SARCLISA
Clinical safety rating
cautionComprehensive clinical and safety monograph for SARCLISA (SARCLISA).
Comprehensive clinical and safety monograph for SARCLISA (SARCLISA).
Treatment of multiple myeloma in combination with pomalidomide and dexamethasone in adults who have received at least two prior therapies including lenalidomide and a proteasome inhibitorTreatment of multiple myeloma in combination with carfilzomib and dexamethasone in adults with relapsed or refractory multiple myeloma after 1-3 prior lines of therapy
Isatuximab is a monoclonal antibody that binds to CD38 on multiple myeloma cells, inducing apoptosis through antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC). It also inhibits CD38 enzymatic activity.
| Metabolism | Isatuximab is a monoclonal antibody, expected to be degraded into small peptides and amino acids via catabolic pathways. Not metabolized by CYP450 enzymes. |
| Excretion | Renal: ~25% unchanged; Biliary/fecal: minor, primarily metabolized via liver, with metabolites excreted in bile/feces. |
| Half-life | Terminal elimination half-life: 9-14 days (approx. 4 weeks to reach steady state in multiple dosing). |
| Protein binding | ~70% bound to plasma proteins (primarily albumin and beta-2 glycoprotein I/apoferritin). |
| Volume of Distribution | Vd: 0.09 L/kg (approx. 6 L), consistent with limited extravascular distribution. |
| Bioavailability | IV only; bioavailability 100% by IV route. Not administered orally. |
| Onset of Action | IV infusion: time to clinical response variable, typically 2-4 weeks for reduction in paraprotein levels. |
| Duration of Action | Prolonged due to long half-life; clinical effect persists for weeks after last dose. Continuous dosing until progression or toxicity. |
| Molecular Weight | 148000 |
10 mg/kg intravenously weekly for the first 8 weeks, then every 2 weeks thereafter until disease progression or unacceptable toxicity.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment (CrCl ≥15 mL/min). Not studied in end-stage renal disease (CrCl <15 mL/min) or dialysis; use caution. |
| Liver impairment | No dose adjustment recommended for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Safety and efficacy not established in pediatric patients. No recommended dose. |
| Geriatric use | No specific dose adjustment required. Consider comorbidities and renal function, but pharmacokinetics are similar to younger adults. |
| 1st trimester | Based on its mechanism of action and animal studies, there is potential for fetal harm. Isatuximab is an IgG antibody that can cross the placenta. Avoid use in first trimester unless benefit outweighs risk. |
| 2nd trimester | IgG antibodies cross the placenta increasingly after 20 weeks. Isatuximab may cause fetal harm due to potential effects on immune function. Use only if clearly needed. |
| 3rd trimester | IgG antibodies cross the placenta readily in third trimester. Isatuximab may cause fetal immunosuppression. Avoid use if possible; consider alternative therapy. |
Clinical note
Comprehensive clinical and safety monograph for SARCLISA (SARCLISA).
| Placental transfer | Isatuximab is an IgG monoclonal antibody. IgG antibodies cross the placenta by FcRn-mediated transport, with increasing transfer as pregnancy progresses. Transfer is minimal in first trimester but significant in second and third trimesters. |
| Breastfeeding | It is unknown if isatuximab is excreted in human milk. However, because many IgG antibodies are present in human milk, and the potential for adverse reactions in the nursing infant is unknown, breastfeeding should be discontinued during treatment and for at least 5 months after the last dose. |
| Lactation Rating | L5 (Contraindicated) – Potential for serious adverse effects in nursing infant; manufacturer recommends discontinuing breastfeeding. |
| Teratogenic Risk | First trimester: IgG1 monoclonal antibodies cross placenta minimally; limited human data, but based on mechanism (CD38 inhibition), potential fetal hematologic effects. Second/third trimesters: Increased placental transfer; risk of fetal cytopenias and immune suppression. |
| Fetal Monitoring | Monitor maternal complete blood counts (CBC) for cytopenias. Fetal monitoring via ultrasound for growth restriction and anemia if used in pregnancy. Neonatal monitoring for hematologic effects after delivery. |
| Fertility Effects | Animal studies show no impairment of male or female fertility. Human data limited; may cause ovarian suppression due to mechanism (CD38 on oocytes), but clinical significance unknown. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Severe hypersensitivity to isatuximab or any excipients
| Precautions | Infusion-related reactions (may require premedication and monitoring), Neutropenia (monitor complete blood counts), Thrombocytopenia, Second primary malignancies, Interference with blood cross-matching (due to CD38 binding), Embryofetal toxicity |
| Food/Dietary | No specific food interactions. Avoid grapefruit juice if taking concurrent CYP3A4 substrates (e.g., pomalidomide) due to potential interaction. Maintain adequate hydration. |
| Clinical Pearls | SARCLISA (isatuximab) is an anti-CD38 monoclonal antibody for multiple myeloma. Premedicate with acetaminophen, H1 and H2 antagonists, and corticosteroids before infusion to reduce infusion-related reactions. Administer pomalidomide and dexamethasone concurrently as per protocol. Monitor for neutropenia, infusion reactions, and second primary malignancies. Do not substitute for other anti-CD38 antibodies. |
| Patient Advice | Infusion reactions: symptoms like fever, chills, rash, or difficulty breathing may occur during or after infusion; seek immediate medical attention. · Blood cell counts: this drug can decrease white blood cells, red blood cells, and platelets; report signs of infection, anemia, or bleeding. · Fetal harm: effective contraception required during and for 5 months after treatment; do not breastfeed. · Vaccinations: avoid live vaccines during treatment. · Laboratory interference: isatuximab may interfere with blood compatibility testing; inform all healthcare providers of treatment. |
Loading safety data…