Daratumumab

Daratumumab is a prescription medicine used to treat the symptoms of bone marrow cancer (multiple myeloma).

• Daratumumab is available under the following different brand names: Darzalex

Adult dosage

Injectable solution, single-use vial

• 100mg/5mL (20mg/mL)
• 400mg/20mL (20mg/mL)
• Requires further dilution prior to administration

Multiple Myeloma

Adult dosage

Newly diagnosed multiple myeloma

Combination therapy with bortezomib, melphalan, and prednisone

• Weeks 1-6: 16 mg/kg IV infusion once weekly (total of 6 doses)  
• Weeks 7-54: 16 mg/kg IV infusion every 3 weeks (total of 16 doses); the first dose of the every-3-week dosing schedule is given at Week 7
• Week 55 onwards until disease progression: 16 mg/kg IV infusion every 4 weeks; the first dose of the every-4-week dosing schedule is given at Week 55

Combination therapy with lenalidomide and dexamethasone

• Weeks 1-8: 16 mg/kg IV infusion once weekly (total of 8 doses)  
• Weeks 9-24: 16 mg/kg IV infusion every 2 weeks (total of 8 doses); the first dose of every-2-week dosing schedule is given at Week 9
• Week 25 onwards until disease progression: 16 mg/kg IV infusion every 4 weeks; the first dose of every-4-week dosing schedule is given at Week 25

Combination therapy with bortezomib, thalidomide, and dexamethasone

• Induction phase (Weeks 1-8): 16 mg/kg IV infusion once weekly (total of 8 doses)  
• Induction phase (Weeks 9-16): 16 mg/kg IV infusion every 2 weeks (total of 4 doses); first dose of the every-2-week dosing schedule is given at Week 9
• Stop treatment for high-dose chemotherapy and ASCT
• Consolidation (Week 1-8): 16 mg/kg IV infusion every 2 weeks (total of 4 doses); first dose of the every-2-week dosing schedule is given at Week 1 upon re-initiation of treatment following ASCT

Relapsed/refractory multiple myeloma

Monotherapy

• Weeks 1-8: 16 mg/kg IV infusion once weekly (total of 8 doses)  
• Weeks 9-24: 16 mg/kg IV infusion every 2 weeks (total of 8 doses); the first dose of every-2-week dosing schedule is given at Week 9
• Week 25 onwards until disease progression: 16 mg/kg IV infusion every 4 weeks; the first dose of every-4-week dosing schedule is given at Week 25

Combination therapy with bortezomib and dexamethasone

• Weeks 1-9: 16 mg/kg IV infusion once weekly (total of 9 doses)  
• Weeks 10-24: 16 mg/kg IV infusion every 3 weeks (total of 5 doses); the first dose of the every-3-week dosing schedule is given at Week 10
• Week 25 onwards until disease progression: 16 mg/kg IV infusion every 4 weeks; the first dose of the every-4-week dosing schedule is given at Week 25

Combination therapy with lenalidomide and dexamethasone

• Weeks 1-8: 16 mg/kg IV infusion once weekly (total of 8 doses)  
• Weeks 9-24: 16 mg/kg IV infusion every 2 weeks (total of 8 doses); the first dose of every-2-week dosing schedule is given at Week 9
• Week 25 onwards until disease progression: 16 mg/kg IV infusion every 4 weeks; the first dose of every-4-week dosing schedule is given at Week 25

Combination therapy with pomalidomide and dexamethasone

• Weeks 1-8: 16 mg/kg IV infusion once weekly  
• Weeks 9-24: 16 mg/kg IV infusion every 2 weeks (total of 8 doses); the first dose of every-2-week dosing schedule is given at Week 9
• Week 25 onwards until disease progression: 16 mg/kg IV infusion every 4 weeks; the first dose of every-4-week dosing schedule is given at Week 25

Combination therapy with carfilzomib and dexamethasone

• Week 1: 8 mg/kg IV on Days 1 and 2 (total 2 doses)  
• Weeks 2-8: 16 mg/kg IV weekly (total of 7 doses)
• Weeks 9-24: 16 mg/kg IV every 2weeks (total of 8 doses)
• Week 25 and thereafter: 16 mg/kg IV every 4weeks; continue until disease progression or toxicity occurs

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Daratumumab include:

• nausea,
• infusion site reactions,
• constipation,
• diarrhea,
• fever,
• shortness of breath,
• nerve problems causing tingling, numbness, or pain,
• tiredness,
• weakness,
• swelling in the hands, ankles, or feet,
• stuffy nose,
• sneezing,
• sore throat
• back pain,
• upper respiratory tract infection,
• joint pain,
• muscle pain,
• loss of appetite,
• high blood pressure, and
• anemia.

Serious side effects of Daratumumab include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• dizziness,
• itchiness,
• nausea,
• headache,
• stuffy nose,
• runny nose,
• cough,
• fever,
• chills,
• wheezing,
• tight feeling in the throat,
• cough with yellow or green mucus,
• stabbing chest pain,
• wheezing,
• shortness of breath,
• numbness,
• tingling,
• burning pain,
• tiredness,
• mouth sores,
• skin sores,
• easy bruising,
• unusual bleeding,
• pale skin,
• cold hands and feet, and
• lightheadedness.

Rare side effects of Daratumumab include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Daratumumab has no noted severe interactions with any other drugs.
• Daratumumab has no noted serious interactions with any other drugs.
• Daratumumab has no noted moderate interactions with any other drugs.
• Daratumumab has no noted minor interactions with any other drugs. 

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Hypersensitivity to drug or components of the formulation

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Daratumumab?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Daratumumab?”

Cautions

• May increase neutropenia and/or thrombocytopenia induced by background therapy; monitor CBC counts periodically during treatment; monitor patients with neutropenia for signs of infection; dose delay may be required to allow recovery of neutrophils; no dose reduction is recommended, consider supportive care with growth factors and/or transfusions
• Binds to CD38 on RBCs and may result in a positive indirect antiglobulin test (Coombs test)
• May cause false-positive results with serum protein electrophoresis (SPE) and immunofixation (IFE) assays
• Hepatitis B virus reactivation was reported in clinical trials; including in fatal cases
• Severe infusion reactions
  • Severe and/or serious reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, and pulmonary edema
  • Nearly all reactions occurred during infusion or within 4 hours of completing an infusion
  • Before the introduction of post-infusion medication in clinical trials, infusion reactions occurred up to 48 hours after infusion
  • Signs and symptoms may include respiratory symptoms (eg, cough, wheezing, larynx, throat tightness, and irritation), laryngeal edema, pulmonary edema, nasal congestion, and allergic rhinitis
  • Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, were reported; if ocular symptoms occur, interrupt the infusion and seek immediate ophthalmologic evaluation before restarting therapy
  • Premedicate patients with antihistamines, antipyretics, and corticosteroids
  • Frequently monitor patients during the entire infusion
  • Patients with a history of chronic obstructive pulmonary disease (COPD) may require additional post-infusion medications to manage respiratory complications; consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with COPD

Pregnancy and Lactation

• There are no human data to inform a risk with the use of daratumumab during pregnancy and animal studies have not been conducted
• Immunoglobulin G1 (IgG1) monoclonal antibodies are transferred across the placenta
• Based on its mechanism of action, daratumumab may cause fetal myeloid or lymphoid-cell depletion and decreased bone density
• The combination of drug and lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women, because these drugs may cause birth defects and death of an unborn child; they are only available through a REMS program; refer to their respective prescribing information on use during pregnancy
• Defer administering live vaccines to neonates and infants exposed to daratumumab in utero until a hematology evaluation is completed
• Immunoglobulin G1 (IgG1) monoclonal antibodies are transferred across the placenta; based on the mechanism of action, the drug may cause depletion of fetal CD38 positive immune cells and decreased bone density
• Contraception
• Women of reproductive potential should use effective contraception during treatment and for 3 months after discontinuing treatment
• Lactation
  • Unknown if distributed in human breast milk
  • Human IgG is known to be present in human milk; published data suggest that antibodies in breast milk do not enter the neonatal and infant circulations in substantial amounts
  • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or the underlying maternal condition
  • Because of the potential for serious adverse reactions in a breastfed child when therapy is administered with lenalidomide, pomalidomide, or thalidomide, advise women not to breastfeed during treatment