Lurbinectedin is an intravenous alkylating agent. It is indicated for the treatment of metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Treatment with lurbinectedin is associated with potentially severe myelosuppression; it is more common in patients 65 years of age or older. Monitor blood counts prior to each dose of lurbinectedin and do not initiate or continue treatment until the neutrophil count is at least 1,500 cells/mm3 and the platelet count is at least 100,000 cells/mm3.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-Approved by FDA after NIOSH 2016 list published. The manufacturer recommends this drug be handled as a hazardous drug.
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Emetic Risk
-Moderate
-To prevent chemotherapy-induced nausea and vomiting, consider premedicating with corticosteroids (i.e., dexamethasone 8 mg IV or equivalent) and serotonin antagonists (i.e., ondansetron 8 mg IV or equivalent).
Extravasation Risk:
-Vesicant
-Consider use of a central venous catheter to reduce the risk of extravasation.
Route-Specific Administration
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Reconstitution and Dilution
-Inject 8 mL of Sterile Water for Injection into each 4 mg vial for a final concentration of 0.5 mg/mL. Shake the vial until complete dissolution.
-Diluted lurbinectedin is compatible with polyolefin containers (e.g., polyethylene, polypropylene, and mixtures).
-For central venous line administration: Add the appropriate volume of reconstituted solution to an infusion container at least 100 mL of 0.9% Sodium Chloride Injection or 5% Dextrose Injection.
-For peripheral venous line administration: Add the appropriate volume of reconstituted solution to an infusion container at least 250 mL of 0.9% Sodium Chloride Injection or 5% Dextrose Injection.
-Storage after reconstitution or dilution: If not used immediately after reconstitution or dilution, lurbinectedin may be stored for up to 24 hours (including infusion time) at either room temperature or refrigerated (2 to 8 degrees C; 36 to 46 degrees F).
Intravenous Infusion
-Diluted lurbinectedin is compatible with non-DEHP containing polyvinyl chloride (PVC), polyurethane, and polyolefin infusion sets (e.g., polyethylene, polypropylene, and polybutadiene). It is also compatible with implantable venous access systems with titanium and plastic resin ports, and with polyurethane or silicone IV catheters.
-Lurbinectedin may be administered with or without an in-line filter.
-Recommended in-line filters, if used, are 0.22 micron polyethersulfone (PES) in-line filters.
-In-line nylon membrane filters are NOT compatible with lurbinectedin that has been diluted with 0.9% Sodium Chloride Injection due to adsorption of lurbinectedin to the filter.
-Administer lurbinectedin as an IV infusion over 60 minutes.
-Do not administer lurbinectedin with other intravenous drugs concurrently within the same IV line.
Grade 3 or 4 anemia occurred in 17% of patients with advanced solid tumors treated with lurbinectedin monotherapy in a pooled safety population. In patients with SCLC who received lurbinectedin, serious cases of anemia occurred in at least 3% of patients; the incidence was higher in patients older than 65 years of age (8%). Decreased hemoglobin from baseline occurred in 74% of patients with platinum-resistant SCLC treated with lurbinectedin (grade 3 or 4, 10%).
Lurbinectedin can cause bone marrow suppression including neutropenia, lymphopenia, and leukopenia. Grade 3 or 4 neutropenia occurred in 41% of patients with advanced solid tumors treated with lurbinectedin monotherapy in a pooled safety population; the median time to onset was 15 days and the median duration was 7 days. In patients with SCLC who received lurbinectedin, serious cases of neutropenia occurred in at least 3% of patients; the incidence was higher in patients older than 65 years of age (11%). An increased incidence of grade 4 neutropenia was observed with increased lurbinectedin exposure in general. A decrease in neutrophils from baseline was reported in 71% of patients with platinum-resistant SCLC treated with lurbinectedin (grade 3 or 4, 7%). Febrile neutropenia occurred in 7% of patients in the pooled safety population and in at least 3% of patients from the SCLC cohort; serious cases of neutropenic fever were also more common in geriatric patients (11%). A decrease from baseline in leukocytes (79%; grade 3 or 4, 29%) and lymphocytes (79%; grade 3 or 4, 43%) also occurred in lurbinectedin-treated patients with SCLC.
Grade 3 or 4 thrombocytopenia occurred in 10% of patients with advanced solid tumors treated with lurbinectedin monotherapy in a pooled safety population; the median time to onset was 10 days and the median duration was 7 days. In patients with SCLC who received lurbinectedin, serious cases of thrombocytopenia occurred in at least 3% of patients; the incidence was higher in patients older than 65 years of age (8%). An increased incidence of grade 3 or higher thrombocytopenia was observed with increased lurbinectedin exposure in general. Decreased platelet counts from baseline occurred in 37% of patients with platinum-resistant SCLC treated with lurbinectedin (grade 3 or 4, 7%).
Lurbinectedin treatment can cause hepatotoxicity and elevated hepatic enzymes. Grade 3 elevations of ALT occurred in 6% and grade 3 elevations of AST occurred in 3% of patients with advanced solid tumors treated with lurbinectedin in a pooled safety population; grade 4 ALT and AST elevations occurred in 0.4% and 0.5% of patients, respectively. The median time to onset of grade 3 or higher transaminitis was 8 days and the median duration was 7 days. Increases from baseline in ALT (66%; grade 3 or 4, 4%) and AST (26%; grade 3 or 4, 2%) were reported in a cohort of patients with metastatic SCLC treated with lurbinectedin.
Hypoalbuminemia has been reported in patients treated with lurbinectedin, with 32% of patients with metastatic SCLC who received lurbinectedin reporting a decrease in albumin from baseline (grade 3 or 4, 1%).
Mild (grade 1 or 2) nausea was reported in 37% of patients with metastatic SCLC treated with lurbinectedin in one cohort of a multicenter, noncomparative study; vomiting occurred in 22% of patients.
Mild (grade 1 or 2) constipation was reported in 31% of patients with metastatic SCLC treated with lurbinectedin in one cohort of a multicenter, noncomparative study; abdominal pain was reported in 11% of patients (grade 3 or 4, 1%).
Diarrhea occurred in 20% of patients with metastatic SCLC treated with lurbinectedin in one cohort of a multicenter, noncomparative study (grade 3 or 4, 4%).
Anorexia was reported in 33% of patients with metastatic SCLC treated with lurbinectedin in one cohort of a multicenter, noncomparative study (grade 3 or 4, 1%); clinically relevant dysgeusia was reported in less than 10% of patients.
Fatigue was reported in 77% of patients with metastatic SCLC treated with lurbinectedin in one cohort of a multicenter, noncomparative study (grade 3 or 4, 12%).
Musculoskeletal pain including back pain, arthralgia, pain in extremities, musculoskeletal chest pain, neck pain, bone pain, and myalgia was reported in 33% of patients with metastatic SCLC treated with lurbinectedin in one cohort of a multicenter, noncomparative study (grade 3 or 4, 4%). Rhabdomyolysis has been reported in postmarketing experience with lurbinectedin. Monitor creatine phosphokinase (CPK) at baseline and periodically during treatment as clinically indicated. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary if rhabdomyolysis occurs.
Fever was reported in 13% of patients with metastatic SCLC treated with lurbinectedin in one cohort of a multicenter, noncomparative study.
Chest pain (unspecified) was reported in 10% of patients with metastatic SCLC treated with lurbinectedin in one cohort of a multicenter, noncomparative study.
Dyspnea (31%; grade 3 or 4, 6%) and cough (20%) were reported in patients with metastatic SCLC treated with lurbinectedin in one cohort of a multicenter, noncomparative study. Pneumonitis occurred in less than 10% of patients.
Upper respiratory tract infection including bronchitis occurred in 18% of patients with metastatic SCLC treated with lurbinectedin in one cohort of a multicenter, noncomparative study (grade 3 or 4, 5%); pneumonia occurred in 10% (grade 3 or 4, 7%) of patients. Sepsis occurred in 2% of patients with advanced tumors treated with lurbinectedin in a pooled safety population and was fatal in 1%.
Peripheral neuropathy including neuralgia, paresthesias, hypoesthesia, and hyperesthesia was reported in 11% of patients with metastatic SCLC treated with lurbinectedin in one cohort of a multicenter, noncomparative study (grade 3 or 4, 1%).
Headache was reported in 10% of patients with metastatic SCLC treated with lurbinectedin in one cohort of a multicenter, noncomparative study (grade 3 or 4, 1%).
Hyponatremia and hypomagnesemia have occurred with lurbinectedin therapy. A decrease from baseline in sodium occurred in 31% (grade 3 or 4, 7%) and a decrease in magnesium in 22% of patients with metastatic SCLC treated with lurbinectedin in one cohort of a multicenter, noncomparative study. Additionally, a mild (grade 1 or 2) increase in serum creatinine from baseline occurred in 69% of SCLC patients treated with lurbinectedin.
Hyperglycemia has occurred with lurbinectedin therapy. An increase in glucose from baseline occurred in 52% (grade 3 or 4, 5%) of patients with metastatic SCLC treated with lurbinectedin in one cohort of a multicenter, noncomparative study.
Extravasation of lurbinectedin has lead to injection site reactions resulting in skin and soft tissue injury, including necrosis requiring debridement, in postmarketing experience. Consider infusing through a central venous catheter to reduce the risk of extravasation, especially in patients with limited venous access. If extravasation occurs, immediately discontinue the infusion, remove the IV catheter, and monitor for signs and symptoms of tissue necrosis; the time to onset may vary. Administer supportive care and consult with an appropriate medical specialist as needed for extravasation. Administer subsequent infusions at a site that was not affected by extravasation.
Tumor lysis syndrome (TLS) has been reported in postmarketing experience with lurbinectedin.
Lurbinectedin can cause bone marrow suppression and should only be administered to patients with a neutrophil count of at least 1,500 cells/mm3 and platelet count of at least 100,000 cells/mm3. Monitor complete blood counts with differential prior to each administration of lurbinectedin; the use of G-CSF is recommended for patients with a neutrophil count less than 500 cells/mm3 or any value less than the lower limit of normal. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for patients who develop neutropenia or thrombocytopenia.
Use lurbinectedin with caution in patients with a history of hepatic disease; lurbinectedin can cause hepatotoxicity. Monitor liver function tests prior to initiating therapy, periodically during treatment, and as clinically indicated. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for patients who develop hepatic impairment.
Rhabdomyolysis has been reported in patients treated with lurbinectedin. Monitor creatine phosphokinase (CPK) at baseline and periodically during treatment as clinically indicated. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary if rhabdomyolysis occurs.
Extravasation resulting in skin and soft tissue injury, including necrosis requiring debridement, may occur with lurbinectedin administration; monitor patients for signs and symptoms of extravasation. Consider infusing through a central venous catheter to reduce the risk of extravasation, especially in patients with limited venous access. If extravasation occurs, immediately discontinue the infusion, remove the IV catheter, and monitor for signs and symptoms of tissue necrosis; the time to onset may vary. Administer supportive care and consult with an appropriate medical specialist as needed for extravasation. Administer subsequent infusions at a site that was not affected by extravasation.
Use lurbinectedin with caution in geriatric patients (65 years or older), as there was a higher incidence of serious hematologic adverse reactions and neutropenic fever reported in these patients.
Pregnancy should be avoided by females of reproductive potential during lurbinectedin treatment and for at least 6 months after the last dose. Although there are no adequately controlled studies in pregnant women, lurbinectedin can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving lurbinectedin should be apprised of the potential hazard to the fetus. Intravenous administration of a single lurbinectedin dose (approximately 0.2 times the 3.2 mg/m2 clinical dose) to pregnant rats during organogenesis resulted in 100% post-implantation loss.
Counsel patients about the reproductive risk and contraception requirements during lurbinectedin treatment. Lurbinectedin can be embryolethal if taken by the mother during pregnancy. Females of reproductive potential should avoid pregnancy and use effective contraception during and for at least 6 months after treatment with lurbinectedin. Due to the risk of male-mediated teratogenicity or embryolethality, males with female partners of reproductive potential should use effective contraception during treatment and for at least 4 months after the last dose. Females of reproductive potential should undergo pregnancy testing prior to initiation of lurbinectedin. Women who become pregnant while receiving lurbinectedin should be apprised of the potential hazard to the fetus.
Due to the potential for serious adverse reactions in nursing infants from lurbinectedin, advise women to discontinue breast-feeding during treatment and for 2 months after the final dose. It is not known whether lurbinectedin is present in human milk, although many drugs are excreted in human milk.
For the treatment of small cell lung cancer (SCLC):
-for the treatment of metastatic SCLC with disease progression on or after platinum-based chemotherapy, as monotherapy:
Intravenous dosage:
Adults: 3.2 mg/m2 IV over 60 minutes on day 1, every 21 days until disease progression or unacceptable toxicity. Initiate treatment only if the ANC is at least 1,500 cells/mm3 and the platelet count is at least 100,000 cells/mm3. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Treatment of progressive, metastatic SCLC with lurbinectedin resulted in an investigator-assessed partial response rate of 45% for a median duration of 6.2 months in patients whose chemotherapy-free interval was 90 days or more in one cohort of a multicenter, noncomparative study; 44% of patients remained in a partial response for 6 months or more. In patients with a chemotherapy-free interval of fewer than 90 days, the investigator-assessed partial response rate was 22% for a median duration of 4.7 months; 10% of patients remained in a partial response for 6 months or more.
Therapeutic Drug Monitoring:
Dosage Adjustments for Treatment-Related Toxicities
-First dose reduction: 2.6 mg/m2 IV
-Second dose reduction: 2 mg/m2 IV
-Permanently discontinue lurbinectedin therapy in patients unable to tolerate 2 mg/m2 or who require a dose delay of more than 2 weeks.
Neutropenia
NOTE: Do not begin a new cycle of treatment until the neutrophil count is 1,500 cells/mm3 or more.
-Grade 4: Hold lurbinectedin therapy. For neutrophil count less than 500 cells/mm3 or any value less than lower limit of normal, the use of G-CSF is recommended. When neutropenia resolves to grade 1 or less, resume treatment at a reduced dose.
-Any grade neutropenic fever: Hold lurbinectedin therapy. When the fever resolves, resume treatment at a reduced dose.
Rhabdomyolysis
-Grade 2: Hold lurbinectedin therapy. When rhabdomyolysis resolves to grade 1 or less, resume treatment at the same dose.
-Grade 3 or 4: Permanently discontinue lurbinectedin.
Thrombocytopenia
NOTE: Do not begin a new cycle of treatment until the platelet count is 100,000 cells/mm3 or more.
-Grade 3 with bleeding or grade 4: Hold lurbinectedin therapy. When the platelet count recovers to 100,000 cells/mm3 or more, resume treatment at a reduced dose.
Other Toxicities
-Grade 2: Hold lurbinectedin therapy. When toxicity resolves to grade 1 or less, resume treatment at the same dose.
-Grade 3 or 4: Hold lurbinectedin therapy. When toxicity resolves to grade 1 or less, resume treatment at a reduced dose or permanently discontinue therapy.
Maximum Dosage Limits:
-Adults
3.2 mg/m2 IV
-Geriatric
3.2 mg/m2 IV
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Baseline Hepatic Impairment
-Mild hepatic impairment (AST greater than the upper limit of normal [ULN] and total bilirubin within normal limits; OR total bilirubin 1.1 to 1.5 times ULN and any AST): No dosage adjustments are recommended.
-Moderate to severe hepatic impairment (total bilirubin greater than 1.5 times ULN and any AST): The effect of moderate or severe hepatic impairment on the pharmacokinetics of lurbinectedin have not been studied.
Treatment-Related Hepatotoxicity
-Grade 2: Hold lurbinectedin therapy. When hepatotoxicity resolves to grade 1 or less, resume treatment at the same dose. Permanently discontinue lurbinectedin treatment in patients unable to tolerate a dose of 2 mg/m2 or in patients requiring a dose delay of more than 2 weeks.
-Grade 3: Hold lurbinectedin therapy. When hepatotoxicity resolves to grade 1 or less, resume treatment at a reduced dose or permanently discontinue therapy. Permanently discontinue lurbinectedin treatment in patients unable to tolerate a dose of 2 mg/m2 every 21 days or in patients requiring a dose delay of more than 2 weeks.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Adagrasib: (Major) Avoid concomitant use of lurbinectedin and adagrasib due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Amobarbital: (Major) Avoid coadministration of lurbinectedin and barbiturates due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid concomitant use of lurbinectedin and clarithromycin due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Apalutamide: (Major) Avoid coadministration of lurbinectedin and apalutamide due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and apalutamide is a strong CYP3A inducer.
Aprepitant, Fosaprepitant: (Major) Avoid coadministration of lurbinectedin with a multi-day regimen of aprepitant due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor. When administered as a single oral or single intravenous dose, the inhibitory effect of aprepitant on CYP3A4 is weak and did not result in a clinically significant increase in the AUC of a sensitive substrate.
Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid coadministration of lurbinectedin and barbiturates due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Atazanavir: (Major) Avoid concomitant use of lurbinectedin and atazanavir due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Atazanavir; Cobicistat: (Major) Avoid concomitant use of lurbinectedin and atazanavir due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold. (Major) Avoid concomitant use of lurbinectedin and cobicistat due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Barbiturates: (Major) Avoid coadministration of lurbinectedin and barbiturates due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Berotralstat: (Major) Avoid coadministration of lurbinectedin and berotralstat due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and berotralstat is a moderate CYP3A inhibitor.
Butalbital; Acetaminophen: (Major) Avoid coadministration of lurbinectedin and barbiturates due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Butalbital; Acetaminophen; Caffeine: (Major) Avoid coadministration of lurbinectedin and barbiturates due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid coadministration of lurbinectedin and barbiturates due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Avoid coadministration of lurbinectedin and barbiturates due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Carbamazepine: (Major) Avoid coadministration of lurbinectedin and carbamazepine due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Ceritinib: (Major) Avoid concomitant use of lurbinectedin and ceritinib due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Chloramphenicol: (Major) Avoid concomitant use of lurbinectedin and chloramphenicol due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Ciprofloxacin: (Major) Avoid coadministration of lurbinectedin and ciprofloxacin due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor.
Clarithromycin: (Major) Avoid concomitant use of lurbinectedin and clarithromycin due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Cobicistat: (Major) Avoid concomitant use of lurbinectedin and cobicistat due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Conivaptan: (Major) Avoid coadministration of lurbinectedin and conivaptan due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor.
Crizotinib: (Major) Avoid coadministration of lurbinectedin and crizotinib due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and crizotinib is a moderate CYP3A inhibitor.
Cyclosporine: (Major) Avoid coadministration of lurbinectedin and cyclosporine due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and cyclosporine is a moderate CYP3A inhibitor.
Danazol: (Major) Avoid coadministration of lurbinectedin and danazol due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and danazol is a moderate CYP3A inhibitor.
Darunavir: (Major) Avoid concomitant use of lurbinectedin and darunavir due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Darunavir; Cobicistat: (Major) Avoid concomitant use of lurbinectedin and cobicistat due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold. (Major) Avoid concomitant use of lurbinectedin and darunavir due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid concomitant use of lurbinectedin and cobicistat due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold. (Major) Avoid concomitant use of lurbinectedin and darunavir due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Delavirdine: (Major) Avoid concomitant use of lurbinectedin and delavirdine due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and delavirdine is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Diltiazem: (Major) Avoid coadministration of lurbinectedin and diltiazem due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and diltiazem is a moderate CYP3A inhibitor.
Dronedarone: (Major) Avoid coadministration of lurbinectedin and dronedarone due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and dronedarone is a moderate CYP3A inhibitor.
Duvelisib: (Major) Avoid coadministration of lurbinectedin and duvelisib due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid concomitant use of lurbinectedin and cobicistat due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of lurbinectedin and cobicistat due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Encorafenib: (Major) Avoid coadministration of lurbinectedin and encorafenib due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and encorafenib is a strong CYP3A inducer.
Enzalutamide: (Major) Avoid coadministration of lurbinectedin and enzalutamide due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and enzalutamide is a strong CYP3A inducer.
Erythromycin: (Major) Avoid coadministration of lurbinectedin and erythromycin due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor.
Fedratinib: (Major) Avoid coadministration of lurbinectedin and fedratinib due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and fedratinib is a moderate CYP3A inhibitor.
Fluconazole: (Major) Avoid coadministration of lurbinectedin and fluconazole due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor.
Fluvoxamine: (Major) Avoid coadministration of lurbinectedin and fluvoxamine due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and fluvoxamine is a moderate CYP3A inhibitor.
Fosamprenavir: (Major) Avoid coadministration of lurbinectedin and fosamprenavir due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Fosphenytoin: (Major) Avoid coadministration of lurbinectedin and fosphenytoin due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and fosphenytoin is a strong CYP3A inducer.
Grapefruit juice: (Major) Advise patients to avoid grapefruit and grapefruit juice due to increased lurbinectedin exposure resulting in treatment-related adverse events. Lurbinectedin is a CYP3A substrate and lurbinectedin is a strong CYP3A inhibitor.
Idelalisib: (Major) Avoid concomitant use of lurbinectedin and idelalisib due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Imatinib: (Major) Avoid coadministration of lurbinectedin and imatinib due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor.
Indinavir: (Major) Avoid concomitant use of lurbinectedin and indinavir due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and indinavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Isavuconazonium: (Major) Avoid coadministration of lurbinectedin and isavuconazonium due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of lurbinectedin and rifampin due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and rifampin is a strong CYP3A inducer.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of lurbinectedin and rifampin due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and rifampin is a strong CYP3A inducer.
Itraconazole: (Major) Avoid concomitant use of lurbinectedin and itraconazole due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and itraconazole is a strong CYP3A inhibitor. Coadministration increased the overall exposure of lurbinectedin by 2.7-fold.
Ketoconazole: (Major) Avoid concomitant use of lurbinectedin and ketoconazole due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of lurbinectedin and clarithromycin due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Lefamulin: (Major) Avoid coadministration of lurbinectedin and lefamulen due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. Lurbinectedin is a CYP3A substrate and lefamulen is a moderate CYP3A inhibitor.
Lenacapavir: (Major) Avoid coadministration of lurbinectedin and lenacapavir due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor.
Letermovir: (Major) Avoid coadministration of lurbinectedin and letermovir due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and letermovir is a moderate CYP3A inhibitor.
Levoketoconazole: (Major) Avoid concomitant use of lurbinectedin and ketoconazole due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Lonafarnib: (Major) Avoid concomitant use of lurbinectedin and lonafarnib due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and lonafarnib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Lopinavir; Ritonavir: (Major) Avoid concomitant use of lurbinectedin and ritonavir due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of lurbinectedin and lumacaftor; ivacaftor due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and lumacaftor is a strong CYP3A inducer.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of lurbinectedin and lumacaftor; ivacaftor due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and lumacaftor is a strong CYP3A inducer.
Methohexital: (Major) Avoid coadministration of lurbinectedin and barbiturates due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Mifepristone: (Major) Avoid concomitant use of lurbinectedin and mifepristone due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Mitotane: (Major) Avoid coadministration of lurbinectedin and mitotane due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and mitotane is a strong CYP3A inducer.
Nefazodone: (Major) Avoid concomitant use of lurbinectedin and nefazodone due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and nefazodone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Nelfinavir: (Major) Avoid concomitant use of lurbinectedin and nelfinavir due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and nelfinavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Netupitant, Fosnetupitant; Palonosetron: (Major) Avoid coadministration of lurbinectedin and netupitant due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and netupitant is a moderate CYP3A inhibitor.
Nilotinib: (Major) Avoid coadministration of lurbinectedin and nilotinib due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and nilotinib is a moderate CYP3A inhibitor.
Nirmatrelvir; Ritonavir: (Major) Avoid concomitant use of lurbinectedin and ritonavir due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Nirogacestat: (Major) Avoid coadministration of lurbinectedin and nirogacestat due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and nirogacestat is a moderate CYP3A inhibitor.
Pentobarbital: (Major) Avoid coadministration of lurbinectedin and barbiturates due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Phenobarbital: (Major) Avoid coadministration of lurbinectedin and barbiturates due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of lurbinectedin and barbiturates due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Phenytoin: (Major) Avoid coadministration of lurbinectedin and phenytoin due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and phenytoin is a strong CYP3A inducer.
Posaconazole: (Major) Avoid concomitant use of lurbinectedin and posaconazole due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Primidone: (Major) Avoid coadministration of lurbinectedin and barbiturates due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Ribociclib: (Major) Avoid concomitant use of lurbinectedin and ribociclib due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Ribociclib; Letrozole: (Major) Avoid concomitant use of lurbinectedin and ribociclib due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Rifampin: (Major) Avoid coadministration of lurbinectedin and rifampin due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and rifampin is a strong CYP3A inducer.
Rifapentine: (Major) Avoid coadministration of lurbinectedin and rifapentine due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and rifapentine is a strong CYP3A inducer.
Ritlecitinib: (Major) Avoid coadministration of lurbinectedin and ritlecitinib due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor.
Ritonavir: (Major) Avoid concomitant use of lurbinectedin and ritonavir due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Saquinavir: (Major) Avoid concomitant use of lurbinectedin and saquinavir due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and saquinavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Secobarbital: (Major) Avoid coadministration of lurbinectedin and barbiturates due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and barbiturates are strong CYP3A inducers.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of lurbinectedin and St. Johns Wort due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and St. Johns Wort is a strong CYP3A inducer.
Tipranavir: (Major) Avoid concomitant use of lurbinectedin and tipranavir due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and tipranavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Trandolapril; Verapamil: (Major) Avoid coadministration of lurbinectedin and verapamil due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and verapamil is a moderate CYP3A inhibitor.
Tucatinib: (Major) Avoid concomitant use of lurbinectedin and tucatinib due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and tucatinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Verapamil: (Major) Avoid coadministration of lurbinectedin and verapamil due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and verapamil is a moderate CYP3A inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of lurbinectedin and clarithromycin due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Voriconazole: (Major) Avoid concomitant use of lurbinectedin and voriconazole due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and voriconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Voxelotor: (Major) Avoid coadministration of lurbinectedin and voxelotor due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor.
Lurbinectedin is an alkylating agent 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.
Lurbinectedin is administered intravenously. It is highly (approximately 99%) bound to both albumin and alpha-1-acid glycoprotein. The volume of distribution of lurbinectedin at steady-state is 504 liters (CV, 39%). The terminal half-life is 51 hours, and the total plasma clearance is 11 liters/hour (CV, 50%). After a single dose of radiolabeled lurbinectedin, 89% of the radioactivity was recovered in the feces (less than 0.2% unchanged), and 6% in the urine (1% unchanged).
Affected cytochrome P-450 (CYP450) isoenzymes: CYP3A
Lurbinectedin is metabolized by CYP3A. It is a substrate of MDR1 and inhibits MDR1, OATP1B1, OATP1B3, and OCT1 in vitro.
-Route-Specific Pharmacokinetics
Oral Route
At the clinical dose of 3.2 mg/m2, the Cmax of lurbinectedin was 107 mcg/liter (CV, 79%) and the AUC was 551 mcg x hour/liter (CV, 94%). There was no accumulation of lurbinectedin in plasma after repeated administrations every 3 weeks.
-Special Populations
Hepatic Impairment
Mild hepatic impairment (AST greater than the upper limit of normal [ULN] and total bilirubin within normal limits; OR total bilirubin 1.1 to 1.5 times ULN and any AST) did not cause a clinically significant difference in the pharmacokinetics of lurbinectedin. The effects of moderate to severe hepatic impairment (total bilirubin greater than 1.5 times ULN and any AST)) on the pharmacokinetics of lurbinectedin have not been studied.
Renal Impairment
Mild to moderate renal impairment (CrCl 30 to 89 mL/min) did not cause a clinically significant difference in the pharmacokinetics of lurbinectedin. The effect of severe renal impairment (CrCl less than 30 mL/min) on the pharmacokinetics of lurbinectedin has not been studied.
Geriatric
Age (18 to 85 years) did not cause a clinically significant difference in the pharmacokinetics of lurbinectedin.
Gender Differences
Gender did not cause a clinically significant difference in the pharmacokinetics of lurbinectedin.
Obesity
Body weight (39 to 154 kg) did not cause a clinically significant difference in the pharmacokinetics of lurbinectedin.