Manufacturer:

Pfizer Inc.

Pharmacological Class:

Kinase inhibitor.

Active Ingredient(s):

Axitinib 1mg, 5mg; tabs.

Indication(s):

Treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy.

Pharmacology:

Axitinib has been shown to inhibit receptor tyrosine kinases including vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations. These receptors are implicated in pathologic angiogenesis, tumor growth, and cancer progression.

Clinical Trials:

The safety and efficacy of Inlyta were evaluated in an open-label, multicenter Phase 3 study. A total of 723 patients with advanced RCC whose disease had progressed on or after treatment with 1 prior systemic therapy, including sunitinib-, bevacizumab-, temsirolimus-, or cytokine-containing regimens were randomized (1:1) to receive Inlyta (N=361) or sorafenib (N=362). Progression-free survival (PFS) was assessed by a blinded independent central review committee. Other endpoints included objective response rate (ORR) and overall survival (OS).

There was a statistically significant advantage for Inlyta over sorafenib for the endpoint of PFS (6.7 months for Inlyta vs. 4.7 months for sorafenib; HR=0.67 (0.54, 0.81); P<0.0001). There was no statistically significant difference between the arms in OS.

Legal Classification:

Rx

Adults:

Take 12 hours apart. Swallow whole with a glass of water. Initially 5mg twice daily. If tolerated for at least two consecutive weeks with no adverse reactions >Grade 2, normotensive, and not receiving antihypertensives, may increase dose to 7mg twice daily, then 10mg twice daily. May reduce dose from 5mg twice daily to 3mg twice daily, then 2mg twice daily if additional dose reduction required. Concomitant strong CYP3A4/5 inhibitors: avoid; if warranted, decrease Inlyta dose by approximately ½. If strong CYP3A4/5 inhibitor discontinued, return Inlyta dose (after 3–5 half-lives of the inhibitor) to that used prior to CYP3A4/5 inhibitor initiation. Moderate hepatic impairment: decrease dose by approximately ½.

Children:

Not studied.

Warnings/Precautions:

Control and monitor BP prior to and during therapy; discontinue if severe and persistent hypertension (despite antihypertensive therapy and dose reduction). Risk of thromboembolic events. Untreated brain metastasis, recent active GI bleed: not recommended. Interrupt therapy if bleeding requires medical intervention. GI perforation and fistula formation; monitor. Monitor thyroid, liver function (ALT, AST, bilirubin), and for proteinuria before starting therapy, then periodically. Reduce dose or temporarily interrupt for moderate to severe proteinuria. Risk of reversible posterior leukoencephalopathy syndrome (permanently discontinue if occurs). Stop treatment at least 24hrs prior to scheduled surgery. Severe hepatic impairment. End-stage renal disease. Pregnancy (Cat. D); avoid. Use adequate contraception during therapy. Nursing mothers: not recommended.

Interaction(s):

See Adult dose. Avoid strong CYP3A4/5 inhibitors (eg, grapefruit juice, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole), CYP3A4/5 inducers (eg, rifampin, dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentin, phenobarbital, St. John’s wort), moderate CYP3A4/5 inducers (eg, bosentan, efavirenz, etravirine, modafinil, nafcillin).

Adverse Reaction(s):

GI upset, hypertension, fatigue, decreased appetite, dysphonia, palmar-plantar erythrodysesthesia (hand-foot) syndrome, weight decreased, asthenia, constipation.

How Supplied:

Tabs 1mg—180; 5mg—60

Last Updated:

3/26/2012