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Xalkori

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Xalkori

Xalkori Side Effects Center

Medical Editor: Charles Patrick Davis, MD, PhD

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). Xalkori is not available in a generic form. Common side effects with Xalkori use include gastrointestinal disorders, upper respiratory infection, decreased appetite, and insomnia.

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.

Safety evaluation of XALKORI is based on more than 1200 patients with ALK-positive metastatic NSCLC who received XALKORI as monotherapy at a starting oral dose of 250 mg twice daily continuously.

The most common adverse reactions ( ≥ 25%) of XALKORI are vision disorder, nausea, diarrhea, vomiting, constipation, edema, elevated transaminases, and fatigue.

ALK-Positive Metastatic NSCLC-Study 1

The data in Table 3 are derived from 343 patients with ALK-positive metastatic NSCLC enrolled in a randomized, multicenter, active-controlled, open-label trial (Study 1). 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 three 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 one dose of study treatment), the median age was 50 years; 84% of patients in the XALKORI arm and 87% of patients in the chemotherapy arm were younger than 65 years. A total of 57% of patients on XALKORI and 55% of chemotherapy patients were female. Forty-six percent (46%) of XALKORI-treated and 45% of chemotherapy-treated patients were from Asia.

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 interstitial lung disease (ILD; 2.9%). Fatal adverse reactions in XALKORI-treated patients in Study 1 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 alanine aminotransferase (ALT) elevation (7.6%) including some patients with concurrent aspartate aminotransferase (AST) elevation, QTc prolongation (2.9%), and neutropenia (2.3%).

Discontinuation of therapy in XALKORI-treated patients for adverse reactions was 17.0%. The most frequent adverse reactions that led to discontinuation in XALKORI-treated patients were ILD (1.7%), ALT and AST elevation (1.2%), dyspnea (1.2%), and pulmonary embolism (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=172)
Chemotherapy (Pemetrexed or Docetaxel)
(N=171)
All Grades (%) Grade 3/4 (%) All Grades (%) Grade 3/4 (%)
Nervous System Disorder
  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
  Weight decreased 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
Includes cases reported within the clustered terms:
aDizziness (Balance disorder, Dizziness, Dizziness postural)
bVision Disorder (Diplopia, Photophobia, Photopsia, Vision blurred, Visual acuity reduced, 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, Edema peripheral, 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, parasthesia, 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 4: Summary of Treatment-Emergent Laboratory Abnormalities with Grade 3 or 4 Incidence of ≥ 4% in XALKORI-Treated Patients

Laboratory Abnormality Crizotinib 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%

ALK-positive metastatic NSCLC-Study 2

The safety analysis population in Study 2 included 934 patients with ALK-positive metastatic NSCLC who received XALKORI in a clinical trial. The median duration of treatment was 23 weeks. Dosing interruptions and reductions due to treatment-related adverse events occurred in 23% and 12% of patients, respectively. The rate of treatment-related adverse events resulting in permanent discontinuation was 5%. The most common adverse reactions ( ≥ 25%) included vision disorder (55%), nausea (51%), vomiting (46%), diarrhea (46%), edema (39%), constipation (38%), and fatigue (26%).

Description Of Selected Adverse Drug Reactions

Vision disorders

Vision disorders, most commonly visual impairment, photopsia, blurred vision, or vitreous floaters, occurred in 691 (56%) patients across clinical trials (n=1225). The majority (99%) of these patients had Grade 1 or 2 visual adverse reactions. Across clinical studies, one patient had a treatment-related grade 3 vision abnormality.

Based on the Visual Symptom Assessment Questionnaire (VSAQ-ALK), patients treated with XALKORI in Study 1 reported a higher incidence of visual disturbances compared to patients treated with chemotherapy. The onset of vision disorders generally started within the first week of drug administration. The majority of patients on the XALKORI arm in Study 1 ( > 50%) reported visual disturbances; these visual disturbances 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 a patient questionnaire.

Neuropathy

Neuropathy, most commonly sensory in nature, occurred in 235 (19%) of 1225 patients. Most events (95%) were Grade 1 or Grade 2 in severity.

Renal Cysts

Renal cysts occurred in 7 (4%) patients treated with XALKORI and 1 (1%) patient treated with chemotherapy in Study 1. 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) »

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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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