Two new subsections have been added to the warning and precautious section of Zepzelca’s label to address serious adverse events that were identified during post-market monitoring.
Jazz Pharmaceuticals and partner PharmaMar have updated the safety label for Zepzelca (lurbinectedin) to add new subsections about serious adverse events related to the therapy. Zepzelca is used to treat adults with metastatic small cell lung cancer.
The FDA approved Zepzelca under an accelerated approval in June 2020. The approval was based on overall response rate and duration of response from in an open-label, monotherapy clinical study with 105 patients.
The new subsections in the warnings and precautions section include information about the possibility of Zepzelca resulting in extravasation, the leakage of the drug into surrounding tissue, and rhabdomyolysis, a serious medical condition that results in the breakdown of damaged muscle.
Jazz and PharmaMar conducted an overview of the safety database for extravasation, rhabdomyolysis and tumor lysis syndrome after receiving a notification of newly identified safety signals from the FDA identifying each condition as important safety risks that were reported during post-marketing adverse event monitoring, according to a Jazz spokesperson. “After this review, we worked with the FDA to update Zepzelca’s label with the appropriate new safety information. The updated prescribing information was made available with information about each condition on April 1, 2022,” the spokesperson told Formulary Watch.
The first new subsection indicates that during infusion Zepzelca, extravasation can cause skin and soft tissue injury, including necrosis requiring debridement. The second added section identifies the need to monitor creatine phosphokinase prior to initiating and periodically during treatment because of rhabdomyolysis.
“At Jazz, patient safety is critical, and we continually evaluate our medicines to provide up-to-date information to healthcare professionals and patients. Jazz remains confident in the benefit-risk profile of Zepzelca as an important treatment option for adults with metastatic small cell lung cancer, an aggressive disease with a historically poor prognosis,” the spokesperson said.
Zepzelca is an alkylating drug that binds guanine residues within DNA. This triggers a cascade of events that can affect the activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in disruption of the cell cycle and eventual cell death
In December 2021, Jazz and PharmaMar began a confirmatory phase 3 trial of Zepzelca for the treatment of adults with relapsed small cell lung cancer. The primary endpoint is overall survival (OS) and the secondary endpoint is progression-free survival (PFS) monotherapy or in combination with the chemotherapy irinotecan compared with investigator’s choice of chemotherapy topotecan or irinotecan, in patients with SCLC whose disease has progressed following prior platinum-containing chemotherapy with or without anti-PD-1 or anti-PD-L1 agents.
The new sections read:
“5.3 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 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.”