This site is intended for US healthcare professionals only.
This site is intended for US healthcare professionals only.
The recommended dose of ZEPZELCA is 3.2 mg/m2 by intravenous infusion over 60 minutes, repeated every 21 days until disease progression or unacceptable toxicity.1
Initiate treatment with ZEPZELCA only if absolute neutrophil count (ANC) is ≥1,500 cells/mm3 and platelet count is ≥100,000/mm3.1
Learn more about the dosing and administration of ZEPZELCA >>
ZEPZELCA is a hazardous drug. Follow applicable special handling and
disposal procedures.1
Follow these steps for the preparation and administration of ZEPZELCA1
Learn more about the preparation and administration of ZEPZELCA >>
Consider administering the following pre-infusion medications for antiemetic prophylaxis before treatment with ZEPZELCA1
ZEPZELCA is distributed by Jazz Pharmaceuticals, Inc., under license from PharmaMar, S.A.1
The FDA granted accelerated approval to ZEPZELCA® (lurbinectedin) on June 15, 2020.2
ZEPZELCA 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).
ZEPZELCA is an alkylating agent that binds to guanine residues in the minor
groove of DNA,
forming adducts and resulting in a bending of the DNA helix
towards the major groove.1
Adduct formation triggers a cascade of events that can affect the subsequent activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in perturbation of the cell cycle and eventual cell death.1
ZEPZELCA was also shown to inhibit human monocyte activity in vitro and to reduce macrophage infiltration in implanted tumors in mice.1
For information about ongoing studies of ZEPZELCA, contact our Medical Information department at 1-800-520-5568 or via email to jazzpharma@medcomsol.com.
Strong and moderate CYP3A inhibitors: 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 dose of ZEPZELCA as appropriate.
Strong CYP3A inducers: avoid coadministration with a strong CYP3A inducer as it may decrease systemic exposure to lurbinectedin, which may decrease the efficacy of ZEPZELCA.1
ZEPZELCA is available for purchase from the authorized Specialty Distributors and group purchasing organizations.
Get details and contact information on our Ordering Information page >>
The phase 2 study was a multicenter, open-label, multi-cohort trial evaluating ZEPZELCA as a single agent in 105 adult patients with advanced or metastatic SCLC with disease progression on or after platinum-based chemotherapy. Patients received ZEPZELCA 3.2 mg/m2 by intravenous infusion every 21 days (one cycle) for a median of 4 cycles (range: 1 to 24 cycles). The median age was 60 years (range: 40 to 83 years). Baseline ECOG performance status was 0–1 in 92% of patients. The major efficacy outcome measure was confirmed investigator-assessed ORR. Additional efficacy outcome measures included duration of response, and an Independent Review Committee assessed ORR using Response Evaluation Criteria in Solid Tumors v1.1.1,3
ECOG=Eastern Cooperative Oncology Group; ORR=overall response rate.
Yes. The JazzCares Program is committed to helping patients get access to Jazz medications and the support they need.
Yes. The Patient Brochure for ZEPZELCA can help patients and caregivers better understand treatment with ZEPZELCA, including dosing and administration, side effects, and support and access.
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.
References: 1. ZEPZELCA (lurbinectedin). Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc. 2. US Food and Drug Administration: Oncology Center of Excellence. FDA grants accelerated approval to lurbinectedin for metastatic small cell lung cancer. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-lurbinectedin-metastatic-small-cell-lung-cancer. Accessed October 26, 2020. 3. Trigo J, Subbiah V, Besse B, et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020;21(5):645-654.
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.