daratumumab/hyaluronidase

General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation:
dar-a-toom-ue-mab/hye-al-yoor-on-i-dase

Trade Name(s)

Darzalex Faspro
Darzalex SC

Ther. Class.

antineoplastics

Pharm. Class.

monoclonal antibodies

Indications

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).
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 Effect(s):

Decreased progression of multiple myeloma.
Decreased progression of light chain amyloidosis.

Pharmacokinetics

Absorption: 69% absorbed following SUBQ administration.

Distribution: Monoclonal antibodies cross the placenta.

Metabolism and Excretion: Unknown.

Half-life: 20 days.

TIME/ACTION PROFILE (plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
SUBQ	unknown	3 days	unknown

Contraindication/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.

Adverse 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

Metabolic: ↓ 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

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

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.

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

Availability

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

Assessment

Monitor for signs and 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, immediately and permanently discontinue daratumumab/hyaluronidase. Consider administering corticosteroids and other medications after administration to minimize the risk of delayed (occurring the day after administration) reactions.
Assess and 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, stop therapy, 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 and 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 of infection (fever, chills, dyspnea, cough, urinary frequency). Consider holding therapy until recovery of neutrophils.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.

Monitor CBC and platelet count 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: 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. Replace needle with a syringe closing cap. Label syringe, including route of administration. Attach injection needle or SUBQ infusion set to syringe immediately prior to injection to avoid needle clogging. Compatible with polypropylene or polyethylene syringe material; polypropylene, polyethylene, or polyvinyl chloride; SUBQ infusion sets; and stainless steel transfer and injection needles. Solution is colorless to yellow and clear to opalescent; do not use solutions that are cloudy, discolored, or contain particulate matter. Inject 15 mL 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 4 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: 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 and symptoms of hypersensitivity, 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 females 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 suspected. Defer administering live vaccines to neonates and infants exposed to daratumumab in utero until a hematology evaluation is completed.

Evaluation/Desired Outcomes

Decreased progression of multiple myeloma.
Decreased progression of light chain amyloidosis.