Darzalex Faspro (daratumumab and hyaluronidase-fihj)

Darzalex Faspro may cause serious reactions, including:

• Serious allergic reactions and other severe injection-related reactions. Serious allergic reactions and reactions due to release of certain substances by your body (systemic) that can lead to death, can happen with Darzalex Faspro. Tell your healthcare provider or get medical help right away if you get any of these symptoms during or after an injection of Darzalex Faspro.
  • shortness of breath or trouble breathing
  • dizziness or lightheadedness (hypotension)
  • cough
  • wheezing
  • heart beating faster than usual
  • low oxygen in the blood (hypoxia)
  • throat tightness
  • runny or stuffy nose
  • headache
  • itching
  • high blood pressure
  • nausea
  • vomiting
  • chills
  • fever
  • chest pain
• Injection site reactions. Skin reactions at or near the injection site (local), including injection site reactions, can happen with Darzalex Faspro. Symptoms may include itching, swelling, bruising, or redness of the skin. These reactions sometimes happen more than 24 hours after an injection of Darzalex Faspro. These reactions sometimes happen more than 24 hours after an injection of Darzalex Faspro.
• Decreases in blood cell counts. Darzalex Faspro can decrease white blood cell counts which help fight infections and blood cells called platelets which help to clot blood. Your healthcare provider will check your blood cell counts during treatment with Darzalex Faspro. Tell your healthcare provider if you develop fever or have signs of bruising or bleeding.
• Changes in blood tests. Darzalex Faspro can affect the results of blood tests to match your blood type. These changes can last for up to 6 months after your final dose of Darzalex Faspro. Your healthcare provider will do blood tests to match your blood type before you start treatment with Darzalex Faspro. Tell all of your healthcareproviders that you are being treated with Darzalex Faspro before receiving blood transfusions.

The most common side effects of Darzalex Faspro when used alone include cold-like symptoms (upperrespiratory infection).

The most common side effects of Darzalex Faspro used in combination therapy include:

• tiredness
• nausea
• diarrhea
• shortness of breath
• trouble sleeping
• fever
• cough
• muscle spasms
• back pain
• vomiting
• cold-like symptoms (upper-respiratory infection)
• nerve damage causing tingling, numbness or pain
• constipation
• lung infection (pneumonia)

These are not all the possible side effects of Darzalex Faspro.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Important Dosing Information

• Darzalex Faspro is for subcutaneous use only.
• Administer medications before and after administration of Darzalex Faspro to minimize administration-related reactions [see the Recommended Concomitant Medications section below].
• Type and screen patients prior to starting Darzalex Faspro.

Recommended Dosage For Multiple Myeloma

The recommended dose of Darzalex Faspro is 1,800 mg/30,000 units (1,800 mg daratumumab and 30,000 units hyaluronidase) administered subcutaneously over approximately 3-5 minutes. Tables 1, 2, 3, and 4 provide the recommended dosing schedule when Darzalex Faspro is administered as monotherapy or as part of a combination therapy.

Monotherapy And In Combination With Lenalidomide And Dexamethasone (D-Rd)

Use the dosing schedule provided in Table 1 when Darzalex Faspro is administered:

• in combination with lenalidomide and dexamethasone (4-week cycle) OR
• as monotherapy.

Table 1: Darzalex Faspro dosing schedule in combination with lenalidomide and dexamethasone (4-week cycle) and for monotherapy

When Darzalex Faspro is administered as part of a combination therapy, see the prescribing information for dosage recommendations for the other drugs.

In Combination With Bortezomib, Melphalan And Prednisone (D-VMP)

Use the dosing schedule provided in Table 2 when Darzalex Faspro is administered in combination with bortezomib, melphalan and prednisone (6-week cycle).

Table 2: Darzalex Faspro dosing schedule in combination with bortezomib, melphalan and prednisone (6-week cycle)

When Darzalex Faspro is administered as part of a combination therapy, see the prescribing information for dosage recommendations for the other drugs.

In Combination With Bortezomib, Thalidomide, And Dexamethasone (D-VTd)

Use the dosing schedule in Table 3 when Darzalex Faspro is administered in combination with bortezomib, thalidomide, and dexamethasone (4-week cycle).

Table 3: Darzalex Faspro dosing schedule in combination with bortezomib, thalidomide and dexamethasone (4-week cycle)

When Darzalex Faspro is administered as part of a combination therapy, see the prescribing information for dosage recommendations for the other drugs.

In Combination With Bortezomib And Dexamethasone (D-Vd)

Use the dosing schedule in Table 4 when Darzalex Faspro is administered in combination with bortezomib and dexamethasone (3-week cycle).

Table 4: Darzalex Faspro dosing schedule in combination with bortezomib and dexamethasone (3week cycle)

When Darzalex Faspro is administered as part of a combination therapy, see the prescribing information for dosage recommendations for the other drugs.

Recommended Dosage For Light Chain Amyloidosis

In Combination With Bortezomib, Cyclophosphamide And Dexamethasone (D-VCd)

Use the dosing schedule provided in Table 5 when Darzalex Faspro is administered in combination with bortezomib, cyclophosphamide and dexamethasone (4-week cycle).

Table 5: Darzalex Faspro dosing schedule in combination with bortezomib, cyclophosphamide and dexamethasone (4-week cycle)

When Darzalex Faspro is administered as part of a combination therapy, see the prescribing information for dosage recommendations for the other drugs.

Administration

If a dose of Darzalex Faspro is missed, administer the dose as soon as possible and adjust the dosing schedule to maintain the dosing interval.

Recommended Concomitant Medications

Pre-Medication

Administer the following pre-medications 1-3 hours before each dose of Darzalex Faspro:

• Acetaminophen 650 to 1,000 mg orally
• Diphenhydramine 25 to 50 mg (or equivalent) orally or intravenously
• Corticosteroid (long- or intermediate-acting)

Monotherapy

Administer methylprednisolone 100 mg (or equivalent) orally or intravenously. Consider reducing the dose of methylprednisolone to 60 mg (or equivalent) following the second dose of Darzalex Faspro.

In Combination

Administer dexamethasone 20 mg (or equivalent) orally or intravenously prior to every Darzalex Faspro 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 Darzalex Faspro administration days.

Do not administer background regimen-specific corticosteroids (e.g. prednisone) on Darzalex Faspro administration days when patients have received dexamethasone (or equivalent) as a pre-medication.

Post-Medication

Administer the following post-medications:

Monotherapy

Administer methylprednisolone 20 mg (or an equivalent dose of an intermediate- or long-acting corticosteroid) orally for 2 days starting the day after the administration of Darzalex Faspro.

In Combination

Consider administering oral methylprednisolone at a dose of less than or equal to 20 mg (or an equivalent dose of an intermediate- or long-acting corticosteroid) beginning the day after administration of Darzalex Faspro.

If a background regimen-specific corticosteroid (e.g. dexamethasone, prednisone) is administered the day after the administration of Darzalex Faspro, additional corticosteroids may not be needed.

If the patient does not experience a major systemic administration-related reaction after the first 3 doses of Darzalex Faspro, consider discontinuing the administration of corticosteroids (excluding any background regimen-specific corticosteroid).

For patients with a history of chronic obstructive pulmonary disease, consider prescribing short and long-acting bronchodilators and inhaled corticosteroids. Following the first 4 doses of Darzalex Faspro, consider discontinuing these additional post-medications, if the patient does not experience a major systemic administration-related reaction.

Prophylaxis For Herpes Zoster Reactivation

Initiate antiviral prophylaxis to prevent herpes zoster reactivation within 1 week after starting Darzalex Faspro and continue for 3 months following the end of treatment.

Dosage Modifications For Adverse Reactions

No dose reductions of Darzalex Faspro are recommended. Consider withholding Darzalex Faspro to allow recovery of blood cell counts in the event of myelosuppression.

Effects Of Daratumumab On Laboratory Tests

Interference With Indirect Antiglobulin Tests (Indirect Coombs Test)

• Daratumumab binds to CD38 on RBCs and interferes with compatibility testing, including antibody screening and cross matching.
• Daratumumab interference mitigation methods include treating reagent RBCs with dithiothreitol (DTT) to disrupt daratumumab binding or genotyping.
• Since the Kell blood group system is also sensitive to DTT treatment, supply K-negative units after ruling out or identifying alloantibodies using DTT-treated RBCs.
• If an emergency transfusion is required, administer non-cross-matched ABO/RhD-compatible RBCs per local blood bank practices.

Interference With Serum Protein Electrophoresis And Immunofixation Tests

• Daratumumab may be detected on serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for monitoring disease monoclonal immunoglobulins (M protein).
• False positive SPE and IFE assay results may occur for patients with IgG kappa myeloma protein impacting initial assessment of complete responses by International Myeloma Working Group (IMWG) criteria.
• In Darzalex Faspro-treated patients with persistent very good partial response, where daratumumab interference is suspected, consider using a FDA-approved daratumumab-specific IFE assay to distinguish daratumumab from any remaining endogenous M protein in the patient’s serum, to facilitate determination of a complete response.

• Darzalex Faspro can cause fetal harm when administered to a pregnant woman.
• The assessment of associated risks with daratumumab products is based on the mechanism of action and data from target antigen CD38 knockout animal models.
• There are no available data on the use of Darzalex Faspro in pregnant women to evaluate drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.
• There is no data on the presence of daratumumab and hyaluronidase in human milk, the effects on the breastfed child, or the effects on milk production.
• Maternal immunoglobulin G 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 Darzalex Faspro is administered with lenalidomide or thalidomide and dexamethasone, advise women not to breastfeed during treatment with Darzalex Faspro.