Bone and connective tissue cancer:

Indications for YONDELIS:

Treatment of unresectable or metastatic liposarcoma or leiomyosarcoma in patients who have received prior anthracycline-containing regimen.

Adult:

Premedicate 30mins prior to each dose with IV dexamethasone 20mg. Give by IV infusion over 24hrs. 1.5mg/m2 every 21 days until disease progression or unacceptable toxicity. Moderate hepatic impairment: 0.9mg/m2 every 21 days. Dose modifications for adverse reactions: see full labeling. Do not increase dose in subsequent cycles once reduced.

Children:

<18yrs: not established.

Warnings/Precautions:

Assess neutrophil count prior to each dose and periodically during the cycle; withhold or reduce dose based on severity of reaction. Assess CPK levels prior to each dose; withhold, reduce dose, or permanently discontinue based on severity of reaction. Assess LFTs prior to each dose and as indicated based on pre-existing hepatic impairment; interrupt, reduce dose, or permanently discontinue based on severity/duration of abnormality. Increased risk of cardiac dysfunction (patients with LVEF <LLN, prior cumulative anthracycline ≥300mg/m2, age ≥65yrs, history of cardiac disease). Assess LVEF by ECHO or MUGA scan prior to initiation and every 2–3 months thereafter until discontinued; permanently discontinue based on severity of reaction. Monitor for capillary leak syndrome; discontinue and treat promptly if occurs. Severe hepatic impairment: not recommended. Embryo-fetal toxicity. Advise to use effective contraception during and for 2 months (females of reproductive potential) or 5 months (males w. female partners) after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended.

Pharmacologic Class:

Alkylating agent.

Interactions:

Avoid concomitant strong CYP3A inhibitors (eg, oral ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin, indinavir, lopinavir, ritonavir, boceprevir, nelfinavir, saquinavir, telaprevir, nefazodone, conivaptan), grapefruit or grapefruit juice; if short-term use (<14 days) necessary, give inhibitor 1 week after infusion and discontinue the day prior to next infusion. Avoid concomitant strong CYP3A inducers (eg, rifampin, phenobarbital, St. John’s wort).

Adverse Reactions:

Nausea, fatigue, vomiting, constipation, decreased appetite, diarrhea, peripheral edema, dyspnea, headache, neutropenia, increased ALT, thrombocytopenia, anemia, increased AST and CPK; anaphylaxis, neutropenic sepsis, rhabdomyolysis, hepatotoxicity, cardiomyopathy, capillary leak syndrome, extravasation resulting in tissue necrosis, infertility.

Generic Availability:

NO

How Supplied:

Single-dose vial—1