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Lurbinectedin

Medically reviewed by Drugs.com. Last updated on June 7, 2020.

Pronunciation

(LOOR bin EK te din)

Index Terms

  • DNA Minor Groove-binding Agent PM01183
  • PM-01183
  • PM01183

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous [preservative free]:

Zepzelca: 4 mg (1 ea)

Brand Names: U.S.

  • Zepzelca

Pharmacologic Category

  • Antineoplastic Agent, Alkylating Agent

Pharmacology

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.

Metabolism

Primarily hepatic, via CYP3A4.

Excretion

Feces: 89% (<0.2% as unchanged drug); urine: 6% (1% as unchanged drug).

Clearance: 11 L/hour.

Half-Life Elimination

51 hours.

Protein Binding

~99% to both albumin and α-1-acid glycoprotein.

Use: Labeled Indications

Small cell lung cancer, metastatic: Treatment of metastatic small cell lung cancer in adults with disease progression on or after platinum-based chemotherapy.

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Dosing: Adult

Note: Initiate only if ANC is ≥1,500/mm3 and platelets are ≥100,000/mm3. Lurbinectedin may be associated with a moderate emetic potential; patients received antiemetic prophylaxis with a 5-HT3 antagonist and dexamethasone in the clinical study (Trigo 2020).

Small cell lung cancer, metastatic: IV: 3.2 mg/m2 once every 21 days until disease progression or unacceptable toxicity (Trigo 2020).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Lurbinectedin Dose Reductions for Adverse Reactions

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

Neutropenia (grade 4 or any grade neutropenic fever): Withhold lurbinectedin until improved to ≤ grade 1, then resume lurbinectedin at a reduced dose. May administer growth factor prophylaxis in place of lurbinectedin dose reduction for isolated grade 4 neutropenia (ANC <500/mm3).

Thrombocytopenia (grade 3 with bleeding or grade 4): Withhold lurbinectedin until platelets are ≥100,000/mm3, then resume lurbinectedin at a reduced dose.

Reconstitution

Reconstitute each vial with 8 mL of SWFI to a concentration of 0.5 mg/mL. Shake vial until powder is completely dissolved. Withdraw appropriate dose from the vial and add to an infusion container containing at least 100 mL (if administering through a central line) or at least 250 mL (if administering through a peripheral line) of NS or D5W. If particulate matter is observed, do not administer.

Administration

IV: Infuse over 60 minutes. Lurbinectedin may be associated with a moderate emetic potential; patients received antiemetic prophylaxis with a 5-HT3 antagonist and dexamethasone in the clinical study (Trigo 2020).

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F). If not used immediately, reconstituted solution or solution diluted for infusion may be stored for up to 24 hours (including infusion time) after reconstitution, either at room temperature and ambient light or refrigerated at 2°C to 8°C (36°F to 46°F).

Drug Interactions

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Lurbinectedin. Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of Lurbinectedin. 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. Consider therapy modification

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Lurbinectedin. Avoid combination

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. Consider therapy modification

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Management: Consider avoiding Echinacea in patients receiving therapeutic immunosuppressants. If coadministered, monitor for reduced efficacy of the immunosuppressant during concomitant use. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Inebilizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Management: Avoid use of immunosuppressants (including systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for immune-related toxicity) is unlikely to affect nivolumab efficacy. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Ozanimod: Immunosuppressants may enhance the immunosuppressive effect of Ozanimod. Monitor therapy

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Management: Consider avoiding concomitant use of roflumilast and immunosuppressants as recommended by the Canadian product monograph. Inhaled or short-term corticosteroids are unlikely to be problematic. Consider therapy modification

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Talimogene Laherparepvec: Immunosuppressants may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk for disseminated herpetic infection may be increased. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Management: Concomitant use of upadacitinib with potent immunosuppressants is not recommended. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated less than 2 weeks before starting or during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>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%), 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%)

Hematologic & oncologic: Febrile neutropenia (7%), thrombocytopenia (grades 3/4: 10%)

Infection: Sepsis (2%)

Nervous system: Headache (10%)

Respiratory: Pneumonia (10%)

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Anemia, neutropenia, and thrombocytopenia have been reported, including grade 3 or 4 events; neutropenic fever and sepsis (with rare fatalities) have occurred as well. The median time to onset of grade 3 or 4 neutropenia or thrombocytopenia was 15 and 10 days, respectively; the median duration of grade 3 or 4 neutropenia or thrombocytopenia was 7 days. Lymphocytopenia has also occurred (including grades 3 and 4). The use of growth factors is recommended for ANC <500/mm3 or any value less than the lower limit of normal. Monitor blood counts prior to each dose and periodically throughout treatment cycle. ANC should be ≥1,500/mm3 and platelets ≥100,000/mm3 prior to treatment initiation. Hematologic toxicity may require treatment interruption, dose reduction, and/or permanent discontinuation.

• GI toxicity: Nausea, constipation, vomiting, and diarrhea were 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 (Trigo 2020).

• Hepatotoxicity: Elevated ALT and AST have occurred, including grade 3 and 4 events. The median time to onset of ≥ grade 3 ALT and/or AST was 8 days (range: 3 to 49 days), with a median duration of 7 days. Monitor LFTs prior to lurbinectedin initiation, periodically during treatment, and as clinically necessary. Hepatotoxicity may require treatment interruption, dose reduction, and/or permanent discontinuation.

Special populations:

• Elderly: 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.

Monitoring Parameters

Blood counts prior to each cycle and as clinically necessary; LFTs prior to therapy initiation, periodically during treatment, and as clinically necessary; evaluate pregnancy status prior to therapy (in females of reproductive potential). Monitor for signs/symptoms of hepatotoxicity and nausea/vomiting.

Reproductive Considerations

Evaluate pregnancy status prior to use in females of reproductive potential.

Females of reproductive potential should use effective contraception during therapy and for 6 months after the last lurbinectedin dose. Males with female partners of reproductive potential should use effective contraception during therapy and for 4 months after the last dose of lurbinectedin.

Pregnancy Considerations

Based on the mechanism of action, and data from animal reproduction studies, in utero exposure to lurbinectedin may cause fetal harm.

Patient Education

What is this drug used for?

• It is used to treat lung cancer.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Feeling tired or weak

• Stomach pain

• Not hungry

• Muscle pain

• Joint pain

• Headache

• Constipation

• Diarrhea

• Throwing up

• Upset stomach

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in your urine; black, red, or tarry stools; bleeding from the gums; menstruation; bruises without a reason or that get bigger; or any severe or persistent bleeding

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin

• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit

• Electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, seizures, not hungry, or very bad upset stomach or throwing up

• Pale skin

• Shortness of breath

• Chest pain

• Burning or numbness feeling

• Not able to pass urine

• Change in amount of urine passed

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.