DARZALEX FASPRO
Clinical safety rating
cautionComprehensive clinical and safety monograph for DARZALEX FASPRO (DARZALEX FASPRO).
Comprehensive clinical and safety monograph for DARZALEX FASPRO (DARZALEX FASPRO).
Multiple myeloma (in combination with other agents for newly diagnosed, relapsed, or refractory disease)Light chain (AL) amyloidosis (in combination with cyclophosphamide, bortezomib, and dexamethasone)
Daratumumab is a human IgG1κ monoclonal antibody that binds to CD38, a transmembrane glycoprotein highly expressed on the surface of multiple myeloma cells. It induces tumor cell death through multiple mechanisms, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and apoptosis via cross-linking. It also reduces the activity of CD38-positive immunosuppressive cells (e.g., regulatory T cells, B cells, and myeloid-derived suppressor cells).
| Metabolism | Daratumumab is a monoclonal antibody; it is eliminated via intracellular catabolism into small peptides and amino acids. No specific metabolic pathways or enzymes are involved. |
| Excretion | Daratumumab is eliminated primarily through intracellular catabolism and subsequent proteolytic degradation; renal excretion is minimal (<1% of dose as unchanged drug in urine), biliary/fecal excretion is negligible. |
| Half-life | Terminal elimination half-life is approximately 16 days (range 11–22 days) after subcutaneous administration of DARZALEX FASPRO, supporting once-monthly dosing due to prolonged target-mediated clearance. |
| Protein binding | Daratumumab is a monoclonal IgG1 antibody; total protein binding is primarily to serum immunoglobulins (IgG) with no specific carrier proteins; essentially 100% bound as a therapeutic antibody. |
| Volume of Distribution | Volume of distribution is approximately 5.0 L (range 4.0–6.5 L) corresponding to plasma volume (0.07 L/kg for a 70 kg patient), indicating limited extravascular distribution, consistent with monoclonal antibodies. |
| Bioavailability | Bioavailability after subcutaneous administration (DARZALEX FASPRO) is approximately 69% relative to intravenous daratumumab, based on co-formulation with recombinant human hyaluronidase. |
| Onset of Action | Time to clinical effect following subcutaneous administration: pharmacodynamic effects (complement-mediated cytotoxicity) begin within 24 hours; measurable reduction in serum M-protein typically observed within 2–4 weeks after initiation. |
| Duration of Action | Duration of action extends throughout the dosing interval (weekly to monthly); clinical efficacy maintained with continued receptor occupancy and M-protein suppression. After cessation, pharmacodynamic effects persist for several months due to slow elimination. |
| Molecular Weight | 148000 |
Daratumumab 1800 mg subcutaneously over 3-5 minutes once weekly for 8 weeks, then every 2 weeks for 8 doses, then every 4 weeks thereafter. Administered in combination with hyaluronidase (fixed dose 30,000 U).
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Data insufficient for severe renal impairment (CrCl <30 mL/min) or hemodialysis. |
| Liver impairment | No dose adjustment required for mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Data insufficient for severe (Child-Pugh C). |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended based on age alone. Monitor for adverse reactions such as infusion-related reactions and infections. |
| 1st trimester | Placental transfer occurs; IgG crosses the placenta after 13 weeks. Data limited due to lack of human studies; monoclonal antibodies may cause fetal immune suppression. Consider if benefit outweighs risk. |
| 2nd trimester | Same as t1; potential for B-cell depletion and immune suppression in fetus. Evaluate risk-benefit. |
| 3rd trimester | Highest transfer of IgG occurs in third trimester; may result in neonatal B-cell depletion and immune suppression. Avoid unless necessary. |
Clinical note
Comprehensive clinical and safety monograph for DARZALEX FASPRO (DARZALEX FASPRO).
| Placental transfer | Da: 148,000 Da. IgG antibodies cross the placenta with increasing transfer after 13 weeks gestation. Fetal exposure is expected, particularly in second and third trimesters. |
| Breastfeeding | Daratumumab is present in human milk; due to high molecular weight, oral absorption is likely low. However, effects on infant immune system are unknown. Consider risks versus benefits; use with caution during lactation. |
| Lactation Rating | L3: Limited Data |
| Teratogenic Risk | Daratumumab (DARZALEX FASPRO) is an IgG1 monoclonal antibody. IgG molecules are known to cross the placental barrier. Based on its mechanism of action (CD38-directed cytolytic activity), there is a potential for fetal B-cell depletion and immunosuppression. Animal studies are not available. Advise patients of potential fetal harm. Avoid use during pregnancy unless benefit outweighs risk. First trimester: minimal transfer; risk theoretical. Second and third trimesters: increased placental transfer; risk of fetal B-cell lymphopenia and immunosuppression. |
| Fetal Monitoring | Monitor for infusion-related reactions during administration. For pregnant patients, consider fetal monitoring (ultrasound) for signs of fetal B-cell depletion or immunosuppression. Monitor maternal blood counts for cytopenias. Assess for infections due to potential immunosuppression. |
| Fertility Effects | No human data on fertility effects. In animal studies, no specific fertility studies conducted. Mechanism of action (CD38 binding) may affect immune cells; however, no direct effect on reproductive organs is expected. Potential indirect effects from disease state (multiple myeloma) may impact fertility. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to daratumumab or any excipient
| Precautions | Infusion-related reactions (severe, including anaphylactic reactions) – premedicate and monitor during infusion; discontinue if severe reactions occur., Increased risk of infections (including opportunistic infections) – monitor for signs of infection and manage promptly., Neutropenia and thrombocytopenia – monitor blood counts regularly., Interference with blood transfusion compatibility testing (daratumumab binds to CD38 on red blood cells) – type and screen patients prior to treatment; notify blood bank about daratumumab use., Hepatitis B virus reactivation – screen for HBV prior to treatment; monitor during and after therapy., Embryo-fetal toxicity – can cause fetal harm; advise contraception in females of reproductive potential. |
| Food/Dietary | No clinically significant food interactions have been reported. Take as directed without regard to meals. |
| Clinical Pearls | Pre-medicate with antihistamines, antipyretics, and corticosteroids to mitigate infusion-related reactions. Do not interchange Daralex Faspro (daratumumab and hyaluronidase-fihj) with intravenous daratumumab due to different dosing and administration routes. Administer subcutaneous injection in the abdomen over 3-5 minutes. Monitor for delayed infusion reactions up to 24 hours post-injection. Assess hepatitis B status before initiation; reactivation can occur. Do not administer live vaccines concurrently. |
| Patient Advice | You will receive this medicine as an injection under your skin, usually in the belly area. The injection takes 3 to 5 minutes. · You may have reactions like fever, chills, headache, or nausea around the time of the injection; you will receive medicines to help prevent these. · Serious allergic reactions can occur; tell your healthcare provider immediately if you have difficulty breathing, chest tightness, or swelling of your face or throat. · You may have a higher risk of infections; report any signs of infection such as fever, cough, or sore throat. · Do not receive live vaccines (e.g., flu nasal spray, shingles vaccine) while on this treatment. · This medication can affect your blood counts; you will need regular blood tests. · Tell all healthcare providers you are taking Darzalex Faspro, as it may interfere with blood typing tests. |
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