SARCLISA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SARCLISA (SARCLISA).
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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SARCLISA (SARCLISA).
| Breastfeeding | No data on human milk excretion; M/P ratio unknown. Human IgG enters breast milk, but degradation in infant GI tract likely limits absorption. Weigh benefits of breastfeeding against potential infant exposure. |
| 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 |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
None known.
| 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"] |
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| 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. |