This site is intended for US healthcare professionals only.
This site is intended for US healthcare professionals only.
Effective October 1, 2021
JazzCares is committed to helping your patients get access to their ZEPZELCA medication and providing personalized support throughout their treatment
ZEPZELCA® (lurbinectedin) is indicated for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Myelosuppression
ZEPZELCA can cause myelosuppression. In clinical studies of 554 patients
with advanced solid tumors receiving ZEPZELCA, Grade 3 or 4 neutropenia
occurred in 41% of patients, with a median time to onset of 15 days and a
median duration of 7 days. Febrile neutropenia occurred in 7% of patients.
Sepsis occurred in 2% of patients and was fatal in 1% (all cases occurred in patients with solid tumors other than SCLC). Grade 3 or 4 thrombocytopenia occurred in 10%, with a median time to onset of 10 days and a median duration of 7 days. Grade 3 or 4 anemia occurred in 17% of patients.
Administer ZEPZELCA only to patients with baseline neutrophil count of at least 1,500 cells/mm3 and platelet count of at least 100,000/mm3.
Monitor blood counts including neutrophil count and platelet count prior to each administration. For neutrophil count less than 500 cells/mm3 or any value less than lower limit of normal, the use of G-CSF is recommended. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity.
Hepatotoxicity
ZEPZELCA can cause hepatotoxicity. In clinical studies of 554 patients with
advanced solid tumors receiving ZEPZELCA, Grade 3 elevations of ALT and AST
were observed in 6% and 3% of patients, respectively, and Grade 4 elevations
of ALT and AST were observed in 0.4% and 0.5% of patients, respectively. The
median time to onset of Grade ≥3 elevation in transaminases was 8 days
(range: 3 to 49), with a median duration of 7 days.
Monitor liver function tests prior to initiating ZEPZELCA, periodically during treatment, and as clinically indicated. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity.
Extravasation Resulting in Tissue Necrosis
Extravasation of ZEPZELCA resulting in skin and soft tissue injury,
including necrosis requiring debridement, can occur. Consider use of a
central venous catheter to reduce the risk of extravasation, particularly in
patients with limited venous access. Monitor patients for signs and symptoms
of extravasation during the ZEPZELCA infusion.
If extravasation occurs, immediately discontinue the infusion, remove the infusion catheter, and monitor for signs and symptoms of tissue necrosis. The time to onset of necrosis after extravasation may vary.
Administer supportive care and consult with an appropriate medical specialist as needed for signs and symptoms of extravasation. Administer subsequent infusions at a site that was not affected by extravasation.
Rhabdomyolysis
Rhabdomyolysis has
been reported in patients treated with ZEPZELCA.
Monitor creatine phosphokinase (CPK) prior to initiating ZEPZELCA and periodically during treatment as clinically indicated. Withhold or reduce the dose based on severity.
Embryo-Fetal Toxicity
ZEPZELCA can cause fetal harm when administered to a pregnant woman. Advise
pregnant women of the potential risk to a fetus. Advise female patients of
reproductive potential to use effective contraception during treatment with
ZEPZELCA and for 6 months after the last dose. Advise male patients with
female partners of reproductive potential to use effective contraception
during treatment with ZEPZELCA and for 4 months after the last dose.
Lactation
There are no data on the presence of ZEPZELCA in human milk, however,
because of the potential for serious adverse reactions from ZEPZELCA in
breastfed children, advise women not to breastfeed during treatment with
ZEPZELCA and for 2 weeks after the last dose.
The most common adverse reactions, including laboratory abnormalities, (≥20%) are leukopenia (79%), lymphopenia (79%), fatigue (77%), anemia (74%), neutropenia (71%), increased creatinine (69%), increased alanine aminotransferase (66%), increased glucose (52%), thrombocytopenia (37%), nausea (37%), decreased appetite (33%), musculoskeletal pain (33%), decreased albumin (32%), constipation (31%), dyspnea (31%), decreased sodium (31%), increased aspartate aminotransferase (26%), vomiting (22%), decreased magnesium (22%), cough (20%), and diarrhea (20%).
Effect of CYP3A Inhibitors and Inducers
Avoid coadministration with a strong or a moderate CYP3A inhibitor (including grapefruit and Seville oranges) as this increases lurbinectedin systemic exposure which may increase the incidence and severity of adverse reactions to ZEPZELCA. If coadministration cannot be avoided, reduce the ZEPZELCA dose as appropriate.
Avoid coadministration with a strong CYP3A inducer as it may decrease systemic exposure to lurbinectedin, which may decrease the efficacy of ZEPZELCA.
Of the 105 patients with SCLC administered ZEPZELCA in clinical studies, 37 (35%) patients were 65 years of age and older, while 9 (9%) patients were 75 years of age and older. No overall difference in effectiveness was observed between patients aged 65 and older and younger patients.
There was a higher incidence of serious adverse reactions in patients ≥65 years of age than in patients <65 years of age (49% vs 26%, respectively). The serious adverse reactions most frequently reported in patients ≥65 years of age were related to myelosuppression and consisted of febrile neutropenia (11%), neutropenia (11%), thrombocytopenia (8%), and anemia (8%).
Please see accompanying full Prescribing Information.
Reference: 1. Centers for Medicare & Medicaid Services. Final rule. https://public-inspection.federalregister.gov/2021-16519.pdf. Accessed September 14, 2021.
Myelosuppression
ZEPZELCA can cause myelosuppression. In clinical studies of 554 patients with advanced solid tumors receiving ZEPZELCA, Grade 3 or 4 neutropenia occurred in 41% of patients, with a median time to onset of 15 days and a median duration of 7 days. Febrile neutropenia occurred in 7% of patients.
Sepsis occurred in 2% of patients and was fatal in 1% (all cases occurred in patients with solid tumors other than SCLC). Grade 3 or 4 thrombocytopenia occurred in 10%, with a median time to onset of 10 days and a median duration of 7 days. Grade 3 or 4 anemia occurred in 17% of patients.