Note: Initiate only if ANC is ≥1,500/mm3 and platelets are ≥100,000/mm3. Lurbinectedin is associated with a moderate emetic potential; patients received antiemetic prophylaxis with a 5-HT3 antagonist and dexamethasone in the clinical study (Ref).
Small cell lung cancer, metastatic: IV: 3.2 mg/m2 once every 21 days until disease progression or unacceptable toxicity (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl 30 to 89 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant differences in lurbinectedin pharmacokinetics were noted based on mild to moderate kidney impairment.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatic impairment prior to treatment initiation:
Mild impairment (total bilirubin ≤ ULN and AST > ULN or total bilirubin 1 to 1.5 times ULN and any AST): No dosage adjustment is necessary.
Moderate or severe impairment (total bilirubin >1.5 times ULN and any AST): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatotoxicity during treatment:
Grade 2: Withhold lurbinectedin until improved to ≤ grade 1, then resume lurbinectedin at the same dose.
Grade 3 or higher: Withhold lurbinectedin until improved to ≤ grade 1, then resume lurbinectedin at a reduced dose (see recommended lurbinectedin dose reduction levels in "Dosing: Adjustment for Toxicity") or permanently discontinue lurbinectedin.
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2 (general guideline recommendations): Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref). Note: Although the BSA was capped at 2 m2 in the clinical trial (Ref), the recommended dose in the manufacturer's labeling is not capped.
Dose reduction level |
Dose |
---|---|
Initial (usual) dose |
3.2 mg/m2 once every 21 days |
First dose reduction |
2.6 mg/m2 once every 21 days |
Second dose reduction |
2 mg/m2 once every 21 days |
If unable to tolerate 2 mg/m2 dose, or require >2 week dose delay |
Permanently discontinue lurbinectedin |
Adverse reaction |
Severity |
Lurbinectedin dosage modification |
---|---|---|
Hematologic toxicity | ||
Neutropenia |
Grade 4 or any grade neutropenic fever |
Withhold lurbinectedin until improved to ≤ grade 1; resume at a reduced dose. May administer growth factor prophylaxis in place of lurbinectedin dose reduction for isolated grade 4 neutropenia (ANC <500/mm3). For ANC <500/mm3 or any value less than the LLN, growth factors are recommended. |
Thrombocytopenia |
Grade 3 with bleeding or grade 4 |
Withhold lurbinectedin until platelets are ≥100,000/mm3; resume at a reduced dose. |
Nonhematologic toxicity | ||
Rhabdomyolysis |
Grade 2 |
Withhold lurbinectedin until improved to ≤ grade 1; resume at the same dose. |
Grade ≥3 |
Permanently discontinue lurbinectedin. | |
Other treatment-related adverse reactions |
Grade 2 |
Withhold lurbinectedin until improved to ≤ grade 1; resume at the same dose. |
Grade ≥3 |
Withhold lurbinectedin until improved to ≤ grade 1; resume at a reduced dose or permanently discontinue. |
Refer to adult dosing.
Anemia, neutropenia, and thrombocytopenia have commonly been reported, including grade 3 or 4 events; febrile neutropenia and sepsis (with rare fatalities) have also been reported. A greater incidence (>70% respectively) was seen with lymphocytopenia and leukopenia (all grades, including grade 3 and 4 events). The median duration of grade 3 or 4 neutropenia or thrombocytopenia was 7 days.
Onset: Varied; median time to onset of grade 3 or 4 neutropenia or thrombocytopenia was 15 and 10 days, respectively.
Nausea, constipation, vomiting, dysgeusia, and diarrhea have been reported commonly, although most events were grade 1 or 2. Lurbinectedin may be associated with a moderate emetic potential; patients received antiemetic prophylaxis in the clinical study (Ref).
Increased serum alanine aminotransferase (ALT) and increased serum aspartate aminotransferase (AST) have been reported commonly, including occurrences of grade 3 and 4 events. Median duration was 7 days.
Onset: Varied; median time to onset of ≥ grade 3 ALT and/or AST was 8 days (range: 3 to 49 days).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Endocrine & metabolic: Decreased serum albumin (32%), decreased serum magnesium (22%), decreased serum sodium (31%), increased serum glucose (52%)
Gastrointestinal: Abdominal pain (11%), constipation (31%), decreased appetite (33%), diarrhea (20%; grades 3/4: 4%), nausea (37%), vomiting (22%)
Hematologic & oncologic: Anemia (grades 3/4: 17%), leukopenia (79%; grades 3/4: 29%), lymphocytopenia (79%; grades 3/4: 43%), neutropenia (grades 3/4: 41%)
Hepatic: Increased serum alanine aminotransferase (66%), increased serum aspartate aminotransferase (26%)
Nervous system: Fatigue (77%), peripheral neuropathy (11%; grades 3/4: 1%)
Neuromuscular & skeletal: Musculoskeletal pain (33%)
Renal: Increased serum creatinine (69%)
Respiratory: Cough (20%), dyspnea (31%), respiratory tract infection (18%)
Miscellaneous: Fever (13%)
1% to 10%:
Cardiovascular: Chest pain (10%)
Gastrointestinal: Dysgeusia
Hematologic & oncologic: Febrile neutropenia (7%), thrombocytopenia (grades 3/4: 10%)
Infection: Sepsis (2%)
Nervous system: Headache (10%)
Respiratory: Pneumonia (10%), pneumonitis
Postmarketing:
Hematologic & oncologic: Tumor lysis syndrome (Wahab 2021)
Neuromuscular & skeletal: Rhabdomyolysis
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to lurbinectedin or any component of the formulation.
Concerns related to adverse effects:
• Extravasation: Vesicant; ensure proper needle or catheter placement prior to and during infusion. Consider infusing through a central line, particularly in patients with limited venous access. Avoid extravasation. Extravasation of lurbinectedin resulting in skin and soft tissue injury, including necrosis, requiring debridement can occur; the time to onset of necrosis after extravasation may vary.
Special populations:
• Older age: Patients ≥65 years of age experienced a higher incidence of serious adverse events, as compared to younger patients. Febrile neutropenia, neutropenia, thrombocytopenia, and anemia were the most frequently reported severe adverse reactions reported in patients ≥65 years of age.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Zepzelca: 4 mg (1 ea)
No
Solution (reconstituted) (Zepzelca Intravenous)
4 mg (per each): $9,540.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Zepzelca: 4 mg (1 ea)
IV: Infuse over 60 minutes. Consider infusing through a central line (to reduce risk of extravasation).
May be administered with or without an inline filter. If an infusion line with an inline filter is used for administration, a polyethersulfone inline filter with a 0.22-micron pore size is recommended; do not use an inline nylon membrane filter with lurbinectedin solutions diluted in NS for infusion (adsorption of lurbinectedin to the filter has been observed). Diluted lurbinectedin has demonstrated compatibility with PVC (non-DEHP-containing), polyurethane, and polyolefin infusion sets (polyethylene, polypropylene, and polybutadiene), with implantable venous access systems with titanium and plastic resin ports, and with polyurethane or silicone IV catheters. Do not administer lurbinectedin in the same IV line with other medications.
Lurbinectedin is associated with a moderate emetic potential; patients received antiemetic prophylaxis with a 5-HT3 antagonist and dexamethasone in the clinical study (Ref).
Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Administer subsequent infusions at a site that was not affected by extravasation.
Hazardous agent (NIOSH [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Small cell lung cancer, metastatic: Treatment of metastatic small cell lung cancer in adults with disease progression on or after platinum-based chemotherapy.
Lurbinectedin may be confused with trabectedin.
Zepzelca may be confused with Zejula, Zelboraf, Zoledex, Zydelig.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Substrate of CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Bitter Orange: May increase the serum concentration of Lurbinectedin. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Lurbinectedin. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Lurbinectedin. Management: Avoid concomitant use of lurbinectedin and moderate CYP3A4 inhibitors when possible. If combined, consider a lurbinectedin dose reduction as clinically indicated. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Lurbinectedin. Management: Avoid concomitant use of lurbinectedin and strong CYP3A4 inhibitors. If coadministration with a strong CYP3A4 inhibitor cannot be avoided, reduce the lurbinectedin dose by 50%. Risk D: Consider therapy modification
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Grapefruit Juice: May increase the serum concentration of Lurbinectedin. Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Coadministration with grapefruit and Seville oranges may increase lurbinectedin exposure. Management: Avoid concomitant administration with grapefruit and Seville oranges.
Verify pregnancy status prior to use in patients who could become pregnant.
Patients who could become pregnant should use effective contraception during therapy and for 6 months after the last lurbinectedin dose. Patients with partners who could become pregnant should use effective contraception during therapy and for 4 months after the last dose of lurbinectedin.
Based on the mechanism of action, and data from animal reproduction studies, in utero exposure to lurbinectedin may cause fetal harm.
It is not known if lurbinectedin is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 2 weeks after the last lurbinectedin dose.
Avoid grapefruit and Seville oranges.
Blood counts prior to each cycle, periodically during treatment, and as clinically necessary; LFTs prior to therapy initiation, periodically during treatment, and as clinically necessary; creatinine phosphokinase prior to therapy initiation, periodically during treatment, and as clinically necessary. Verify pregnancy status prior to therapy (in patients who could become pregnant). Monitor for signs/symptoms of hepatotoxicity. Monitor infusion site during infusion for signs/symptoms of extravasation or tissue necrosis.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Lurbinectedin is an alkylating agent and a selective inhibitor of oncogenic transcription which binds preferentially to guanine residues in the minor groove of DNA (Trigo 2020); this forms adducts and bends the DNA helix towards the major groove. Adduct formation affects the activities of DNA binding proteins, including some transcription factors and DNA repair pathways. Inhibition of oncogenic transcription results in tumor cell apoptosis (Trigo 2020).
Distribution: Vdss: 504 L.
Protein binding: ~99% to both albumin and α-1-acid glycoprotein.
Metabolism: Primarily hepatic, via CYP3A.
Half-life elimination: 51 hours.
Excretion: Feces: 89% (<0.2% as unchanged drug); urine: 6% (1% as unchanged drug).
Clearance: 11 L/hour.
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