Zepzelca

Q: Who makes Zepzelca?

Zepzelca is listed by 1 labeler in the FDA NDC directory, including Jazz Pharmaceuticals, Inc..

Lurbinectedin · Injection, Powder, Lyophilized, For Solution · Intravenous

Uses

1 INDICATIONS AND USAGE ZEPZELCA is an alkylating drug indicated:
• in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs, for the maintenance treatment of adult patients with extensive-stage small cell lung cancer whose disease has not progressed after first-line induction therapy with atezolizumab or atezolizumab and hyaluronidase-tqjs, carboplatin and etoposide. ( 1.1 )
• For the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. ( 1.2 ) 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). ( 1.2 ) 1.1 Extensive-Stage Small Cell Lung Cancer ZEPZELCA, in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs, is indicated for the maintenance treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease has not progressed after first-line induction therapy with atezolizumab or atezolizumab and hyaluronidase-tqjs, carboplatin and etoposide. 1.2 Metastatic Small Cell Lung Cancer 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 [see Clinical Studies (14) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Dosage and administration

• Recommended Dosage : 3.2 mg/m 2 administered intravenously every 21 days until disease progression or unacceptable toxicity.
• Administration via a central venous line is recommended to reduce the risk of extravasation that can cause tissue necrosis requiring debridement ( 5.3 )
• Administer ZEPZELCA as an intravenous infusion over 60 minutes.
• To reduce the risk of nausea, administer corticosteroids and serotonin agonists prior to Cycle 1 and consider use for subsequent cycles. ( 2.5 )
• To reduce the risk of febrile neutropenia during treatment with ZEPZELCA in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs, administer granulocyte colony-stimulating factor (G-CSF) [Refer to Prescribing Information].
• Moderate Hepatic Impairment : Recommended dosage is 1.6 mg/m 2 administered intravenously every 21 days until disease progression or unacceptable toxicity. ( 2.4 , 8.6 )
• Severe Hepatic Impairment : Avoid use of ZEPZELCA. If use cannot be avoided, the recommended dosage is 1.6 mg/m 2 administered intravenously every 21 days until disease progression or unacceptable toxicity. ( 2.4 , 8.6 ) 2.1 Recommended Dosage The recommended dosage of ZEPZELCA as a single-agent and as a combination with atezolizumab or atezolizumab and hyaluronidase-tqjs is 3.2 mg/m 2 by intravenous infusion over 60 minutes every 21 days until disease progression or unacceptable toxicity [see Dosage and Administration (2.4) ]. Initiate treatment with ZEPZELCA only if absolute neutrophil count (ANC) is at least 1,500 cells/mm 3 and platelet count is at least 100,000/mm 3 . ZEPZELCA with Intravenous Atezolizumab or atezolizumab and hyaluronidase-tqjs When administering ZEPZELCA on the same day as atezolizumab or atezolizumab and hyaluronidase-tqjs, administer the chosen atezolizumab drug first. For the recommended dosage of atezolizumab or atezolizumab and hyaluronidase-tqjs refer to the respective Prescribing Information. If discontinuation of atezolizumab or atezolizumab and hyaluronidase-tqjs is required due to an immune-related severe adverse event, treatment with ZEPZELCA may be continued at the same dose as a single agent. If immune toxicity does not resolve or recurs despite discontinuation of atezolizumab, permanently discontinue ZEPZELCA. 2.2 Dosage Modifications for Adverse Reactions The recommended dose reductions for adverse reactions are listed in Table 1. Permanently discontinue ZEPZELCA in patients who require a dose interruption of greater than two weeks and in patients who are unable to tolerate 2 mg/m 2 every 21 days. Table 1: Dose Reduction for ZEPZELCA for Adverse Reactions Dose Reduction Total Dose First Second 2.6 mg/m 2 every 21 days 2 mg/m 2 every 21 days Dosage modifications for ZEPZELCA for adverse reactions are presented in Table 2. Table 2: Dosage Modifications for ZEPZELCA for Adverse Reactions a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. b Patients who have not received primary prophylaxis of G-CSF with isolated Grade 4 neutropenia (neutrophil count less than 500 cells/mm 3 ) may receive G-CSF prophylaxis rather than undergo lurbinectedin dose reduction. Adverse Reaction Severity a Dosage Modification Neutropenia b [see Warnings and Precautions (5.1) ] Grade 4 or Any grade febrile neutropenia
• Withhold ZEPZELCA until absolute neutrophil count (ANC) is ≥ 1500/mm 3
• Resume ZEPZELCA at a reduced dose Thrombocytopenia [see Warnings and Precautions (5.1) ] Grade 3 with bleeding or Grade 4
• Withhold ZEPZELCA until platelet ≥ 100,000/mm 3
• Resume ZEPZELCA at reduced dose Hepatotoxicity [see Warnings and Precautions (5.2) ] 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 [see Warnings and Precautions (5.4) ] Grade 2
• Withhold ZEPZELCA until Grade ≤ 1
• Resume ZEPZELCA at same dose Grade ≥ 3
• Permanently discontinue ZEPZELCA Other Adverse Reactions [see Adverse Reactions (6.1) , Postmarketing (6.2) ] 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 2.3 Dosage Modifications for Use with Strong and Moderate CYP3A Inhibitors Avoid coadministration of ZEPZELCA with strong or moderate CYP3A inhibitors. If coadministration of ZEPZELCA with a strong or moderate CYP3A inhibitor cannot be avoided, reduce the dose of ZEPZELCA by 50% [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] . After discontinuation of a strong or moderate CYP3A inhibitor for 5 half-lives of the inhibitor, increase the ZEPZELCA dose to the dose used before starting the inhibitor . 2.4 Dosage Modifications for Patients with Severe and Moderate Hepatic Impairment Avoid administration of ZEPZELCA in patients with severe hepatic impairment (total bilirubin > 3 × Upper Limit of Normal (ULN)). If administration of ZEPZELCA cannot be avoided, the recommended dosage is 1.6 mg/m 2 by intravenous infusion over 60 minutes every 21 days until disease progression or unacceptable toxicity [see Use In Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . In patients with moderate hepatic impairment (total bilirubin > 1.5 to ≤ 3 × ULN and any AST), the recommended dosage of ZEPZELCA is 1.6 mg/m 2 by intravenous infusion over 60 minutes every 21 days until disease progression or unacceptable toxicity .

Dosage forms and strengths

For injection: 4 mg of lurbinectedin as a sterile, preservative-free, white to off-white lyophilized powder in a single-dose vial for reconstitution prior to intravenous infusion. For injection: 4 mg lyophilized powder in a single-dose vial. ( 3 )

Contraindications

None. None. ( 4 )

Warnings and precautions

• Myelosuppression : Monitor blood counts prior to each administration. Initiate treatment with ZEPZELCA only if baseline neutrophil count is ≥ 1,500 cells/mm 3 and platelet count is ≥ 100,000/mm 3 . For neutrophil count less than 500 cells/mm 3 or any value less than lower limit of normal, administer G-CSF. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity. ( 5.1 )
• Hepatotoxicity : 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. ( 5.2 )
• Extravasation Resulting in Tissue Necrosis : Consider use of a central venous catheter to reduce the risk of extravasation. 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. ( 5.3 )
• Rhabdomyolysis : Monitor creatine phosphokinase (CPK) prior to initiating ZEPZELCA and periodically during treatment as clinically indicated. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity. ( 5.4 )
• Embryo-Fetal Toxicity : Can cause fetal harm. Advise females and males of reproductive potential of the potential risk to a fetus and to use an effective method of contraception. ( 5.5 ) 5.1 Myelosuppression ZEPZELCA can cause severe and fatal myelosuppression including febrile neutropenia and sepsis, thrombocytopenia and anemia. Administer ZEPZELCA only to patients with baseline neutrophil count of at least 1,500 cells/mm 3 and platelet count of at least 100,000/mm 3 . To reduce the risk of febrile neutropenia during treatment with ZEPZELCA in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs, administer granulocyte colony-stimulating factor (G-CSF) [refer to Prescribing Information] . Monitor blood counts including neutrophils, red blood cells and platelets prior to each ZEPZELCA administration. For neutrophil count less than 500 cells/mm 3 or any value less than lower limit of normal, administer G-CSF. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity [see Dosage and Administration (2.2) ] . ZEPZELCA with Intravenous Atezolizumab In the IMforte study [see Adverse Reactions (6.1) ] , primary prophylaxis of G-CSF was administered to 84% of patients. Based on laboratory values, decreased neutrophils occurred in 36%, including 18% Grade 3 or Grade 4 in patients who received ZEPZELCA in combination with atezolizumab. The median time to onset of Grade 3 and 4 decreased neutrophil cells was 31 days and a median duration of 10 days. Febrile neutropenia occurred in 1.7%. Sepsis occurred in 1%. There were 7 fatal infections: pneumonia (n=3), sepsis (n=3), and febrile neutropenia (n=1). Based on laboratory values, decreased platelets occurred in 54%, including 15% Grade 3 or Grade 4 in patients who received ZEPZELCA in combination with atezolizumab. The median time to onset of Grade 3 and 4 decreased platelet cells was 31 days and a median duration of 12 days. Based on laboratory values, decreased hemoglobin occurred in 51%, including 13% Grade 3 or Grade 4 in patients who received ZEPZELCA in combination with atezolizumab. The median time to onset of Grade 3 and 4 decreased hemoglobin was 64 days and a median duration of 8 days. ZEPZELCA as a Single Agent In clinical studies of 554 patients with advanced solid tumors receiving ZEPZELCA as a single agent [see Adverse Reactions (6.1) ] , 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. 5.2 Hepatotoxicity ZEPZELCA can cause hepatotoxicity which may be severe. Monitor liver function tests prior to initiating ZEPZELCA and periodically during treatment as clinically indicated. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity [see Dosage and Administration (2.2) ]. ZEPZELCA with Intravenous Atezolizumab In the IMforte study [see Adverse Reactions (6.1) ] , based on laboratory values, increased alanine aminotransferase (ALT) occurred in 25%, including 3% Grade 3 or Grade 4 in patients who received ZEPZELCA in combination with atezolizumab. Increased aspartate aminotransferase (AST) occurred in 24% including 3% Grade 3 or Grade 4. The median time to onset of Grade ≥ 3 elevation in transaminases was 52 days (range: 6 to 337). ZEPZELCA as a Single Agent In clinical studies of 554 patients with advanced solid tumors receiving ZEPZELCA as a single agent [see Adverse Reactions (6.1) ] , 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. 5.3 Extravasation Resulting in Tissue Necrosis Extravasation of ZEPZELCA can cause skin and soft tissue injury, including necrosis requiring debridement. 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.

Side effects

The following clinically significant adverse reactions are described elsewhere in the labeling:
• Myelosuppression [see Warnings and Precautions (5.1) ]
• Hepatotoxicity [see Warnings and Precautions (5.2) ]
• Extravasation Resulting in Tissue Necrosis [see Warnings and Precautions (5.3) ]
• Rhabdomyolysis [see Warnings and Precautions (5.4) ] The most common adverse reactions for ZEPZELCA as a single agent, including laboratory abnormalities, (≥ 20%) are leukopenia, lymphopenia, fatigue, anemia, neutropenia, increased creatinine, increased alanine aminotransferase, increased glucose, thrombocytopenia, nausea, decreased appetite, musculoskeletal pain, decreased albumin, constipation, dyspnea, decreased sodium, increased aspartate aminotransferase, vomiting, cough, decreased magnesium and diarrhea. ( 6.1 ) The most common adverse reactions, for ZEPZELCA in combination with atezolizumab including laboratory abnormalities, (≥ 30%) are: decreased lymphocytes, decreased platelets, decreased hemoglobin, decreased neutrophils, nausea, and fatigue/asthenia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Jazz Pharmaceuticals, Inc. at 1-800-520-5568 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety population described in the WARNINGS AND PRECAUTIONS reflects exposure to ZEPZELCA in combination with intravenous atezolizumab in the IMforte study [see Clinical Studies (14.1) ] , in 242 patients with extensive stage small cell lung cancer (ES-SCLC) whose disease had not progressed after initial therapy with atezolizumab, carboplatin, and etoposide. Patients received ZEPZELCA 3.2 mg/m 2 intravenously (IV) in combination with atezolizumab 1200 mg IV every 21 days until disease progression or unacceptable toxicity. Among 242 patients who received ZEPZELCA in combination with intravenous atezolizumab, 34% were exposed for 6 months or longer and 8% were exposed for greater than one year. The most common adverse reactions (≥ 30%), including laboratory abnormalities, in patients who received ZEPZELCA with atezolizumab were decreased lymphocytes, decreased platelets, decreased hemoglobin, decreased neutrophils, nausea, and fatigue/asthenia. The pooled safety population described in the WARNINGS AND PRECAUTIONS also reflects exposure to ZEPZELCA as a single agent at a dose of 3.2 mg/m 2 intravenously every 21 days in 554 patients with advanced solid tumors. Among 554 patients who received ZEPZELCA, including 105 patients with small cell lung cancer (SCLC) in PM1183-B-005-14 (Study B-005), 24% were exposed for 6 months or longer and 5% were exposed for greater than one year. The most common adverse reactions for ZEPZELCA as a single agent, (Study B-005), including laboratory abnormalities, (≥ 20%) are leukopenia, lymphopenia, fatigue, anemia, neutropenia, increased creatinine, increased alanine aminotransferase, increased glucose, thrombocytopenia, nausea, decreased appetite, musculoskeletal pain, decreased albumin, constipation, dyspnea, decreased sodium, increased aspartate aminotransferase, vomiting, cough, decreased magnesium and diarrhea. Extensive-Stage Small Cell Lung Cancer (IMforte) The safety of ZEPZELCA in combination with intravenous (IV) atezolizumab was evaluated in IMforte [see Clinical Studies (14) ] . Patients received intravenous ZEPZELCA 3.2 mg/m 2 in combination with intravenous atezolizumab 1200 mg on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity. Primary prophylaxis of G-CSF was administered to 84% of patients. Among 242 patients who received ZEPZELCA with atezolizumab, the median duration of exposure to lurbinectedin was 4.1 months, 33% were exposed for 6 months or longer and 8% were exposed for greater than one year. The median age of patients who received ZEPZELCA in combination with intravenous atezolizumab was 66 years (range: 35 to 85); 62% male; 82% White, 13% Asian, and 0.8% Black or African American. Serious adverse reactions occurred in 31% of patients receiving ZEPZELCA in combination with atezolizumab. Serious adverse reactions occurring in > 2% were pneumonia (2.5%), respiratory tract infection (2.1%), dyspnea (2.1%), and decreased platelet count (2.1%). Fatal adverse reactions occurred in 5% of patients receiving ZEPZELCA with atezolizumab including pneumonia (3 patients), sepsis (3 patients), cardio-respiratory arrest (2 patients), myocardial infarction (2 patients), and febrile neutropenia (1 patient). Permanent discontinuation of ZEPZELCA due to an adverse reaction occurred in 5% of patients. The adverse reaction resulting in permanent discontinuation in ≥ 1% of patients who received ZEPZELCA was decreased neutrophil count. Dosage interruptions of ZEPZELCA due to an adverse reaction occurred in 25%. Adverse reactions which required dosage interruption in ≥ 2% of patients included anemia, fatigue, decreased neutrophil count, and decreased platelet count. Dose reductions of ZEPZELCA due to an adverse reaction occurred in 15% of patients. Adverse reactions which required dosage reduction in ≥ 2% of patients included decreased platelet count, fatigue, nausea and vomiting. Table 3 summarizes the adverse reactions in IMforte. Table 3: Adverse Reactions (≥ 10%) in Patients with ES-SCLC Who Received ZEPZELCA in Combination with Intravenous Atezolizumab in IMforte Graded per NCI CTCAE v5.0 1 Includes diarrhea and colitis. 2 Includes fatigue and asthenia. 3 Includes arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, and pain in extremity. 4 Includes cough, productive cough, and upper-airway cough syndrome.

Drug interactions

Effect of Other Drugs on ZEPZELCA : Avoid coadministration with strong or a moderate CYP3A inhibitors and strong CYP3A inducers. ( 7.1 ) 7.1 Effect of Other Drugs on ZEPZELCA Strong and Moderate CYP3A Inhibitors Coadministration of ZEPZELCA with a strong or a moderate CYP3A inhibitor increases lurbinectedin systemic exposure [see Clinical Pharmacology (12.3) ], which may increase the incidence and severity of adverse reactions to ZEPZELCA. Avoid grapefruit and Seville oranges during ZEPZELCA treatment, as these contain strong or moderate inhibitors of CYP3A. Avoid coadministration of ZEPZELCA with strong or moderate CYP3A inhibitors. If coadministration cannot be avoided, reduce the dose of ZEPZELCA [see Dosage and Administration (2.3) ] . Strong CYP3A Inducers Avoid coadministration of ZEPZELCA with strong CYP3A inducers. Coadministration of ZEPZELCA with a strong CYP3A inducer may decrease lurbinectedin systemic exposure, which may decrease the efficacy of ZEPZELCA [see Clinical Pharmacology (12.3) ].

Use in specific populations

• Lactation : Advise not to breastfeed. ( 8.2 )
• Hepatic Impairment : Avoid use of ZEPZELCA in patients with severe hepatic impairment. In patients with moderate hepatic impairment, reduce the dose of ZEPZELCA. ( 8.6 ) 8.1 Pregnancy Risk Summary Based on animal data and its mechanism of action [see Clinical Pharmacology (12.1) ] , ZEPZELCA can cause fetal harm when administered to a pregnant woman. There are no available data to inform the risk of ZEPZELCA use in pregnant women. Intravenous administration of a single lurbinectedin dose (approximately 0.2 times the 3.2 mg/m 2 clinical dose) to pregnant rats during the period of organogenesis caused embryolethality (see Data) . Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In a reproductive toxicity study, administration of a single lurbinectedin dose of 0.6 mg/m 2 (approximately 0.2 times of the human dose of 3.2 mg/m 2 ) to pregnant rats on Gestation Day 10 resulted in 100% post-implantation loss. 8.2 Lactation Risk Summary There are no data on the presence of lurbinectedin in human milk or its effects on the breastfed child or on milk production. 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. 8.3 Females and Males of Reproductive Potential ZEPZELCA can cause embryolethality at doses lower than the human dose of 3.2 mg/m 2 [see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating ZEPZELCA. Contraception Females Advise female patients of reproductive potential to use effective contraception during treatment with ZEPZELCA and for 7 months after the last dose. Males Advise males with a female sexual partner of reproductive potential to use effective contraception during treatment with ZEPZELCA and for 4 months after the last dose. 8.4 Pediatric Use The safety and effectiveness of ZEPZELCA in pediatric patients have not been established. 8.5 Geriatric Use ZEPZELCA with Intravenous Atezolizumab Of the 242 patients with ES-SCLC treated with ZEPZELCA and atezolizumab in IMforte, 124 (51%) patients were 65 years of age and older, while 29 (12%) patients were 75 years of age and older. No overall differences in effectiveness were observed between older and younger patients. There was no overall difference in the incidence of serious adverse reactions in patients ≥ 65 years of age and patients < 65 years of age (33% vs. 29%, respectively). There was a higher incidence of Grade 3 or 4 adverse reactions in patients ≥ 65 years of age compared to younger patients (45% vs. 31%, respectively). ZEPZELCA as a Single Agent 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%) [see Adverse Reactions (6.1) ] . There was a higher incidence of Grade 3 or 4 adverse reactions in patients ≥ 65 years of age compared to younger patients (76% vs. 50%, respectively). 8.6 Hepatic Impairment Avoid administration of ZEPZELCA in patients with severe hepatic impairment (total bilirubin > 3 × ULN). If administration of ZEPZELCA cannot be avoided, reduce the dose [see Dosage and Administration (2.4) ] . Monitor for increased adverse reactions in patients with severe hepatic impairment. Reduce the dose of ZEPZELCA in patients with moderate hepatic impairment (total bilirubin > 1.5 to 3 × ULN and any AST) [see Dosage and Administration (2.4) ] . Monitor for increased adverse reactions in patients with moderate hepatic impairment. No dose adjustment of ZEPZELCA is recommended for patients with mild hepatic impairment (total bilirubin ≤ ULN and AST > ULN, or total bilirubin 1 to ≤ 1.5 × ULN and any AST) [see Clinical Pharmacology (12.3) ] .

Pregnancy

8.1 Pregnancy Risk Summary Based on animal data and its mechanism of action [see Clinical Pharmacology (12.1) ] , ZEPZELCA can cause fetal harm when administered to a pregnant woman. There are no available data to inform the risk of ZEPZELCA use in pregnant women. Intravenous administration of a single lurbinectedin dose (approximately 0.2 times the 3.2 mg/m 2 clinical dose) to pregnant rats during the period of organogenesis caused embryolethality (see Data) . Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In a reproductive toxicity study, administration of a single lurbinectedin dose of 0.6 mg/m 2 (approximately 0.2 times of the human dose of 3.2 mg/m 2 ) to pregnant rats on Gestation Day 10 resulted in 100% post-implantation loss.

Pediatric use

8.4 Pediatric Use The safety and effectiveness of ZEPZELCA in pediatric patients have not been established.

Geriatric use

8.5 Geriatric Use ZEPZELCA with Intravenous Atezolizumab Of the 242 patients with ES-SCLC treated with ZEPZELCA and atezolizumab in IMforte, 124 (51%) patients were 65 years of age and older, while 29 (12%) patients were 75 years of age and older. No overall differences in effectiveness were observed between older and younger patients. There was no overall difference in the incidence of serious adverse reactions in patients ≥ 65 years of age and patients < 65 years of age (33% vs. 29%, respectively). There was a higher incidence of Grade 3 or 4 adverse reactions in patients ≥ 65 years of age compared to younger patients (45% vs. 31%, respectively). ZEPZELCA as a Single Agent 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%) [see Adverse Reactions (6.1) ] . There was a higher incidence of Grade 3 or 4 adverse reactions in patients ≥ 65 years of age compared to younger patients (76% vs. 50%, respectively).

Description

11 DESCRIPTION ZEPZELCA is an alkylating drug. The chemical name of ZEPZELCA (lurbinectedin) is (1’R,6R,6aR,7R,13S,14S,16R)-8,14-dihydroxy-6’,9-dimethoxy-4,10,23-trimethyl-19-oxo-2’,3’,4’,6,7,9’,12,13,14,16-decahydro-6aH-spiro[7,13-azano-6,16-(epithiopropanooxymethano) [1,3]dioxolo[7,8]isoquinolino[3,2-b][3]benzazocine-20,1’-pyrido[3,4-b]indol]-5-yl acetate. The molecular formula is C 41 H 44 N 4 O 10 S. The molecular weight is 784.87g/mol, and the chemical structure is: ZEPZELCA for injection 4 mg is supplied as a lyophilized powder in a single-dose vial for reconstitution for intravenous use. The ZEPZELCA lyophilized formulation is comprised of 4 mg lurbinectedin, sucrose (800 mg), lactic acid (22.1 mg), and sodium hydroxide (5.1 mg). Before use, the lyophilizate is reconstituted by addition of 8 mL Sterile Water for Injection USP, yielding a solution containing 0.5 mg/mL lurbinectedin (the calculated concentration is 0.47 mg/mL based on the final volume of 8.5 mL). chemical structure

Mechanism of action

12.1 Mechanism of Action Lurbinectedin is an alkylating drug that binds guanine residues in the minor groove of DNA, forming adducts and resulting in a bending of the DNA helix towards the major groove. 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. Lurbinectedin inhibited human monocyte activity in vitro and reduced macrophage infiltration in implanted tumors in mice.

How supplied

How Supplied ZEPZELCA (lurbinectedin) for injection is supplied as a sterile, preservative-free, white to off-white lyophilized powder in a single-dose clear glass vial. Each carton (NDC 68727-712-01) contains 4 mg in one single-dose vial. Storage and Handling Store refrigerated at 2°C to 8°C (36°F to 46°F). ZEPZELCA is a hazardous drug. Follow applicable special handling and disposal procedures 1 .

Patient information

Advise the patient to read the FDA-approved patient labeling (Patient Information). Myelosuppression Advise patients that ZEPZELCA can cause myelosuppression. Inform patients about the signs and symptoms of myelosuppression and to immediately contact their healthcare provider if signs or symptoms occur [see Warnings and Precautions (5.1) ] . Hepatotoxicity Advise patients that ZEPZELCA can cause hepatotoxicity and to contact their healthcare provider immediately if signs or symptoms occur [see Warnings and Precautions (5.2) ] . Extravasation Resulting in Tissue Necrosis Advise patients that administration of ZEPZELCA through a central venous catheter is recommended because extravasation of ZEPZELCA can cause skin and soft tissue injury, including necrosis requiring debridement. Advise patients to contact their healthcare provider immediately for signs or symptoms of extravasation. The time to onset of necrosis after extravasation may vary [see Warnings and Precautions (5.3) ] . Rhabdomyolysis Advise patients that rhabdomyolysis has been reported with the use of ZEPZELCA and to contact their healthcare provider immediately for signs and symptoms of rhabdomyolysis [see Warnings and Precautions (5.4) ] . Embryo-Fetal Toxicity
• Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.5) , Use in Specific Populations (8.1) ] .
• Advise females of reproductive potential to use effective contraception during treatment with ZEPZELCA and for 7 months after the last dose [see Use in Specific Populations (8.3) ] .
• Advise males with female partners of reproductive potential to use effective contraception during treatment with ZEPZELCA and for 4 months after the last dose [see Use in Specific Populations (8.3) ] . Lactation Advise women not to breastfeed during treatment with ZEPZELCA and for at least 2 weeks after the last dose [see Use in Specific Populations (8.2) ] . Drug Interactions Advise patients to inform their healthcare providers of all concomitant medications, herbal and dietary supplements. Advise patients to avoid grapefruit products and Seville oranges during treatment with ZEPZELCA [see Drug Interactions (7.1) ] . Distributed by: Jazz Pharmaceuticals, Inc. Palo Alto, CA 94306 Under license from Pharma Mar, S.A. Protected by U.S. Patent No. 7,763,615

Label text from the FDA structured product label by Jazz Pharmaceuticals, Inc. (revised Feb 27, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Lurbinectedin in 1 product

Zepzelca NDC products (1)

NDC	Strength & form	Labeler	Type
68727-712	Lurbinectedin .5 mg/mL Injection, Powder, Lyophilized, For Solution	Jazz Pharmaceuticals, Inc.	NDA

Frequently asked questions

What is Zepzelca used for?

What are the side effects of Zepzelca?

Who makes Zepzelca?

Zepzelca is listed by 1 labeler in the FDA NDC directory, including Jazz Pharmaceuticals, Inc..