Xalkori

Last reviewed on RxList: 1/25/2021
Xalkori Side Effects Center

What Is Xalkori?

Xalkori (crizotinib) is an oral receptor tyrosine kinase inhibitor indicated for the treatment of patients with advanced or metastatic non-small cell lung cancer (NSCLC).

What Are Side Effects of Xalkori?

Common side effects of Xalkori include:

Tell your doctor if you have serious side effects of Xalkori including:

  • severe dizziness, fainting, fast or pounding heartbeats;
  • vision problems such as blurred vision, increased sensitivity of your eyes to light, or seeing flashes of light or "floaters";
  • chest pain, dry cough or cough with mucus, wheezing, shortness of breath;
  • easy bruising, unusual bleeding, purple or red pinpoint spots under your skin;
  • fever, chills, body aches, flu symptoms, sores in your mouth and throat;
  • loss of appetite, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes).

Dosage for Xalkori

Xalkori (crizotinib) is available in a 200 and 250 mg strength capsules. The recommended dose and schedule of Xalkori is 250 mg taken orally twice daily. Capsules should be swallowed whole. Xalkori may be taken with or without food. If a dose of Xalkori is missed, then it should be taken as soon as the patient remembers unless it is less than six hours until the next dose, in which case the patient should not take the missed dose. Patients should not take two doses at the same time to make up for a missed dose. Serious side effects include pneumonitis, QT prolongation and hepatic alterations.

Xalkori During Pregnancy and Breastfeeding

Patients should inform their doctors if they or their partner are pregnant or planning to become pregnant. Xalkori may harm unborn babies. Patients should also inform their doctors if they are breastfeeding or if they plan to breastfeed. It is not known if Xalkori passes into breast milk. Women who are able to become pregnant and men who take Xalkori should use birth control during treatment and for three months after stopping Xalkori. The safety and efficacy of Xalkori in pediatric patients has not been established.

Additional Information

Our Xalkori Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

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.

QUESTION

Lung cancer is a disease in which lung cells grow abnormally in an uncontrolled way. See Answer
Xalkori Consumer Information

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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:

  • increased sensitivity of your eyes to light, seeing flashes of light or "floaters";
  • blurred vision, double vision, or vision loss;
  • fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness (like you might pass out);
  • very slow heartbeats;
  • 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, tiredness, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

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

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.

Read the entire detailed patient monograph for Xalkori (crizotinib)

SLIDESHOW

Lung Cancer: Early Signs, Symptoms, Stages See Slideshow
Xalkori Professional Information

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]

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 reflect exposure to XALKORI in 1719 patients with NSCLC 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). The data also reflect exposure to XALKORI in 121 patients ages 1 to ≤21 years with relapsed or refractory tumors, including 26 patients with systemic ALCL, in a single-arm trial (Study ADVL0912).

ALK-Or ROS1-Positive Metastatic NSCLC

The data described below is based primarily on 343 patients with ALK-positive metastatic NSCLC who received XALKORI 250 mg orally 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 in patients with NSCLC 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 (PROFILE 1014)

The data in Table 7 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 with cisplatin 75 mg/m2 (n=91) or carboplatin at a dose calculated to produce an 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 34% of patients 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% 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%. 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 7 and 8 summarize common adverse reactions and laboratory abnormalities in XALKORI-treated patients.

Table 7. 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

Adverse ReactionXALKORI
(N=171)
Chemotherapy
(Pemetrexed/ Cisplatin or Pemetrexed/ Carboplatin)
(N=169)
All Grades
(%)
Grade 3-4
(%)
All Grades
(%)
Grade 3-4
(%)
Cardiac
  Bradycardiaa14110
  Electrocardiogram QT prolonged6220
Eye
  Vision disorderb711100
Gastrointestinal
  Diarrhea612131
  Vomiting462363
  Constipation432300
  Abdominal painc260120
  Dyspepsia14020
  Dysphagia10121
  Esophagitisd6210
General
  Edemae491121
  Pyrexia190111
Infections
  Upper respiratory infectionf320121
Investigations
  Increased weight8120
Musculoskeletal and Connective Tissue
  Pain in extremity16070
  Muscle spasm8021
Nervous System
  Dysgeusia26050
  Headache221150
  Dizzinessg180101
Adverse reactions were graded using NCI CTCAE version 4.0.
Includes cases reported within the clustered terms:
a Bradycardia (Bradycardia, Sinus bradycardia).
b Vision Disorder (Diplopia, Photophobia, Photopsia, Reduced visual acuity, Blurred vision, Vitreous floaters, Visual impairment).
c Abdominal pain (Abdominal discomfort, Abdominal pain, Lower abdominal pain, Upper abdominal pain, Abdominal tenderness).
d Esophagitis (Esophagitis, Esophageal ulcer).
e Edema (Edema, Peripheral edema, Face edema, Generalized edema, Local swelling, Periorbital edema).
f Upper respiratory infection (Nasopharyngitis, Pharyngitis, Rhinitis, Upper respiratory tract infection).
g Dizziness (Balance disorder, Dizziness, Postural dizziness, Presyncope).

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 8. Laboratory Abnormalities with Grades 3-4 Occurring in ≥4% of XALKORI-Treated Patients in Study 1

Laboratory AbnormalityXALKORIChemotherapy
Any Grade
(%)
Grade 3-4
(%)
Any Grade
(%)
Grade 3-4
(%)
Hematology
  Neutropenia52115916
  Lymphopenia4875313
Chemistry
  Increased ALT7915332
  Increased AST668281
  Hypophosphatemia3210216
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 (PROFILE 1007)

The data in Table 9 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 37% of patients treated with XALKORI and 23% of patients 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 5% of 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 increased ALT (8%) including some patients with concurrent increased AST, 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%), increased ALT and AST (1.2%), dyspnea (1.2%), and pulmonary embolism (1.2%).

Tables 9 and 10 summarize common adverse reactions and laboratory abnormalities in XALKORI-treated patients.

Table 9. 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

Adverse ReactionXALKORI
(N=172)
Chemotherapy
(Pemetrexed or Docetaxel)
(N=171)
All Grades
(%)
Grade 3-4
(%)
All Grades
(%)
Grade 3-4
(%)
Nervous System
  Dysgeusia26090
  Dizzinessa22180
  Syncope3300
Eye
  Vision disorderb60090
Cardiac
  Electrocardiogram QT prolonged5300
  Bradycardiac5000
Investigations
  Decreased weight10140
Gastrointestinal
  Diarrhea600191
  Nausea551371
  Vomiting471180
  Constipation422230
  Dyspepsia8030
Infections
  Upper respiratory infectiond260131
Respiratory, Thoracic and Mediastinal
  Pulmonary embolisme6522
General
  Edemaf310160
Adverse reactions were graded using NCI CTCAE version 4.0.
Includes cases reported within the clustered terms:
a Dizziness (Balance disorder, Dizziness, Postural dizziness).
b Vision Disorder (Diplopia, Photophobia, Photopsia, Blurred vision, Reduced visual acuity, Visual impairment, Vitreous floaters).
c Bradycardia (Bradycardia, Sinus bradycardia).
d Upper respiratory infection (Laryngitis, Nasopharyngitis, Pharyngitis, Rhinitis, Upper respiratory tract infection).
e Pulmonary embolism (Pulmonary artery thrombosis, Pulmonary embolism).
f Edema (Face edema, Generalized edema, Local swelling, Localized edema, Edema, Peripheral edema, Periorbital edema).

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 10. Laboratory Abnormalities with Grades 3-4 Occurring in ≥4% of XALKORI-Treated Patients in Study 2

Laboratory AbnormalityXALKORIChemotherapy
Any Grade
(%)
Grade 3-4
(%)
Any Grade
(%)
Grade 3-4
(%)
Hematology
  Lymphopenia5196025
  Neutropenia49122812
Chemistry
  Increased ALT7617384
  Increased AST619330
  Hypophosphatemia285256
  Hypokalemia184101
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 (PROFILE 1001)

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 Reactions In Patients With Metastatic NSCLC

Vision disorders

Vision disorders, most commonly visual impairment, photopsia, blurred vision, or vitreous floaters, occurred in 63% of 1719 patients. The majority (95%) of these patients had Grade 1 visual adverse reactions. There were 0.8% of patients with Grade 3 and 0.2% of 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

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

Renal cysts

Renal cysts were experienced by 3.0% 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.

Renal toxicity

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.

Relapsed Or Refractory, Systemic ALK-Positive ALCL -Study ADVL0912

The safety of XALKORI was evaluated in Study ADVL0912 [see Clinical Studies], which included 26 patients with relapsed or refractory, systemic ALCL after at least one systemic therapy. Eligible patients were 1 to ≤21 years of age and were required to have an absolute neutrophil count ≥1000/mm3 (750/mm3 if bone marrow was involved), platelet count ≥75,000/mm3 (25,000/mm3 if bone marrow was involved), creatinine clearance ≥70ml/min/1.73m2, and QTc ≤480 msec. The study excluded patients with ALT >2.5 times upper limit of normal (ULN), bilirubin ≤1.5 times ULN, and central nervous system tumors.

Patients with ALCL received XALKORI 165 mg/m2 or 280 mg/m2 orally twice daily until disease progression or unacceptable toxicity. The median duration of exposure was 5.4 months (range 1.8, 82.3 months), with 46% of patients treated for at least 6 months and 35% of patients treated for at least 12 months.

Serious adverse reactions occurred in 35% of patients treated with XALKORI. The most frequent serious adverse reactions were neutropenia (12%) and hypotension (8%).

Dose interruptions and dose reductions occurred in 77% and 19% of patients, respectively. XALKORI was discontinued for an adverse reaction in 8% of patients.

The most common adverse reactions (≥35%), excluding laboratory abnormalities, were diarrhea, vomiting, nausea, vision disorder, headache, musculoskeletal pain, stomatitis, fatigue, decreased appetite, pyrexia, abdominal pain, cough, and pruritis.

The most common Grade 3 or 4 laboratory abnormalities (≥15%) included neutropenia, lymphopenia, and thrombocytopenia. Grade 4 laboratory abnormalities (≥15%) included neutropenia (62%), lymphopenia (35%), and thrombocytopenia (19%).

Selected adverse reactions are summarized in Table 11.

Table 11. Adverse Reactions in ≥20% of Patients with Systemic ALCL in Study ADVL0912

Adverse ReactionXALKORI
N=26
All Grades
(%)
Grade 3-4
(%)
Blood and Lymphatic System Disordersa
  Neutropeniab10077
  Lymphopeniac5838
  Anemia543.8
  Thrombocytopeniad3819
Gastrointestinal Disorders
  Diarrhea9212
  Vomiting923.8
  Nausea773.8
  Abdominal Pain500
  Stomatitise468
  Constipation310
Renal Disordersa
  Blood creatinine increased1000
Investigationsa
  ALT increased813.8
  AST increased653.8
  Hypocalcemia623.8
  Hypoalbuminemia540
  Hyperglycemia460
  Hypomagnesemia460
  Hypoglycemia350
  Hypokalemia313.8
  Hypermagnesemia270
  Hyperkalemia230
Nervous System Disorders
  Headache583.8
  Dysgeusia230
  Dizziness230
Eye Disorders
  Vision disordersf650
Musculoskeletal Disorders
  Musculoskeletal paing5812
General Disorders
  Fatigue460
  Pyrexia380
  Edemah270
  Chills230
Metabolism and Nutrition Disorders
  Decreased appetite420
Skin and Subcutaneous Disorders
  Pruritus350
  Rashi230
Infections
  Upper respiratory tract infectionj310
Respiratory Disorders
  Cough350
  Rhinitis allergic230
Vascular Disorders
  Hypertension310
Adverse reactions were graded using NCI CTCAE version 4.0.
a Derived from laboratory values collected in Cycle 1 and adverse reaction data.
b Includes neutrophil count decreased.
c Includes lymphocyte count decreased.
d Includes platelet count decreased.
e Includes oral pain, oropharyngeal pain, stomatitis.
f Includes blurred vision, visual impairment, photophobia, photopsia, reduced visual acuity, vitreous floaters, cyanopsia, heterophoria, visual field defect.
g Includes arthralgia, back pain, myalgia, non-cardiac chest pain, pain in extremity.
h Includes peripheral edema, face edema, periorbital edema, localized edema.
i Includes rash maculopapular, rash pustular.
j Includes upper respiratory tract infection, pharyngitis, rhinitis, sinusitis.

Clinically relevant adverse reactions in <20% of patients treated with XALKORI included:

  • Cardiac disorders: Bradycardia (19%), electrocardiogram QT prolonged (8%)
  • Vascular Disorders: Hypotension (19%)
  • Investigations: Alkaline phosphatase increase (19%), hypernatremia (19%), GGT increase (8%), hyponatremia (12%), hyperuricemia (12%), hypophosphatemia (12%)
  • Nervous System Disorders: Peripheral neuropathy (12%)
  • Gastrointestinal disorders: Esophagitis (8%)
  • Blood and lymphatic disorders: Febrile neutropenia (3.8%)
  • Musculoskeletal disorders: Muscular weakness (8%)
  • Renal Disorder: Acute renal injury (8%)

Postmarketing Experience

The following additional adverse reaction has been identified during postapproval use of XALKORI. Because this reaction is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.

Investigations: Increased blood creatine phosphokinase

Read the entire FDA prescribing information for Xalkori (crizotinib)

© Xalkori Patient Information is supplied by Cerner Multum, Inc. and Xalkori Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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