Answers to frequently asked questions about ZEPZELCA® (lurbinectedin)

Questions about ZEPZELCA

The FDA granted accelerated approval of ZEPZELCA® (lurbinectedin) on June 15, 2020.1

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.2

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).

Explore efficacy for ZEPZELCA.

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.2

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.2

ZEPZELCA was also shown to inhibit human monocyte activity in vitro and to reduce macrophage infiltration in implanted tumors in mice.2

Learn more about the MOA of ZEPZELCA.

For information about ongoing studies of ZEPZELCA, contact our Medical Information department at 1-800-520-5568 or via email to medinfo-us@jazzpharma.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 the coadministration of ZEPZELCA cannot be avoided, reduce the dose of ZEPZELCA as appropriate.2

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.2

Learn more about the drug interactions for ZEPZELCA.

ZEPZELCA is available for purchase from the authorized Specialty Distributors and group purchasing organizations.

Get details and contact information on our ordering information page.

Questions about dosing and administration

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.2

Initiate treatment with ZEPZELCA only if absolute neutrophil count (ANC) is ≥1,500 cells/mm3 and platelet count is ≥100,000/mm3.2

Learn more about the dosing and administration of ZEPZELCA.

ZEPZELCA is a hazardous drug. Follow applicable special handling and disposal procedures.2

Follow these steps for the preparation and administration of ZEPZELCA.2

  • Inject 8 mL of Sterile Water for Injection USP into the vial, yielding a solution containing 0.5 mg/mL of ZEPZELCA. Shake the vial until complete dissolution

  • Visually inspect the solution for particulate matter and discoloration. The reconstituted solution is a clear, colorless, or slightly yellowish solution, essentially free of visible particles

  • Calculate the required volume of reconstituted solution as follows:

Volume (mL) = Body Surface Area (m2) x Individual Dose (mg/m2)/0.5 mg/mL

  • For administration through a central venous line, withdraw the appropriate amount of reconstituted solution from the vial and add to an infusion container containing at least 100 mL of diluent (0.9% Sodium Chloride Injection USP or 5% Dextrose Injection USP)

  • For administration through a peripheral venous line, withdraw the appropriate amount of reconstituted solution from the vial and add to an infusion container containing at least 250 mL of diluent (0.9% Sodium Chloride Injection USP or 5% Dextrose Injection USP)

  • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If particulate matter is observed, do not administer2

    • Do not use in-line nylon membrane filters when the reconstituted ZEPZELCA solution is diluted using 0.9% Sodium Chloride Injection, USP. Adsorption of ZEPZELCA to the nylon membrane filters has been observed when 0.9% Sodium Chloride Injection, USP is used as the diluent

  • Compatibility with other intravenous administration materials and the diluted ZEPZELCA solution has been demonstrated in the following materials2:

    • Polyolefin containers (polyethylene, polypropylene, and mixtures)

    • Polyvinyl chloride (PVC) (non-DEHP-containing), polyurethane, and polyolefin infusion sets (polyethylene, polypropylene, and polybutadiene)

    • Implantable venous access systems with titanium and plastic resin ports and with polyurethane or silicone intravenous catheters

  • Do not co-administer ZEPZELCA and other intravenous drugs concurrently within the same intravenous line2

Learn more about the preparation and administration of ZEPZELCA.

Consider administering the following pre-infusion medications for antiemetic prophylaxis before treatment with ZEPZELCA2

  • Corticosteroids (dexamethasone 8 mg intravenously or equivalent)

  • Serotonin antagonists (ondansetron 8 mg intravenously or equivalent)

Get ordering information for ZEPZELCA.

Questions about the study design

Questions about patient support

Yes. The JazzCares Program is committed to helping patients get access to Jazz medications and the support they need.

Learn more about access and support at JazzCares.com.

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. This brochure is available in both English and Spanish.

Download the ZEPZELCA patient brochure in English.

Download the ZEPZELCA patient brochure in Spanish.

IMPORTANT SAFETY INFORMATION

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.

MOST COMMON ADVERSE REACTIONS

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%).

DRUG INTERACTIONS

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.

GERIATRIC USE

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.

INDICATION

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).

IMPORTANT SAFETY INFORMATION

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.

References: 1. 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. 2. ZEPZELCA (lurbinectedin) Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc. 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. 4. Data on file. LUR-2020-003. Jazz Pharmaceuticals, Inc.