Xalkori

Before you start treatment, your doctor may perform tests to make sure crizotinib is the best treatment for your type of lung cancer.

Crizotinib is usually taken twice per day. Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You may take crizotinib with or without food.

Do not crush, chew, dissolve, or open a crizotinib capsule. Swallow it whole.

While using crizotinib, your heart rate and blood pressure will need to be checked often. You will also need frequent blood tests to check your liver function. Your heart function may need to be checked using an electrocardiograph or ECG (sometimes called an EKG). Your cancer treatments may be delayed based on the results of these tests.

You should not stop taking crizotinib without your doctor's advice.

Store at room temperature away from moisture and heat.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Take the missed dose as soon as you remember. Skip the missed dose if your next dose is less than 6 hours away. Do not take extra medicine to make up the missed dose.

ALK-Positive Metastatic NSCLC

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 [see Clinical Studies].

ROS1-Positive Metastatic NSCLC

XALKORI is indicated for the treatment of patients with metastatic NSCLC whose tumors are ROS1-positive [see Clinical Studies].

The following adverse reactions are discussed in greater detail in other sections of 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]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The data in the Warnings and Precautions section reflect exposure to XALKORI in 1719 patients who received XALKORI 250 mg twice daily enrolled on Studies 1 (including an additional 109 patients who crossed over from the control arm), 2, 3, a single arm trial (n=1063) of ALK-positive NSCLC, and an additional ALK-positive NSCLC expansion cohort of a dose finding study (n=154) [see WARNINGS AND PRECAUTIONS].

The data described below is based primarily on 343 patients with ALK-positive metastatic NSCLC who received XALKORI 250 mg twice daily from 2 open-label, randomized, active-controlled trials (Studies 1 and 2). The safety of XALKORI was also evaluated in 50 patients with ROS1-positive metastatic NSCLC from a single-arm study (Study 3).

The most common adverse reactions ( ≥ 25%) of XALKORI are vision disorders, nausea, diarrhea, vomiting, edema, constipation, elevated transaminases, fatigue, decreased appetite, upper respiratory infection, dizziness, and neuropathy.

Previously Untreated ALK-Positive Metastatic NSCLC - Study 1

The data in Table 3 are derived from 340 patients with ALK-positive metastatic NSCLC who had not received previous systemic treatment for advanced disease who received treatment in a randomized, multicenter, open-label, active-controlled trial (Study 1). Patients in the XALKORI arm (n=171) received XALKORI 250 mg orally twice daily until documented disease progression, intolerance to therapy, or the investigator determined that the patient was no longer experiencing clinical benefit. A total of 169 patients in the chemotherapy arm received pemetrexed 500 mg/m² in combination with cisplatin 75 mg/m² (n=91) or carboplatin at a dose calculated to produce an area under the concentration-time curve (AUC) of 5 or 6 mg min/mL (n=78). Chemotherapy was given by intravenous infusion every 3 weeks for up to 6 cycles, in the absence of dose-limiting chemotherapy-related toxicities. After 6 cycles, patients remained on study with no additional anticancer treatment, and tumor assessments continued until documented disease progression.

The median duration of study treatment was 10.9 months for patients in the XALKORI arm and 4.1 months for patients in the chemotherapy arm. Median duration of treatment was 5.2 months for patients who received XALKORI after cross over from chemotherapy. Across the 340 patients who were treated in Study 1, the median age was 53 years; 16% of patients were older than 65 years. A total of 62% of patients were female and 46% were Asian.

Serious adverse events were reported in 58 patients (34%) treated with XALKORI. The most frequent serious adverse events reported in patients treated with XALKORI were dyspnea (4.1%) and pulmonary embolism (2.9%). Fatal adverse events in XALKORI-treated patients occurred in 2.3% patients, consisting of septic shock, acute respiratory failure, and diabetic ketoacidosis.

Dose reductions due to adverse reactions were required in 6.4% of XALKORI-treated patients. The most frequent adverse reactions that led to dose reduction in these patients were nausea (1.8%) and elevated transaminases (1.8%).

Permanent discontinuation of XALKORI treatment for adverse reactions was 8.2%. The most frequent adverse reactions that led to permanent discontinuation in XALKORI-treated patients were elevated transaminases (1.2%), hepatotoxicity (1.2%), and ILD (1.2%).

Tables 3 and 4 summarize common adverse reactions and laboratory abnormalities in XALKORI-treated patients.

Table 3: Adverse Reactions Reported at a Higher Incidence ( ≥ 5% Higher for All Grades or ≥ 2% Higher for Grades 3-4) with XALKORI than Chemotherapy in Study 1†

Additional adverse reactions occurring at an overall incidence between 1% and 60% in patients treated with XALKORI included nausea (56%), decreased appetite (30%), fatigue (29%), neuropathy (21%; gait disturbance, hypoesthesia, muscular weakness, neuralgia, neuropathy peripheral, paresthesia, peripheral sensory neuropathy, polyneuropathy, sensory disturbance), rash (11%), renal cyst (5%), ILD (1%; ILD, pneumonitis), syncope (1%), and decreased blood testosterone (1%; hypogonadism).

Table 4: Laboratory Abnormalities with Grade 3 or 4 Incidence of ≥ 4% in XALKORI-Treated Patients in Study 1

Additional laboratory test abnormality in patients treated with XALKORI was an increase in creatinine (Any Grade: 99%; Grade 3: 2%; Grade 4: 0%) compared to the chemotherapy arm (Any Grade: 92%; Grade 3: 0%; Grade 4: 1%).

Previously Treated ALK-Positive Metastatic NSCLC - Study 2

The data in Table 5 are derived from 343 patients with ALK-positive metastatic NSCLC enrolled in a randomized, multicenter, active-controlled, open-label trial (Study 2). Patients in the XALKORI arm (n=172) received XALKORI 250 mg orally twice daily until documented disease progression, intolerance to therapy, or the investigator determined that the patient was no longer experiencing clinical benefit. A total of 171 patients in the chemotherapy arm received pemetrexed 500 mg/m² (n=99) or docetaxel 75 mg/m² (n=72) by intravenous infusion every 3 weeks until documented disease progression, intolerance to therapy, or the investigator determined that the patient was no longer experiencing clinical benefit. Patients in the chemotherapy arm received pemetrexed unless they had received pemetrexed as part of first-line or maintenance treatment.

The median duration of study treatment was 7.1 months for patients who received XALKORI and 2.8 months for patients who received chemotherapy. Across the 347 patients who were randomized to study treatment (343 received at least 1 dose of study treatment), the median age was 50 years; 14% of patients were older than 65 years. A total of 56% of patients were female and 45% of patients were Asian.

Serious adverse reactions were reported in 64 patients (37.2%) treated with XALKORI and 40 patients (23.4%) in the chemotherapy arm. The most frequent serious adverse reactions reported in patients treated with XALKORI were pneumonia (4.1%), pulmonary embolism (3.5%), dyspnea (2.3%), and ILD (2.9%). Fatal adverse reactions in XALKORI-treated patients in Study 2 occurred in 9 (5%) patients, consisting of: acute respiratory distress syndrome, arrhythmia, dyspnea, pneumonia, pneumonitis, pulmonary embolism, ILD, respiratory failure, and sepsis.

Dose reductions due to adverse reactions were required in 16% of XALKORI-treated patients. The most frequent adverse reactions that led to dose reduction in the patients treated with XALKORI were ALT elevation (7.6%) including some patients with concurrent AST elevation, QTc prolongation (2.9%), and neutropenia (2.3%).

XALKORI was discontinued for adverse reactions in 15% of patients. The most frequent adverse reactions that led to discontinuation of XALKORI were ILD (1.7%), ALT and AST elevation (1.2%), dyspnea (1.2%), and pulmonary embolism (1.2%).

Tables 5 and 6 summarize common adverse reactions and laboratory abnormalities in XALKORI-treated patients.

Table 5: Adverse Reactions Reported at a Higher Incidence ( ≥ 5% Higher for All Grades or ≥ 2% Higher for Grades 3/4) with XALKORI than Chemotherapy in Study 2†

Additional adverse reactions occurring at an overall incidence between 1% and 30% in patients treated with XALKORI included decreased appetite (27%), fatigue (27%), neuropathy (19%; dysesthesia, gait disturbance, hypoesthesia, muscular weakness, neuralgia, peripheral neuropathy, paresthesia, peripheral sensory neuropathy, polyneuropathy, burning sensation in skin), rash (9%), ILD (4%; acute respiratory distress syndrome, ILD, pneumonitis), renal cyst (4%), esophagitis (2%), hepatic failure (1%), and decreased blood testosterone (1%; hypogonadism).

Table 6: Laboratory Abnormalities with Grade 3 or 4 Incidence of ≥ 4% in XALKORI-Treated Patients in Study 2

Additional laboratory test abnormality in patients treated with XALKORI was an increase in creatinine (Any Grade: 96%; Grade 3: 1%; Grade 4: 0%) compared to the chemotherapy arm (Any Grade: 72%; Grade 3: 0%; Grade 4: 0%).

ROS1-Positive Metastatic NSCLC - Study 3

The safety profile of XALKORI from Study 3, which was evaluated in 50 patients with ROS1-positive metastatic NSCLC, was generally consistent with the safety profile of XALKORI evaluated in patients with ALK-positive metastatic NSCLC (n=1669). Vision disorders occurred in 92% of patients in Study 3; 90% were Grade 1 and 2% were Grade 2. The median duration of exposure to XALKORI was 34.4 months.

Description Of Selected Adverse Drug Reactions

Vision disorders, most commonly visual impairment, photopsia, blurred vision, or vitreous floaters, occurred in 1084 (63.1%) of 1719 patients. The majority (95%) of these patients had Grade 1 visual adverse reactions. There were 13 (0.8%) patients with Grade 3 and 4 (0.2%) patients with Grade 4 visual impairment.

Based on the Visual Symptom Assessment Questionnaire (VSAQ-ALK), patients treated with XALKORI in Studies 1 and 2 reported a higher incidence of visual disturbances compared to patients treated with chemotherapy. The onset of vision disorder generally was within the first week of drug administration. The majority of patients on the XALKORI arms in Studies 1 and 2 ( > 50%) reported visual disturbances which occurred at a frequency of 4-7 days each week, lasted up to 1 minute, and had mild or no impact (scores 0 to 3 out of a maximum score of 10) on daily activities as captured in the VSAQ-ALK questionnaire.

Neuropathy, most commonly sensory in nature, occurred in 435 (25%) of 1719 patients. Most events (95%) were Grade 1 or Grade 2 in severity.

Renal cysts were experienced by 52 (3%) of 1719 patients.

The majority of renal cysts in XALKORI-treated patients were complex. Local cystic invasion beyond the kidney occurred, in some cases with imaging characteristics suggestive of abscess formation. However, across clinical trials no renal abscesses were confirmed by microbiology tests.

The estimated glomerular filtration rate (eGFR) decreased from a baseline median of 96.42 mL/min/1.73 m² (n=1681) to a median of 80.23 mL/min/1.73 m² at 2 weeks (n=1499) in patients with ALK-positive advanced NSCLC who received XALKORI in clinical trials. No clinically relevant changes occurred in median eGFR from 12 to 104 weeks of treatment. Median eGFR slightly increased (83.02 mL/min/1.73 m²) 4 weeks after the last dose of XALKORI. Overall, 76% of patients had a decrease in eGFR to < 90 mL/min/1.73 m², 38% had a decrease to eGFR to < 60 mL/min/1.73 m², and 3.6% had a decrease to eGFR to < 30 mL/min/1.73 m² .

Xalkori is a prescription medication used to treat non-small cell lung cancer. Xalkori belongs to a group of drugs called tyrosine kinase inhibitors which work by blocking the action of a specific enzyme necessary for cancer cells to grow.

This medication comes in capsule form and is taken twice daily, with or without food. Swallow Xalkori capsules whole.

Common side effects of Xalkori include nausea, vomiting, and diarrhea.

Tell your doctor about the medicines you take, including prescription medicines, nonprescription medicines, vitamins, and herbal supplements.

Especially tell your doctor if you take:

• St. John’s Wort (Hypericum perforatum)
• Medicines for:
  • depression (antidepressants)
  • fungal infections (antifungals)
  • bacterial infections (antibiotics)
  • tuberculosis (TB)
  • HIV-AIDS
  • heart conditions
  • seizures

Know the medicines you take. Keep a list of them to show your doctor or pharmacist when you get a new medicine.

Tell your doctor if you are pregnant, or plan to become pregnant. 

Xalkori may harm your unborn baby. 

Women who are able to become pregnant and men who take Xalkori should use birth control during treatment and for 3 months after stopping Xalkori. 

Males who have female partners who can become pregnant should use condoms during treatment with Xalkori and for at least 90 days after the final dose of Xalkori.

• Talk to your doctor about the birth control methods that may be right for you.
• If you or your partner becomes pregnant, tell your doctor right away.

Tell your doctor if you are breastfeeding or plan to breastfeed. It is not known if Xalkori passes into your breast milk or if it will harm your nursing baby. Do not breastfeed during treatment with Xalkori and for 45 days after the final dose. Talk to your healthcare provider about the best way to feed your baby during this time.

You should not use crizotinib if you are allergic to it.

To make sure crizotinib is safe for you, tell your doctor if you have:

• liver or kidney disease;

• a heart rhythm disorder;

• an electrolyte imbalance (such as low levels of potassium or magnesium in your blood);

• a personal or family history of Long QT syndrome; or

• if you take any heart or blood pressure medicines.

Crizotinib can harm an unborn baby. Use birth control to prevent pregnancy while you are taking crizotinib, whether you are a man or a woman. Crizotinib use by either parent may cause birth defects.

• If you are a woman, do not take crizotinib if you are pregnant. Use effective birth control to prevent pregnancy while you are taking this medicine and for at least 45 days after your last dose.

• If you are a man, use effective birth control if your sexual partner is able to get pregnant. An unborn baby can be harmed if a man fathers the child while he is taking crizotinib. Keep using birth control for at least 3 months after your last dose.

• Tell your doctor right away if a pregnancy occurs while either the mother or the father is taking crizotinib.

It is not known whether crizotinib passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using crizotinib.

Take the missed dose as soon as you remember. Skip the missed dose if your next dose is less than 6 hours away. Do not take extra medicine to make up the missed dose.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• severe vision problems, including loss of vision;

• headache with chest pain and severe dizziness, fainting, fast or pounding heartbeats;

• very slow heart rate;

• a light-headed feeling, like you might pass out;

• sudden chest pain or discomfort, wheezing, dry cough or cough with mucus, feeling short of breath;

• fever, swollen gums, painful mouth sores, pain when swallowing, cold or flu symptoms;

• easy bruising or bleeding (nosebleeds, bleeding gums); or

• liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

• nausea, vomiting, decreased appetite;

• abnormal liver function tests;

• diarrhea, constipation;

• swelling in your hands or feet;

• tired feeling; or

• vision problems such as blurred vision, increased sensitivity of your eyes to light, or seeing flashes of light or "floaters."

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Antineoplastic agent; an inhibitor of several receptor tyrosine kinases including anaplastic lymphoma kinase (ALK).1 2 3 4 5 7 15 16

Contraindications

• Manufacturer states none known.1

Warnings/Precautions

Hepatic Toxicity

Fatal drug-induced hepatotoxicity has occurred; such cases reported in <1% of crizotinib-treated patients in clinical trials.1 ALT elevations >5 times ULN reported in 4–7% of patients in 2 main clinical trials; elevations were generally asymptomatic and reversible upon dosage interruption.1 Transaminase elevations usually develop within the first 2 months of treatment.1 (See Advice to Patients.)

Monitor liver function tests, including ALT and total bilirubin, once every month and as clinically indicated.1 More frequent repeat testing for increased transaminases, alkaline phosphatase, or total bilirubin necessary in patients who develop grade 2–4 transaminase elevations.1 (See Hepatic Toxicity under Dosage and Administration.)

Pneumonitis

Severe, life-threatening, or fatal pneumonitis reported in 1.6% of patients in 2 main clinical studies; all cases occurred within 2 months of therapy initiation.1 4

Monitor patients for pulmonary symptoms indicative of pneumonitis (see Advice to Patients).1 Exclude other causes of pneumonitis (e.g., disease progression, other pulmonary disease, infection, radiation therapy).1 If treatment-related pneumonitis occurs, permanently discontinue crizotinib.1

Prolongation of QT Interval

QTc-interval prolongation reported.1

Avoid use in patients with congenital long QT syndrome.1

Consider periodic monitoring of ECGs and serum electrolytes in patients with CHF, bradyarrhythmias, or electrolyte abnormalities or during concomitant use of drugs known to prolong the QT interval.1 (See Cardiovascular Toxicity under Dosage and Administration and see Specific Drugs and Foods under Interactions.)

Anaplastic Lymphoma Kinase Testing

Detection of ALK-positive NSCLC using an FDA-approved companion diagnostic test (Vysis ALK Break Apart FISH Probe Kit) indicated for this use is necessary for selecting patients for crizotinib therapy.1

Only laboratories with demonstrated proficiency in the specific technology being used should perform ALK testing; improper assay performance may cause unreliable results.1

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; embryotoxicity and fetotoxicity demonstrated in animals.1

Avoid pregnancy during therapy.1 Women of childbearing potential and men who are partners of such women should use adequate methods of contraception while receiving the drug and for ≥90 days after the drug is discontinued.1 If used during pregnancy or if the patient or their partner becomes pregnant during therapy, apprise of potential fetal hazard.1

Specific Populations

Category D.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Not known whether crizotinib is distributed into milk.1 Discontinue nursing or the drug.1

Safety and efficacy not established in pediatric patients.1

Decreased bone formation in growing long bones observed in juvenile animals; other toxicities of potential concern not evaluated in juvenile animal studies.1

No overall differences in safety or efficacy in patients ≥65 years of age compared with younger adults.1

Not studied in patients with hepatic impairment.1 Because extensively metabolized in the liver, increased plasma crizotinib concentrations likely.1 Use with caution.1 (See Hepatic Impairment under Dosage and Administration.)

Mild or moderate renal impairment did not substantially affect plasma crizotinib concentrations in one clinical study.1

Limited data in patients with severe renal impairment and no data in patients with end-stage renal disease; use with caution in such patients.1 (See Renal Impairment under Dosage and Administration and also see Special Populations under Pharmacokinetics.)

Common Adverse Effects

Visual disturbances (e.g., diplopia, photopsia, photophobia, blurred vision, visual field defect, visual impairment, vitreous floaters, visual brightness, reduced visual acuity),1 2 4 7 13 nausea,1 2 4 7 13 diarrhea,1 2 4 7 13 vomiting,1 2 4 7 13 constipation,1 2 13 esophageal disorder,1 abdominal pain,1 stomatitis,1 edema (e.g., localized edema, peripheral edema),1 2 13 fatigue,1 2 13 chest pain/discomfort,1 fever,1 upper respiratory infection,1 increased ALT1 2 4 13 or AST concentrations,1 2 decreased appetite,1 2 13 arthralgia,1 back pain,1 dizziness,1 2 13 neuropathy,1 13 headache,1 dysgeusia,1 13 insomnia,1 dyspnea,1 4 cough,1 rash.1

Predominantly metabolized by CYP3A4/5.1 Moderate inhibitor of CYP3A.1 Inhibitor and substrate of P-glycoprotein (P-gp) in vitro.1

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A inhibitors: Possible pharmacokinetic interaction (increased plasma concentrations of crizotinib).1 Avoid concomitant use of potent CYP3A inhibitors; use caution with concomitant use of moderate CYP3A inhibitors.1

Potent CYP3A inducers: Possible pharmacokinetic interaction (decreased plasma concentrations of crizotinib).1 Avoid concomitant use.1

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP3A: Possible pharmacokinetic interaction (increased plasma concentrations of CYP3A substrate).1 May need to reduce dosage of concurrently used drugs that are predominantly metabolized by CYP3A.1 Avoid concomitant use of crizotinib and CYP3A substrates with narrow therapeutic indices.1

Substrates of CYP1A2, 2B6, 2C8, 2C9, 2C19, or 2D6: Clinically important pharmacokinetic interactions not expected.1

Drugs Affecting Gastric Acidity

Potential pharmacokinetic interaction (decreased solubility and reduced oral bioavailability of crizotinib) with drugs that increase gastric pH.1

Substrates of P-glycoprotein Transport Systems

Substrates of P-gp: Possible pharmacokinetic interaction (increased plasma concentrations of the P-gp substrate).1

Substrates of Organic Anion-transporting Polypeptide 1B1 and 1B3

Substrates of hepatic uptake transport proteins OATP1B1 or OATP1B3: Clinically important pharmacokinetic interactions unlikely.1

Drugs that Prolong QT Interval

Potential pharmacologic interactions (additive effect on QT-interval prolongation).1 Consider periodic monitoring of ECGs and electrolytes during concomitant use.1 (See Prolongation of QT Interval under Cautions.)

Specific Drugs and Foods

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Black, tarry stools
• bloating or swelling of the face, arms, hands, lower legs, or feet
• body aches or pain
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chest pain or discomfort
• cough or hoarseness
• difficult or labored breathing
• ear congestion
• fever or chills
• headache
• increased sensitivity to pain or touch
• lightheadedness, dizziness, or fainting
• loss of voice
• lower back or side pain
• nerve pain
• painful or difficult urination
• pale skin
• rapid weight gain
• runny or stuffy nose
• slow or irregular heartbeat
• sneezing
• sore throat
• tightness in the chest
• ulcers, sores, or white spots in the mouth
• unsteadiness or awkwardness
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusual weight gain or loss
• weakness in the arms, hands, legs, or feet

• Bleeding gums
• blood in the urine or stools
• pinpoint red spots on the skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Abdominal or stomach discomfort, pain, or tenderness
• acid or sour stomach
• back pain
• belching
• change in taste
• decrease or change in vision
• decreased appetite
• diarrhea
• difficulty having a bowel movement (stool)
• difficulty with moving
• difficulty with swallowing
• heartburn
• increased sensitivity of the eyes to sunlight
• indigestion
• muscle pain or stiffness
• nausea
• pain in the joints
• pain or burning in the throat
• pain or discomfort in the chest, upper stomach, or throat
• problems with balance
• rash
• redness, swelling, or soreness of the tongue
• scaling, redness, burning, pain, chapping, swelling, or other signs of inflammation of the lips
• seeing flashes or sparks of light
• swelling or inflammation of the mouth
• trouble sleeping

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

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

Use Xalkori as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
• To gain the most benefit, do not miss doses.
• Take with or without food.
• Swallow whole. Do not chew, open, or crush.
• If you throw up after taking a dose, do not repeat the dose. Take your next dose at your normal time.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is less than 6 hours until the next dose, skip the missed dose and go back to the normal time.
• Do not take 2 doses at the same time or extra doses.

Take the missed dose as soon as you remember. Skip the missed dose if your next dose is less than 6 hours away. Do not take extra medicine to make up the missed dose.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.