Zepsyre
Zepsyre Uses, Dosage, Side Effects, Food Interaction and all others data.
Zepsyre is a DNA alkylating agent that has been investigated in the treatment of a variety of cancers, including mesothelioma, chronic lymphocytic leukemia (CLL), breast cancer, and small-cell lung cancer (SCLC). It is a derivative of the marine-derived agent ecteinascidin (trabectedin), an anticancer agent found in extracts of the tunicate Ecteinascidia turbinata, with the primary difference being the substitution of the tetrahydroisoquinoline with a tetrahydro β‐carboline that results in increased antitumour activity of lurbinectedin as compared to its predecessor.
On June 15, 2020, the FDA granted accelerated approval and orphan drug designation to lurbinectedin for the treatment of adult patients with metastatic SCLC who have experienced disease progression despite therapy with platinum-based agents. This accelerated approval is based on the rate and duration of therapeutic response observed in ongoing clinical trials and is contingent on the verification of these results in confirmatory trials.
Zepsyre exerts its chemotherapeutic activity by covalently binding to DNA, resulting in double-strand DNA breaks and subsequent cell death. Zepsyre has been associated with myelosuppression, and patients receiving therapy with this agent should be closely monitored for evidence of cytopenias. Prior to beginning therapy, ensure baseline neutrophil counts are >1,500 cells/mm3 The supplementary use of granulocyte colony-stimulating factor (G-CSF) should be considered if the neutrophil count falls below 500 cells/mm3 Zepsyre has also been associated with hepatotoxicity. Monitor liver function tests at baseline and regular intervals throughout therapy, and consider holding, reducing, or permanently discontinuing therapy based on the severity of observed hepatotoxicity.
| Trade Name | Zepsyre |
| Availability | Prescription only |
| Generic | Lurbinectedin |
| Lurbinectedin Other Names | Lurbinectedin |
| Related Drugs | methotrexate, atezolizumab, etoposide, durvalumab, Tecentriq, Imfinzi |
| Type | |
| Formula | C41H44N4O10S |
| Weight | Average: 784.88 Monoisotopic: 784.277814807 |
| Protein binding | Lurbinectedin is highly protein-bound in plasma (~99%) to both serum albumin and α-1-acid glycoprotein. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Zepsyre is a chemotherapeutic DNA alkylating agent used in the treatment of metastatic small-cell lung cancer.
Zepsyre is indicated for the treatment of adult patients with metastatic small-cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.
Zepsyre is also used to associated treatment for these conditions: Metastatic Small Cell Lung Cancer
How Zepsyre works
Zepsyre is a DNA alkylating agent. It covalently binds to guanine residues in the DNA minor groove, forming adducts that bend the DNA helix towards the major groove. This process triggers a cascade of events that affect the activity of transcription factors and impairs DNA repair pathways, ultimately leading to double-strand DNA breaks and eventual cell death. Additional mechanism(s) of action include inhibition of RNA-polymerase-II activity, inactivation of Ewing Sarcoma Oncoprotein (EWS-FL11) via nuclear redistribution, and the inhibition of human monocyte activity and macrophage infiltration into tumor tissue.
Toxicity
Data regarding overdosage with lurbinectedin are not available. Symptoms of overdose are likely to be consistent with lurbinectedin's adverse effect profile.
Food Interaction
No interactions found.[Moderate] GENERALLY AVOID: Coadministration with inhibitors of CYP450 3A4 such as grapefruit juice may increase the plasma concentrations of lurbinectedin, which may increase the incidence and severity of adverse reactions, such as myelosuppression and hepatotoxicity.
No drug interaction studies are available for lurbinectedin, but in vitro studies suggest that lurbinectedin is metabolized by CYP450 3A4.
MANAGEMENT: The manufacturer recommends avoiding eating or drinking grapefruit or products that contain grapefruit juice during treatment with lurbenectedin.
Zepsyre Drug Interaction
Unknown: omega-3 polyunsaturated fatty acids, chlorpheniramine / hydrocodone, metoprolol, doxylamine, tiotropium
Zepsyre Disease Interaction
Volume of Distribution
The steady-state volume of distribution of lurbinectedin is 504 L.
Elimination Route
Following intravenous administration, the Cmax and AUC0-inf were 107 µg/L and 551 µg*h/L, respectively. No accumulation between dosing intervals (every 3 weeks) has been observed. No significant differences in absorption were found between special populations (e.g. based on age, sex, ethnicity, etc.), but lurbinectedin has not been studied in the setting of severe renal impairment or moderate/severe hepatic impairment.
Half Life
The terminal half-life of lurbinectedin is 51 hours.
Clearance
The total plasma clearance of lurbinectedin is approximately 11 L/h.
Elimination Route
Approximately 89% of a given dose is recovered in the feces (7
Innovators Monograph
You find simplified version here Zepsyre
