Prescription Drug Information: Xalkori (Page 6 of 7)

14.2 Relapsed or Refractory, Systemic ALK-Positive Anaplastic Large Cell Lymphoma

The efficacy of XALKORI was evaluated in Study ADVL0912 (NCT00939770), a multicenter, single arm, open-label study in patients 1 to ≤21 years of age that included 26 patients with relapsed or refractory, systemic ALK-positive ALCL after at least one systemic treatment. ALK-positive status (confirmation of an ALK fusion) was determined locally by immunohistochemistry or fluorescence in situ hybridization. The study excluded patients with primary cutaneous ALCL or central nervous system involvement by lymphoma.

Patients received XALKORI 280 mg/m2 (20 patients) or 165 mg/m2 (6 patients) orally twice daily until disease progression or unacceptable toxicity. Patients were permitted to discontinue XALKORI to undergo hematopoietic stem cell transplantation (HSCT).

Of the 26 patients evaluated, the median age was 11 years (range: 3 to 20); 69% were male, 54% were White, 19% Black, 8% Asian. Patient enrollment by age category was 4 patients from 3 to <6 years, 11 patients from 6 to <12 years, 7 patients from 12 to <18 years, and 4 patients from 18 to ≤21 years.

All patients had received multi-agent systemic therapy, 2 (8%) had received a prior HSCT and 4 (15%) had received at least 3 prior therapies.

Efficacy was based on objective response rate and duration of response, as assessed by an independent review committee (Table 18). The median time to first response was 3.9 weeks (range: 3.5 to 9.1 weeks).

Table 18. Efficacy in Relapsed or Refractory, Systemic ALK-Positive ALCL
Efficacy Parameter N=26
CI=confidence interval; N/n=number of patients
*
Based on Lugano Classification.
95% CI based on Wilson score method.
Of 23 patients with objective response, 2 had disease progression and the remainder (91% of responding patients) were censored.

Objective response rate (95% CI, %) * ,

88% (71, 96)

Complete response, n

21 (81%)

Partial response, n

2 (8%)

Duration of response

Patients maintaining response at 3 months, n/N

13/23 (57%)

Patients maintaining response at 6 months, n/N

9/23 (39%)

Patients maintaining response at 12 months, n/N

5/23 (22%)

14.3 Unresectable, Recurrent, or Refractory ALK-Positive Inflammatory Myofibroblastic Tumor

Pediatric Patients with ALK-positive IMT

Study ADVL0912

The efficacy of XALKORI was evaluated in Study ADVL0912 (NCT00939770), a multicenter, single-arm, open-label study in patients 1 to ≤21 years of age that included 14 pediatric patients with unresectable, recurrent, or refractory ALK-positive IMT. Patients were required to have an ALK fusion determined locally by immunohistochemistry or fluorescence in situ hybridization. Patients (n=12) received XALKORI 280 mg/m2 twice daily until disease progression or unacceptable toxicity. Two patients received a lower dose.

The demographic characteristics were median age 6.5 years (range: 2 to 13); 64% female; 71% White; 7% Black, 21% unknown; 21% Hispanic; and 71% had a Lansky/Karnofsky Score of 100. Patient enrollment by age was 4 patients from 2 to <6 years, 8 patients from 6 to <12 years, and 2 patients from 12 to <18 years.

A total of 12 (86%) patients received prior therapy. The most common prior therapy was surgery (57%).

The major efficacy outcome was objective response rate according to RECIST version 1.0 as assessed by an independent review committee (Table 19).

Table 19. Efficacy in Pediatric Patients with Unresectable, Recurrent, or Relapsed ALK-Positive IMT
Efficacy Parameter N=14
CI=confidence interval; N/n=number of patients.
*
95% CI based on Clopper–Pearson exact method.
Estimated using descriptive statistics.

Objective response rate (95% CI, %) *

86% (57, 98)

Complete response, n (%)

5 (36)

Partial response n (%)

7 (50)

Duration of response

N=12

≥6 months, n (%)

7 (58)

≥12 months, n (%)

7 (58)

Adult Patients with ALK-positive IMT

Study A8081013

The efficacy of XALKORI was evaluated in Study A8081013 (NCT01121588), a multicenter, single-arm, open-label study that included 7 adult patients with unresectable, recurrent, or refractory ALK-positive IMT. ALK fusion was determined locally by immunohistochemistry or fluorescence in situ hybridization. Patients received XALKORI 250 mg twice daily.

The demographic characteristics were median age 38 years (range: 23 to 73); 57% male; 57% White, 43% Asian; and 86% ECOG performance status of 0 or 1. Two (29%) patients had at least one prior systemic treatment.

The major efficacy outcome was objective response rate according to RECIST version 1.1 per investigator assessment. For the 7 patients with ALK-positive IMT, 5 experienced a response including 1 complete response. The DOR was ≥6 months for all 5 patients and ≥12 months for 2 patients.

16 HOW SUPPLIED/STORAGE AND HANDLING

250 mg capsulesHard gelatin capsule with pink opaque cap and body, printed with black ink “Pfizer” on the cap, “CRZ 250” on the body; available in:

Bottles of 60 capsules:

NDC 0069-8140-20

200 mg capsulesHard gelatin capsule with pink opaque cap and white opaque body, printed with black ink “Pfizer” on the cap, “CRZ 200” on the body; available in:

Bottles of 60 capsules:

NDC 0069-8141-20

Store at room temperature 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Hepatotoxicity

Inform patients to immediately report symptoms of hepatotoxicity [see Warnings and Precautions (5.1)].

Interstitial Lung Disease (Pneumonitis)

Advise patients to immediately report any new or worsening pulmonary symptoms [see Warnings and Precautions (5.2)].

Bradycardia

Advise patients to report any symptoms of bradycardia and to inform their healthcare provider about the use of any heart or blood pressure medications [see Warnings and Precautions (5.4)].

Severe Visual Loss

Inform patients of the potential risk of severe visual loss and to immediately contact their healthcare provider if they develop severe visual loss. Inform patients that visual changes such as perceived flashes of light, blurry vision, light sensitivity, and floaters are commonly reported adverse reactions and may occur while driving or operating machinery. The onset of visual disorders most commonly occurs during the first week of treatment [see Warnings and Precautions (5.5), Adverse Reactions (6)].

Gastrointestinal Toxicity in Pediatric and Young Adult Patients with ALCL or Pediatric Patients with IMT

Inform patients with ALCL or pediatric patients with IMT of the risk of severe nausea, vomiting, diarrhea, and stomatitis. Advise patients to immediately inform their healthcare provider of problems with swallowing, vomiting, or diarrhea [see Warnings and Precautions (5.6)].

Drug Interactions

Inform patients to avoid grapefruit or grapefruit juice while taking XALKORI. Advise patients to inform their healthcare providers of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products [see Drug Interactions (7)].

Photosensitivity

Inform patients of the signs and symptoms of photosensitivity. Advise patients to avoid prolonged sun exposure and to use sunscreen or protective clothing during treatment with XALKORI [see Adverse Reactions (6.1)].

Dosage and Administration

Advise patients to take XALKORI with or without food and to swallow XALKORI capsules whole. If a patient misses a dose, advise the patient to take it as soon as remembered unless it is less than 6 hours until the next dose, in which case, advise the patient not to take the missed dose. If a patient vomits after taking a dose of XALKORI, advise the patient not to take an extra dose, but to take the next dose at the regular time.

Embryo-Fetal Toxicity

Advise females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.7), Use in Specific Populations (8.1)].

Females and Males of Reproductive Potential

Advise females of reproductive potential to use effective contraception during treatment with XALKORI and for at least 45 days after the final dose [see Use in Specific Populations (8.3)].

Advise males with female partners of reproductive potential to use condoms during treatment with XALKORI and for at least 90 days after the final dose [see Use in Specific Populations (8.3), Nonclinical Toxicology (13.1)].

Lactation

Advise females not to breastfeed during treatment with XALKORI and for 45 days after the final dose [see Use in Specific Populations (8.2)].

Infertility

Advise females and males of reproductive potential of the potential for reduced fertility from XALKORI [see Use in Specific Populations (8.3), Nonclinical Toxicology (13.1)].

This product’s labeling may have been updated. For the most recent prescribing information, please visit www.Pfizer.com. For medical information about XALKORI, please visit www.pfizermedinfo.com or call 1-800-438-1985.

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LAB-0440-26.0

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Revised: July 2022

MEDICATION GUIDE XALKORI® (zal-KOR-ee)(crizotinib) capsules

What is the most important information I should know about XALKORI? XALKORI may cause serious side effects, including:

Liver problems. XALKORI may cause life-threatening liver injury that may lead to death. Your healthcare provider should do blood tests to check your liver every 2 weeks during the first 2 months of treatment with XALKORI, then once a month and as recommended by your healthcare provider during treatment. Tell your healthcare provider right away if you develop any of the following new or worsening symptoms:
o
yellowing of your skin or the white part of your eyes
o
severe tiredness
o
dark or brown (tea color) urine
o
nausea or vomiting
o
decreased appetite
o
pain on the right side of your stomach
o
bleed or bruise more easily than normal
o
itching
Lung problems (pneumonitis). XALKORI may cause life-threatening lung problems that may lead to death. Symptoms may be similar to those symptoms from lung cancer. Tell your healthcare provider right away if you have any new or worsening symptoms, including:
o
trouble breathing or shortness of breath
o
cough with or without mucous
o
fever
Heart problems. XALKORI may cause very slow, very fast, or abnormal heartbeats. Your healthcare provider may check your pulse rate and blood pressure regularly during treatment with XALKORI. Tell your healthcare provider right away if you feel dizzy or faint or have abnormal heartbeats. Tell your healthcare provider if you take any heart or blood pressure medicines.
Severe vision problems. Vision problems are common with XALKORI. These problems usually happen within 1 week of starting treatment with XALKORI. Vision problems with XALKORI can be severe and may cause partial or complete loss of vision in one or both eyes. Your healthcare provider may hold or permanently stop your treatment with XALKORI and refer you to an eye specialist if any vision problems develop during treatment with XALKORI. Tell your healthcare provider right away if you have any new vision problems, loss of vision or any change in vision, including:
o
double vision
o
seeing flashes of light
o
blurry vision
o
light hurting your eyes
o
new or increased floaters

In addition, for children or young adults taking XALKORI to treat anaplastic large cell lymphoma (ALCL) or children taking XALKORI to treat inflammatory myofibroblastic tumor (IMT):Your healthcare provider may refer you to an eye specialist before starting XALKORI, and within 1 month of starting XALKORI to check for vision problems. You should have an eye examination every 3 months during treatment with XALKORI and more often if there are any new vision problems.

Severe stomach, intestine, and mouth (gastrointestinal) problems in children or young adults with ALCL or children with IMT. XALKORI may cause severe diarrhea, nausea, vomiting, or mouth sores. Tell your healthcare provider right away if problems with swallowing, vomiting, or diarrhea develop during treatment with XALKORI.
o
Your healthcare provider may give medicines as needed to prevent or treat diarrhea, nausea, and vomiting.
o
Your healthcare provider may recommend drinking more fluids or may prescribe electrolyte supplements or other kinds of nutritional support if severe symptoms develop.

See “What are possible side effects of XALKORI?” for more information about side effects.

What is XALKORI? XALKORI is a prescription medicine that is used to treat:

people with non-small cell lung cancer (NSCLC) that has spread to other parts of the body and is caused by a defect in either a gene called ALK (anaplastic lymphoma kinase) or a gene called ROS1.
children 1 year of age and older and young adults with ALCL or children 1 year of age and older and adults with IMT when your ALCL or IMT with a defect in a gene called ALK has returned, or you have tried a treatment and it did not work or is no longer working, or specifically for IMT, when the tumor cannot be surgically removed.

It is not known if XALKORI is safe and effective in older adults with ALCL or in children younger than 1 year of age with ALCL or IMT.

Before taking XALKORI, tell your healthcare provider about all of your medical conditions, including if you:

have liver or kidney problems
have lung problems
have heart problems, including a condition called long QT syndrome
have vision or eye problems
are pregnant, or plan to become pregnant. XALKORI can harm the unborn baby.Females who are able to become pregnant: Males who have female partners who can become pregnant:
o
Your healthcare provider will check to see if you are pregnant before starting treatment with XALKORI.
o
Effective birth control (contraception) should be used during treatment with XALKORI and for at least 45 days after the final dose of XALKORI.
o
Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with XALKORI.
o
You should use condoms during treatment with XALKORI and for at least 90 days after the final dose of XALKORI.
are breastfeeding or plan to breastfeed. It is not known if XALKORI passes into the breast milk. 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 the baby during this time.

Tell your healthcare provider about the medicines you take, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements.

How should I take XALKORI?

XALKORI should be taken exactly as prescribed by your healthcare provider.
XALKORI capsules should be swallowed whole.
XALKORI may be taken with or without food.
Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with XALKORI if you have certain side effects. Do not change the dose or stop treatment with XALKORI unless your healthcare provider tells you to.
If a dose of XALKORI is missed, it should be taken as soon as you remember. If it is close to the time of the next dose (within 6 hours), the missed dose should be skipped, and the next dose should be taken at the regular time.
If you vomit after taking a dose of XALKORI, do not take an extra dose. The next dose should be taken at the regular time.
XALKORI should be given to children under adult supervision.

What should I avoid while taking XALKORI?

Do not drink grapefruit juice, eat grapefruit or take supplements containing grapefruit extract during treatment with XALKORI. These may increase the amount of XALKORI in the blood.
XALKORI can cause changes in vision, dizziness, and tiredness. Do not drive or operate machinery if you have any of these symptoms.
Avoid spending prolonged time in sunlight. XALKORI can make your skin sensitive to the sun (photosensitivity), and you may burn more easily. You should use sunscreen and wear protective clothing that covers your skin to help protect against sunburn if you have to be in the sunlight during treatment with XALKORI.

What are the possible side effects of XALKORI? XALKORI may cause serious side effects, including:

See “What is the most important information I should know about XALKORI?”

The most common side effects of XALKORI in adults with NSCLC include:

vision problems
nausea, diarrhea, or vomiting
swelling of your hands, feet, face, or eyes
constipation
increased liver function blood tests
tiredness
decreased appetite
upper respiratory infection
dizziness
feeling of numbness or tingling in your arms or legs

The most common side effects of XALKORI in people with ALCL include:

diarrhea, vomiting, or nausea
vision problems
headache
muscle and joint pain
mouth sores
tiredness
decreased appetite
fever
stomach-area (abdominal) pain
cough
itchy skin
low blood counts

The most common side effects of XALKORI in adults with IMT include:

vision problems
nausea
swelling of your hands, feet, face, or eyes

The most common side effects of XALKORI in children with IMT include:

diarrhea, vomiting, or nausea
stomach-area (abdominal) pain
rash
vision problems
upper respiratory infection
cough
fever
muscle and joint pain
tiredness
swelling of your hands, feet, face, or eyes
constipation
headache

XALKORI may cause fertility problems in females and males, which may affect the ability to have children. Talk to your healthcare provider if you have concerns about fertility.These are not all of the possible side effects of XALKORI. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store XALKORI?

Store XALKORI at room temperature between 68°F to 77°F (20°C to 25°C).

Keep XALKORI and all medicines out of the reach of children.

General information about the safe and effective use of XALKORI. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use XALKORI for a condition for which it was not prescribed. Do not give XALKORI to other people, even if they have the same symptoms that you have. It may harm them. You can ask your healthcare provider or pharmacist for more information about XALKORI that is written for health professionals.

What are the ingredients in XALKORI? Active ingredient: crizotinibInactive ingredients: colloidal silicon dioxide, microcrystalline cellulose, anhydrous dibasic calcium phosphate, sodium starch glycolate, and magnesium stearate. Pink opaque capsule shell contains: gelatin, titanium dioxide, and red iron oxide. White opaque capsule shell contains: gelatin and titanium dioxide.Printing ink contains: shellac, propylene glycol, strong ammonia solution, potassium hydroxide, and black iron oxide.

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