Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.
daratumumab (subcut)
Daratumumab is an IgG1Ƙ human monoclonal antibody (mAb) that targets CD38 on the surface of cells in a variety of hematological malignancies. Based on in vitro studies, by binding to CD38, daratumumab induces immune mediated tumour cell death or apoptosis through Fc mediated cross-linking. The subcutaneous formulation contains recombinant human hyaluronidase (rHuPH20) to increase dispersion and absorption.
| Bioavailability | 69% (multiple myeloma patients) |
| T max | 70-72 h |
| Time to reach steady state | Approximately by the 21st infusion (in monotherapy dosing schedule) |
Daratumumab is primarily localized to the vascular system with limited extravascular tissue distribution.
Likely metabolized via degradation into small peptides and amino acids via catabolic pathways
Cleared by parallel linear and nonlinear (saturable) target-mediated clearances.
| Half-life | 20 days (multiple myeloma patients) |
- Multiple myeloma
- AL amyloidosis
Refer to the product monograph for a full list and details of approved indications.
Emetogenic Potential:
The following table lists adverse effects that occurred in > 5% of patients in a Phase 3 non-inferiority study comparing daratumumab (subcut) 1800 mg with daratumumab (IV) 16 mg/kg. It also includes severe or life-threatening adverse effects from other sources and post-marketing.
The incidences below were mostly reported for daratumumab IV. Adverse events associated with the subcutaneous formulation are denoted with “^”.
| ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
|---|---|---|---|---|---|
| Cardiovascular | Atrial fibrillation (1%) | E | |||
| Cardiotoxicity (<1%) | E | ||||
| Hypertension (9%) (may be severe) | I E | ||||
| Tachycardia (1%) | E | ||||
| Gastrointestinal | Abdominal pain (6%) | E | |||
| Constipation (8%) | E | ||||
| Diarrhea (11%) | E | ||||
| Nausea, vomiting (11%) | I E | ||||
| General | Edema - limbs (6%) | E | |||
| Fatigue (16%) | E | ||||
| Hematological | ↓ Immunoglobulins (2%) | E | |||
| Myelosuppression ± infection, bleeding (23%) (including anemia) (14% severe) | E D | ||||
| Hepatobiliary | ↑ LFTs (<5%) (may be severe) | E D | |||
| Pancreatitis (1%) | E D | ||||
| Hypersensitivity | Administration-related reactions (systemic) (13%) (2% severe) ^ | I E | |||
| Anaphylaxis (rare) | I | ||||
| Immune | Antibody response (anti-daratumumab antibodies - <1%; anti-rHuPH20 antibodies - 7%) ^ | D | |||
| Injection site | Injection site reaction (7%) ^ | I E | |||
| Metabolic / Endocrine | Abnormal electrolyte(s) (6%) | E | |||
| Musculoskeletal | Musculoskeletal pain (12%) | E | |||
| Nervous System | Headache (9%) | E | |||
| Insomnia (5%) | E | ||||
| Ophthalmic | Blurred vision (6%) | E | |||
| Renal | Renal failure (<2%) | E D | |||
| Respiratory | Cough, dyspnea (14%) | E | |||
| Rhinitis (5%) | E | ||||
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.
** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)
The most common side effects for daratumumab (subcut) include myelosuppression ± infection, bleeding, fatigue, cough/dyspnea, administration-related reactions, musculoskeletal pain, diarrhea, and nausea/vomiting.
Daratumumab (subcut) may cause severe administration-related reaction (ARRs), including anaphylactic reactions. During clinical trials, most reactions occurred after the first injection and were mild to moderate. The majority of reactions occurred on the day of treatment (median was 3 hours). Delayed reactions have occurred in < 1% of patients.
Serious cardiac adverse reactions (16%), including fatal events (10%), have occurred in patients with AL amyloidosis who received daratumumab (subcut) in combination with bortezomib, cyclophosphamide, and dexamethasone. Patients with NYHA Class IIIA or Mayo Stage IIIA disease may be at an increased risk for serious cardiac disorders.
Neutropenia, febrile neutropenia, and thrombocytopenia have been associated with daratumumab (subcut). Higher rates of neutropenia and thrombocytopenia, including Grade 3-4 events, were observed in lower body weight patients. Daratumumab (subcut) may worsen myelosuppression when used in combination with other chemotherapy agents.
Infections may be severe in patients treated with daratumumab (subcut). Opportunistic infections (e.g. cytomegalovirus) and herpes zoster virus reactivation, including fatal outcomes, were also reported. Hepatitis B reactivation has been observed post-marketing.
Refer to protocol by which patient is being treated.
HBV screening should be performed in all patients prior to starting daratumumab.
Consider antiviral prophylaxis for herpes zoster reactivation.
Daratumumab can interfere with cross-matching for blood transfusions; type and screen and RBC genotyping tests should be done before starting this drug.
Pre-medications for daratumumab (subcut) monotherapy (prophylaxis for administration-related reactions (ARRs)):
To be given at least 1 hour prior to each dose:
- Corticosteroid IV/PO (e.g., methylprednisolone 100 mg or equivalent)*,†
- Oral antipyretic (e.g., acetaminophen 650-1000 mg)
- H1-receptor antagonist IV/PO (e.g., diphenhydramine 25-50 mg or equivalent)
- Montelukast 10 mg PO‡
*This dose may be reduced after the 2nd injection (e.g., methylprednisolone 60 mg IV or equivalent).
†For combination therapy, dexamethasone 20 mg IV/PO (or equivalent) is recommended. Refer to the respective regimen monographs.
‡Montelukast 10 mg was optional on Cycle 1 Day 1 during clinical trials of daratumumab (subcut). The addition of montelukast given prior to the first daratumumab IV infusion numerically reduced the incidence of respiratory IRs in the study by Nooka et al.
Post-injection medications for daratumumab (subcut) monotherapy (prevention of delayed ARRs):
- Oral corticosteroid (e.g., methylprednisolone 20 mg or equivalent) for 2 days post-injection§,¶
- Consider bronchodilators (e.g., short and long acting) and inhaled corticosteroids (for patients with a history of COPD)||,#
§These may be discontinued after the 3rd injection if no major systemic ARRs occurred.
¶For combination therapy, consider low-dose oral methylprednisolone (≤ 20 mg) or equivalent for 1 day post-injection.
||For combination therapy, consider adding an H1-receptor antagonist if the patient is at higher risk of respiratory complications.
#These may be discontinued after the 4th injection if no major ARRs occurred.
For pre/post injection medications used in daratumumab combination regimens, see the respective regimen monographs.
Daratumumab IV and subcutaneous formulations are not interchangeable. The dosing and administration of these products are different.
Monotherapy:
Subcutaneous: 1800 mg as per the following schedule:
| Week | Schedule |
|---|---|
| 1 - 8 | Weekly (8 doses) |
| 9 - 24 | Every 2 weeks (8 doses) |
| 25+ | Every 4 weeks |
Combination therapy:
Various schedules are used depending on the regimen. Refer to the product monograph or related regimen monographs for details.
Dose Levels: No dose reductions of daratumumab (subcut) are recommended. Dose delays may be required.
| Toxicity | Grade/Severity | Action |
|---|---|---|
| Neutropenia | Grade 4 | Hold until < Grade 2. Consider use of colony-stimulating factors (e.g., G-CSF). |
| Thrombocytopenia | Grade 3 or 4 | Hold until < Grade 2. |
| Hepatitis B virus (HBV) reactivation | Hold daratumumab, concomitant steroids and chemotherapy. Consult with an HBV expert and manage appropriately. Restart of daratumumab treatment in patients whose HBV reactivation is adequately controlled should be discussed with physicians with expertise in managing HBV. |
Management of Administration-Related Reactions (ARRs):
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
| Grade | Management | Re-challenge |
| 1 or 2 |
Restart:
|
|
3 |
Restart:
|
|
| 4 |
|
|
| Hepatic Impairment | Daratumumab (Subcut) Dose |
| Mild (total bilirubin 1 to 1.5 times ULN or AST > ULN) | No dose adjustment necessary. |
| Moderate (total bilirubin >1.5 to 3 times ULN and any AST) | Limited data. |
| Severe (total bilirubin >3 times ULN and any AST) |
No dosage adjustment is necessary for patients with renal impairment.
No dose adjustment is required in patients ≥ 65 years of age. No overall differences in efficacy were observed but patients ≥ 65 years were more likely to experience serious adverse events (e.g., pneumonia) than those < 65 years.
Gender had no clinically significant effect on PK parameter in patients with multiple myeloma.
Based on PK analyses, no clinically significant differences were seen between white and non-white patients.
The safety and efficacy of daratumumab (subcut) have not been established in children < 18 years of age.
Daratumumab IV and subcutaneous formulations are not interchangeable. The dosing and administration of these products are different.
- Daratumumab (subcut) does not require reconstitution or dilution.
- Compatible with polypropylene or polyethylene syringe material, polypropylene, polyethylene, or polyvinyl chloride (PVC) subcutaneous infusion sets, and stainless steel transfer and injection needles.
- Administer by subcutaneous injection, over approximately 3-5 minutes.
- Inject into the abdominal wall only (approximately 7.5 cm to the right or left of the navel). Do not give in areas where the skin is red, bruised, tender, hard or where there are scars.
- If pain occurs during injection, pause or slow rate of injection. If pain is not improved, the remaining dose may be given at an alternate injection site (on the opposite side of the abdomen).
- If there are other subcutaneous medications, they should be given at separate sites.
- Do not shake vials.
- Store vials at 2-8°C. Bring vials to room temperature (15-30°C) before use. Keep out of direct sunlight.
- Patients who have a hypersensitivity to this drug or any of its components
Other Warnings/Precautions:
- Daratumumab can cause severe administration-related reactions (ARRs), including anaphylaxis. It should only be administered by healthcare professionals with appropriate medical support to manage these reactions. Pre- and post-injection medications should be administered. Refer to Dosing section.
- Daratumumab (subcut) is not recommended for use in patients with AL amyloidosis with advanced cardiac disease.
Other Drug Properties:
- Carcinogenicity: Unknown
Pregnancy and Lactation:
- Crosses placental barrier: Likely
Daratumumab (subcut) has not been studied in pregnant women. IgG1 monoclonal antibodies are known to transfer across the placenta.
- Fetotoxicity: Likely
Based on its mechanism of action, daratumumab may cause fetal myeloid or lymphoid-cell depletion and decreased bone density. If exposure to daratumumab occurred in utero, live vaccines should not be administered to the infant until a hematology evaluation has been completed.
Daratumumab (subcut) should not be used in pregnancy. Adequate contraception should be used by both sexes during treatment, and for at least 3 months after the last dose.
- Breastfeeding: Not recommended
It is not known whether daratumumab is excreted into breastmilk. Human IgG is excreted in breast milk.
- Fertility effects: Unknown
Daratumumab interferes with the indirect antiglobulin (Coombs) test by binding to CD38 on RBCs. Daratumumab-mediated positive Coombs test may persist for up to 6 months after treatment completion. Patient's blood should be typed and screened prior to initiating treatment. Notify blood transfusion centres of this in the event of a planned transfusion and educate patients.
Daratumumab may interfere with the serum protein electrophoreses (SPE) and immunofixation (IFE) assays used to monitor M-protein. This can impact the monitoring of response and disease progression in some patients with IgG kappa myeloma protein.
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
| Monitor Type | Monitor Frequency |
|---|---|
CBC | Baseline and before each dose |
Blood | Type and screen prior to initiation. In the event of a planned transfusion, notify blood transfusion centres. |
Electrolytes, renal function tests | Baseline and as clinically indicated |
Liver function tests | Baseline and as clinically indicated |
Immunoglobulin levels | Baseline and as clinically indicated |
HBV serology | Baseline for all patients and as clinically indicated. For patients with evidence of HBV serology at baseline, monitor during treatment and for at least 6 months post treatment. Consult with an expert in HBV. |
Clinical toxicity assessment for systemic administration-related reactions, injection-site reactions, hypersensitivity, infection, bleeding, anemia, cardiac, and GI effects | Baseline and at each visit (more frequent cardiac monitoring in patients with AL amyloidosis) |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
New Drug Funding Program (NDFP Website )
- Daratumumab in Combination with a Bortezomib-Based Regimen for Newly Diagnosed Transplant Ineligible Multiple Myeloma
- Daratumumab in Combination with Lenalidomide and Dexamethasone for Newly Diagnosed Transplant Ineligible Multiple Myeloma
- Daratumumab - In Combination with Bortezomib and Dexamethasone for Relapsed Multiple Myeloma
- Daratumumab - In Combination with Lenalidomide and Dexamethasone for Relapsed Multiple Myeloma
- Daratumumab and Bortezomib in combo with Cyclophosphamide and Dexamethasone - Previously Untreated Light Chain (AL) Amyloidosis
Daratumumab drug monograph. Cancer Care Ontario.
Mateos MV, Nahi H, Legiec W, et al. Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial. Lancet Haematol. 2020 May;7(5):e370-e380.
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Antiemesis. Version 2.2022, March 23, 2022.
Nooka AK, Gleason C, Sargeant MO, et al. Managing Infusion Reactions to New Monoclonal Antibodies in Multiple Myeloma: Daratumumab and Elotuzumab. J Oncol Pract. 2018 Jul;14(7):414-22.
Prescribing information: Darzalex Faspro®. Janssen Pharmaceutical Companies. April 2022.
Product Monograph. Darzalex® SC (daratumumab). Janssen Inc. June 22, 2022.
September 2022 Updated pregnancy section; added NDFP forms
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.