ONIVYDE Dosage & Rx Info | Uses, Side Effects

Onivyde Generic Name & Formulations

Legal Class

General Description

Irinotecan 43mg/10mL; liposomal dispersion for IV infusion after dilution.

Pharmacological Class

Topoisomerase inhibitor.

How Supplied

Single-dose vial—1

Manufacturer

Ipsen Biopharmaceuticals, Inc.

Generic Availability

Mechanism of Action

Irinotecan liposome injection is a topoisomerase 1 inhibitor encapsulated in a lipid bilayer vesicle or liposome. Topoisomerase 1 relieves torsional strain in DNA by inducing single-strand breaks. Irinotecan and its active metabolite SN-38 bind reversibly to the topoisomerase 1-DNA complex and prevent re-ligation of the single-strand breaks, leading to exposure time-dependent double-strand DNA damage and cell death. In mice bearing human tumor xenografts, irinotecan liposome administered at irinotecan HCl-equivalent doses 5-fold lower than irinotecan HCl achieved similar intratumoral exposure of SN-38.

Onivyde Indications

Indications

In combination with oxaliplatin, fluorouracil and leucovorin, for the first-line treatment of metastatic pancreatic adenocarcinoma. In combination with fluorouracil and leucovorin, for treatment of metastatic pancreatic adenocarcinoma after disease progression following gemcitabine-based therapy.

Limitations of Use

As a single agent, not for the treatment of metastatic pancreatic adenocarcinoma.

Onivyde Dosage and Administration

Adult

Do not substitute for other irinotecan HCl-containing drugs. Give by IV infusion over 90mins prior to oxaliplatin/fluorouracil/leucovorin or fluorouracil/leucovorin. In combination with oxaliplatin/fluorouracil/leucovorin for first-line treatment: 50mg/m² every 2 weeks. In combination with fluorouracil/leucovorin after disease progression: 70mg/m² every 2 weeks; if homozygous UGT1A1*28 allele: initially 50mg/m²; may increase to 70mg/m² as tolerated in subsequent cycles. If serum bilirubin >ULN: no dose recommended. Premedicate with corticosteroid and antiemetic 30mins prior to infusion. Dose modifications: see full labeling.

Children

Not established.

Onivyde Contraindications

Not Applicable

Onivyde Boxed Warnings

Boxed Warning

Severe neutropenia. Severe diarrhea.

Onivyde Warnings/Precautions

Warnings/Precautions

Severe and life-threatening neutropenia, neutropenic sepsis, diarrhea can occur. Monitor CBCs on Days 1 and 8 of every cycle and more frequently if indicated; withhold if ANC <1500/mm³ or neutropenic fever occurs; reduce dose in subsequent cycles for Grade 3–4 neutropenia or neutropenic fever after recovery. Bowel obstruction: do not administer. Withhold for Grade 2–4 diarrhea; initiate loperamide if late onset or atropine IV/SC (unless contraindicated) if early onset and follow institutional guidelines if no improvement within 48hrs; resume at reduced dose after recovery to Grade 1. Pre-existing lung disease (monitor). Withhold if new or progressive dyspnea, cough, and fever occurs, pending evaluation; discontinue if interstitial lung disease confirmed. Permanently discontinue if severe hypersensitivity reaction occurs. Advise females of reproductive potential to use effective contraception during and for 7 months after the last dose; males should use condoms during and for 4 months after the last dose. Pregnancy. Nursing mothers: not recommended (during and for 1 month after the last dose).

Onivyde Pharmacokinetics

Distribution

Plasma protein bound: <0.44%.

Metabolism

Hepatic.

Elimination

Renal (11–20%). Half-life: 25.8 hours.

Onivyde Interactions

Interactions

Avoid concomitant strong CYP3A4 inducers (eg, rifampin, phenytoin, carbamazepine, rifabutin, rifapentine, phenobarbital, St. John’s wort) if possible; substitute non-enzyme inducing therapies at least 2 weeks before initiating irinotecan. Avoid concomitant strong CYP3A4 (eg, clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole) or UGT1A1 inhibitors (eg, atazanavir, gemfibrozil, indinavir) if possible; discontinue CYP3A inhibitors at least 1 week before initiating irinotecan. Risk for interstitial lung disease with pneumotoxic medicinal products, colony stimulating factors or previously received radiation therapy; monitor closely.

Onivyde Adverse Reactions

Adverse Reactions

Diarrhea, fatigue/asthenia, vomiting, nausea, decreased appetite, abdominal pain, stomatitis, mucosal inflammation, pyrexia, constipation, decreased weight, lab abnormalities; neutropenic fever or sepsis, dehydration, septic shock, pneumonia, acute renal failure, thrombocytopenia.

Onivyde Clinical Trials

See Literature

Onivyde Note