EMPLICITI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EMPLICITI (EMPLICITI).
Elotuzumab is a humanized monoclonal antibody that targets the SLAMF7 (signaling lymphocytic activation molecule F7) receptor expressed on myeloma cells and natural killer (NK) cells. It enhances NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) via direct activation of NK cells through SLAMF7 and CD16 engagement, and also directly activates NK cells to induce killing of myeloma cells.
| Metabolism | Elotuzumab is a monoclonal antibody; metabolism involves catabolism via proteolytic degradation into small peptides and amino acids. No specific CYP450 enzyme involvement. |
| Excretion | Empliciti (elotuzumab) is a monoclonal antibody; elimination occurs via intracellular catabolism, yielding amino acids. Renal excretion of intact drug is negligible (<1%). Biliary/fecal excretion is minimal; no specific data on percentage. |
| Half-life | Terminal elimination half-life is approximately 26-29 days. This long half-life supports biweekly IV dosing after initial weekly schedule. |
| Protein binding | Elotuzumab is a monoclonal antibody; protein binding is not clinically meaningful. Typically, monoclonal antibodies have negligible binding to plasma proteins other than target antigen. |
| Volume of Distribution | Volume of distribution is approximately 5-7 L (or ~0.07 L/kg for a 70 kg patient), indicating distribution primarily in the vascular space. |
| Bioavailability | Empliciti is administered intravenously, thus bioavailability is 100% by IV route. No other routes are approved. |
| Onset of Action | Onset of action is observed after the first few weeks of treatment; objective response rates increase over time. Time to first response in clinical trials was around 4-6 weeks. |
| Duration of Action | Duration of action is prolonged due to long half-life. Pharmacodynamic effects (e.g., NK cell activation) persist for weeks after last dose. Clinical responses, if achieved, are maintained with continued dosing. |
10 mg/kg IV weekly for first 8 weeks, then every 2 weeks thereafter; administer with lenalidomide and dexamethasone.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or dialysis. |
| Liver impairment | No formal studies in hepatic impairment. Use caution in patients with moderate to severe hepatic impairment (Child-Pugh B or C) as exposure may be increased. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment required; monitor for toxicity due to age-related comorbidities and potential decreased organ function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EMPLICITI (EMPLICITI).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. Human IgG is excreted in breast milk but not systemically absorbed in significant amounts. M/P ratio unknown. Consider developmental and health benefits of breastfeeding along with maternal need for therapy and potential adverse effects on infant (B-cell depletion). |
| Teratogenic Risk | Pregnancy Category N (not classified). Empliciti (elotuzumab) is a monoclonal antibody. IgG molecules cross the placenta, with increasing transfer in the second and third trimesters. Based on its mechanism of action (SLAMF7-directed immunostimulatory), there is potential for fetal harm including B-cell depletion and immune alterations. No adequate human data; animal studies have not been conducted. Avoid use during pregnancy unless benefit outweighs risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["History of severe hypersensitivity reactions to elotuzumab or any of its excipients"]
| Precautions | ["Infusion reactions: Premedicate with acetaminophen, H1 and H2 blockers, and corticosteroids; monitor during infusion; may require interruption or discontinuation","Infections: Increased risk, especially with lymphopenia; monitor for signs and manage promptly","Second primary malignancies: Observed in clinical trials; consider risk","Hepatotoxicity: Elevations in liver enzymes; monitor hepatic function","Interference with serum protein electrophoresis and immunofixation assays: Elotuzumab may produce a band that interferes with detection of M-protein; monitor using alternative methods"] |
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| Fetal Monitoring | Monitor for infusion reactions (premedicate with antihistamines, acetaminophen, corticosteroids). Assess blood counts (neutropenia, thrombocytopenia). Monitor for infections. During pregnancy, consider fetal ultrasound for growth and development if exposure occurs. No specific maternal-fetal monitoring guidelines. |
| Fertility Effects | No human data on effects on fertility. Animal studies not conducted. Based on mechanism, potential for immunosuppression; no direct evidence of impaired fertility. |