Pancreatic, thyroid, and other endocrine cancers:

Indications for COMETRIQ:

Treatment of progressive, metastatic medullary thyroid cancer (MTC).

Adult:

Swallow whole. Take at least 1hr before or 2hrs after food. 140mg once daily until disease progression or unacceptable toxicity. Upon improvement of adverse reaction to Grade 1 or to baseline, reduce dose as follows: if previously on 140mg daily, resume at 100mg daily; if previously on 100mg daily, resume at 60mg daily; if previously on 60mg daily, resume at 60mg if tolerated, otherwise discontinue. Concomitant strong CYP3A4 inhibitors: if unavoidable, reduce daily dose by 40mg; resume dose used prior to starting inhibitor 2–3 days after discontinuation of inhibitor. Concomitant strong CYP3A4 inducers: if unavoidable, increase daily dose by 40mg; resume dose used prior to starting inhibitor 2–3 days after discontinuation of inhibitor. Mild to moderate hepatic impairment: initially 80mg daily. Max daily dose: 180mg.

Children:

Not studied.

Warnings/Precautions:

Not substitutable with cabozantinib tabs. Permanently discontinue if the following occurs: GI perforation, GI fistula (Grade 4), severe hemorrhage (Grade 3/4), acute MI, serious thromboembolic events that require medical intervention, hypertensive crisis or severe hypertension despite optimal medical management, nephrotic syndrome, reversible posterior leukoencephalopathy syndrome. Withhold for intolerable Grade 2 reactions, Grade 3/4 reactions, or osteonecrosis of the jaw. Recent history of hemorrhage (including hemoptysis, hematemesis, melena): do not administer. Monitor for GI perforations/fistulas. Monitor BP regularly; withhold for hypertension inadequately controlled with medical management; resume at reduced dose when resolved. Withhold therapy if intolerable Grade 2 diarrhea, unmanageable Grade 3/4 diarrhea, or intolerable Grade 2/3 palmar-plantar erythrodysesthesia (PPE) develops until improvement to Grade 1; resume at reduced dose. Monitor urine protein regularly. Perform oral exam prior to initiation and periodically during therapy. Withhold treatment for at least 3 weeks prior to elective surgery (including dental) and for at least 2 weeks after major surgery and until adequate wound healing. Severe hepatic impairment: not recommended. Severe renal impairment. Embryo-fetal toxicity. Advise females of reproductive potential to use effective contraception during and for 4 months after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 4 months after the last dose).

Pharmacologic Class:

Kinase inhibitor.

Interactions:

Avoid concomitant strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole, grapefruit or grapefruit juice) and strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St. John’s wort): see Adults dose. May be potentiated by MRP2 inhibitors (eg, abacavir, adefovir, cidofovir, furosemide, lamivudine, nevirapine, ritonavir, probenecid, saquinavir, tenofovir); monitor for increased toxicity.

Adverse Reactions:

Diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome, decreased weight/appetite, nausea, fatigue, oral pain, hair color changes, dysgeusia, hypertension, abdominal pain, constipation, increased AST, ALT, alkaline phosphatase, lymphopenia, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, hyperbilirubinemia.

Metabolism:

Hepatic (CYP3A4).

Elimination:

Fecal (~54%). Renal (~27%). Half-life (predicted): ~55 hours.

Generic Availability:

NO

How Supplied:

140mg daily-dose carton—4 blister cards (each: 7x80mg and 21x20mg caps); 100mg daily-dose carton—4 blister cards (each: 7x80mg and 7x20mg caps); 60mg daily-dose carton—4 blister cards (each: 21x20mg caps)