XALKORI CAPSULES*
Manufacturer DetailsPFIZER INC
Compositions:
Crizotinib- mg capsules,
Crizotinib- mg capsules,
| Strength | Rate | Packing Style |
|---|---|---|
| mg | 0.00 | unit capsules |
List of Related Indications:
- Metastatic Non-small cell Cancer(NSCLC) Patients whose tumors are Anaplastic Lymphoma Kinase (ALK) positive
List Of Drugs:
- Crizotinib - Xalkori-@- Anti-Cancer (Aug 2011)
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
CYP3A Inhibitors: Avoid concurrent use of XALKORI with strong (creatinine
clearance <30 mL/min) not requiring dialysis. CYP3A inhibitors.
.CYP3A Inducers: Avoid concurrent use of XALKORI with strong CYP3A inducers
CYP3A Substrates: Dose reduction may be needed for coadministered
drugs that are predominantly metabolized by CYP3A. Avoid concurrent
use of XALKORI WITH CYP3A substrate with narrow therapeutic indices
Indication:
XALKORI® (crizotinib) Capsules, oral treatment-related pneumonitis.
Initial U.S. Approval: August 2011
Drug Name- Xalkori
Active Ingredient - Crizotinib
To treat certain patients with late-stage (locally advanced or metastatic),
non-small lung cancers(NSCLC) who express abnormal anaplastic
kinase (ALK) gene
Indication-
To treat certain patients with late-stage (locally advanced or metastatic),
non-small lung cancers(NSCLC) who express abnormal anaplastic
kinase (ALK) gene
Approved by FDA on 26-8-2011 (Ref- FDA approved List- 2011)
Proprietary Name- XALKORI CAPSULES*
Established Name- Sorafenib
Applicant- PFIZER INC.
Indication- For the treatment of patients with metastatic Non-small cell
Cancer(NSCLC) whose tumors are anaplastic lymphoma kinase
(ALK) positive as deteceted by an FDA approved test
Approval Date- November 20,2013
Approved by U.S.FDA (Ref- FDA approved List- 2013)
Approved by (DCI) Drug Controller GENERAL - India For Marketing
(Ref- IDMA Publication)
Name of Drug Indication Date of Approval
Crizotinib Hard Gelatin capsules 16-12-2011
200mg/250mg
Adverse Reaction:
The most common adverse reactions (.25%) are vision disorder, nausea,diarrhea
Contra-Indications:
CONTRAINDICATIONS
None
WARNINGS AND PRECAUTIONS
1 Hepatotoxicity
Drug-induced hepatotoxicity with fatal outcome has occurred. These cases have
occurred during XALKORI treatment in less than 1% of patients in clinical trials.
Monitor with liver function tests including ALT and total bilirubin once a month
and as clinically indicated, with more frequent repeat testing for increased
liver transaminases, alkaline phosphatase, or total bilirubin in patients
who develop transaminase elevations
2 Pneumonitis
XALKORI has been associated with severe, life-threatening, or fatal
treatment-related pneumonitis in clinical trials with a frequency of 4 in 255 (1.6%)
patients. All of these cases occurred within 2 months after the initiation of treatment.
Monitor patients for pulmonary symptoms indicative of pneumonitis.
Exclude other causes of pneumonitis, and permanently discontinue
XALKORI in patients diagnosed with treatment-related pneumonitis .
3 QT Interval Prolongation
QTc prolongation has been observed. Avoid use of XALKORI in patients
with congenital long QT syndrome.
Consider periodic monitoring with electrocardiograms (ECGs) and
electrolytes in patients with congestive heart failure, bradyarrhythmias,
electrolyte abnormalities, or who are taking medications that are known
to prolong the QT interval.
Permanently discontinue XALKORI in patients who develop Grade
4 QTc prolongation.
Withhold XALKORI in patients who develop Grade 3 QTc prolongation
until recovery to less than or equal to Grade 1, then resume XALKORI
at 200 mg twice daily.
In case of recurrence of Grade 3 QTc prolongation, withhold XALKORI
until recovery to less than or equal to Grade 1, then resume XALKORI
at 250 mg once daily.
Permanently discontinue XALKORI if Grade 3 QTc prolongation recurs
4. Bradycardia
Symptomatic bradycardia can occur in patients receiving XALKORI.
Avoid using XALKORI in combination with other agents known to cause
bradycardia (e.g., beta-blockers, non-dihydropyridine calcium channel
blockers, clonidine and digoxin) to the extent possible.
Monitor heart rate and blood pressure regularly. In cases of Grade 2 and 3
symptomatic bradycardia hold XALKORI, re-evaluate the use of
concomitant medications, and adjust the dose of XALKORI.
Permanently discontinue for Grade 4 bradycardia due to XALKORI.
In cases of Grade 4 bradycardia associated with concomitant medications
known to cause bradycardia or hypotension, hold XALKORI
until Grade 1 or less, and if concomitant medications can be discontinued,
restart XALKORI at 250 mg once daily with frequent monitoring
Dosages/ Overdosage Etc:
1. INDICATIONS AND USAGE
XALKORI is indicated for the treatment of patients with locally advanced or metastatic
non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase
(ALK)-positive as detected by an FDA-approved test.
DOSAGE AND ADMINISTRATION
1 Recommended Dosing
The recommended dose and schedule of XALKORI is 250 mg taken orally twice daily.
Continue treatment as long as the patient is deriving clinical benefit from therapy.
XALKORI may be taken with or without food. Swallow capsules whole.
If a dose of XALKORI is missed, make up that dose unless the next dose is due
within 6 hours.
2 Dose Modification
Dosing interruption and/or dose reduction may be required based on individual
safety and tolerability. If dose reduction is necessary, then reduce the dose of
XALKORI to 200 mg taken orally twice daily. If further dose reduction is necessary,
then reduce the dosage to 250 mg taken orally once daily.
. DOSAGE FORMS AND STRENGTHS
250 mg capsules
Hard gelatin capsule, size 0, pink opaque cap and body, with Pfizer on the cap
and CRZ 250 on the body.
200 mg capsules
Hard gelatin capsule, size 1, white opaque body and pink opaque cap,
with Pfizer on the cap and CRZ 200 on the body
Patient Information:
1.Inform patients that symptoms of weakness, fatigue, anorexia, nausea, vomiting,
abdominal pain (especially RUQ abdominal pain), jaundice, dark urine,
generalized pruritus, and bleeding diathesis, especially in combination
with fever and rash, should be reported immediately
2.Inform patients that symptoms of bradycardia including dizziness, lightheadedness,
and syncope can occur while taking XALKORI.
3.Advise patients to report dizziness or lightheadedness and to inform their physician
about the use of any heart or blood pressure medications .
4.Inform patients that nausea, diarrhea, vomiting, and constipation are the most
commonly reported gastrointestinal adverse events occurring in patients who
received XALKORI. Supportive care for gastrointestinal adverse events
requiring treatment may include standard anti-emetic and/or anti-diarrheal
or laxative medications
5.Inform patients that visual changes such as perceived flashes of light, blurry vision,
light sensitivity, and floaters are commonly reported adverse events.
These events began most commonly during the first two weeks of treatment.
6.Advise patients to report flashes or floaters to their physicians
Pharmacology/ Pharmacokinetics:
1 Mechanism of Action
Crizotinib is an inhibitor of receptor tyrosine kinases including ALK, Hepatocyte
Growth Factor Receptor (HGFR, c-Met), and Recepteur d’Origine Nantais (RON).
Translocations can affect the ALK gene resulting in the expression of oncogenic
fusion proteins.
The formation of ALK fusion proteins results in activation and
dysregulation of the gene’s expression and signaling which can contribute
to increased cell proliferation and survival in tumors expressing these proteins.
Crizotinib demonstrated concentration-dependent inhibition of ALK and
c-Met phosphorylation in cell-based assays using tumor cell lines .
2. Pharmacokinetics
Absorption
Following oral single-dose administration, crizotinib was absorbed with median time
to achieve peak concentration of 4 to 6 hours. Following crizotinib 250 mg twice daily,
steady state was reached within 15 days
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1 Pregnancy
Pregnancy Category D
XALKORI can cause fetal harm when administered to a pregnant woman based
on its mechanism of action. There are no adequate and well-controlled studies
of XALKORI in pregnant women.
2. Nursing Mothers
It is not known whether XALKORI is excreted in human milk. Because many drugs
are excreted in human milk and because of the potential for serious adverse
reactions in nursing infants from XALKORI, consider whether to discontinue
nursing or to discontinue the drug, taking into account the importance of the
drug to the mother.
3 Pediatric Use
The safety and efficacy of XALKORI in pediatric patients has not been established.
4. Geriatric Use
Clinical studies of XALKORI did not include sufficient numbers of patients aged
65 and older to determine whether they respond differently from younger patients.
