lurbinectedin

General

Pronunciation:
loor-bin-ek-te-din


Trade Name(s)

  • Zepzelca

Ther. Class.

antineoplastics

Pharm. Class.

alkylating agents

Indications

Metastatic small cell lung cancer (SCLC) in patients with disease progression on or after platinum-based chemotherapy.

Action

Acts as an alkylating agent and a selective inhibitor of oncogenic transcription which results in DNA double-strand breaks and tumor cell apoptosis.

Therapeutic Effect(s):

Decreased progression of metastatic SCLC.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Extensively distributed to extravascular tissues.

Metabolism and Excretion: Primarily metabolized by the liver by the CYP3A4 isoenzyme. Primarily excreted in feces (89%, <0.2% as unchanged drug), with 6% excreted in urine (<1% as unchanged drug).

Half-life: 51 hr.

TIME/ACTION PROFILE (plasma concentrations)

ROUTEONSETPEAKDURATION
IVunknownend of infusionunknown

Contraindication/Precautions

Contraindicated in:

  • Baseline neutrophil count <1,500 cells/mm3 
  • Baseline platelet count <100,000 cells/mm3 
  • OB:   Pregnancy (may cause fetal harm);
  • Lactation:  Lactation.

Use Cautiously in:

  • Moderate or severe hepatic impairment
  • Rep:   Women of reproductive potential and men with female partners of reproductive potential
  • Pedi:   Safety and effectiveness not established in children;
  • Geri:   ↑ risk of myelosuppression.

Adverse Reactions/Side Effects

Endo: hyperglycemia

F and E: hypomagnesemia, hyponatremia

GI: abdominal pain, constipation, diarrhea, hypoalbuminemia, ↑ liver enzymes, nausea, vomiting

GU: ↑ serum creatinine

Hemat: NEUTROPENIA, anemia, leukopenia, lymphopenia, thrombocytopenia

Metabolic: ↓ appetite

MS: pain

Neuro: peripheral neuropathy, headache, dysgeusia

Resp: cough, dyspnea, respiratory tract infection

Misc: fatigue, fever

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  •  Strong CYP3A4 inhibitors  and  moderate CYP3A4 inhibitors  may ↑ levels and risk of toxicity; avoid concurrent use. If concurrent use with moderate CYP3A4 inhibitor unavoidable, consider ↓ lurbinectedin dose.
  •  Strong CYP3A4 inducers  and  moderate CYP3A4 inducers  may ↓ levels and effectiveness; avoid concurrent use.

Drug-Food:

Grapefruit juice may ↑ levels and risk of toxicity; avoid concurrent use.

Route/Dosage

IV (Adults): 3.2 mg/m2  every 21 days until disease progression or unacceptable toxicity.  Concurrent use of moderate CYP3A4 inhibitors– 2.6 mg/m2  every 21 days until disease progression or unacceptable toxicity.

Availability

Lyophilized powder for injection: 4 mg/vial

Assessment

  • Assess respiratory status (lung sounds, respiratory rate) before starting and periodically during therapy. Monitor for signs and symptoms of upper respiratory tract infection and bronchitis (shortness of breath, cough, fever, chills, decreased lung sounds) periodically during therapy.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.

  • Administer lurbinectedin only to patients with baseline neutrophil count ≥1,500 cells/mm3  and platelet count ≥100,000/mm3 .
  • Monitor CBC including neutrophil count and platelet count before each administration.  For neutrophil count <500 cells/mm3  or any value <lower limit of normal,  use of G-CSF is recommended.  If Grade 4 neutropenia or any grade febrile neutropenia occurs,  hold lurbinectedin until ≤Grade 1. Resume lurbinectedin at reduced dose.  If Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia occur,  hold lurbinectedin until platelet count ≥100,000/mm3 . Resume at reduced dose.
  • May cause hepatotoxicity. Monitor liver function tests, before starting therapy, periodically during treatment, and as clinically indicated. If Grade 2 hepatotoxicity occurs, hold lurbinectedin until ≤Grade 1. Resume at same dose. If ≥Grade 3 hepatotoxicity occurs, hold lurbinectedin until ≤Grade 1. Resume with reduced dose.

Implementation

  • Dose reduction recommendations:  1st dose reduction:  2.6 mg/m2  every 21 days.  2nd dose reduction:  2 mg/m2  every 21 days.
  • Premedicate with corticosteroids (dexamethasone 8 mg IV or equivalent) and serotonin antagonists (ondansetron 8 mg IV or equivalent) for antiemetic prophylaxis.

IV Administration

  • IV Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. If powder or solution comes in contact with skin or mucosa, wash thoroughly with soap and water. Discard equipment in specially designated containers.
  •  Reconstitution: Inject 8 mL of Sterile Water for Injection into vial; shake until complete dissolution.  Concentration:  0.5 mg/mL. Reconstituted solution is clear, colorless or slightly yellowish; do not administer solutions that are cloudy, discolored or contain particulate matter. Dilution:  For administration via central venous line,  withdraw dose from reconstituted solution and add to at least 100 mL 0.9% NaCl or D5W.  For administration through a peripheral venous line,  withdraw dose from reconstituted solution and add to at least 250 mL 0.9% NaCl or D5W.Do not administer solutions that are discolored or contain particulate matter. Solution is stable for up to 24 hr, including infusion time, at room temperature or if refrigerated.
  • Rate: Infuse over 60 min.

Patient/Family Teaching

  • Explain purpose of lurbinectedin to patient. Advise patient to read  Patient Information  before starting and periodically during therapy in case of changes.
  • Instruct patient to avoid eating grapefruit or drinking grapefruit juice during therapy.
  • Advise patient to notify health care professional if signs and symptoms of low blood cell counts (fever, any other signs of infection, tiredness, unusual bruising or bleeding, pale colored skin) or liver problems (loss of appetite, nausea or vomiting, pain on the right side of abdomen) occur.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • Rep:  May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for at least 6 mo after last dose and to avoid breastfeeding during and for at least 2 wk after last dose. Advise males with female partners of reproductive potential to use effective contraception during and for 4 mo after last dose. Advise patient to notify health care professional immediately if pregnancy is suspected.

Evaluation/Desired Outcomes

Decreased progression of metastatic SCLC.