"The U.S. Food and Drug Administration today approved Gazyva (obinutuzumab) for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia (CLL).
CLL is a blood and bone ma"...
- Clinician Information:
Iclusig Side Effects Center
Medical Editor: John P. Cunha, DO, FACOEP
Iclusig (ponatinib) is a kinase inhibitor used to treat chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) who do not benefit from or who do not tolerate other treatment. Common side effects include skin rash, abdominal pain, tiredness, headache, dry skin, constipation, fever, joint pain, or nausea.
The recommended dose for Iclusig is 45 mg administered orally once daily. Iclusig may interact with conivaptan, imatinib, isoniazid, nefazodone, heart or blood pressure medicines, antibiotics, antifungals, hepatitis C medications, or HIV or AIDS medications. Tell your doctor all medications and supplements you use. Do not take Iclusig if you are pregnant or plan to become pregnant during treatment. It can harm a fetus. It is unknown if Iclusig passes into breast milk. Consult your doctor before breastfeeding.
Our Iclusig (ponatinib) 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 Prescribing information?
The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.
Iclusig FDA Prescribing Information: Side Effects
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The following adverse reactions are discussed in greater detail in other sections of the prescribing information:
- Vascular Occlusion [see WARNINGS AND PRECAUTIONS]
- Heart Failure [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS]
- Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
- Hypertension [see WARNINGS AND PRECAUTIONS]
- Pancreatitis [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS]
- Neuropathy [see WARNINGS AND PRECAUTIONS]
- Ocular Toxicity [see WARNINGS AND PRECAUTIONS]
- Hemorrhage [see WARNINGS AND PRECAUTIONS]
- Fluid Retention [see WARNINGS AND PRECAUTIONS]
- Cardiac Arrhythmias [see WARNINGS AND PRECAUTIONS]
- Myelosuppression [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS]
The adverse reactions described in this section were identified in a single-arm, open-label, international, multicenter trial in 449 patients with CML or Ph+ ALL whose disease was considered to be resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy including those with the BCR-ABL T315I mutation. All patients received a starting dose of 45 mg Iclusig once daily. At the time of analysis, the median duration of treatment with Iclusig was 337 days in patients with CPCML, 362 days in patients with AP-CML, 89 days in patients with BP-CML, and 81 days in patients with Ph+ ALL. The median dose intensity was 37 mg or 83% of the expected 45 mg dose. The events of arterial ischemia, cardiac failure, and peripheral neuropathy reported in Tables 5 and 6 below include data from an additional 13 months of follow-up (median duration of treatment CP-CML: 672 days, AP-CML: 590 days, BP-CML: 89 days, Ph+ ALL: 81 days).
Adverse reactions reported in more than 10% of all patients treated with Iclusig in this trial are presented in Table 5. Overall, the most common non-hematologic adverse reactions ( ≥ 20%) were hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, arthralgia, nausea, and pyrexia.
The rates of treatment-emergent adverse events resulting in discontinuation were 13% in CP-CML, 11% in AP-CML, 15% in BP-CML, and 9% in Ph+ ALL. The most common adverse events that led to treatment discontinuation were thrombocytopenia (4%) and infections (1%).
Dose modifications (dose delays or dose reductions) due to adverse reactions occurred in 74% of the patients. The most common adverse reactions ( ≥ 5%) that led to dose modifications include thrombocytopenia (30%), neutropenia (13%), lipase increased (12%), rash (11%), abdominal pain (11%), pancreatitis (6%), and ALT, AST, or GGT increased (6%).
Table 5: Adverse Reactions Occurring in > 10% of
Patients, Any Group
|System Organ Class||CP-CML (N=270)||AP-CML (N=85)||BP-CML (N=62)||Ph+ ALL (N=32)|
|Any Grade (%)||CTCAE Grade 3 / 4 (%)||Any Grade (%)||CTCAE Grade 3 / 4 (%)||Any Grade (%)||CTCAE Grade 3 / 4 (%)||Any Grade (%)||CTCAE Grade 3 / 4 (%)|
|Cardiac or Vascular disorders|
|GI hemorrhagef||2||< 1||8||1||11||5||9||6|
|Blood and lymphatic system disorders|
|Febrile neutropenia||1||< 1||4||4||11||11||25||25|
|Infections and infestations|
|Urinary tract infection||7||1||12||1||0||0||9||0|
|Upper respiratory tract infection||11||1||8||0||11||2||0||0|
|Nervous system disorders|
|Respiratory, thoracic, and mediastinal disorders|
|Skin and subcutaneous tissue disorders|
|Rash and related conditions||54||5||48||8||39||5||34||6|
|Musculoskeletal and connective tissue disorders|
|Pain in extremity||17||2||17||0||13||0||9||0|
|Bone pain||12||< 1||12||1||11||3||9||3|
|General disorders and administration site conditions|
|Fatigue or asthenia||39||3||36||6||35||5||31||3|
|Edema, peripheral||13||< 1||19||0||13||0||22||0|
|Metabolism and nutrition disorders|
|Decreased appetite||8||< 1||12||1||8||0||31||0|
|Weight decreased||6||< 1||7||0||5||0||13||0|
|Adverse drug reactions,
reported using MedDRA and graded using NCI-CTC-AE v 4.0 (NCI Common Terminology
Criteria for Adverse Events) for assessment of toxicity. Treatment-emergent,
all causality events
a derived from blood pressure (BP) measurement recorded monthly while on trial
b includes cardiovascular, cerebrovascular, and peripheral vascular ischemia
c includes cardiac failure, cardiac failure congestive, cardiogenic shock, cardiopulmonary failure, ejection fraction decreased, pulmonary edema, right ventricular failure
d includes abdominal pain, abdominal pain upper, abdominal pain lower, abdominal discomfort
e includes aphthous stomatitis, lip blister, mouth ulceration, oral mucosal eruption, oral pain, oropharyngeal pain, pharyngeal ulceration, stomatitis, tongue ulceration
f includes gastric hemorrhage, gastric ulcer hemorrhage, hemorrhagic gastritis, gastrointestinal hemorrhage, hematemesis, hematochezia, hemorrhoidal hemorrhage, intra-abdominal hemorrhage, melena, rectal hemorrhage, and upper gastrointestinal hemorrhage
g includes burning sensation, skin burning sensation, hyperesthesia, hypoesthesia, neuralgia, neuropathy peripheral, paresthesia, peripheral sensorimotor neuropathy, peripheral motor neuropathy, peripheral sensory neuropathy, polyneuropathy
* represents an additional 13 months of follow-up
Table 6: Serious Adverse
|Arterial ischemic event*||53 (11.8%)|
|Peripheral vascular||16 (3.6%)|
|CNS hemorrhage||10 (2.2%)|
|Gastrointestinal hemorrhage||10 (2.2%)|
|Cardiac failure*||22 (4.9%)|
|Atrial fibrillation||11 (2.4%)|
|Venous thromboembolism||10 (2.2%)|
|Abdominal pain||17 (3.8%)|
|Blood and lymphatic system disorders|
|Febrile neutropenia||13 (2.9%)|
|aincludes pericardial effusion, pleural effusion, and
* represents an additional 13 months of follow-up
Myelosuppression was commonly reported in all patient populations. The frequency of grade 3 or 4 thrombocytopenia, neutropenia, and anemia was higher in patients with AP-CML, BP-CML, and Ph+ ALL than in patients with CP-CML (see Table 7).
Table 7: Incidence of
Clinically Relevant Grade 3/4* Hematologic Abnormalities
|Thrombocytopenia (platelet count decreased)||36||47||57||47|
|Neutropenia (ANC decreased)||24||51||55||63|
|Leukopenia (WBC decreased)||14||35||53||63|
|Anemia (Hgb decreased)||9||26||55||34|
|ANC=absolute neutrophil count,
Hgb=hemoglobin, WBC=white blood cell count
*Reported using NCI-CTC-AE v 4.0
Table 8: Incidence of
Clinically Relevant Non-Hematologic Laboratory Abnormalities
|Laboratory Test||Safety Population
|Any Grade* (%)||CTCAE Grade 3/4 (%)|
|Liver function tests|
|Alkaline phosphatase increased||37||2|
|Amylase increased||3||< 1|
|Sodium increased||10||< 1|
|Bicarbonate decreased||11||< 1|
|Creatinine increased||7||< 1|
|Triglycerides increased||3||< 1|
|ALT=alanine aminotransferase, AST=aspartate
*Graded using NCI-CTC-AE v 4.0
Read the entire FDA prescribing information for Iclusig (Ponatinib Tablets) »
Additional Iclusig Information
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