Brand names: Darzalex, Darzalex Faspro
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Jul 10, 2025. Written by ASHP.

Introduction

Daratumumab: antineoplastic agent; a recombinant humanized anti-CD38 monoclonal antibody.

Hyaluronidase: an endoglycosidase.

Uses for Daratumumab

Multiple Myeloma

Used IV (as daratumumab [Darzalex]) and subcutaneously (as daratumumab/hyaluronidase-fihj [Darzalex Faspro]) in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma in newly diagnosed adults who are ineligible for autologous stem cell transplant and in adults with relapsed or refractory multiple myeloma who have received at least 1 prior therapy[ (daratumumab [Darzalex] designated an orphan drug by FDA for this use).

Used IV (as daratumumab [Darzalex]) and subcutaneously (as daratumumab/hyaluronidase-fihj [Darzalex Faspro]) in combination with bortezomib, melphalan, and prednisone for the treatment of multiple myeloma in newly diagnosed adults who are ineligible for autologous stem cell transplant (daratumumab [Darzalex] designated an orphan drug by FDA for this use).

Used IV (as daratumumab [Darzalex]) and subcutaneously (as daratumumab/hyaluronidase-fihj [Darzalex Faspro]) in combination with bortezomib, thalidomide, and dexamethasone for the treatment of multiple myeloma in newly diagnosed adults who are eligible for autologous stem cell transplant (daratumumab [Darzalex] designated an orphan drug by FDA for this use).

Used IV (as daratumumab [Darzalex]) and subcutaneously (as daratumumab/hyaluronidase-fihj [Darzalex Faspro]) in combination with bortezomib and dexamethasone for the treatment of multiple myeloma in adults who received at least 1 prior therapy (daratumumab [Darzalex] designated an orphan drug by FDA for this use).

Used IV (as daratumumab [Darzalex]) and subcutaneously (as daratumumab/hyaluronidase-fihj [Darzalex Faspro]) in combination with carfilzomib and dexamethasone for the treatment of relapsed or refractory multiple myeloma in adults who received 1–3 prior lines of therapy (daratumumab [Darzalex] designated an orphan drug by FDA for this use).

Used IV (as daratumumab [Darzalex]) and subcutaneously (as daratumumab/hyaluronidase-fihj [Darzalex Faspro]) in combination with pomalidomide and dexamethasone for the treatment of multiple myeloma in adults who have received at least 1 prior line of therapy (daratumumab/hyaluronidase-fihj) or 2 prior therapies (daratumumab) including lenalidomide and a proteasome inhibitor (daratumumab [Darzalex] designated an orphan drug by FDA for this use).

Used IV (as daratumumab [Darzalex]) and subcutaneously (as daratumumab/hyaluronidase-fihj [Darzalex Faspro]) as monotherapy for the treatment of multiple myeloma in adults who have received ≥3 prior therapies, including a proteasome inhibitor and an immunomodulatory agent, or in those double refractory to a proteasome inhibitor and an immunomodulatory agent (daratumumab [Darzalex] designated an orphan drug by FDA for this use).

Used subcutaneously (as daratumumab/hyaluronidase-fihj [Darzalex Faspro]) in combination with bortezomib, lenalidomide, and dexamethasone for the treatment of multiple myeloma for induction and consolidation in newly diagnosed adults who are eligible for autologous stem cell transplant.

The American Society of Clinical Oncology (ASCO) and Cancer Care Ontario (CCO) guidelines state that, for relapsed or refractory multiple myeloma, triplet therapies (e.g., bortezomib, lenalidomide, and dexamethasone) should be considered; daratumumab plus bortezomib, melphalan, and prednisone may also be considered. Choice of therapy should be based on patient, disease, and treatment factors, including prior therapies. Additional indications in multiple myeloma added to daratumumab labeling after publication of this guideline. Daratumumab/hyaluronidase-fihj was also approved after guideline publication.

Updated information on treatment of multiple myeloma is also available from the National Cancer Institute (NCI). For patients in good or well-controlled health, triplet or quadruplet induction chemotherapy that includes bortezomib may be used in the absence of a clinical trial. Patients responding to therapy after 4–8 months may then receive autologous stem cell transplant consolidation. Maintenance therapy is then given until disease relapse.[r39] For patients who are less fit who have significant comorbidities or advanced age, induction chemotherapy with a triplet or quadruplet regimen may be received; for better tolerability, a doublet regimen that includes either daratumumab or isatuximab may also be received. Therapy is continued until maximal response, and maintenance therapy is then given until disease relapse. Options for maintenance therapy include lenalidomide, ixazomib, and daratumumab alone or in combination, as well as bortezomib. For patients who relapse after therapy, new combinations of drugs or single agents may be given sequentially as required.

Amyloidosis

Used subcutaneously (as daratumumab/hyaluronidase-fihj [Darzalex Faspro]) in combination with bortezomib, cyclophosphamide, and dexamethasone for the treatment of light chain amyloidosis in newly diagnosed adults (designated an orphan drug by FDA for this use).

Accelerated approval based on response rate. Continued approval may be contingent on verification and description of clinical benefit in confirmatory studies.

Not indicated and not recommended for treatment of light chain amyloidosis in patients with New York Heart Association (NYHA) Class IIIB or Class IV cardiac disease or Mayo Stage IIIB outside of controlled clinical trials.

International experts suggest that treatment of amyloidosis follow clinical presentation and that all patients be considered for clinical trials where available. Choice of therapy should be based on degree of organ involvement, performance status, age, and bone marrow findings. For untreated patients who are ineligible for high dose therapy, daratumumab, in combination with bortezomib, cyclophosphamide, and dexamethasone, is recommended. Routine maintenance and consolidation not currently recommended. For relapsed disease, general treatment approach is to use a class of agents not previously used with consideration of limitations due to the fitness and frailty of the patient and any end organ damage.

Daratumumab Dosage and Administration

General

Pretreatment Screening

• Perform blood typing and screening in patients prior to starting therapy due to interference with serological testing.

• Verification of pregnancy status in females of reproductive potential may be required, depending on concomitant therapies used (consult the manufacturer’s labeling for more information).

Patient Monitoring

• Monitor for infusion-related reactions frequently during the entire infusion period for IV daratumumab.

• Monitor for local reactions and systemic administration-related reactions, particularly following the first and second injections, with subcutaneous daratumumab/hyaluronidase-fihj.

• Monitor CBC periodically during therapy.

• Monitor for signs and symptoms of infection in patients with neutropenia.

• Monitor for cardiac adverse reactions more frequently in patients with cardiac involvement of light chain amyloidosis receiving daratumumab/hyaluronidase-fihj.

Premedication and Prophylaxis

• Start antiviral prophylaxis within 1 week of beginning treatment to prevent herpes zoster reactivation and continue until 3 months after completing treatment.

• Administer the following medications 1–3 hours before daratumumab infusion or daratumumab/hyaluronidase-fihj subcutaneous injection: corticosteroids (long or intermediate-acting), acetaminophen, and diphenhydramine. Specific premedication regimens vary depending on concomitant therapies; consult the manufacturer’s labeling for more detailed information on dosing and recommended agents for premedication.

• Administer corticosteroids (long or intermediate-acting) after daratumumab infusion or daratumumab/hyaluronidase-fihj subcutaneous injection; specific recommendations vary depending on the daratumumab formulation and concomitant therapies. Consult the manufacturer’s labeling for more detailed information.

• For patients with a history of chronic obstructive pulmonary disease (COPD), consider prescribing short- and long-acting bronchodilators along with inhaled corticosteroids as post-infusion medication. After the first 4 doses of daratumumab or daratumumab/hyaluronidase-fihj, consider discontinuation of these additional post-infusion medications if the patient does not experience a major infusion-related reaction.

Dispensing and Administration Precautions

• Based on the Institute for Safe Medication Practices (ISMP), daratumumab is a high-alert medication that has a heightened risk of causing significant patient harm when used in error.

• To prevent medication errors, check the vial labels to ensure that the appropriate drug product (i.e., Darzalex for IV infusion or Darzalex Faspro for subcutaneous injection) is being prepared and administered.

Other General Considerations

• Administer daratumumab IV infusion in a healthcare setting with immediate access to emergency equipment and appropriate medical support to address any infusion-related reactions if they arise.

• Daratumumab/hyaluronidase-fihj should be administered by a healthcare provider.

Administration

Administer by IV infusion (daratumumab; Darzalex) or sub-Q injection (daratumumab/hyaluronidase-fihj; Darzalex Faspro).

IV Administration

Administer daratumumab (Darzalex) by IV infusion.

Administer diluted daratumumab solution using polyurethane, polybutadiene, PVC, polypropylene, or polyethylene administration set fitted with flow regulator and a low-protein-binding 0.2- or 0.22-μm inline polyethersulfone filter.

Do not administer any other drug simultaneously in the same IV line.

If a dose is missed or delayed, administer the dose as soon as possible. Adjust administration schedule to maintain appropriate dosage interval.

May combine daratumumab vials of the same strength but with different NDCs in the same infusion bag. Discard any unused portion of injection concentrate or diluted solution; vials of daratumumab injection concentrate contain no preservative and are intended for single use only.

Dilution

Must be diluted prior to IV infusion.

Dilute in PVC, polypropylene, polyethylene, or polyolefin blend bags.

To prepare first dose (16 mg/kg): Remove volume of diluent equal to total required volume of injection concentrate from a 1-L bag of 0.9% sodium chloride injection. Slowly add total required volume of injection concentrate to diluent in the infusion bag. Mix the diluted solution by gentle inversion; do not shake.

Alternatively, may split first dose into two 8 mg/kg doses (administered on 2 consecutive days); for each 8 mg/kg dose, remove volume of diluent equal to total required volume of injection concentrate from a 500-mL bag of 0.9% sodium chloride injection. Slowly add total required volume of injection concentrate to diluent in the infusion bag and mix by gentle inversion.

To prepare subsequent doses (16 mg/kg), if no infusion reactions observed with first dose: Remove volume of diluent equal to total required volume of injection concentrate from a 500-mL bag of 0.9% sodium chloride injection. Slowly add total required volume of injection concentrate to diluent in the infusion bag. Mix the diluted solution by gentle inversion; do not shake.

Rate of Administration

Administer daratumumab IV at infusion rates specified in Table 1. Consider increasing infusion rate gradually after the first hour if no infusion-related reactions occur.

Sub-Q Administration

Administer daratumumab/hyaluronidase-fihj (Darzalex Faspro) by sub-Q injection. Do not administer IV.

Remove vial from refrigeration and allow to reach room temperature (15–30°C) before use. Withdraw 15 mL from vial into a polypropylene or polyethylene syringe using a stainless steel transfer needle. Replace transfer needle with syringe close cap and label syringe appropriately to include administration route per institutional standards. To avoid needle clogging, attach hypodermic stainless steel injection needle or sub-Q infusion set to the syringe immediately prior to injection.

Administer using polypropylene, polyethylene, or PVC subcutaneous infusion sets.

Do not administer other sub-Q medications at the same injection site. Administer immediately after preparation. Inject sub-Q into the abdominal tissue approximately 3 inches (7.5 cm) to the left or right of the navel, rotating injection sites with each dose. Avoid injecting into red, bruised, tender, hardened, or scarred areas.

Administer over 3–5 minutes. If pain occurs, pause or slow the injection rate; if pain is not alleviated by pausing or slowing down the delivery rate, may choose a second injection site on the opposite side of the abdomen to deliver the remainder of the dose.

If a dose is missed or delayed, administer the dose as soon as possible. Adjust administration schedule to maintain appropriate dosage interval.

Dosage

Adults

Multiple Myeloma

IV (Daratumumab)

Combination with Lenalidomide and Dexamethasone:16 mg/kg (actual body weight) once a week for 8 weeks (weeks 1–8), followed by every 2 weeks for 16 weeks (weeks 9–24), then every 4 weeks thereafter (from week 25 onward).

Continue therapy until disease progression.

Combination with Bortezomib, Melphalan, and Prednisone: 16 mg/kg (actual body weight) once a week for 6 weeks (weeks 1–6), followed by every 3 weeks for 48 weeks (weeks 7–54), then every 4 weeks thereafter (from week 55 onward).

Continue therapy until disease progression.

Combination with Bortezomib, Thalidomide, and Dexamethasone: 16 mg/kg (actual body weight). For induction, the dose is given once a week for 8 weeks (weeks 1–8), followed by every 2 weeks for 8 weeks (weeks 9–16).

Pause dosing schedule for high-dose chemotherapy and autologous stem cell transplant.

For consolidation, the dose is given every 2 weeks for 4 total doses (weeks 1–8).

Combination with Bortezomib and Dexamethasone: 16 mg/kg (actual body weight) once a week for 9 weeks (weeks 1–9), followed by every 3 weeks for 15 weeks (weeks 10–24), then every 4 weeks thereafter (from week 25 onward).

Continue therapy until disease progression.

Combination with Carfilzomib and Dexamethasone: 8 mg/kg (actual body weight) for 2 doses in week 1 (days 1 and 2), followed by 16 mg/kg once a week for 7 weeks (weeks 2–8), then 16 mg/kg every 2 weeks for 8 doses (weeks 9–24), then 16 mg/kg every 4 weeks thereafter (from week 25 onward).

Continue therapy until disease progression.

Combination with Pomalidomide and Dexamethasone: 16 mg/kg (actual body weight) once a week for 8 weeks (weeks 1–8), followed by every 2 weeks for 16 weeks (weeks 9–24), then every 4 weeks thereafter (from week 25 onward).

Continue therapy until disease progression.

Monotherapy: 16 mg/kg (actual body weight) once a week for 8 weeks (weeks 1–8), followed by every 2 weeks for 16 weeks (weeks 9–24), then every 4 weeks thereafter (from week 25 onward).

Continue therapy until disease progression.

Sub-Q (Daratumumab/hyaluronidase-fihj)

Combination with Lenalidomide and Dexamethasone: 1800 mg/30,000 units administered once a week for 8 weeks (weeks 1–8), followed by every 2 weeks for 16 weeks (weeks 9–24), then every 4 weeks thereafter (from week 25 onward).

Continue therapy until disease progression.

Combination with Bortezomib, Melphalan, and Prednisone: 1800 mg/30,000 units administered once a week for 6 weeks (weeks 1–6), followed by every 3 weeks for 48 weeks (weeks 7–54), then every 4 weeks thereafter (from week 55 onward).

Continue therapy until disease progression.

Combination with Bortezomib, Thalidomide, and Dexamethasone: 1800 mg/30,000 units administered once a week for 8 weeks (weeks 1–8), followed by every 2 weeks for 8 weeks (weeks 9–16) in the induction phase.

Pause dosing schedule for high-dose chemotherapy and autologous stem cell transplant.

1800 mg/30,000 units administered sub-Q every 2 weeks for 4 total doses (weeks 1–8) during the consolidation phase.

Combination with Bortezomib and Dexamethasone: 1800 mg/30,000 units administered once a week for 9 weeks (weeks 1–9), followed by every 3 weeks for 15 weeks (weeks 10–24), then every 4 weeks thereafter (from week 25 onward).

Continue therapy until disease progression.

Combination with Carfilzomib and Dexamethasone:1800 mg/30,000 units administered once a week for 8 weeks (weeks 1–8), followed by every 2 weeks for 16 weeks (weeks 9–24), then every 4 weeks thereafter (from week 25 onward).

Continue therapy until disease progression.

Combination with Pomalidomide and Dexamethasone: 1800 mg/30,000 units administered once a week for 8 weeks (weeks 1–8), followed by every 2 weeks for 16 weeks (weeks 9–24), then every 4 weeks thereafter (from week 25 onward).

Continue therapy until disease progression.

Monotherapy:1800 mg/30,000 units administered once a week for 8 weeks (weeks 1-8), followed by every 2 weeks for 16 weeks (weeks 9-24), then every 4 weeks thereafter (from week 25 onward).

Continue therapy until disease progression.

Combination with Bortezomib. Lenalidomide and Dexamethasone: 1800 mg/30,000 units administered sub-Q once a week for 8 weeks (weeks 1–8), followed by every 2 weeks for 8 weeks (weeks 9–16) for the induction phase.

Pause dosing schedule for high-dose chemotherapy and autologous stem cell transplant.

1800 mg/30,000 units administered sub-Q every 2 weeks for 4 total doses (weeks 1–8) during the consolidation phase.

Light Chain Amyloidosis

Sub-Q (Daratumumab/hyaluronidase-fihj)

1800 mg/30,000 units administered sub-Q once a week for 8 weeks (weeks 1–8), followed by every 2 weeks for 16 weeks (weeks 9–24), then every 4 weeks thereafter (from week 25 onward).

Continue therapy until disease progression or for maximum of 2 years.

Therapy Interruption for Toxicity

Infusion-Related Reactions (daratumumab): Interrupt infusion and reduce the infusion rate or permanently discontinue therapy depending on the severity of the reaction.

Grade 4 Reaction: Permanently discontinue therapy.

Grade 3 Reaction: First or second occurrence: Interrupt infusion. Once the reaction improves to grade 2 or less, resume infusion at a rate reduced by at least 50%. If no further reactions occur, increase infusion rate in increments and intervals appropriate for the treatment dose. Third occurrence: Permanently discontinue treatment.

Grade 1 or 2 Reaction: Interrupt infusion. Once the reaction resolves, resume infusion at a rate reduced by at least 50%. If no further reactions occur, increase infusion rate in increments and intervals appropriate for the treatment dose, up to a maximum of 200 mL/hour.

Systemic Administration-Related Reactions (daratumumab/hyaluronidase-fihj): For anaphylactic or life-threatening (Grade 4) reactions, discontinue treatment immediately. Post-administration corticosteroids may reduce risk of delayed reactions.

Myelosuppression: No dosage reductions recommended; consider withholding treatment to allow recovery of blood cell counts.

Ocular Symptoms (daratumumab): If ocular symptoms occur (e.g., acute myopia, ciliochoroidal effusions), interrupt infusion immediately and seek ophthalmologic evaluation before resuming treatment.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Patients

No specific dosage recommendations at this time.

Cautions for Daratumumab

Contraindications

• Serious hypersensitivity to daratumumab or any component of the product formulation.

Warnings/Precautions

Infusion-related Reactions

Infusion-related reactions (sometimes serious) reported with IV daratumumab. Generally more frequent during the first infusion than during subsequent infusions. Such reactions generally occurred with a median onset time of 1.5 hours; delayed reactions also occurred up to 48 hours after infusion without post-infusion medications.

Serious infusion-related reactions including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions (e.g., acute myopia, ciliochoroidal effusions) reported. Signs or symptoms of such reactions may include respiratory effects as well as chills, nausea, and vomiting. Hypotension, pruritus, wheezing, allergic rhinitis, pyrexia, chest discomfort, and blurred vision have occurred less frequently.

Administer an antihistamine, antipyretic, and corticosteroid prior to each daratumumab infusion to prevent infusion-related reactions; administer an oral corticosteroid following each infusion to reduce the risk of delayed reactions. Patients with a history of chronic obstructive pulmonary disorders may require short- and long-acting inhaled bronchodilators and/or inhaled corticosteroids following the infusion.

Monitor patients frequently during infusions for manifestations of infusion- related reactions.

Reduce infusion rate, temporarily interrupt the infusion, or permanently discontinue the infusion depending on severity of reaction; institute medical management as necessary. If life-threatening infusion-related reactions occur, permanently discontinue therapy.

If ocular symptoms arise, interrupt the infusion immediately and seek an ophthalmologic evaluation before resuming treatment.

Hypersensitivity and Other Administration Reactions

Systemic and local administration-related reactions (sometimes serious) reported with daratumumab/hyaluronidase-fihj. Median onset time was 2.9 hours, with most reactions occurring on the day of administration.

Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular issues like choroidal effusion, acute myopia, and acute angle closure glaucoma. Other symptoms included respiratory symptoms, anaphylaxis, fever, chest pain, chills, pruritus, nausea, hypotension, and blurred vision. Most common local reaction was injection site erythema, typically appearing within 5 minutes.

Prior to administration of daratumumab/hyaluronidase-fihj, premedicate patients with a histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Consider administering corticosteroids and other medications after daratumumab/hyaluronidase-fihj depending on the dosing regimen and medical history to minimize the risk of delayed systemic administration-related reactions.

Monitor patients for local and systemic reactions, and consider symptomatic management as needed. Immediately and permanently discontinue daratumumab/hyaluronidase-fihj in patients who experience anaphylactic or life-threatening (grade 4) administration-related reactions. If ocular symptoms arise, interrupt treatment immediately and seek an ophthalmologic evaluation before resuming treatment.

Interference with Serologic Testing

Positive indirect antiglobulin (Indirect Coombs') test results reported following administration of daratumumab; daratumumab-mediated positive indirect antiglobulin test results may persist for up to 6 months following last infusion. Detection of antibodies to minor antigens may be masked during therapy; determination of ABO and Rh blood type not affected.

Perform blood typing and screening prior to initiation of therapy. If blood transfusion is required, notify blood centers of serologic test interference and inform them of treatment with a daratumumab-containing product. If blood typing and screening occur after initiation of therapy, use genotyping or dithiothreitol (DTT) to treat reagent RBCs to disrupt daratumumab binding.

Administer K-negative units to patients after ruling out or identifying alloantibodies using DTT-treated RBCs. If immediate transfusion is required, can administer non- cross-matched ABO/RhD blood type-compatible RBCs according to local blood center practices.

Neutropenia

Daratumumab-containing products may exacerbate neutropenia caused by background therapy.

Monitor CBC periodically during treatment, according to prescribing guidelines for background therapies. Observe for signs of infection. May temporarily withhold treatment until neutrophil levels recover.

Thrombocytopenia

Daratumumab-containing products may worsen thrombocytopenia caused by background therapy.

Monitor CBC periodically during treatment, according to prescribing guidelines for background therapies. May temporarily withhold treatment until platelet levels recover.

Interference with Serum Protein Electrophoresis and Immunofixation Electrophoresis Assays

Daratumumab may interfere with serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE) assays used for clinical monitoring of myeloma (M) protein.

Daratumumab may cause false-positive SPE and IFE assay results, impacting assessment of complete response or disease progression in some patients. Use an FDA-approved daratumumab-specific IFE assay to differentiate daratumumab from any residual endogenous M protein in the patient’s serum.

Fetal/Neonatal Morbidity and Mortality

Based on its mechanism of action, may cause fetal harm. Daratumumab may cause fetal immune cell depletion and reduced bone density if administered during pregnancy. Inform pregnant women of potential fetal risk. Advise females of reproductive potential to use effective contraception during treatment and for 3 months following the last dose of daratumumab-containing products.

Combination therapy with daratumumab-containing products and lenalidomide, pomalidomide, or thalidomide contraindicated during pregnancy due to the risk of birth defects and fetal death. Refer to the prescribing information for lenalidomide, pomalidomide, or thalidomide for guidance on use during pregnancy.

Cardiac Toxicity in Patients with Light Chain Amyloidosis

Serious or fatal cardiac adverse reactions reported with daratumumab/hyaluronidase-fihj use in combination with bortezomib, cyclophosphamide, and dexamethasone for the treatment of light chain amyloidosis.

Monitor patients with cardiac involvement of light chain amyloidosis more frequently; provide supportive care as needed.

Immunogenicity

Anti-daratumumab antibodies, including neutralizing antibodies, observed in patients treated with daratumumab or daratumumab/hyaluronidase-fihj. Effect of these antibodies on the pharmacokinetics, pharmacodynamics, safety, and/or effectiveness of daratumumab-containing products unknown.

Antibodies against recombinant human hyaluronidase, including neutralizing antibodies, observed in patients treated with daratumumab/hyaluronidase-fihj; no clinically important effect of these antibodies on pharmacokinetics, pharmacodynamics, safety, or effectiveness of daratumumab/hyaluronidase-fihj identified.

Specific Populations

Pregnancy

No adequate and well-controlled studies in pregnant women, but daratumumab-containing products may cause fetal harm based on mechanism of action. Because human IgG crosses the placenta, adverse effects may occur in infants born to pregnant women treated with daratumumab-containing products. Avoid pregnancy during therapy. If used during pregnancy or if patient becomes pregnant during therapy, apprise patient of potential fetal hazard.

Combination therapy with daratumumab-containing products and lenalidomide, pomalidomide, or thalidomide also contraindicated during pregnancy. Consult the prescribing information for lenalidomide, pomalidomide, or thalidomide for guidance on use during pregnancy.

Possible fetal CD38 positive immune cell depletion and decreased bone density in infants born to pregnant women treated with daratumumab-containing products; avoid live vaccines in exposed infants until completion of hematologic evaluation.

Lactation

Not known whether daratumumab or hyaluronidase is distributed into milk; however, maternal IgG is distributed into milk. Effects of daratumumab and hyaluronidase on breast-fed infants or on human milk production unknown.

When daratumumab-containing products are used in combination with lenalidomide, pomalidomide, or thalidomide, advise women not to breast-feed during treatment. Refer to the prescribing information for lenalidomide, pomalidomide, or thalidomide for further information.

Females and Males of Reproductive Potential

May cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for 3 months following the last dose.

For patients receiving daratumumab-containing products in combination with lenalidomide, pomalidomide, or thalidomide, refer to the drug labeling of lenalidomide, pomalidomide, or thalidomide for pregnancy testing requirements before initiating treatment. Consult the prescribing information for lenalidomide, pomalidomide, or thalidomide for further contraception recommendations.

Pediatric Use

Safety and efficacy not established.

Safety and efficacy of daratumumab in combination with chemotherapy evaluated but not established in a single open-label trial (DELPHINUS) involving 34 pediatric patients (ages 2 to <17 years) with relapsed or refractory acute lymphoblastic leukemia or lymphoblastic lymphoma. No new safety concerns identified in these patients. Pharmacokinetic parameters observed were consistent with those previously reported in adults with multiple myeloma receiving the same weight-based dosage.

Geriatric Use

No overall differences in safety or efficacy relative to younger patients. No clinically meaningful differences in pharmacokinetics of daratumumab observed in geriatric patients compared to younger adult patients.

In clinical trials for multiple myeloma, serious and fatal adverse reactions (e.g., pneumonia, sepsis) were more common in patients ≥65 years of age compared with younger adult patients.

In clinical studies of daratumumab/hyaluronidase-fihj monotherapy for multiple myeloma, older patients experienced higher rates of upper respiratory tract infections, urinary tract infections, dizziness, cough, dyspnea, diarrhea, nausea, fatigue, and peripheral edema compared to younger adult patients.

In clinical studies of daratumumab/hyaluronidase-fihj administered in combination with pomalidomide and dexamethasone or lenalidomide and low-dose dexamethasone, patients ≥65 years of age had increased rates of fatigue, fever, peripheral edema, urinary tract infections, GI adverse effects, dyspnea, cough, and hyperglycemia compared to younger adult patients.

In transplant-eligible multiple myeloma patients who received daratumumab/hyaluronidase-fihj in combination with bortezomib, lenalidomide, and dexamethasone, older adults had higher rates of constipation, hemorrhoids, nausea, injection site erythema, bronchitis, nasopharyngitis, back pain, myalgia, extremity pain, dysgeusia, peripheral motor neuropathy, and insomnia.

Among patients treated with daratumumab/hyaluronidase-fihj for light chain amyloidosis, adverse reactions that were more frequent in patients ≥65 years of age included peripheral edema, asthenia, pneumonia, and hypotension.

Hepatic Impairment

Systemic exposure not substantially altered by mild or moderate hepatic impairment. Effect of severe hepatic impairment (total bilirubin >3 times ULN with any AST) on pharmacokinetics unknown.

Renal Impairment

Systemic exposure not substantially altered by renal impairment (Cl_Cr15–89 mL/minute).

Common Adverse Effects

Daratumumab infusion (incidence ≥20%): upper respiratory infection, neutropenia, infusion-related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia.

Daratumumab/hyaluronidase-fihj monotherapy (incidence ≥20%): upper respiratory tract infection.

Daratumumab/hyaluronidase-fihj in combination with bortezomib, lenalidomide, and dexamethasone (incidence ≥20%): peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash.

Daratumumab/hyaluronidase-fihj in combination with bortezomib, melphalan, and prednisone (incidence ≥20%): upper respiratory tract infection, constipation, nausea, fatigue, pyrexia, peripheral sensory neuropathy, diarrhea, cough, insomnia, vomiting, and back pain.

Daratumumab/hyaluronidase-fihj in combination with lenalidomide and dexamethasone (incidence ≥20%): fatigue, diarrhea, upper respiratory tract infection, muscle spasms, constipation, pyrexia, pneumonia, and dyspnea.

Daratumumab/hyaluronidase-fihj in combination with pomalidomide and dexamethasone (incidence ≥20%): fatigue, pneumonia, upper respiratory tract infection, and diarrhea.

Daratumumab/hyaluronidase-fihj in combination with carfilzomib and dexamethasone (incidence ≥20%): upper respiratory tract infection, fatigue, insomnia, hypertension, diarrhea, cough, dyspnea, headache, pyrexia, nausea, and peripheral edema.

Daratumumab/hyaluronidase-fihj monotherapy for light chain amyloidosis (incidence ≥20%): upper respiratory tract infection, diarrhea, peripheral edema, constipation, fatigue, peripheral sensory neuropathy, nausea, insomnia, dyspnea, and cough.

Common hematologic laboratory abnormalities (incidence ≥40%) associated with daratumumab/hyaluronidase-fihj: decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.

Drug Interactions

No formal drug interaction studies to date.

Daratumumab Pharmacokinetics

Absorption

Bioavailability

IV administration (daratumumab): AUC increases more than dose proportionally over dosage range of 1–24 mg/ kg for daratumumab monotherapy and 1–16 mg/kg as combination therapy. Split dosing of the first dose results in a different pharmacokinetic profile on the first day, but similar maximum concentrations and minimum concentrations following administration of the second split dose on day 2 of week 1. Steady-state concentrations achieved approximately 5 months following administration as monotherapy every 4 weeks.

Sub-Q administration (daratumumab/hyaluronidase-fihj): Absolute bioavailability is 69%. After sub-Q administration once weekly for 8 weeks, daratumumab peak concentration increased 4.8-fold, and AUC increased 5.4-fold. Maximum trough concentrations generally reached at the end of the weekly dosing period for both monotherapy and combination therapies. Peak concentrations occur around 3 days in multiple myeloma and 4 days in light chain amyloidosis.

Special Populations

Mild hepatic impairment (total bilirubin concentrations 1–1.5 times ULN or AST concentrations exceeding the ULN): no substantial differences in systemic exposure compared with patients with normal hepatic function.

Moderate hepatic impairment (total bilirubin 1.5–3 times ULN and any AST): no substantial differences in systemic exposure compared with patients with normal hepatic function for daratumumab infusion ; data not available for daratumumab/hyaluronidase-fihj.

Severe hepatic impairment (total bilirubin >3 times ULN with any AST): Data not available.

Renal impairment (Cl_Cr15–89 mL/minute): no substantial differences in systemic exposure compared to patients with normal renal function.

Age and sex do not substantially affect daratumumab pharmacokinetics.

Sub-Q administration: serum drug levels were increased in lighter patients (≤50 kg) and decreased in heavier patients (>85 kg). African-American and Asian patients had higher serum trough concentrations than white patients.

Distribution

Extent

Human IgG crosses the placenta and distributes into human milk. Not known whether daratumumab is distributed into human milk.

Elimination

Metabolism

Cleared by parallel linear and nonlinear saturable target-mediated clearance.

Half-life

IV administration: estimated terminal half-life is 18 days.

Sub-Q administration: estimated mean elimination half-life for linear clearance is 20 days in patients with multiple myeloma and 28 days in patients with light chain amyloidosis.

Stability

Storage

Parenteral

Injection for IV Administration (Darzalex)

Unopened vials: 2–8°C. Do not freeze or shake; protect from light.

Diluted solution: 2–8°C for up to 24 hours or room temperature (15–25°C) for up to 15 hours (including infusion time). Do not freeze; protect from light.

Injection for Sub-Q Administration (Darzalex Faspro)

Unopened vials: 2–8°C. Do not freeze or shake; protect from light.

Prepared syringe: 2–8°C for up to 24 hours or room temperature (15–25°C) for up to 12 hours under ambient light.

Actions

• Daratumumab is an IgG₁ kappa immunoglobulin produced in mammalian (Chinese hamster ovary) cells.

• Binds specifically to antigen CD38, a glycoprotein expressed on surface of normal and malignant hematopoietic stem cells, that triggers host immune responses resulting in cell lysis.

• Mechanism of cell lysis is thought to involve antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC).

• Hyaluronidase is an endoglycosidase that increases subcutaneous tissue permeability by depolymerizing hyaluronan. Effects are reversible, with subcutaneous tissue permeability returning to normal within 24–48 hours.

Advice to Patients

• Advise patients to read manufacturer's patient information.

• Inform patients receiving IV daratumumab of the risk of infusion-related reactions. Instruct patients to immediately report signs or symptoms of such reactions (e.g., fever, nasal itching, congestion, or rhinitis, chills, nausea, vomiting, throat irritation, cough, headache, breathing difficulty, shortness of breath, dizziness or lightheadedness, tachycardia, chest discomfort, wheezing, itching, and blurred vision).

• Advise patients receiving daratumumab/hyaluronidase-fihj to seek immediate medical attention for any of the following signs and symptoms of systemic administration-related reactions: nasal itching, congestion, or rhinitis, chills, nausea, throat irritation, cough, headache, shortness of breath or difficulty breathing, and blurred vision.

• Advise patients receiving daratumumab/hyaluronidase-fihj for light chain amyloidosis to immediately contact their clinician if they have signs or symptoms of cardiac adverse reactions.

• Advise patients about the possibility for serologic test interference in the event of a planned blood transfusion and of the need to inform clinicians, including blood center personnel, that they are receiving daratumumab.

• Advise patients that daratumumab may affect the results of some tests used to determine complete response to the drug and that additional tests may be needed to evaluate the response.

• Advise patients to contact their clinician if they have a fever.

• Advise patients to contact their clinician if they notice signs of bruising or bleeding.

• Advise patients to inform their clinician if they have ever had or might have a hepatitis B infection, as daratumumab could cause hepatitis B virus to become active again.

• Advise pregnant women of the risk of fetal harm, and instruct them to inform their clinician of any known or suspected pregnancy. Advise females of reproductive potential to use an effective method of contraception while receiving the drug and for at least 3 months after the last dose. Advise patients that use of lenalidomide, pomalidomide, or thalidomide has the potential to cause fetal harm and has specific requirements regarding contraception, pregnancy testing, blood and sperm donation, and transmission in sperm. Lenalidomide, pomalidomide, and thalidomide are only available through a REMS program.

• Advise patients with hereditary fructose intolerance of the risks related to sorbitol because IV daratumumab contains sorbitol.

• Advise women to inform their clinician if they plan to breast-feed.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.

• Advise patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Reload page with references included

Related/similar drugs

Biological Products Related to daratumumab

Find detailed information on biosimilars for this medication.

Frequently asked questions

• How long does Darzalex work?
• Can Darzalex cure Multiple Myeloma?
• Is Darzalex chemotherapy?
• How is Darzalex administered?

View more FAQ

Medical Disclaimer