EMPLICITI
Clinical safety rating
cautionComprehensive clinical and safety monograph for EMPLICITI (EMPLICITI).
Comprehensive clinical and safety monograph for EMPLICITI (EMPLICITI).
FDA-approved: In combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received one to three prior therapiesFDA-approved: In combination with pomalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor
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. |
| Molecular Weight | 149000 |
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 | Empliciti (elotuzumab) is a monoclonal antibody. IgG antibodies are known to cross the placenta increasingly as pregnancy progresses, with minimal transfer in the first trimester. No well-controlled studies in pregnant women. Based on mechanism, potential for fetal harm. Use only if clearly needed. |
| 2nd trimester | IgG antibodies cross the placenta more readily in the second trimester. Risk of fetal B-cell depletion and immune suppression. Avoid use unless maternal benefit outweighs potential risk. |
| 3rd trimester | IgG antibodies cross the placenta most actively in the third trimester, leading to significant fetal exposure. Risk of neonatal B-cell lymphopenia and immunosuppression. Avoid use near term. |
Clinical note
Comprehensive clinical and safety monograph for EMPLICITI (EMPLICITI).
| Placental transfer | IgG monoclonal antibody; placental transfer occurs, increasing through gestation. Fetal exposure in second and third trimester expected. |
| Breastfeeding | Unknown if distributed in human breast milk. Human IgG is present in breast milk but absorption by infant gastrointestinal tract may be limited. However, potential for serious adverse reactions in nursing infants. Discontinue breastfeeding or drug based on importance of drug to mother. |
| Lactation Rating | L3 (Moderately Safe) / Avoid |
| 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. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to elotuzumab or any 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 |
| Food/Dietary | No specific food interactions with Empliciti have been identified. However, when used in combination with lenalidomide and dexamethasone, patients should avoid grapefruit and grapefruit juice due to potential interaction with lenalidomide metabolism (CYP3A4). Maintain adequate hydration and nutrition as tolerated. |
| Clinical Pearls | Empliciti (elotuzumab) is an immunostimulatory monoclonal antibody used in combination with lenalidomide and dexamethasone for relapsed/refractory multiple myeloma. Premedicate with diphenhydramine, acetaminophen, and H2 blocker to mitigate infusion reactions (IRs). Monitor for IRs, notably hypotension, bronchospasm, and urticaria, especially during the first dose. Administer corticosteroids prior to empliciti infusion to reduce IR risk. Do not administer as an intravenous push or bolus; use a controlled intravenous infusion. If a dose is missed, administer as soon as possible; do not wait until the next scheduled dose. Empliciti carries a boxed warning for increased mortality when used with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma who are not candidates for transplant. Advise patients of potential teratogenicity with lenalidomide and dexamethasone; ensure pregnancy prevention. |
| Patient Advice | You will receive Empliciti as an intravenous infusion over several hours, and you will be monitored for infusion reactions such as chills, fever, difficulty breathing, or rash. · Before each infusion, you will receive medicines to reduce the risk of infusion reactions, including acetaminophen, an antihistamine, and a corticosteroid. · If you miss an appointment, contact your healthcare provider immediately to reschedule; do not wait until the next scheduled dose. · Empliciti may cause serious infections; report any signs of infection such as fever, cough, or pain. · Avoid pregnancy while on Empliciti combination therapy; use effective contraception and discuss appropriate methods with your doctor. · You may experience fatigue, diarrhea, constipation, or nerve pain; inform your doctor if these become bothersome. |
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