daratumumab/hyaluronidase

High Alert

Multiple myeloma in patients who have received ≥1 prior therapy (in combination with bortezomib and dexamethasone).
Relapsed or refractory multiple myeloma in patients who have received ≥1 prior therapy (in combination with lenalidomide and dexamethasone).
Relapsed or refractory multiple myeloma in patients who have received 1–3 prior lines of therapy (in combination with carfilzomib and dexamethasone).
Multiple myeloma in patients who have received ≥3 prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.
Multiple myeloma in patients who have received ≥1 prior line of therapy, including lenalidomide and a proteasome inhibitor (in combination with pomalidomide and dexamethasone).
Newly diagnosed multiple myeloma in patients who are ineligible for autologous stem cell transplant (in combination with bortezomib, melphalan, and prednisone).
Newly diagnosed multiple myeloma in patients who are ineligible for autologous stem cell transplant (in combination with lenalidomide and dexamethasone).
Newly diagnosed multiple myeloma in patients who are eligible for autologous stem cell transplant (in combination with bortezomib, thalidomide, and dexamethasone).
Newly diagnosed multiple myeloma in patients who are eligible for autologous stem cell transplant (in combination with bortezomib, lenalidomide, and dexamethasone).
High-risk smoldering multiple myeloma.
Newly diagnosed light chain amyloidosis (in combination with bortezomib, cyclophosphamide, and dexamethasone).

Action ⬆ ⬇

Daratumumab: Binds to CD38 on tumor cells, causing apoptosis, thereby inhibiting growth of CD38-expressing tumor cells.Hyaluronidase: Acts locally by depolymerizing hyalyonan, which increases permeability of the SUBQ tissue.

Therapeutic effects:

Decreased progression of multiple myeloma.
Reduction in diagnosis of multiple myeloma in high-risk smoldering multiple myeloma.
Decreased progression of light chain amyloidosis.

Pharmacokinetics ⬆ ⬇

Absorption: 69% absorbed following SUBQ administration.

Distribution: Monoclonal antibodies cross the placenta.

Metabolism/Excretion: Unknown.

Half-Life: 20 days.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
SUBQ	unknown	3 days	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Severe hypersensitivity;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Cardiovascular disease (for light chain amyloidosis only);
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, hypotension, peripheral edema, atrial fibrillation, CARDIAC ARREST, HF

Derm: pruritus, rash

Endo: hyperglycemia

F and E: hypocalcemia

GI: abdominal pain, constipation, diarrhea, nausea, vomiting

Hemat: anemia, leukopenia, lymphocytopenia, thrombocytopenia, NEUTROPENIA

Local: injection site reactions

Metab: ↓appetite

MS: muscle spasms, arthralgia

Neuro: dizziness, insomnia, peripheral neuropathy, headache, paresthesia

Resp: cough, dyspnea, pulmonary edema

Misc: fatigue, fever, hypersensitivity reactions (including anaphylaxis), infection, infusion reactions

Interactions ⬆ ⬇

Drug-drug:

None reported.

Route/Dosage ⬆ ⬇

Multiple Myeloma—Monotherapy and Combination Therapy with Lenalidomide + Dexamethasone, Pomalidomide + Dexamethasone, or Carfilzomib + Dexamethasone

SUBQ (Adults ): Daratumumab 1800 mg/hyaluronidase 30,000 units once weekly starting at Wk 1 through Wk 8 (total of 8 doses); then daratumumab 1800 mg/hyaluronidase 30,000 units every 2 wk starting at Wk 9 until Wk 24 (total of 8 doses); then daratumumab 1800 mg/hyaluronidase 30,000 units every 4 wk starting at Wk 25 and onward; continue until disease progression.

Multiple Myeloma—Combination Therapy with Bortezomib + Melphalan + Prednisone

SUBQ (Adults ): Daratumumab 1800 mg/hyaluronidase 30,000 units once weekly starting at Wk 1 through Wk 6 (total of 6 doses); then daratumumab 1800 mg/hyaluronidase 30,000 units every 3 wk starting at Wk 7 until Wk 54 (total of 16 doses); then daratumumab 1800 mg/hyaluronidase 30,000 units every 4 wk starting at Wk 55 and onward; continue until disease progression.

Multiple Myeloma—Combination Therapy with Bortezomib + Thalidomide + Dexamethasone or Bortezomib + Lenalidomide + Dexamethasone

SUBQ (Adults ): Induction therapy: Daratumumab 1800 mg/hyaluronidase 30,000 units once weekly starting at Wk 1 through Wk 8 (total of 8 doses); then daratumumab 1800 mg/hyaluronidase 30,000 units every 2 wk starting at Wk 9 until Wk 16 (total of 4 doses); then stop for high-dose chemotherapy and autologous stem cell transplant; Consolidation therapy: Daratumumab 1800 mg/hyaluronidase 30,000 units every 2 wk starting at Wk 1 upon reinitiation of treatment following autologous stem cell transplant and continued until Wk 8 (total of 4 doses).

Multiple Myeloma—Combination Therapy with Bortezomib + Dexamethasone

SUBQ (Adults ): Daratumumab 1800 mg/hyaluronidase 30,000 units once weekly starting at Wk 1 through Wk 9 (total of 9 doses); then daratumumab 1800 mg/hyaluronidase 30,000 units every 3 wk starting at Wk 10 until Wk 24 (total of 5 doses); then daratumumab 1800 mg/hyaluronidase 30,000 units every 4 wk starting at Wk 25 and onward; continue until disease progression.

High-Risk Smoldering Multiple Myeloma

SUBQ (Adults ): Daratumumab 1800 mg/hyaluronidase 30,000 units once weekly starting at Wk 1 through Wk 8 (total of 8 doses); then daratumumab 1800 mg/hyaluronidase 30,000 units every 2 wk starting at Wk 9 until Wk 24 (total of 8 doses); then daratumumab 1800 mg/hyaluronidase 30,000 units every 4 wk starting at Wk 25 and onward; continue until diagnosis myeloma or a max of 3 yr.

Light Chain Amyloidosis—Combination Therapy with Bortezomib + Cyclophosphamide + Dexamethasone

SUBQ (Adults ): Daratumumab 1800 mg/hyaluronidase 30,000 units once weekly starting at Wk 1 through Wk 8 (total of 8 doses); then daratumumab 1800 mg/hyaluronidase 30,000 units every 2 wk starting at Wk 9 until Wk 24 (total of 8 doses); then daratumumab 1800 mg/hyaluronidase 30,000 units every 4 wk starting at Wk 25 and onward; continue until disease progression or a maximum of 2 yr.

Availability ⬆ ⬇

Solution for injection: daratumumab 120 mg and hyaluronidase 2000 units/mL

Assessment ⬆ ⬇

Monitor for signs/symptoms of hypersensitivity (hypoxia, dyspnea, hypertension, tachycardia) and infusion-related reactions (hypoxia, dyspnea, hypertension, tachycardia, bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, wheezing, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension), especially after the 1st and 2nd injections. For anaphylactic reaction or life-threatening administration-related (Grade 4) reactions,permanently discontinue daratumumab/hyaluronidase. Consider administering corticosteroids and other medications after administration to minimize the risk of delayed (occurring the day after administration) reactions.
Monitor for ocular reactions (acute myopia, narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential to ↑ intraocular pressure or glaucoma). If ocular reactions occur, discontinue daratumumab/hyaluronidase, and immediately seek ophthalmologic evaluation before restarting.
Monitor for local reactions (itching, swelling, bruising, pain, rash, bleeding, redness of the skin); may happen >24 hr after injection. Consider symptomatic management.
Monitor patients with cardiac involvement of light chain amyloidosis more frequently for signs/symptoms of cardiac adverse reactions (chest pain, feeling faint, swollen legs, shortness of breath, abnormal heart rhythm); administer supportive care as appropriate.
Monitor patients with neutropenia for signs/symptoms of infection (fever, chills, dyspnea, cough, urinary frequency). Consider holding therapy until recovery of neutrophils.
Monitor for signs/symptoms of infection before and during treatment and treat appropriately. Administer prophylactic antimicrobials according to guidelines.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
- Monitor CBC periodically during therapy. May hold therapy until recovery of neutrophils and platelets.
- Type and screen patients prior to starting therapy. May cause a positive indirect antiglobulin test (indirect Coombs’ test); may persist for up to 6 mo after last dose. Determination of a patient’s ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received daratumumab/hyaluronidase.

Implementation ⬆ ⬇

Should be administered by a health care provider.
Administer medications before and after administration to minimize administration-related reactions.
Premedication: Administer acetaminophen 650–1000 mg PO, diphenhydramine 25–50 mg (or equivalent) PO or IV, corticosteroid (long or intermediate acting), 1–3 hr before each dose.
- For monotherapy:Administer methylprednisolone 100 mg (or equivalent) PO or IV. Consider ↓ dose of methylprednisolone to 60 mg following 2nd dose of daratumumab/hyaluronidase.
- In combination with other drugs: Administer dexamethasone 20 mg (or equivalent) PO or IV prior to every daratumumab/hyaluronidase dose. When dexamethasone is the background regimen-specific corticosteroid, the dexamethasone dose that is part of the background regimen will serve as premedication on daratumumab/hyaluronidase administration days. Do not administer background regimen-specific corticosteroids (e.g., prednisone) on daratumumab/hyaluronidase administration days when patient has received dexamethasone as a premedication.
SUBQ: Remove vial from refrigerator and allow to warm to room temperature. Do not shake. Withdraw 15 mL from vial into a syringe using an 18–22 gauge transfer needle with a regular bevel. Insert needle into the vial at 90° angle into the ring of the stopper. Visually inspect for particulate matter and discoloration. Do not use if opaque particles, discoloration or other foreign particles are present. Compatible with polypropylene or polyethylene syringe material; polypropylene, polyethylene, or polyvinyl chloride; SUBQ infusion sets; and stainless steel transfer and injection needles. Replace the transfer needle with a syringe closing cap. Label syringe appropriately per institutional standards and the peel-off label. Inject 15 mL immediately into SUBQ tissue of abdomen approximately 3 inches to the right or left of the navel over approximately 3–5 min. If a dose is missed, administer as soon as possible and adjust dosing schedule to maintain dosing interval. If patient experiences pain, pause or slow down delivery rate. If pain is not alleviated by pausing or slowing down delivery rate, a 2nd injection site may be chosen on opposite side of abdomen to deliver the remainder of the dose. Do not administer IV. Solution is stable for 24 hr if refrigerated or for 12 hr at room temperature; discard if unused beyond these time limits.
Postmedication: For monotherapy: Administer methylprednisolone 20 mg (or an equivalent dose of an intermediate- or long-acting corticosteroid) PO for 2 days starting the day after administration of daratumumab/hyaluronidase.
- In combination with other drugs:Consider administering methylprednisolone PO at a dose of ≤20 mg (or an equivalent dose of an intermediate- or long-acting corticosteroid) beginning the day after administration of daratumumab/hyaluronidase. If a background regimen-specific corticosteroid (dexamethasone, prednisone) is administered the day after the administration of daratumumab/hyaluronidase, additional corticosteroids may not be needed. If the patient does not experience a major systemic administration-related reaction after the first three doses of daratumumab/hyaluronidase, consider discontinuing the administration of corticosteroids (excluding any background regimen-specific corticosteroid). For patients with a history of COPD, consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids. Following the first four doses of daratumumab/hyaluronidase, consider discontinuing these additional postmedications if the patient does not experience a major systemic administration-related reaction.
Start antiviral prophylaxis to prevent herpes zoster reactivation within 1 wk after starting daratumumab/hyaluronidase and continue for 3 mo following end of treatment.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Advise patient to notify health care professional immediately if signs/symptoms of hypersensitivity, infection, infusion-related reactions, anaphylaxis, cardiac adverse reactions, neutropenia, bleeding, bruising, or fever occur. Seek immediate medical attention if necessary.
Advise patients to notify health care professional if they have ever had or might have a hepatitis B infection. May cause reactivation of hepatitis B virus.
Advise patient to inform health care professionals of medication regimen, including personnel at blood transfusion centers.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during therapy and for 3 mo after last dose and to avoid breastfeeding during therapy. Advise patient to notify health care professional if pregnancy is planned or suspected. Defer administering live vaccines to neonates and infants exposed to daratumumab in utero until a hematology evaluation is completed.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇