Darzalex Dosage/Direction for Use

Concentrate for solution for IV infusion: DARZALEX should be administered by a healthcare professional, in an environment where resuscitation facilities are available.
Pre- and post-infusion medicinal products should be administered to reduce the risk of infusion-related reactions (IRRs) with daratumumab. See Recommended concomitant medicinal products, Management of infusion-related reactions as follows and Precautions.
Posology: Dosing schedule in combination with lenalidomide and dexamethasone (4‑week cycle regimen) and for monotherapy: The recommended dose is DARZALEX 16 mg/kg body weight administered as an intravenous infusion according to the following dosing schedule in Table 13. (See Table 13.)

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Dexamethasone should be administered at 40 mg/week (or a reduced dose of 20 mg/week for patients >75 years).
For dose and schedule of medicinal products administered with DARZALEX, see Pharmacology: Pharmacodynamics under Actions and the corresponding product insert.
Dosing schedule in combination with bortezomib, melphalan and prednisone (6-week cycle regimens): The recommended dose is DARZALEX 16 mg/kg body weight administered as an intravenous infusion according to the following dosing schedule in Table 14. (See Table 14.)

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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 under Actions.
Dosing schedule in combination with bortezomib, thalidomide and dexamethasone (4-week cycle regimens) for treatment of newly diagnosed patients eligible for autologous stem cell transplant (ASCT): The recommended dose is DARZALEX 16 mg/kg body weight administered as an intravenous infusion according to the following dosing schedule in Table 15. (See Table 15.)

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Dexamethasone should be administered at 40 mg on days 1, 2, 8, 9, 15, 16, 22 and 23 of cycles 1 and 2, and at 40 mg on days 1-2 and 20 mg on subsequent dosing days (days 8, 9, 15, 16) of cycles 3-4. Dexamethasone 20 mg should be administered on days 1, 2, 8, 9, 15, 16 in cycles 5 and 6.
For dose and schedule of medicinal products administered with DARZALEX, see Pharmacology: Pharmacodynamics under Actions and the corresponding product insert.
Dosing schedule in combination with bortezomib and dexamethasone (3‑week cycle regimen): The recommended dose is DARZALEX 16 mg/kg body weight administered as an intravenous infusion according to the following dosing schedule in Table 16. (See Table 16.)

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Dexamethasone should be administered at 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 of the first 8 bortezomib treatment cycles or a reduced dose of 20 mg/week for patients >75 years, underweight (BMI <18.5), poorly controlled diabetes mellitus or prior intolerance to steroid therapy.
For dose and schedule of medicinal products administered with DARZALEX, see Pharmacology: Pharmacodynamics under Actions and the corresponding package insert.
Infusion rates: Following dilution the DARZALEX infusion should be intravenously administered at the initial infusion rate presented in Table 17 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 17 as follows.

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Management of infusion-related reactions: Pre-infusion medicinal products should be administered to reduce the risk of infusion-related reactions (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 Precautions).
Grade 1-2 (mild to moderate): Once reaction symptoms resolve, the infusion should be resumed 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 be resumed at increments and intervals as clinically appropriate up to the maximum rate of 200 mL/hour (Table 17).
Grade 3 (severe): Once reaction symptoms resolve, restarting of the infusion may be considered at no more than half the rate at which the reaction occurred. If the patient does not experience additional symptoms, infusion rate escalation may be resumed at increments and intervals as appropriate (Table 17). The procedure previously mentioned should be repeated 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.
Solution for SC injection: DARZALEX subcutaneous formulation is not intended for intravenous administration and should be given by subcutaneous injection only, using the doses specified.
DARZALEX should be administered by a healthcare professional, and the first dose should be administered in an environment where resuscitation facilities are available.
It is important to check the vial labels to ensure that the appropriate formulation (intravenous or subcutaneous formulation) and dose is being given to the patient as prescribed.
For patients currently receiving daratumamab intravenous formulation, DARZALEX solution for subcutaneous injection may be used as an alternative to the intravenous daratumumab formulation starting at the next scheduled dose.
Pre- and post-injection medicinal products should be administered to reduce the risk of infusion-related reactions (IRRs) with daratumumab. See "Recommended concomitant medicinal products" as follows and Precautions.
Posology: Multiple myeloma: Dosing schedule in combination with lenalidomide and dexamethasone or pomalidomide and dexamethasone (4-week cycle regimen) and for monotherapy: The recommended dose is 1800 mg of DARZALEX solution for subcutaneous injection administered over approximately 3-5 minutes according to the following dosing schedule in Table 18. (See Table 18.)

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Dexamethasone should be administered at 40 mg/week (or a reduced dose of 20 mg/week for patients > 75 years). For dose and schedule of medicinal products administered with DARZALEX solution for subcutaneous injection, see Pharmacology: Pharmacodynamics under Actions and the corresponding package insert.
Dosing schedule in combination with bortezomib, melphalan and prednisone (6-week cycle regimens): The recommended dose is 1800 mg of DARZALEX solution for subcutaneous injection administered over approximately 3-5 minutes according to the following dosing schedule in Table 19. (See Table 19.)

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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 solution for subcutaneous injection, see Pharmacology: Pharmacodynamics under Actions.
Dosing schedule in combination with bortezomib, thalidomide and dexamethasone (4-week cycle regimens) for treatment of newly diagnosed patients eligible for autologous stem cell transplant (ASCT): The recommended dose is 1800 mg of DARZALEX solution for subcutaneous injection administered over approximately 3-5 minutes according to the following dosing schedule in Table 20. (See Table 20.)

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Dexamethasone should be administered at 40 mg on days 1, 2, 8, 9, 15, 16, 22 and 23 of cycles 1 and 2, and at 40 mg on days 1-2 and 20 mg on subsequent dosing days (days 8, 9, 15, 16) of cycles 3-4. Dexamethasone 20 mg should be administered on days 1, 2, 8, 9, 15, 16 in cycles 5 and 6.
For dose and schedule of medicinal products administered with DARZALEX solution for subcutaneous injection, see Pharmacology: Pharmacodynamics under Actions and the corresponding package insert.
Dosing schedule in combination with bortezomib and dexamethasone (3-week cycle regimen): The recommended dose is 1800 mg of DARZALEX solution for subcutaneous injection administered over approximately 3-5 minutes according to the following dosing schedule in Table 21. (See Table 21.)

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Dexamethasone should be administered at 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 of the first 8 bortezomib treatment cycles or a reduced dose of 20 mg/week for patients > 75 years, underweight (BMI < 18.5), poorly controlled diabetes mellitus or prior intolerance to steroid therapy.
For dose and schedule of medicinal products administered with DARZALEX solution for subcutaneous injection, see Pharmacology: Pharmacodynamics under Actions and the corresponding package insert.
AL amyloidosis: Dosing schedule in combination with bortezomib, cyclophosphamide and dexamethasone (4-week cycle regimens): The recommended dose is 1800 mg of DARZALEX solution for subcutaneous injection administered over approximately 3-5 minutes according to the following dosing schedule in Table 22. (See Table 22.)

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For dose and schedule of medicinal products administered with DARZALEX solution for subcutaneous injection, see Pharmacology: Pharmacodynamics under Actions and the corresponding package insert.
Missed dose: 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.
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 haematological toxicity (see Precautions). For information concerning medicinal products given in combination with DARZALEX, see corresponding package insert.
Recommended concomitant medicinal products: Prophylaxis for herpes zoster virus reactivation: Anti-viral prophylaxis should be considered for the prevention of herpes zoster virus reactivation.
Concentrate for solution for IV infusion: Pre-infusion medicinal product: Pre-infusion medicinal products 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): 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: Dexamethasone 20 mg (or equivalent), administered prior to every DARZALEX infusion. When dexamethasone is the background‑regimen specific corticosteroid, the dexamethasone treatment dose will instead serve as pre‑infusion medicinal product on DARZALEX infusion days (see Pharmacology: Pharmacodynamics 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-infusion medicinal product.
Antipyretics (oral paracetamol 650 to 1,000 mg).
Antihistamine (oral or intravenous diphenhydramine 25 to 50 mg or equivalent).
Post-infusion medicinal product: Post-infusion medicinal products should be administered to reduce the risk of delayed IRRs as follows: Monotherapy: Oral corticosteroid (20 mg methylprednisolone or equivalent dose of an intermediate-acting or long-acting corticosteroid in accordance with local standards) should be administered on each of the two days following all 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 medicinal products may not be needed (see Pharmacology: Pharmacodynamics under Actions).
Additionally, for patients with a history of chronic obstructive pulmonary disease, the use of post-infusion medicinal products including short and long acting bronchodilators, and inhaled corticosteroids should be considered. Following the first four infusions, if the patient experiences no major IRRs, these inhaled post-infusion medicinal products may be discontinued at the discretion of the physician.
Solution for SC injection: Pre-injection medicinal product: Pre-injection medicinal products (oral or intravenous) should be administered to reduce the risk of IRRs to all patients 1-3 hours prior to every administration of DARZALEX solution for subcutaneous injection as follows: Corticosteroid (long-acting or intermediate-acting): Monotherapy: Methylprednisolone 100 mg, or equivalent. Following the second injection, the dose of corticosteroid may be reduced to methylprednisolone 60 mg.
Combination therapy: Dexamethasone 20 mg (or equivalent), administered prior to every DARZALEX solution for subcutaneous 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 (see Pharmacology: Pharmacodynamics under Actions). 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 medicinal product.
Antipyretics (paracetamol 650 to 1000 mg).
Antihistamine (oral or intravenous diphenhydramine 25 to 50 mg or equivalent).
Post-injection medicinal product: Post-injection medicinal products should be administered to reduce the risk of delayed IRRs as follows: Monotherapy: Oral corticosteroid (20 mg methylprednisolone or equivalent dose of an intermediate-acting or long-acting corticosteroid in accordance with local standards) should be administered on each of the two days following all injections (beginning the day after the injection).
Combination therapy: Consider administering low-dose oral methylprednisolone (≤ 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 medicinal products may not be needed (see Pharmacology: Pharmacodynamics under Actions).
If the patient experiences no major IRRs after the first three injections, post-injection corticosteroids (excluding any background regimen corticosteroids) may be discontinued.
Additionally, for patients with a history of chronic obstructive pulmonary disease, the use of post-injection medicinal products 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 medicinal products may be discontinued at the discretion of the physician.
Special populations: 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.
Based on population PK analyses, no dosage adjustments are necessary for patients with hepatic impairment (see Pharmacology: Pharmacokinetics under Actions).
Elderly: No dose adjustments are considered necessary (see Pharmacology: Pharmacokinetics under Actions).
Paediatric population: The safety and efficacy of DARZALEX in children aged below 18 years of age have not been established.
No data are available (see Pharmacology: Pharmacodynamics under Actions).
Body weight (> 120 kg): Solution for SC injection: Limited number of patients with body weight > 120 kg have been studied using flat-dose (1800 mg) DARZALEX solution for subcutaneous injection and efficacy in these patients has not been established. No dose adjustment based on body weight can currently be recommended (see Precautions and Dosage & Administration).
Method of administration: Concentrate for solution for IV infusion: DARZALEX is for intravenous use. It is administered as an intravenous infusion following dilution with sodium chloride 9 mg/mL (0.9%) solution for injection. For instructions on dilution of the medicinal product before administration, see Special precautions for disposal and other handling under Cautions for Usage.
Solution for SC injection: DARZALEX subcutaneous formulation is not intended for intravenous administration and should be given by subcutaneous injection only, using the doses specified. See Cautions for Usage for special precautions prior to administration.
To avoid needle clogging, attach the hypodermic injection needle or subcutaneous infusion set to the syringe immediately prior to injection.
Inject 15 mL DARZALEX solution for subcutaneous injection into the subcutaneous tissue of the abdomen approximately 7.5 cm to the right or left of the navel over approximately 3-5 minutes. Do not inject DARZALEX solution for subcutaneous injection at other sites of the body as no data are available.
Injection sites should be rotated for successive injections.
DARZALEX solution for subcutaneous injection should never be injected into areas where the skin is red, bruised, tender, hard or areas where there are scars.
Pause or slow down delivery rate if the patient experiences pain. In the event pain is not alleviated by slowing down the injection, a second injection site may be chosen on the opposite side of the abdomen to deliver the remainder of the dose.
During treatment with DARZALEX solution for subcutaneous injection, do not administer other medicinal products for subcutaneous use at the same site as DARZALEX.