May 5, 2016
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Xalkori

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Xalkori




Xalkori Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Last reviewed on RxList 9/29/2015

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). Common side effects with Xalkori use include upper respiratory infection, nausea, vomiting, stomach pain, decreased appetite, insomnia, dizziness, tired feeling, diarrhea, constipation, rash or itching, cold symptoms (stuffy nose, sneezing, sore throat), numbness or tingling, or swelling in your hands or feet.

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. Patients should inform their doctors if they of 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.

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.

What is Patient Information in Detail?

Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.

Xalkori in Detail - Patient Information: Side Effects

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

Stop using crizotinib and call your doctor at once if you have a serious side effect such as:

  • 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, feeling short of breath;
  • easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;
  • fever, chills, body aches, flu symptoms, sores in your mouth and throat; or
  • nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

  • mild dizziness;
  • tired feeling;
  • nausea, vomiting, stomach pain, loss of appetite;
  • diarrhea, constipation;
  • mild rash or itching;
  • cold symptoms such as stuffy nose, sneezing, sore throat;
  • numbness or tingling; or
  • swelling in your hands or feet.

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)

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Xalkori FDA Prescribing Information: Side Effects
(Adverse Reactions)

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in other sections of the labeling:

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†

Adverse Reaction XALKORI
(N=171)
Chemotherapy (Pemetrexed/ Cisplatin or Pemetrexed/ Carboplatin)
(N=169)
All Grades (%) Grade 3-4 (%) All Grades (%) Grade 3-4 (%)
Cardiac Disorders
  Electrocardiogram QT prolonged 6 2 2 0
  Bradycardiaa 14 1 1 0
Eye Disorders
  Vision disorderb 71 1 10 0
Gastrointestinal Disorders
  Vomiting 46 2 36 3
  Diarrhea 61 2 13 1
  Constipation 43 2 30 0
  Dyspepsia 14 0 2 0
  Dysphagia 10 1 2 1
  Abdominal painc 26 0 12 0
General Disorders and Administration Site Conditions
  Edemad 49 1 12 1
  Pyrexia 19 0 11 1
Infections and Infestations
  Upper respiratory infectione 32 0 12 1
Investigations
  Increased weight 8 1 2 0
Musculoskeletal and Connective Tissue Disorders
  Pain in extremity 16 0 7 0
  Muscle spasm 8 0 2 1
Nervous System Disorders
  Dizzinessf 18 0 10 1
  Dysgeusia 26 0 5 0
  Headache 22 1 15 0
†Adverse reactions were graded using NCI CTCAE version 4.0. Includes cases reported within the clustered terms:
aBradycardia (Bradycardia, Sinus bradycardia).
bVision Disorder (Diplopia, Photophobia, Photopsia, Reduced visual acuity, Blurred vision, Vitreous floaters, Visual impairment).
cAbdominal pain (Abdominal discomfort, Abdominal pain, Lower abdominal pain, Upper abdominal pain, Abdominal tenderness).
dEdema (Edema, Peripheral edema, Face edema, Generalized edema, Local swelling, Periorbital edema).
eUpper respiratory infection (Nasopharyngitis, Pharyngitis, Rhinitis, Upper respiratory tract infection).
fDizziness (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%; which included gait disturbance, hypoesthesia, muscular weakness, neuralgia, neuropathy peripheral, paresthesia, peripheral sensory neuropathy, polyneuropathy, sensory disturbance), rash (11%), renal cyst (5%), ILD (1%; ILD, pneumonitis), and syncope (1%).

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

Laboratory Abnormality XALKORI Chemotherapy
Any Grade (%) Grade 3-4 (%) Any Grade (%) Grade 3-4 (%)
Hematology
  Neutropenia 52 11 59 16
  Lymphopenia 48 7 53 13
Chemistry
  ALT elevation 79 15 33 2
  AST elevation 66 8 28 1
  Hypophosphatemia 32 10 21 6

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†

Adverse Reaction XALKORI
(N=172)
Chemotherapy (Pemetrexed or Docetaxel)
(N=171)
All Grades (%) Grade 3-4 (%) All Grades (%) Grade 3-4 (%)
Nervous System Disorders
  Dizzinessa 22 1 8 0
 Dysgeusia 26 0 9 0
  Syncope 3 3 0 0
Eye Disorders
  Vision disorderb 60 0 9 0
Cardiac Disorders
  Electrocardiogram QT prolonged 5 3 0 0
  Bradycardiac 5 0 0 0
Investigations
  Decreased weight 10 1 4 0
Gastrointestinal Disorders
  Vomiting 47 1 18 0
  Nausea 55 1 37 1
  Diarrhea 60 0 19 1
  Constipation 42 2 23 0
  Dyspepsia 8 0 3 0
Infections and Infestations
  Upper respiratory infectiond 26 0 13 1
Respiratory, Thoracic and Mediastinal Disorders
  Pulmonary embolisme 6 5 2 2
General Disorders and Administration Site Conditions
  Edemaf 31 0 16 0
†Adverse reactions were graded using NCI CTCAE version 4.0. Includes cases reported within the clustered terms:
aDizziness (Balance disorder, Dizziness, Postural dizziness).
bVision Disorder (Diplopia, Photophobia, Photopsia, Blurred vision, Reduced visual acuity, Visual impairment, Vitreous floaters).
cBradycardia (Bradycardia, Sinus bradycardia).
dUpper respiratory infection (Laryngitis, Nasopharyngitis, Pharyngitis, Rhinitis, Upper respiratory tract infection).
ePulmonary embolism (Pulmonary artery thrombosis, Pulmonary embolism).
fEdema (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%), and hepatic failure (1%).

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

Laboratory Abnormality XALKORI Chemotherapy
Any Grade (%) Grade 3-4 (%) Any Grade (%) Grade 3-4 (%)
Hematology
  Neutropenia 49 12 28 12
  Lymphopenia 51 9 60 25
Chemistry
  ALT elevation 76 17 38 4
  AST elevation 61 9 33 0
  Hypokalemia 18 4 10 1
  Hypophosphatemia 28 5 25 6

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

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

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

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.

Read the entire FDA prescribing information for Xalkori (crizotinib)

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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