DESCRIPTION
Crizotinib is a white to pale-yellow powder with a pKa of 9.4 (piperidinium cation) and 5.6 (pyridinium cation). The
solubility of crizotinib in aqueous media decreases over the range pH 1.6 to pH 8.2 from greater than 10 mg/mL to less
than 0.1 mg/mL. The log of the distribution coefficient (octanol/water) at pH 7.4 is 1.65.

INGREDIENTS
XALKORI capsules are supplied as printed hard-shell capsules containing 250 mg or 200 mg of crizotinib together with
colloidal silicon dioxide, microcrystalline cellulose, anhydrous dibasic calcium phosphate, sodium starch glycolate,
magnesium stearate, and hard gelatin capsule shells as inactive ingredients.

INDICATIONS AND USAGE
XALKORI is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors
are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.

DOSAGE AND ADMINISTRATION
The recommended dose of XALKORI is 250 mg orally, twice daily until disease progression or no longer tolerated by
the patient.

CLINICAL PHARMACOLOGY

Mechanism of Action
Crizotinib is an inhibitor of receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met),
ROS1 (c-ros), and Recepteur d'Origine Nantais (RON). Translocations can affect the ALK gene resulting in the
expression of oncogenic fusion proteins. The formation of ALK fusion proteins results in activation and dysregulation of
the gene's expression and signaling which can contribute to increased cell proliferation and survival in tumors
expressing these proteins. Crizotinib demonstrated concentration-dependent inhibition of ALK, ROS1, and c-Met
phosphorylation in cell-based assays using tumor cell lines and demonstrated antitumor activity in mice bearing tumor
xenografts that expressed EML4- or NPM-ALK fusion proteins or c-Met.
.

Pharmacokinetics
Following a single oral dose, crizotinib was absorbed with median time to achieve peak concentration of 4 to 6 hours.
Following crizotinib 250 mg twice daily, steady state was reached within 15 days and remained stable, with a median
accumulation ratio of 4.8. Steady-state systemic exposure (Cmin and AUC) appeared to increase in a greater than
dose proportional manner over the dose range of 200–300 mg twice daily.

The mean absolute bioavailability of crizotinib was 43% (range: 32% to 66%) following a single 250 mg oral dose.

A high-fat meal reduced crizotinib AUCinf and Cmax by approximately 14%. XALKORI can be administered with or
without food.

Crizotinib is predominantly metabolized by CYP3A4/5. Following single doses of crizotinib, the mean apparent plasma
terminal half-life of crizotinib was 42 hours in patients. Following the administration of a single 250 mg radiolabeled
crizotinib dose to healthy subjects, 63% and 22% of the administered dose was recovered in feces and urine,
respectively. Unchanged crizotinib represented approximately 53% and 2.3% of the administered dose in feces and
urine, respectively.

The most common side effects
Vision disorder, diarrhea, nausea, vomiting,  constipation etc. Crizotinib can cause some other side effects, please,
consult with your medical doctor for details.
____________________________________________________________________________________________
FDA Messages
On August 26, 2011, the U.S. Food and Drug Administration approved crizotinib (XALKORI(R) Capsules, Pfizer Inc.) for
treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic
lymphoma kinase (ALK)-positive as detected by an FDA-approved test. The Vysis ALK Break-Apart FISH Probe Kit
(Abbott Molecular, Inc.) was approved concurrently. In two multicenter, single-arm trials, patients with locally advanced
or metastatic ALK-positive NSCLC previously treated with one or more systemic therapies received crizotinib orally at a
dose of 250 mg twice daily. In 119 patients with ALK-positive NSCLC by local trial assay, the objective response rate
(ORR) was 61% (95% CI: 52%, 70%) with a median response duration of 48 weeks. In 136 patients with ALK-positive
NSCLC by the to-be-marketed test, the ORR was 50% (95% CI: 42%, 59%) with a median response duration of 42
weeks. The most common adverse reactions (>/=25%) were vision disorder, nausea, diarrhea, vomiting, edema, and
constipation. Accelerated approval was granted based on the high objective response rates and durable responses.
On November 20, 2013, crizotinib received full approval based on an improvement in progression-free survival in
patients with metastatic ALK-positive NSCLC previously treated with one platinum-based chemotherapy regimen.
http://www.accessdata.fda.gov/scripts/publications/search_result_record.cfm?id=49185
XALKORI  capsule   2014
Proprietary Name
Active Ingredient
Dosage Form; Route
Strength
Appl No
XALKORI  capsule
crizotinib
TABLET; ORAL
200 mg, 250 mg
 
Approval Date
Application Number
1st Orange Book Patent
Patent Expiration
 
Aug 26, 2011
N202570
7230098
      Mar 1, 2025
 
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