Full Prescribing Information
Important Safety Information

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One-hour dosing, every 21 days means minimal infusion visits with ZEPZELCA® (lurbinectedin)

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

Premedication1

Consider administering the following pre-infusion medications to antiemetic prophylaxis:

  • Corticosteroids (intravenous dexamethasone 8 mg or equivalent)
  • Serotonin antagonists (intravenous ondansetron 8 mg or equivalent)
A Straightforward Dose-Reduction Schedule to Help Manage Adverse Reactions1
First dose reduction
2.6 mg/m2 every 21 days
Second dose reduction
2 mg/m2 every 21 days

Permanently discontinue ZEPZELCA in patients who are unable to tolerate 2 mg/m2 or require a dose delay greater than 2 weeks.1

Discontinue ZEPZELCA if patients are unable to tolerate 2 mg/m2 every 21 days.1

Dosage Modifications for Adverse Reactions1
Adverse reaction
Severitya
Dosage modification
Neutropeniab
Grade 4 or any grade febrile neutropenia
  • Withhold ZEPZELCA until Grade ≤1
  • Resume ZEPZELCA at a reduced dose
Thrombocytopenia
Grade 3 with bleeding
or 
Grade 4
  • Withhold ZEPZELCA until platelet ≥100,000/mm3
  • Resume ZEPZELCA at reduced dose
Hepatotoxicity
Grade 2
  • Withhold ZEPZELCA until Grade ≤1
  • Resume ZEPZELCA at same dose
 
Grade ≥3
  • Withhold ZEPZELCA until Grade ≤1
  • Resume ZEPZELCA at reduced dose or permanently discontinue
Rhabdomyolysis
Grade 2
  • Withhold ZEPZELCA until Grade ≤1
  • Resume ZEPZELCA at same dose
 
Grade ≥3
  • Permanently discontinue ZEPZELCA
Other Adverse
Reactions
Grade 2
  • Withhold ZEPZELCA until Grade ≤1
  • Resume ZEPZELCA at same dose
 
Grade ≥3
  • Withhold ZEPZELCA until Grade ≤1
  • Resume ZEPZELCA at reduced dose or permanently discontinue

aNational Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.

bPatients with isolated Grade 4 neutropenia (neutrophil count <500 cells/mm3) may receive granulocyte colony-stimulating factor (G-CSF) prophylaxis rather than undergo lurbinectedin dose reduction.

  • For neutrophil count <500 cells/mm3 or any value less than lower limit of normal, the use of G-CSF
    is recommended1


Preparation, ADMINISTRATION, AND STORAGE of ZEPZELCA® (lurbinectedin)

ZEPZELCA is a hazardous drug. Follow applicable special handling and disposal procedures.1

Preparation1

Sterile Water in ZEPZELCA Vial Icon
  • 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
ZEPZELCA Solution Inspection Magnifying Glass Icon
  • 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
Required ZEPZELCA Volume Calculator Icon
  • Calculate the required volume of reconstituted solution as follows:
    Volume (mL) =
    Body Surface Area (m2) x Individual Dose (mg/m2)
    0.5 mg/mL
ZEPZELCA Administration Central Venous Line Icon
  • 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)
ZEPZELCA Administration Peripheral Venous Line Icon
  • 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)

Administration1

ZEPZELCA Solution Inspection Magnifying Glass Icon
  • 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 administer
ZEPZELCA (lurbinectedin) Recommended Polyethersulfone (PES) Inline Filters Syringe Icon
  • ZEPZELCA can be administered with or without an in-line filter. If infusion lines containing in-line filters are utilized for administration of ZEPZELCA, Polyethersulfone (PES) in-line filters with pore sizes of 0.22 micron are recommended
    • 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
ZEPZELCA (lurbinectedin) Compatible Intravenous (IV) Administration Materials Icon
  • Compatibility with other administration materials and the diluted ZEPZELCA solution has been demonstrated in the following materials:
    • 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
Icon Representing Other IV Drugs
  • Do not co-administer ZEPZELCA and other intravenous drugs concurrently within the same intravenous line

Storage of Infusion Solution1

Proper ZEPZELCA Storing Temperature Thermometer Icon
  • If not used immediately after reconstitution or dilution, the ZEPZELCA solution can be
    stored prior to administration for up to 24 hours following reconstitution, including infusion
    time, at either room temperature/ambient light or under refrigerated (2 °C–8 °C;
    36 °F–46 °F) conditions
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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.

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 final dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ZEPZELCA and for 4 months after the final 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 final 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

Strong and Moderate CYP3A Inhibitors

Avoid coadministration with a strong or a moderate CYP3A inhibitor as this increases lurbinectedin systemic exposure which may increase the incidence and severity of adverse reactions to ZEPZELCA. If coadministration of ZEPZELCA with a moderate CYP3A inhibitor cannot be avoided, consider dose reduction of ZEPZELCA, if clinically indicated.

Strong and Moderate CYP3A Inducers

Avoid coadministration with a strong or moderate CYP3A inducer. Coadministration with a strong CYP3A inducer decreases lurbinectedin systemic exposure which may reduce ZEPZELCA efficacy.

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.

Reference: 1. ZEPZELCA (lurbinectedin). Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc.

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ZEPZELCA is a registered trademark of PharmaMar, S.A. used by Jazz Pharmaceuticals under license.

©2022 Jazz Pharmaceuticals   US-LUR-2200225   Rev1122

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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.