Overview
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.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 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. 12.2 Pharmacodynamics Lurbinectedin exposure-response relationships and the pharmacodynamic time-course for efficacy have not been fully characterized.
Indications
- 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.
Common Doses
- 3.2 mg
- 1.6 mg
- 2 mg
- 2.6 mg
Dosage
2 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.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS 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,...
Interactions
- 7 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.