dar-a-TOOM-ue-mab/hye-al-yoor-ON-i-dase

Therapeutic Classification: antineoplastics

Pharmacologic Classification: monoclonal antibodies

• 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).
• 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.
• 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 light chain amyloidosis (in combination with bortezomib, cyclophosphamide, and dexamethasone).

• 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 subcutaneous tissue.

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

Absorption: 69% absorbed following subcutaneous administration.

Distribution: Monoclonal antibodies cross the placenta.

Metabolism/Excretion: Unknown.

Half-life: 20 days.

(blood levels)

Contraindicated in:

• Severe hypersensitivity
• OB: May cause fetal harm
• 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.

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

Derm: pruritus, rash.

Endo: hyperglycemia.

F and E: hypocalcemia.

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

Hemat: NEUTROPENIA, anemia, leukopenia, lymphocytopenia, thrombocytopenia.

Local: injection site reactions.

Metab: ↓appetite.

MS: muscle spasms, arthralgia.

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

Resp: cough, dyspnea, pulmonary edema.

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

Drug-Drug:

• None reported.

Multiple Myeloma — Monotherapy and Combination Therapy with Lenalidomide and Dexamethasone

• SC (Adults): Daratumumab 1,800 mg/hyaluronidase 30,000 units once weekly starting at Week 1 through Week 8 (total of 8 doses), then daratumumab 1,800 mg/hyaluronidase 30,000 units every 2 wk starting at Week 9 until Week 24 (total of 8 doses), then daratumumab 1,800 mg/hyaluronidase 30,000 units every 4 wk starting at Week 25 and onward; continue until disease progression.

Multiple Myeloma — Combination Therapy with Bortezomib, Melphalan, and Prednisone

• SC (Adults): Daratumumab 1,800 mg/hyaluronidase 30,000 units once weekly starting at Week 1 through Week 6 (total of 6 doses), then daratumumab 1,800 mg/hyaluronidase 30,000 units every 3 wk starting at Week 7 until Week 54 (total of 16 doses), then daratumumab 1,800 mg/hyaluronidase 30,000 units every 4 wk starting at Week 55 and onward; continue until disease progression.

Multiple Myeloma — Combination Therapy with Bortezomib, Thalidomide, and Dexamethasone

• SC (Adults): Induction therapy — Daratumumab 1,800 mg/hyaluronidase 30,000 units once weekly starting at Week 1 through Week 8 (total of 8 doses), then daratumumab 1,800 mg/hyaluronidase 30,000 units every 2 wk starting at Week 9 until Week 16 (total of 4 doses), then stop for high-dose chemotherapy and autologous stem cell transplant; Consolidation therapy — Daratumumab 1,800 mg/hyaluronidase 30,000 units every 2 wk starting at Week 1 upon reinitiation of treatment following autologous stem cell transplant and continued until Week 8 (total of 4 doses).

Multiple Myeloma — Combination Therapy with Bortezomib and Dexamethasone

• SC (Adults): Daratumumab 1,800 mg/hyaluronidase 30,000 units once weekly starting at Week 1 through Week 9 (total of 9 doses), then daratumumab 1,800 mg/hyaluronidase 30,000 units every 3 wk starting at Week 10 until Week 24 (total of 5 doses), then daratumumab 1,800 mg/hyaluronidase 30,000 units every 4 wk starting at Week 25 and onward; continue until disease progression.

Light Chain Amyloidosis — Combination Therapy with Bortezomib, Cyclophosphamide, and Dexamethasone

• SC (Adults): Daratumumab 1,800 mg/hyaluronidase 30,000 units once weekly starting at Week 1 through Week 8 (total of 8 doses), then daratumumab 1,800 mg/hyaluronidase 30,000 units every 2 wk starting at Week 9 until Week 24 (total of 8 doses), then daratumumab 1,800 mg/hyaluronidase 30,000 units every 4 wk starting at Week 25 and onward; continue until disease progression or a maximum of 2 yr.

• Solution for injection: daratumumab 120 mg and hyaluronidase 2,000 units/mL;

• Monitor for signs and symptoms of hypersensitivity 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 (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.
• Monitor for local reactions (itching, swelling, bruising, pain, rash, bleeding, or redness of the skin); may happen >24 hr after injection. Consider symptomatic management.
• Monitor patients with cardiac involvement of light chain (AL) 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.

• 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 daratumumab/hyaluronidase. May cause a positive Indirect Antiglobulin Test (Indirect Coombs test); may persist for up to 6 mos after last dose. Determination of a patient’s ABO and Rh blood type are not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received daratumumab/hyaluronidase.

• Administer medications before and after administration to minimize administration-related reactions.
• Premedication: Administer acetaminophen 650–1,000 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 reducing dose of methylprednisolone to 60 mg following second dose of daratumumab/hyaluronidase.
  • In Combination: Administer dexamethasone 20 mg (or equivalent) PO or IV prior to every daratumumab/hyaluronidase administration. When dexamethasone is the background regimen-specific corticosteroid, the dexamethasone dose that is part of the background regimen will serve as pre-medication on daratumumab/hyaluronidase administration days. Do not administer background regimen-specific corticosteroids (e.g. prednisone) on daratumumab/hyaluronidase administration days when patients have received dexamethasone as a pre-medication.
• SC: Remove vial from refrigerator and allow to come 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. Administer immediately. Attach injection needle or subcut infusion set to syringe immediately prior to injection. Compatible with polypropylene or polyethylene syringe material; polypropylene, polyethylene, or polyvinyl chloride (PVC) subcut 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. Administer subcut in the abdomen over 3–5 min. If a dose is missed, administer as soon as possible and adjust dosing schedule to maintain dosing interval. Do not administer IV. Solution is stable for 4 hr at room temperature; discard if unused in 4 hr.
• Post-medication: 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 the 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 3 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 4 doses of daratumumab/hyaluronidase, consider discontinuing these additional post-medications, 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 months following end of treatment.

• Explain purpose of daratumumab/hyaluronidase to patient. Instruct patient to read the Patient Information sheet prior to therapy.
• Advise patient to notify health care professional immediately if signs and symptoms of infusion reactions (itchy, runny, or blocked nose; chills, nausea, throat irritation, cough, headache, shortness of breath, difficulty breathing), bleeding, bruising, or fever occur.
• Advise patients to notify health care professional if they have ever had or might have a hepatitis B infection. Daratumumab/hyaluronidase may cause reactivation of hepatitis B virus.
• 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 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 and for 3 months after last dose and to avoid breastfeeding during therapy. Advise patient to notify health care professional if pregnancy is suspected.

• Decreased progression of multiple myeloma.

Darzalex Faspro