daratumumab

REMS

Multiple myeloma in patients whose disease has relapsed or is refractory despite receiving ≥1 prior therapy (in combination with lenalidomide and dexamethasone).
Multiple myeloma in patients who have received ≥1 prior therapy (in combination with bortezomib and dexamethasone).
Multiple myeloma in patients whose disease has relapsed or is refractory despite receiving 1–3 previous drug therapies (in combination daratumumab and dexamethasone).
Multiple myeloma in patients who received ≥2 lines of therapy including lenalidomide and a proteasome inhibitor (in combination with pomalidomide 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).

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Severe hypersensitivity;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Chronic obstructive pulmonary disease;
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, peripheral edema

EENT: nasal congestion

GI: ↓appetite, diarrhea, nausea, vomiting

Hemat: anemia, lymphopenia, neutropenia, thrombocytopenia

MS: arthralgia, muscle spasms, pain

Neuro: headache, peripheral neuropathy

Resp: cough, dyspnea

Misc: fatigue, fever, INFUSION REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

None known.

Availability ⬆ ⬇

Solution for injection: 20 mg/mL
In combination with: hyaluronidase (Darzalex Faspro). See Appendix [not included in this PDA edition].

Route/Dosage ⬆ ⬇

During Week 1 ONLY, the 16 mg/kg dose may administered in one dose or may be split into two doses (8 mg/kg) administered over 2 days (Days 1 and 2).

Combination Therapy with Bortezomib, Melphalan, and Prednisone

IV (Adults ): 16 mg/kg every wk starting at Week 1 through Week 6 (total of 6 doses), then 16 mg/kg every 3 wk starting at Week 7 until Week 54 (total of 16 doses), then 16 mg/kg every 4 wk starting at Week 55 and onward; continue until disease progression or unacceptable toxicity.

Monotherapy and Combination Therapy with Lenalidomide or Pomalidomide and Dexamethasone

IV (Adults ): 16 mg/kg every wk starting at Week 1 through Week 8 (total of 8 doses), then 16 mg/kg every 2 wk starting at Week 9 until Week 24 (total of 8 doses), then 16 mg/kg every 4 wk starting at Week 25 and onward; continue until disease progression or unacceptable toxicity.

Combination Therapy with Bortezomib and Dexamethasone

IV (Adults ): 16 mg/kg every wk starting at Week 1 through Week 9 (total of 9 doses), then 16 mg/kg every 3 wk starting at Week 10 until Week 24 (total of 5 doses), then 16 mg/kg every 4 wk starting at Week 25 and onward; continue until disease progression or unacceptable toxicity.

Combination Therapy with Bortezomib, Thalidomide, and Dexamethasone

IV (Adults ): Induction treatment: 16 mg/kg every wk starting at Week 1 through Week 8 (total of 8 doses), then 16 mg/kg 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 treatment (following autologous stem cell treatment): 16 mg/kg every 2 wk starting at Week 1 through Week 8 (total of 4 doses).

Combination Therapy with Carfilzomib and Dexamethasone

IV (Adults ): 8 mg/kg once daily for 2 days (Days 1 and 2 of Week 1), then 16 mg/kg every wk starting at Week 2 through Week 8 (total of 7 doses), then 16 mg/kg every 2 wk starting at Week 9 until Week 24 (total of 8 doses), then 16 mg/kg every 4 wk starting at Week 25 and onward; continue until disease progression or unacceptable toxicity.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Binds to CD38 on tumor cells causing apoptosis, thereby inhibiting growth of CD38-expressing tumor cells.

Therapeutic effects:

Improved survival and decreased progression of multiple myeloma.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: monoclonal antibodies

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Monoclonal antibodies cross the placenta.

Metabolism/Excretion: Unknown.

Half-Life: 18 days (as monotherapy); 23 days (when used as combination therapy).

Time/Action Profile ⬆ ⬇

(blood levels)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	end of infusion	unknown

Patient/Family Teaching ⬆ ⬇

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 patient to inform blood transfusion centers/personnel they are taking daratumumab in the event of a planned transfusion.
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.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 3 mo after completion of therapy and to avoid breastfeeding during therapy. Immunoglobulin G1 monoclonal antibodies are transferred across the placenta. May cause fetal myeloid or lymphoid-cell depletion and decreased bone density. Defer administering live vaccines to neonates and infants exposed to daratumumab in utero until a hematology evaluation is completed.

section name header

Indications ⬇