Daratumumab-Hyaluronidase

Daratumumab-Hyaluronidase is a prescription medication used for the treatment of multiple myeloma and amyloidosis.

• Daratumumab-Hyaluronidase is available under the following different brand names: Darzalex Faspro,  Daratumumab-Hyaluronidase-fihj

Common side effects of  Daratumumab-Hyaluronidase include:

• constipation
• diarrhea
• vomiting
• nausea
• stomach pain
• loss of appetite
• fatigue
• difficulty falling asleep or staying asleep
• pain, burning, or tingling in the hands or feet
• swelling of the hands, ankles, or feet
• joint or back pain
• muscle spasms
• headache
• itching, swelling, bruising, or redness of the skin at the injection site

Serious side effects of  Daratumumab-Hyaluronidase include:

• hives
• difficult breathing
• swelling of your face, lips, tongue, or throat
• fever, cough, sore throat, or signs of infection
• unusual bruising or bleeding
• pale skin, fatigue, or shortness of breath
• yellow eyes or skin; dark urine; or pain or discomfort in the right upper stomach area
• chest pain, feeling faint, swollen legs, fast or irregular heartbeat, or shortness of breath (especially if you are being treated for amyloidosis)

Rare side effects of  Daratumumab-Hyaluronidase include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because 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.

Adult dosage

Injectable solution

• (1,800 mg/30,000 units)/15 mL
• Ready-to-use SC solution contains daratumumab and hyaluronidase human

Multiple myeloma

Adult dosage

• Newly diagnosed multiple myeloma
• Combination therapy with bortezomib, melphalan, and prednisone
  • Weeks 1-6: 1,800 mg/30,000 units SC once weekly (total of 6 doses)
  • Weeks 7-54: 1,800 mg/30,000 units SC every 3 weeks (total of 16 doses); the first dose of the every-3-week dosing schedule is given at week 7
  • Week 55 onward until disease progression: 1,800 mg/30,000 units SC every 4 weeks; the first dose of the every-4-week dosing schedule is given at week 55
  • See prescribing information for chemotherapy agents' doses administered in combination with  Daratumumab-Hyaluronidase
• Combination therapy with lenalidomide and dexamethasone
  • Weeks 1-8: 1,800 mg/30,000 units SC once weekly (total of 8 doses)
  • Weeks 9-24: 1,800 mg/30,000 units SC every 2 weeks (total of 8 doses); the first dose of the every-2-week dosing schedule is given at week 9.
  • Week 25 onwards until disease progression: 1,800 mg/30,000 units SC every 4 weeks; the first dose of every-4-week dosing schedule is given at week 25.
  • See prescribing information for chemotherapy agents’ doses administered in combination with  Daratumumab-Hyaluronidase
• Combination therapy with bortezomib, thalidomide, and dexamethasone
  • Induction weeks 1-8: 1,800 mg/30,000 units SC once weekly (total of 8 doses)
  • Induction weeks 9-16: 1,800 mg/30,000 units SC every 2 weeks (total of 4 doses); the first dose of the every-2-week dosing schedule is given at week 9
• Stop high-dose chemotherapy and ASCT
  • Consolidation weeks 1-8: 1,800 mg/30,000 units SC every 2 weeks (total of 4 doses)
  • See prescribing information for chemotherapy agents' doses administered in combination with  Daratumumab-Hyaluronidase

Relapsed or refractory multiple myeloma

• Monotherapy
  • Weeks 1-8: 1,800 mg/30,000 units SC once weekly (total of 8 doses)
  • Weeks 9-24: 1,800 mg/30,000 units SC every 2 weeks (total of 8 doses); the first dose of the every-2-week dosing schedule is given at week 9
  • Week 25 onward until disease progression: 1,800 mg/30,000 units SC 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: 1,800 mg/30,000 units SC once weekly (total of 8 doses)
  • Weeks 9-24: 1,800 mg/30,000 units SC every 2 weeks (total of 8 doses); the first dose of the every-2-week dosing schedule is given at week 9.
  • Week 25 onward until disease progression: 1,800 mg/30,000 units SC every 4 weeks; the first dose of every-4-week dosing schedule is given at week 25
  • See prescribing information for chemotherapy agents' doses administered in combination with  Daratumumab-Hyaluronidase
• Combination therapy with bortezomib and dexamethasone
  • Weeks 1-9: 1,800 mg/30,000 units SC once weekly (total of 9 doses)
  • Weeks 10-24: 1,800 mg/30,000 units SC every 3 weeks (total of 5 doses); the first dose of the every-3-week dosing schedule is given at week 10
  • Week 25 onward until disease progression: 1,800 mg/30,000 units SC every 4 weeks; the first dose of the every-4-week dosing schedule is given at week 25
  • See prescribing information for chemotherapy agents' doses administered in combination with  Daratumumab-Hyaluronidase
• Combination therapy with pomalidomide and dexamethasone
  • Weeks 1-8: 1,800 mg/30,000 units SC once weekly (total of 8 doses)
  • Weeks 9-24: 1,800 mg/30,000 units SC every 2 weeks (total of 8 doses); the first dose of the every-2-week dosing schedule is given at week 9.
  • Week 25 onwards until disease progression: 1,800 mg/30,000 units SC every 4 weeks; the first dose of every-4-week dosing schedule is given at week 25.
  • See prescribing information for chemotherapy agents' doses administered in combination with  Daratumumab-Hyaluronidase
• Combination therapy with carfilzomib and dexamethasone
  • Weeks 1-8: 1,800 mg/30,000 units SC once weekly (total of 8 doses)
  • Weeks 9-24: 1,800 mg/30,000 units SC every 2 weeks (total of 8 doses); the first dose of the every-2-week dosing schedule is given at week 9
  • Week 25 onward until disease progression: 1,800 mg/30,000 units SC every 4 weeks; the first dose of every-4-week dosing schedule is given at week 25
  • See prescribing information for chemotherapy agents' doses administered in combination with  Daratumumab-Hyaluronidase

Amyloidosis

Adult dosage

• Weeks 1-8: 1,800 mg/30,000 units SC once weekly (total of 8 doses)
• Weeks 9-24: 1,800 mg/30,000 units SC every 2 weeks (total of 8 doses); the first dose of the every-2-week dosing schedule is given at week 9
• Week 25 and thereafter: 1,800 mg/30,000 units SC every 4 weeks until disease progression or a maximum of 2 years

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

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, healthcare provider, or pharmacist first.

• Daratumumab-Hyaluronidase has severe interactions with no other drugs.
• Daratumumab-Hyaluronidase has serious interactions with the following drugs:
  • axicabtagene ciloleucel
  • beclomethasone, inhaled
  • brexucabtagene autoleucel
• Daratumumab-Hyaluronidase has moderate interactions with at least 52 other drugs.
• Daratumumab-Hyaluronidase has minor interactions with the following drugs:
  • bupivacaine
  • mepivacaine
  • prilocaine
  • ropivacaine

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 healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Severe hypersensitivity to daratumumab, hyaluronidase, or any other components

Effects of drug abuse

• None

Short-Term Effects

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

Long-Term Effects

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

Cautions

• May increase neutropenia and/or thrombocytopenia induced by background therapy; monitor CBC count periodically during treatment; consider withholding dose to allow recovery of neutrophils and/or thrombocytopenia
• Can cause fetal harm
• Cardiac reactions with light-chain (AL) amyloidosis
• Serious or fatal cardiac adverse reactions reported
• Patients with NYHA class IIIA or Mayo stage IIIA disease may be at greater risk
• Patients with NYHA class IIIB or IV disease were not studied
• Monitor patients with cardiac involvement more frequently for cardiac adverse reactions; administer supportive care as appropriate
• Hypersensitivity and other administration reactions
  • Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur
  • Severe reactions included hypoxia, dyspnea, hypertension, and tachycardia, and ocular adverse reactions included choroidal effusion, acute myopia, and acute angle-closure glaucoma; if ocular symptoms occur, interrupt therapy and seek immediate ophthalmologic evaluation before restarting treatment
  • Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision
  • Premedicate patients with histamine-1 receptor antagonists, acetaminophen, and corticosteroids
  • Monitor for local or systemic administration-related reactions, especially following the first or second injection
  • Permanently discontinue for life-threatening reactions
• Drug interaction overview
  • May cause false-positive results with serum protein electrophoresis and immunofixation assays
  • Interference with cross-matching and red blood cell antibody screening
  • Binds to CD38 on red blood cells and may result in a positive indirect antiglobulin test (Coombs test)
  • Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration
  • Determination of a patient’s ABO and Rh blood type are not affected
  • Type and screen patients before starting treatment
  • Inform blood banks that a patient has received daratumumab

Pregnancy and Lactation

• Based on the mechanism of action and animal data, fetal harm may occur when administered to pregnant women
• No data available on use in pregnant women to evaluate the drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes
• Animal reproduction studies not conducted
• Treated in combination with lenalidomide, thalidomide, or pomalidomide
• Lenalidomide may cause birth defects and death of the unborn child; therefore, coadministration with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women; refer to the lenalidomide, thalidomide, or pomalidomide, prescribing information on use during pregnancy and contraception
• Test women for reproductive potential before initiating treatment
• Contraception
  • Women of reproductive potential: Use effective contraception during treatment and for 3 months after the final dose
• Clinical considerations
  • IgG1 monoclonal antibodies are transferred across the placenta
• Lactation
  • No data are available on the presence of daratumumab and hyaluronidase in human breast milk, its effects on breastfeeding, or milk production
  • 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
  • Because of the potential for serious adverse reactions in the breastfed child when administered with lenalidomide, thalidomide, or pomalidomide, advise women not to breastfeed during treatment; refer to lenalidomide, thalidomide, or pomalidomide prescribing information for additional information
  • 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