral administration may be considered prior to the subsequent infusions. Additional background regimen specific corticosteroids (e.g. prednisone) should not be taken on Daratumumab (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 Daratumumab (Darzalex) infusions (beginning the day after the infusion).
Combination therapy: Consider administering low-dose oral methylprednisolone (≤ 20 mg) or equivalent the day after the Daratumumab (Darzalex) infusion.
However, if a background regimen-specific corticosteroid (e.g. dexamethasone, prednisone) is administered the day after the Daratumumab (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 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 Daratumumab (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 a population pharmacokinetic (PK) analysis, 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 a population PK analysis, no dosage adjustments are necessary for patients with hepatic impairment (see Pharmacology: Pharmacokinetics under Actions).
Administration: Daratumumab (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 Daratumumab (Darzalex) infusion should be intravenously administered at the appropriate initial infusion rate, as presented in Table 11 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 11 as follows. (See Table 11.)

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Management of infusion-related reactions: Administer pre-infusion medications to reduce the risk of IRRs prior to treatment with Daratumumab (Darzalex).
For IRRs of any grade/severity, immediately interrupt the Daratumumab (Darzalex) infusion and manage symptoms.
Management of IRRs may further require reduction in the rate of infusion, or treatment discontinuation of Daratumumab (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 11).
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 11). Repeat the procedure previously in the event of recurrence of Grade 3 symptoms. Permanently discontinue Daratumumab (Darzalex) upon the third occurrence of a Grade 3 or greater infusion reaction.
Grade 4 (life-threatening): Permanently discontinue Daratumumab (Darzalex) treatment.