ICLUSIG*
Manufacturer DetailsGENERIC*
USA AND CANADA
Compositions:
Ponatinib-mg,
Ponatinib-mg,
| Strength | Rate | Packing Style |
|---|---|---|
| mg | 0.00 | unit |
List of Related Indications:
- To treat adults with chronic myeloid leukemia(CML) and Philadelphia chromosome positive acute lymphoblastic leukemia(Ph+ ALL), two rare blood and bone marrow diseases
List Of Drugs:
- Ponatinib- Iclusig -@-(Dec 2012)- Chemotherapeutic agent
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
Strong CYP3A Inhibitors: Reduce Iclusig dose if co-administration
cannot be avoided
Indication:
ICLUSIG® (ponatinib) tablets for oral use
Initial U.S. Approval: 2012
WARNING: VASCULAR OCCLUSION, HEART FAILURE, and HEPATOTOXICITY
See full prescribing information for complete boxed warning
Vascular Occlusion: Arterial and venous thrombosis and occlusions have
occurred in at least 27% of Iclusig treated patients, including fatal myocardial
infarction, stroke, stenosis of large arterial vessels of the brain, severe
peripheral vascular disease, and the need for urgent revascularization
procedures.
Patients with and without cardiovascular risk factors, including patients less
than 50 years old, experienced these events.
Monitor for evidence of thromboembolism and vascular occlusion.
Interrupt or stop Iclusig immediately for vascular occlusion.
Heart Failure, including fatalities, occurred in 8% of Iclusigtreated patients.
Monitor cardiac function. Interrupt or stop Iclusig for new or worsening heart failure
Hepatotoxicity, liver failure and death have occurred in Iclusigtreated patients.
Monitor hepatic function. Interrupt Iclusig if hepatotoxicity is suspected
RECENT MAJOR CHANGES
Boxed Warning 12/2013 Indications and Usage (1) 12/2013
Dosage and Administration (2.1) 12/2013
Warnings and Precautions (5.1, 5.2, 5.4, 5.6, and 5.7) 12/2013
Drug Name- Iclusig
Active Ingredient - Ponatinib
To treat adults with chronic myeloid leukemia (CLL) and Philadelphia
chromosome positive acute lymphoblastic leukemia (Ph+ALL), two
rare blood and bone marrow diseases
Indication-
To treat adults with chronic myeloid leukemia (CLL) and Philadelphia
chromosome positive acute lymphoblastic leukemia (Ph+ALL), two
rare blood and bone marrow diseases
Approved by FDA on 14-12--2012 (Ref- FDA approved List- 2012)
Adverse Reaction:
The most common non-hematologic adverse reactions (. 20%) were
hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation,
arthralgia, nausea, and pyrexia. Hematologic adverse reactions included
thrombocytopenia, anemia, neutropenia, lymphopenia, and leukopenia
Contra-Indications:
CONTRAINDICATIONS
None
WARNINGS AND PRECAUTIONS
Hypertension: Monitor for high blood pressure and manage as clinically indicated
.
Pancreatitis: Monitor serum lipase monthly; interrupt or discontinue Iclusig
.
Neuropathy: Monitor for symptoms of peripheral and cranial neuropathy.
.
Ocular Toxicity: Conduct comprehensive eye exams at baseline and periodically
during treatment
.
Hemorrhage: Interrupt Iclusig for serious or severe hemorrhage
.
Fluid Retention: Monitor patients for fluid retention; interrupt, reduce,
or discontinue Iclusig
.
Cardiac Arrhythmias: Monitor for symptoms of arrhythmias
.
Myelosuppression: Thrombocytopenia, neutropenia, and anemia may
require dose interruption or reduction. Monitor complete blood counts
every 2 weeks for 3 months and then monthly and as clinically indicated.
Interrupt Iclusig for ANC < 1000/mm3 or thrombocytopenia < 50,000/ mm3
.
Tumor Lysis Syndrome: Ensure adequate hydration and correct elevated
uric acid levels prior to initiating therapy with Iclusig
.
Compromised Wound Healing and Gastrointestinal Perforation:
Temporarily interrupt therapy in patients undergoing major surgical
procedures
.
Embryo-Fetal Toxicity: Can cause fetal harm. Advise women of potential
risk to a fetus
Dosages/ Overdosage Etc:
Indication-
To treat adults with chronic myeloid leukemia (CLL) and Philadelphia
chromosome positive acute lymphoblastic leukemia (Ph+ALL), two
rare blood and bone marrow diseases
INDICATIONS AND USAGE
Iclusig is a kinase inhibitor indicated for the:
Treatment of adult patients with T315I-positive chronic myeloid leukemia
(chronic phase, accelerated phase, or blast phase) or T315Ipositive
Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL).
Treatment of adult patients with chronic phase, accelerated phase, or blast phase
chronic myeloid leukemia or Ph+ ALL for whom no other tyrosine kinase
inhibitor (TKI) therapy is indicated.
These indications are based upon response rate. There are no trials verifying
an improvement in disease-related symptoms or increased survival with Iclusig.
DOSAGE AND ADMINISTRATION
45 mg taken orally once daily with or without food
Modify or interrupt dosing for hematologic and non-hematologic toxicity
DOSAGE FORMS AND STRENGTHS
Tablets: 15 mg and 45 mg
Patient Information:
PATIENT COUNSELING INFORMATION
See FDA-Approved Patient Labeling (Medication Guide).
Advise patients of the following and provide a copy of the Medication Guide:
Vascular Occlusions
Inform patients that serious arterial thromboses (including arterial stenosis
sometimes requiring revascularization) and venous thromboembolism events
have occurred. Advise patients to immediately contact their health care provider
with any symptoms suggestive of a blood clot such as chest pain,
shortness of breath, weakness on one side of the body, speech problems,
leg pain, or leg swelling
Heart Failure and Cardiac Arrhythmias
Inform patients of the possibility of heart failure, and abnormally slow or fast
heart rates. Advise patients to contact their health care provider if they
experience symptoms such as shortness of breath, chest pain, palpitations,
dizziness, or fainting
Hepatotoxicity
Inform patients of the possibility of developing liver function abnormalities
and serious hepatic toxicity. Advise patients to immediately contact their
health care provider if signs of liver failure occur, including yellowing
of the eyes or skin, “tea”colored urine, or drowsiness
Hypertension
Inform patients of the possibility of new or worsening of existing hypertension.
Advise patients to contact their health care provider for elevated blood
pressure or if symptoms of hypertension occur including headache,
dizziness, chest pain, or shortness of breath
Pancreatitis
Inform patients of the possibility of developing pancreatitis that may be
accompanied by nausea, vomiting, abdominal pain, or abdominal discomfort,
and to promptly report these symptoms
Neuropathy
Inform patients of the possibility of developing peripheral or cranial neuropathy
while being treated with Iclusig. Advise patients to report symptoms
of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort,
a burning sensation, neuropathic pain or weakness
Ocular Toxicity
Inform patients of the possibility of ocular toxicity while being treated
with Iclusig. Advise patients to report symptoms of ocular toxicity, such as
blurred vision, dry eye, or eye pain
Hemorrhage
Inform patients of the possibility of serious bleeding and to immediately
contact their health care provider with any signs or symptoms suggestive
of hemorrhage such as unusual bleeding or easy bruising
Fluid Retention
Inform patients of the possibility of developing fluid retention and to contact
their health care provider for symptoms such as leg swelling, abdominal
swelling, weight gain, or shortness of breath
Myelosuppression
Inform patients of the possibility of developing low blood cell counts;
inform patients to report immediately should fever develop, particularly
in association with any suggestion of infection
Compromised Wound Healing and Gastrointestinal Perforation
Advise patients to inform their health care provider if they plan to undergo
a surgical procedure or had recent surgery
Warning-
Inform patients that cases of gastrointestinal perforation have been reported
Embryo-Fetal Toxicity
Inform patients that Iclusig can cause fetal harm when administered to a pregnant
woman. Advise women of the potential hazard to a fetus and to avoid
becoming pregnant
Instructions for Taking Iclusig
Advise patients to take Iclusig exactly as prescribed and not to change
their dose or to stop taking Iclusig unless they are told to do so by their
health care provider. Iclusig may be taken with or without food.
Iclusig tablets should be swallowed whole.
Patients should not crush or dissolve the tablets.
Patients should not take two doses at the same time to make up for a missed dose.
Lactose
Inform patients that Iclusig contains 121 mg of lactose monohydrate in
a 45 mg daily dose.
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Ponatinib is a kinase inhibitor. Ponatinib inhibited the in vitro tyrosine kinase
activity of ABL and T315I mutant ABL with IC50 concentrations of 0.4 and 2.0 nM,
respectively.
Ponatinib inhibited the in vitro viability of cells expressing native or mutant
BCR-ABL, including T315I. In mice, treatment with ponatinib reduced the size
of tumors expressing native or T315I mutant BCR-ABL when compared to controls.
2. Pharmacokinetics
The geometric mean (CV%) C max and AUC( 0-ô) of Iclusig 45 mg daily at
presumed steady state in patients with advanced hematologic malignancies
were 73 ng/mL (74%) and 1253 ng•hr/mL (73%), respectively.
Ponatinib administered as an investigational capsule formulation to patients
with cancer exhibited approximately dose proportional increases in both
Cmax and AUC over the dose range of 15 to 60 mg.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Pregnancy Category D
Risk Summary
Based on its mechanism of action and findings in animals, Iclusig can cause fetal harm
when administered to a pregnant woman. There are no adequate and well-controlled
studies with Iclusig in pregnant women. Advise women to avoid becoming pregnant
while taking Iclusig. If this drug is used during pregnancy, or if the patient becomes
pregnant while taking this drug, the patient should be apprised of the potential
hazard to a fetus.
2.Nursing Mothers
It is unknown whether ponatinib 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 ponatinib, a decision should be made whether to discontinue
nursing or to discontinue Iclusig, taking into account the importance of the drug to
the mother.
3.Pediatric Use
The safety and efficacy of Iclusig in patients less than 18 years of age have not been
established.
4.Geriatric Use
One hundred and fifty-five of 449 patients (35%) in the clinical trial of Iclusig were
65 years of age and over. In patients with CP-CML, patients of age . 65 years had
a lower major cytogenetic response rate (38%) as compared with
patients < 65 years of age (64%).
In patients with AP-CML, BP-CML, and Ph+ ALL, patients of age . 65 years had
a higher major hematologic response rate (47%) as compared with
patients < 65 years of age (40%). Forty-six percent of patients . 65 years
had vascular occlusion events. Patients of age . 65 years are more likely to
experience adverse reactions including vascular occlusion decreased platelet
count, peripheral edema, increased lipase, dyspnea, asthenia, muscle spasms,
and decreased appetite. In general, dose selection for an elderly patient
should be cautious, reflecting the greater frequency of decreased hepatic,
renal, or cardiac function, and of concomitant disease or other drug therapy.
