lurbinectedin

Absorption: IV administration results in complete bioavailability.

Distribution: Extensively distributed to extravascular tissues.

Metabolism/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)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	end of infusion	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Baseline neutrophil count <1,500 cells/mm³;
Baseline platelet count <100,000 cells/mm³;
OB: Pregnancy;
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 in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

Endo: hyperglycemia

F and E: hypomagnesemia, hyponatremia

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

GU: ↑serum creatinine

Hemat: anemia, leukopenia, lymphopenia, neutropenia, thrombocytopenia

Metab: ↓appetite

Local: extravasation

MS: pain, rhabdomyolysis

Neuro: fatigue, headache, peripheral neuropathy, dysgeusia

Resp: cough, dyspnea, respiratory tract infection

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including itraconazole, may ↑ levels and the risk of toxicity; avoid concurrent use. If concurrent use unavoidable, ↓ lurbinectedin dose.
Moderate CYP3A4 inhibitors may ↑ levels and the risk of toxicity; avoid concurrent use. If concurrent use unavoidable, consider ↓ lurbinectedin dose.
Strong CYP3A4 inducers may ↓ levels and effectiveness; avoid concurrent use.

Grapefruit juice and Seville oranges may ↑ levels and the 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 strong CYP3A4 inhibitors: ↓lurbinectedin dose by 50%.

Availability ⬆ ⬇

Lyophilized powder for injection: 4 mg/vial

Assessment ⬆ ⬇

Assess respiratory status before starting and periodically during therapy. Monitor for signs and symptoms of upper respiratory tract infection and bronchitis (shortness of breath, cough, fever, chills, ↓ 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 rhabdomyolysis. Monitor for elevated CK. If Grade 2 rhabdomyolysis occurs,hold lurbinectedin until ≤ Grade 1 and resume at same dose. If Grade ≥3 rhabdomyolysis occurs,permanently discontinue lurbinectedin.
- 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, and resume at same dose. If ≥Grade 3 hepatotoxicity occurs, hold lurbinectedin until ≤Grade 1, and 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. If unable to tolerate 2 mg/m²dose, or require >2-wk dose delay, permanently discontinue lurbinectedin.
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.
May be administered with or without an in-line filter. If using an in-line filter, use a polyethersulfone inline filter with a 0.22-mircon pore size.
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. Diluent: 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. Solution is stable for up to 24 hr, including infusion time, at room temperature and ambient light or refrigerated.
Rate: Infuse over 60 min.
Consider infusing through a central line (to reduce risk of extravasation). If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasation solution (do NOT flush the line); remove needle/cannula; elevate extremity.

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 Seville oranges 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. Report high blood sugar (confusion), trouble breathing, chest pain, change in urine frequency, severe muscle pain, burning, numbness, or tingling feeling that is not normal.
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 therapy and for at least 6 mo after last dose and to avoid breastfeeding during therapy and for at least 2 wk after last dose. Advise males with female partners of reproductive potential to use effective contraception during therapy and for 4 mo after last dose. Advise patient to notify health care professional immediately if pregnancy is suspected.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇