What is Xalkori and how is it used?

Xalkori is a prescription medicine used to treat the symptoms of Non-Small Cell Lung Cancer. Xalkori may be used alone or with other medications.

Xalkori belongs to a class of drugs called Antineoplastics, Tyrosine Kinase Inhibitor; Antineoplastics, Anaplastic Lymphoma Kinase Inhibitor.

It is not known if Xalkori is safe and effective in children younger than 1 years of age.

What are the possible side effects of Xalkori?

Xalkori may cause serious side effects including:

• hives,
• difficulty breathing,
• swelling of your face, lips, tongue, or throat,
• increased sensitivity to light,
• seeing flashes of light or “floaters”,
• blurred vision,
• double vision,
• vision loss,
• fast or pounding heartbeats,
• fluttering in your chest,
• shortness of breath,
• sudden dizziness,
• very slow heartbeats,
• lightheadedness,
• sudden chest pain or discomfort,
• wheezing,
• dry cough,
• cough with mucus,
• fever,
• swollen gums,
• painful mouth sores,
• pain when swallowing,
• cold or flu symptoms,
• easy bruising,
• unusual bleeding (nosebleeds, bleeding gums),
• nausea,
• upper stomach pain,
• itching,
• tiredness,
• loss of appetite,
• dark urine,
• clay-colored stools, and
• yellowing of the skin or eyes (jaundice)

Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of Xalkori include:

• nausea,
• vomiting,
• decreased appetite,
• diarrhea,
• constipation,
• abnormal liver function tests,
• swelling in your hands, feet, and eyes,
• numbness or tingling in your hands and feet,
• muscle weakness,
• trouble walking,
• stuffy nose,
• sneezing,
• sore throat,
• dizziness,
• tiredness, and
• vision problems

Tell the doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Xalkori. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

DESCRIPTION

XALKORI (crizotinib) is an oral receptor tyrosine kinase inhibitor. The molecular formula for crizotinib is C₂₁H₂₂Cl₂FN₅O. The molecular weight is 450.34 daltons. Crizotinib is described chemically as (R)-3-[1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridin-2-amine.  The chemical structure of crizotinib is shown below:

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.

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.

The pink opaque capsule shell components contain gelatin, titanium dioxide, and red iron oxide. The white opaque capsule shell components contain gelatin and titanium dioxide. The printing ink contains shellac, propylene glycol, strong ammonia solution, potassium hydroxide, and black iron oxide.

INDICATIONS

ALK-Or ROS1-Positive Metastatic Non-Small Cell Lung Cancer

XALKORI is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test [see DOSAGE AND ADMINISTRATION].

Relapsed Or Refractory, Systemic ALK-Positive Anaplastic Large Cell Lymphoma

XALKORI is indicated for the treatment of pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive.

Limitations Of Use

The safety and efficacy of XALKORI have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL.

DOSAGE AND ADMINISTRATION

Patient Selection

Select patients for the treatment of metastatic NSCLC with XALKORI based on the presence of ALK or ROS1 positivity in tumor specimens [see Clinical Studies].

Information on FDA-approved tests for the detection of ALK and ROS1 rearrangements in NSCLC is available at http://www.fda.gov/companiondiagnostics.

Recommended Dosage For ALK-Or ROS1-Positive Metastatic Non-Small Cell Lung Cancer

The recommended dosage of XALKORI for patients with NSCLC is 250 mg orally twice daily, with or without food, until disease progression or no longer tolerated by the patient.

Swallow capsules whole. If a dose of XALKORI is missed, make up that dose unless the next dose is due within 6 hours. If vomiting occurs after taking a dose of XALKORI, take the next dose at the regular time.

Recommended Dosage For Relapsed Or Refractory, Systemic ALK-Positive Anaplastic Large Cell Lymphoma

The recommended dosage of XALKORI for patients with ALCL is 280 mg/m² orally twice daily until disease progression or unacceptable toxicity. The recommended dosage of XALKORI is based on body surface area (BSA) is provided in Table 1. If needed, attain the desired dose by combining different strengths of XALKORI capsules.

Assess pediatric patients for their ability to swallow intact capsules before prescribing XALKORI. Administer XALKORI to pediatric patients under adult supervision.

Take XALKORI with or without food. Swallow capsules whole. If a dose of XALKORI is missed, make up that dose unless the next dose is due within 6 hours. If vomiting occurs after taking a dose of XALKORI, take the next dose at the regular time.

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
• Interstitial Lung Disease/Pneumonitis [see WARNINGS AND PRECAUTIONS]
• QT Interval Prolongation [see WARNINGS AND PRECAUTIONS]
• Bradycardia [see WARNINGS AND PRECAUTIONS]
• Severe Visual Loss [see WARNINGS AND PRECAUTIONS]
• Gastrointestinal Toxicity in Patients with ALCL [see WARNINGS AND PRECAUTIONS]