Ponatinib: Drug information

(For additional information see "Ponatinib: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

ALERT: US Boxed Warning

Arterial occlusive events:

Arterial occlusive events (AOEs), including fatalities, have occurred in ponatinib-treated patients. AOEs included 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 50 years of age and younger, experienced these events. Monitor for evidence of AOEs. Interrupt or discontinue ponatinib based on severity. Consider benefit-risk to guide a decision to restart ponatinib.

Heart failure:

Heart failure, including fatalities, occurred in ponatinib-treated patients. Monitor for heart failure and manage patients as clinically indicated. Interrupt or discontinue ponatinib for new or worsening heart failure.

Hepatotoxicity:

Hepatotoxicity, liver failure, and death have occurred in ponatinib-treated patients. Monitor liver function tests. Interrupt or discontinue ponatinib based on severity.

Venous thromboembolic events:

Venous thromboembolic events (VTEs) have occurred in ponatinib-treated patients. Monitor for evidence of VTEs. Interrupt or discontinue ponatinib based on severity.

Brand Names: US

Iclusig

Brand Names: Canada

Iclusig

Pharmacologic Category

Antineoplastic Agent, BCR-ABL Tyrosine Kinase Inhibitor;
Antineoplastic Agent, Tyrosine Kinase Inhibitor

Dosing: Adult

Note: Withhold ponatinib treatment for at least 1 week prior to elective surgery; do not administer ponatinib for at least 2 weeks following major surgery and until adequate wound healing.

Acute lymphoblastic leukemia, Philadelphia chromosome-positive

Acute lymphoblastic leukemia, Philadelphia chromosome-positive (Ph+) (in patients for whom no other kinase inhibitors are indicated): Oral: Initial: 45 mg once daily; continue until loss of response or unacceptable toxicity. Consider discontinuing if response has not occurred by 3 months.

Acute lymphoblastic leukemia, Ph+, T315I-positive

Acute lymphoblastic leukemia, Ph+, T315I-positive: Oral: Initial: 45 mg once daily; continue until loss of response or unacceptable toxicity. Consider discontinuing if response has not occurred by 3 months.

Chronic myeloid leukemia, chronic phase

Chronic myeloid leukemia, chronic phase (with resistance or intolerance to at least 2 prior kinase inhibitors): Oral: Initial: 45 mg once daily; reduce the dose to 15 mg once daily upon achievement of ≤1% BCR-ABL 1^IS; patients with a loss of response can reescalate dose to a previously tolerated dose of 30 or 45 mg once daily. Continue treatment until a loss of response at the reescalated dose or until unacceptable toxicity; consider discontinuing if hematologic response has not occurred by 3 months. Note: Ponatinib is not recommended for treatment of newly diagnosed chronic phase chronic myeloid leukemia.

Chronic myeloid leukemia, accelerated or blast phase

Chronic myeloid leukemia, accelerated or blast phase (in patients for whom no other kinase inhibitors are indicated): Oral: Initial: 45 mg once daily; consider reducing the dose for patients with accelerated phase who have achieved a major cytogenetic response. Continue until loss of response or unacceptable toxicity; consider discontinuing if response has not occurred by 3 months.

Chronic myeloid leukemia, T315I-positive, chronic phase

Chronic myeloid leukemia, T315I-positive, chronic phase : Oral: Initial: 45 mg once daily; reduce the dose to 15 mg once daily upon achievement of ≤1% BCR-ABL 1^IS; patients with a loss of response can reescalate dose to a previously tolerated dose of 30 or 45 mg once daily. Continue treatment until a loss of response at the reescalated dose or until unacceptable toxicity; consider discontinuing if hematologic response has not occurred by 3 months.

Chronic myeloid leukemia, T315I-positive, accelerated or blast phase

Chronic myeloid leukemia, T315I-positive, accelerated or blast phase: Oral: Initial: 45 mg once daily; consider reducing the dose for patients with accelerated phase who have achieved a major cytogenetic response. Continue until loss of response or unacceptable toxicity; consider discontinuing if response has not occurred by 3 months.

Missed dose: If a dose is missed, administer the next dose at the regularly scheduled time the next day.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, mild to moderate impairment had no clinically significant effect on ponatinib pharmacokinetics.

CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Adult

Hepatic impairment prior to treatment initiation: Mild-to-severe impairment (Child-Pugh class A, B, or C): Reduce initial dose to 30 mg once daily.

Hepatotoxicity during treatment:

AST or ALT >3 times ULN: Interrupt ponatinib until grade 0 or 1, then resume at the next lower dose (see Dosing: Adjustment for Toxicity for dosage reduction levels).

ALT or AST ≥3 times ULN with concurrent bilirubin >2 times ULN and alkaline phosphatase <2 times ULN: Discontinue ponatinib.

Dosing: Adjustment for Toxicity: Adult

**Ponatinib Dosage Reduction Levels for Adverse Reactions**
Dose reduction	Dose for chronic phase chronic myeloid leukemia (CML)	Dose for accelerated or blast phase CML and for Ph+ acute lymphoblastic leukemia
Usual (initial) dose	45 mg once daily	45 mg once daily
First dose reduction	30 mg once daily	30 mg once daily
Second dose reduction	15 mg once daily	15 mg once daily
Third dose reduction	10 mg once daily	Permanently discontinue ponatinib if unable to tolerate 15 mg once daily.
Subsequent dose reductions	Permanently discontinue ponatinib if unable to tolerate 10 mg once daily.

**Ponatinib Dosage Modifications for Adverse Reactions**
Adverse reaction	Severity	Ponatinib dose modification
Hematologic toxicity	ANC <1,000/mm³ or platelets <50,000/mm³	Interrupt ponatinib until ANC ≥1,500/mm³ and platelets ≥75,000/mm³, then resume at the same dose. For recurrence, interrupt ponatinib until resolution, then resume at the next lower dose.
Cardiovascular: Arrhythmia	Symptoms of slow or rapid heart rate	Manage as clinically indicated. Interrupt ponatinib; upon recovery, resume at the same dose, at a reduced dose, or discontinue (based on the severity and/or recurrence).
Cardiovascular: Heart failure	Grades 2 or 3	Interrupt ponatinib until grade 0 or 1, then resume at the next lower dose. Discontinue ponatinib for recurrence.
Cardiovascular: Heart failure	Grade 4	Discontinue ponatinib.
Cardiovascular: Hypertension	If indicated, initiate appropriate antihypertensive therapy to reduce the risk for cardiovascular complications (ASCO [Armenian 2017], ESC [Lyon 2022]).
	Associated with confusion, headache, chest pain, or dyspnea	May require urgent clinical intervention.
	Medically uncontrolled	Interrupt, reduce dose, or discontinue ponatinib.
	Significant worsening, labile, or treatment-resistant	Interrupt ponatinib and evaluate for renal artery stenosis.
Arterial occlusive event (cardiovascular or cerebrovascular)	Grade 1	Interrupt ponatinib until resolved, then resume at the same dose.
	Grade 2	Interrupt ponatinib until grade 0 or 1, then resume at the next lower dose. Discontinue ponatinib for recurrence.
	Grades 3 or 4	Discontinue ponatinib.
Arterial occlusive event (peripheral vascular and other) or venous thromboembolic event	Grade 1	Interrupt ponatinib until resolved, then resume at the same dose.
	Grade 2	Interrupt ponatinib until grade 0 or 1, then resume at the same dose. For recurrence, interrupt ponatinib until grade 0 or 1, then resume at the next lower dose.
	Grade 3	Interrupt ponatinib until grade 0 or 1, then resume at the next lower dose. Discontinue ponatinib for recurrence.
	Grade 4	Discontinue ponatinib.
Fluid retention		Manage as clinically indicated. Interrupt ponatinib; upon recovery, resume at the same dose, at a reduced dose, or discontinue (based on the severity and/or recurrence).
GI perforation		Permanently discontinue ponatinib.
Hemorrhage		Manage as clinically indicated. Interrupt ponatinib; upon recovery, resume at the same dose, at a reduced dose, or discontinue (based on the severity and/or recurrence).
Neuropathy	Hypoesthesia, hyperesthesia, paresthesia, discomfort, burning sensation, neuropathic pain, or weakness	Interrupt ponatinib; upon recovery, resume at the same dose, at a reduced dose, or discontinue (based on the severity and/or recurrence).
Pancreatitis and elevated lipase	Serum lipase >1 to 1.5 times ULN	Consider interrupting ponatinib until resolution, then resume at the same dose.
	Serum lipase >1.5 to 2 times ULN, 2 to 5 times ULN and asymptomatic, or asymptomatic radiographic pancreatitis	Interrupt ponatinib until grade 0 or 1 (<1.5 times ULN), then resume at the next lower dose.
	Serum lipase >2 to 5 times ULN and symptomatic, symptomatic grade 3 pancreatitis, or serum lipase >5 times ULN and asymptomatic	Interrupt ponatinib until complete resolution of symptoms and after recovery of lipase elevation to grade 0 or 1, then resume at the next lower dose.
	Symptomatic pancreatitis and serum lipase >5 times ULN	Discontinue ponatinib.
Reversible posterior leukoencephalopathy syndrome		Interrupt ponatinib until resolution. The safety of resuming ponatinib is unknown.
Other nonhematologic adverse reactions	Grade 1	Interrupt ponatinib until resolved, then resume at the same dose.
	Grade 2	Interrupt ponatinib until grade 0 or 1, then resume at the same dose. For recurrence, interrupt ponatinib until grade 0 or 1, then resume at the next lower dose.
	Grades 3 or 4	Interrupt ponatinib until grade 0 or 1, then resume at the next lower dose. Discontinue ponatinib for recurrence.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.

>10%:

Cardiovascular: Cardiac arrhythmia (17% to 25%; ventricular arrhythmia: 3%), edema (≤41%), heart failure (6% to 16%), hypertension (31% to 53%; severe hypertension: 3% to 13%), occlusive arterial disease (13% to 31%; including carotid, vertebral, and middle cerebral artery and renal artery stenosis), peripheral edema (17%)

Dermatologic: Alopecia (6% to 11%), cellulitis (4% to 13%), skin rash (50% to 75%), xeroderma (25% to 42%)

Endocrine & metabolic: Decreased serum albumin (28%), decreased serum bicarbonate (20%), decreased serum calcium (30%), decreased serum phosphate (34%), decreased serum sodium (27%), fluid retention (≤41%), hyperlipidemia (3% to 13%), increased serum glucose (54%), increased serum potassium (20%), weight loss (5% to 13%)

Gastrointestinal: Abdominal pain (34% to 54%; severe abdominal pain: 6%), constipation (27% to 53%), decreased appetite (8% to 31%), diarrhea (13% to 29%; grades 3/4: ≤3%), increased serum amylase (18%), increased serum lipase (≤40%), nausea (22% to 34%; grades 3/4: ≤2%), pancreatitis (≤32%), stomatitis (9% to 24%; grades 3/4: 1% to 3%), vomiting (19% to 27%; grades 3/4: 2%)

Genitourinary: Urinary tract infection (2% to 14%)

Hematologic & oncologic: Anemia (52%; grades 3/4: 20%; severe anemia: 3%), decreased white blood cell count (grades 3/4: 12% to 63%), febrile neutropenia (1% to 25%), hemorrhage (23% to 38%; grade 3/4: 3% to 13%; major hemorrhage: 6%), lymphocytopenia (grades 3/4: 10% to 32%), neutropenia (56%; grades 3/4: 34%), thrombocytopenia (63%; grades 3/4: 40%; severe thrombocytopenia: 3%)

Hepatic: Hepatotoxicity (16% to 39%), increased serum alanine aminotransferase (41%), increased serum alkaline phosphatase (40%), increased serum aspartate aminotransferase (35%), increased serum bilirubin (13%)

Infection: Sepsis (3% to 28%)

Nervous system: Anxiety (5% to 18%), chills (8% to 13%), dizziness (3% to 17%), fatigue (≤47%), headache (25% to 43%), insomnia (11% to 13%), neuropathy (13% to 26%), peripheral neuropathy (5% to 20%; grades 3/4: 2%)

Neuromuscular & skeletal: Arthralgia (41% to 61%), asthenia (≤47%), muscle spasm (5% to 14%), musculoskeletal pain (6% to 11%), myalgia (6% to 24%), ostealgia (9% to 14%)

Ophthalmic: Ocular toxicity (30%; including blindness, blurred vision, dry eye syndrome, eye pain)

Renal: Increased serum creatinine (21%)

Respiratory: Cough (6% to 24%), dyspnea (16% to 23%), nasopharyngitis (3% to 18%), pneumonia (8% to 22%), upper respiratory tract infection (3% to 14%)

Miscellaneous: Fever (25% to 40%)

1% to 10%:

Cardiovascular: Acute myocardial infarction (2%), atrial fibrillation (8%), bradycardia (≤1%; including leading to pacemaker implantation), cerebral infarction (grade 3/4: 2%), cerebrovascular occlusion (7%), coronary artery disease (grade 3/4: 2%), deep vein thrombosis (2%), pericardial effusion (4%), peripheral arterial disease (occlusive: grades 3/4: 3%), pulmonary embolism (2%), reduced ejection fraction (3%), syncope (2%), venous thromboembolism (4% to 10%)

Endocrine & metabolic: Hyperuricemia (7%), hypothyroidism (3%), impaired glucose tolerance/prediabetes (9%)

Hematologic & oncologic: Second primary malignant neoplasm (6%)

Nervous system: Cranial nerve disorder (3%), hypoesthesia (4%), paresthesia (5%)

Neuromuscular & skeletal: Swelling of the extremities (4%)

Ophthalmic: Retinal toxicity (4%; including macular edema, retinal hemorrhage, retinal vein occlusion, vitreous floaters)

Respiratory: Pleural effusion (9%)

<1%:

Cardiovascular: Atrial flutter, atrial tachycardia, complete atrioventricular block, hypertensive crisis, prolonged QT interval on ECG, retinal thrombosis, sinus bradycardia, sinus node dysfunction, subdural hematoma, superficial thrombophlebitis, supraventricular tachycardia, tachycardia, ventricular tachycardia

Gastrointestinal: Gastrointestinal hemorrhage

Hematologic & oncologic: Tumor lysis syndrome

Hepatic: Hepatic failure

Hypersensitivity: Angioedema

Nervous system: Loss of consciousness

Frequency not defined: Endocrine & metabolic: Increased gamma-glutamyl transferase

Postmarketing:

Cardiovascular: Aneurysm (arterial), aortic aneurysm, aortic dissection, cerebrovascular accident, coronary artery dissection, myocardial rupture (aortic rupture and arterial rupture), peripheral vascular disease

Dermatologic: Erythema multiforme, severe dermatological reaction, Stevens-Johnson syndrome

Endocrine & metabolic: Dehydration, hyperthyroidism

Gastrointestinal: Gastrointestinal fistula, gastrointestinal perforation

Hematologic & oncologic: Thrombotic microangiopathy

Nervous system: Reversible posterior leukoencephalopathy syndrome

Miscellaneous: Wound healing impairment

Contraindications

There are no contraindications listed in the manufacturer’s US labeling.

Canadian labeling: Hypersensitivity to ponatinib or any component of the formulation; unmanaged cardiovascular risk factors, including uncontrolled hypertension; patients not adequately hydrated and with uncorrected hyperuricemia

Warnings/Precautions

Concerns related to adverse effects:

• Arrhythmias: Cardiac arrhythmias have been reported with ponatinib. Grade 3 or 4 arrhythmias included atrial fibrillation, atrial flutter, atrioventricular block, bradyarrhythmia (symptomatic; leading to pacemaker implant), bradycardia, cardio-respiratory arrest, loss of consciousness, QT interval prolongation, sinus node dysfunction, supraventricular extrasystoles, syncope, tachycardia, and ventricular arrhythmia. Some cases required hospitalization. Manage arrhythmia as clinically indicated.

• Arterial occlusion: Arterial occlusive events (AOEs), including fatalities, have occurred in ponatinib-treated patients. AOEs included fatal myocardial infarction (MI), stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures. Grade 3 or 4 AOEs have been observed; the most frequent grade 3 or higher AOEs were myocardial infarction, acute coronary syndrome, cardiac arrest, coronary artery disease, arterial thrombosis, ischemic stroke, ischemic cerebral infarction, peripheral arterial occlusive disease, and unstable angina. Some patients experienced recurrent or multisite vascular occlusion. The median time to onset of the first cardiovascular, cerebrovascular, or peripheral vascular event was ~4 months to ~2 years. Some patients developed heart failure concurrent or subsequent to a myocardial ischemic event. Ponatinib caused stenosis over multiple segments in major arterial vessels that supply the brain (eg, carotid, vertebral, middle cerebral artery). Patients developed digital or distal extremity necrosis and required amputations. Patients with and without cardiovascular risk factors, including patients 50 years of age and younger, experienced these events. AOEs were more frequent with increasing age and in patients with a history of ischemia, hypertension, diabetes, or hypercholesterolemia. Renal artery stenosis (associated with worsening or refractory hypertension) has been reported.

• Bone marrow suppression: Neutropenia, thrombocytopenia, and anemia commonly occur with ponatinib, including grade 3 or 4 hematologic toxicity. The median onset of grade 3 or 4 hematologic toxicity was ~1 to 1.4 months (range: 1 day to 4 years). The incidence of myelosuppression was greater in patients with accelerated or blast phase chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) than in chronic phase CML.

• Fluid retention: Serious and fatal fluid retention events have occurred with ponatinib. Peripheral edema, pleural effusion, pericardial effusions, angioedema, and a case of brain edema have been reported.

• GI perforation: GI perforation or fistula have occurred with ponatinib.

• Heart failure: Serious or severe heart failure, including fatalities, occurred in ponatinib-treated patients. Grade 3 and 4 heart failure events have been reported, including left ventricular hypertrophy, increased brain natriuretic peptide, congestive cardiac failure, decreased ejection fraction, and cardiac failure. Manage heart failure as clinically indicated.

• Hemorrhage: Serious and fatal hemorrhagic events occurred with ponatinib, including events such as subdural hematoma and GI hemorrhages. Serious bleeding episodes occurred more frequently in patients with accelerated or blast phase CML, and Ph+ ALL; most hemorrhages occurred in patients with grade 4 thrombocytopenia.

• Hepatotoxicity: Hepatotoxicity, liver failure, and death have occurred in ponatinib-treated patients. Fulminant hepatic failure leading to death has been reported, with hepatic failure occurring within 1 week of ponatinib initiation in one patient. Grade 3 or 4 hepatotoxicity has been observed. The median time to onset of hepatotoxicity was 1.9 to 3.1 months (range: 1 day to 4.9 years). The most frequent hepatotoxic events were elevations of ALT, AST, bilirubin, alkaline phosphatase, and gamma-glutamyl transferase. Some events had not resolved by date of last follow-up.

• Hypertension: Serious or severe hypertension, including hypertensive crisis, has occurred with ponatinib. Manage hypertension as clinically indicated; urgent clinical intervention may be necessary for hypertension associated with confusion, headache, chest pain, or shortness of breath. Interrupt therapy and consider evaluating for renal artery stenosis for significant worsening, labile, or treatment-resistant hypertension.

• Neuropathy: Peripheral neuropathy has occurred, including grade 3 and 4 events. The most frequently reported peripheral neuropathies were hypoesthesia, muscular weakness, and paresthesia. Cases of cranial neuropathy developed (rarely), including grade 3 or 4 events. The median time to onset of peripheral neuropathy was 5.3 to 7.7 months (range: 1 day to 4.6 years) and for cranial neuropathy was 1.2 years (range: 18 days to 4 years).

• Ocular toxicity: Serious or severe ocular events leading to blindness and blurred vision have occurred with ponatinib. Blurred vision, eye pain, and dry eye were the most frequent ocular toxicities. Retinal toxicities, including macular edema, age-related macular degeneration, retinal vein occlusion, retinal hemorrhage, and vitreous floaters have also been reported.

• Pancreatitis: Serious or severe pancreatitis has occurred with ponatinib, including grade 3 or 4 events. Amylase and lipase elevations have occurred. The median time to onset of pancreatitis was 23 to 29 days (range: 1 day to 4 years). A majority of clinical pancreatitis cases that led to dose modification or discontinuation resolved within 2 weeks. Evaluate for pancreatitis if lipase elevation is accompanied by abdominal symptoms.

• Reversible posterior leukoencephalopathy syndrome: Reversible posterior leukoencephalopathy syndrome (RPLS), also known as posterior reversible encephalopathy syndrome, has been reported with ponatinib. Patients may present with hypertension, seizure, headache, decreased alertness, altered mental status, vision loss, and other visual and/or neurological disturbances. MRI is necessary to diagnose RPLS.

• Tumor lysis syndrome: Hyperuricemia and serious tumor lysis syndrome (rare) were reported with ponatinib. Ensure adequate hydration. Manage elevated uric acid levels prior to initiating therapy.

• Venous thromboembolism: Serious or severe venous thromboembolic events (VTEs) have occurred in ponatinib-treated patients. VTEs included deep vein thrombosis, pulmonary embolism, superficial thrombophlebitis, retinal vein occlusion, and retinal vein thrombosis (with vision loss).

• Wound healing impairment: Wound healing impairment has occurred with ponatinib. Withhold ponatinib treatment for at least 1 week prior to elective surgery; do not administer ponatinib for at least 2 weeks following major surgery and until adequate wound healing. The safety of resuming ponatinib treatment after resolution of wound healing complications has not been established.

Disease-related concerns:

• Chronic phase CML (newly diagnosed): In a randomized study of first-line treatment of newly diagnosed chronic phase CML, a 2-fold increased risk of serious adverse reaction was demonstrated for ponatinib as compared to imatinib; the study was stopped due to safety concerns. Arterial and venous thrombosis and occlusions occurred at least twice as frequently in the ponatinib arm of the study (compared to the imatinib arm); a higher incidence of hematologic toxicity, pancreatitis, hepatotoxicity, heart failure, hypertension, and dermatologic/subcutaneous tissue disorders was also observed in patients receiving ponatinib. Ponatinib is not indicated and not recommended for treatment of newly diagnosed chronic phase CML.

• Hepatic impairment: Patients with preexisting hepatic impairment are more likely to experience adverse reactions (eg, GI disorders, pancreatitis).

Special populations:

• Older adult: Patients ≥65 years of age are more likely to experience vascular occlusion, weakness, decreased appetite, dyspnea, increased lipase, muscle spasms, peripheral edema, and thrombocytopenia.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride:

Iclusig: 10 mg, 15 mg, 30 mg, 45 mg

Generic Equivalent Available: US

Pricing: US

Tablets (Iclusig Oral)

10 mg (per each): $833.24

15 mg (per each): $833.24

30 mg (per each): $833.24

45 mg (per each): $833.24

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride:

Iclusig: 15 mg, 45 mg

Prescribing and Access Restrictions

Patient access and support is available through the ARIAD PASS program. Information regarding program enrollment may be found at http://www.ariadpass.com or by calling 1-855-447-PASS (7277). In Canada, ponatinib is available through the Iclusig Controlled Distribution Program; information about the program may be found at www.iclusigcdp.ca or by calling 1-888-867-7426.

Administration: Adult

Oral: Administer with or without food. Swallow tablets whole; do not crush, break, cut or chew.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/203469s035lbl.pdf#page=34, must be dispensed with this medication.

Use: Labeled Indications

Acute lymphoblastic leukemia: Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in adults for whom no other kinase inhibitors are indicated; treatment of T315I-positive Ph+ ALL.

Chronic myeloid leukemia: Treatment of chronic myeloid leukemia (CML) in chronic phase in adults with resistance or intolerance to at least 2 prior kinase inhibitors; treatment of CML in accelerated or blast phase in adults for whom no other kinase inhibitors are indicated; treatment of T315I-positive CML in chronic, accelerated, or blast phase.

Limitations of use: Ponatinib is not indicated and not recommended for treatment of newly diagnosed chronic phase CML.

Medication Safety Issues

Sound-alike/look-alike issues:

PONATinib may be confused with axitinib, bosutinib, cabozantinib, crizotinib, dasatinib, enasidenib, imatinib, neratinib, nilotinib, panobinostat, PAZOPanib, pegaptanib, pemigatinib, pexidartinib, pralsetinib, regorafenib, ruxolitinib, vemurafenib

High alert medication:

This medication is in a class the Institute for Safe Medical Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

Substrate of BCRP/ABCG2, CYP2C8 (minor), CYP2D6 (minor), CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BSEP/ABCB11

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Androgens: Hypertension-Associated Agents may enhance the hypertensive effect of Androgens. Risk C: Monitor therapy

Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of PONATinib. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of PONATinib. Management: Avoid coadministration of ponatinib with strong CYP3A4 inducers unless the potential benefit of concomitant treatment outweighs the risk of reduced ponatinib exposure. Monitor patients for reduced ponatinib efficacy if combined. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of PONATinib. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of PONATinib. Management: Avoid concomitant use if possible. If combined, reduce ponatinib dose as follows: If taking 45 mg, reduce to 30 mg; if taking 30 mg, reduce to 15 mg; if taking 15 mg, reduce to 10 mg. If taking 10 mg, avoid concomitant use with strong CYP3A4 inhibitors. Risk D: Consider therapy modification

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification

Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification

Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Risk C: Monitor therapy

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Food Interactions

Ponatinib serum concentrations may be increased when taken with grapefruit or grapefruit juice. Management: Avoid grapefruit and grapefruit juice.

Reproductive Considerations

Verify pregnancy status prior to use in patients who may become pregnant. Patients who could become pregnant should use effective contraception during treatment and for 3 weeks after the last ponatinib dose.

Changes in menstrual patterns have been reported with tyrosine kinase inhibitor (TKI) therapy (Yu 2019).

Based on the mechanism of action, TKIs have the potential to adversely affect fertility by acting on receptors in the ovaries or testis; primarily when administered prior to puberty in males. Although there are cases showing difficulty conceiving, successful pregnancies have also been reported. Fertility data related to long-term TKI use are limited. Recommendations are available for fertility preservation prior to TKI treatment (ASCO [Oktay 2018]; Madabhavi 2019; Rambhatla 2021).

Patients planning to become pregnant but currently receiving a TKI should minimize the risk of first trimester exposure (Rambhatla 2021). Discontinuing TKI therapy for chronic myeloid leukemia can be considered if the patient is eligible for a tumor-free remission, allowing a washout period before attempting to conceive (Baccarani 2019; ELN [Hochhaus 2020]; Madabhavi 2019). Because the time to conception can be highly variable, treatment may also be discontinued at the first positive pregnancy test, prior to organogenesis in select patients (Abruzzese 2020).

Pregnancy Considerations

Based on findings from animal reproduction studies and its mechanism of action, in utero exposure to ponatinib may cause fetal harm.

Treatment of chronic myeloid leukemia in pregnant patients should be individualized based on gestational age, hematologic parameters, and clinical condition at presentation. If pregnancy is detected in the first trimester in patients already on a tyrosine kinase inhibitor (TKI), treatment should be discontinued as soon as pregnancy is confirmed. Treatments other than a TKI are recommended in pregnant patients not eligible for a tumor-free remission. If a TKI is needed, use of agents other than ponatinib may be considered after the first trimester. Close maternal and fetal monitoring is recommended (Abruzzese 2020; BSH [Smith 2020]; ELN [Hochhaus 2020]; Madabhavi 2019).

The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team) approach (ESMO [Peccatori 2013]).

Breastfeeding Considerations

It is not known if ponatinib is present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends that breastfeeding be discontinued during therapy and for 6 days after the last ponatinib dose. Patients diagnosed with chronic myeloid leukemia requiring a tyrosine kinase inhibitor may consider short-term breastfeeding for the first 2 to 5 days postpartum to provide the benefits of colostrum to the newborn prior to starting or restarting therapy (Abruzzese 2020; Madabhavi 2019).

Dietary Considerations

Avoid grapefruit juice.

Monitoring Parameters

CBC with differential and platelets every 2 weeks for the first 3 months, then monthly or as clinically indicated; liver function tests at baseline and at least monthly thereafter or more frequently if clinically warranted; serum lipase every 2 weeks for the first 2 months and monthly thereafter or as clinically indicated (consider additional monitoring in patients with a history of pancreatitis or alcohol abuse); serum electrolytes; uric acid (assess prior to treatment). Evaluate pregnancy status prior to treatment initiation (in females of reproductive potential). Monitor blood pressure at baseline and as clinically indicated. Monitor for signs/symptoms of arterial occlusive events or venous thromboembolic events, hemorrhage, heart failure, fluid retention, pancreatitis (clinical signs), gastrointestinal perforation/fistula, hepatotoxicity (jaundice, anorexia, bleeding, bruising), neuropathy (hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness), reversible posterior leukoencephalopathy syndrome, and tumor lysis syndrome. Monitor for signs/symptoms suggestive of slow heart rate (fainting, dizziness) or rapid heart rate (chest pain, palpitations, or dizziness). Perform a comprehensive ocular exam at baseline and periodically during treatment. Monitor adherence.

Additional cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking; repeat assessment every 3 months for the first year and then every 6 to 12 months thereafter (ASCO [Armenian 2017]; ESC [Lyon 2022]). Check ECG at baseline, every 3 months for the first year and every 6 to 12 months thereafter. Consider baseline echocardiography in all patients; repeat every 3 months for high- and very high-risk patients (ESC [Lyon 2022]).

The American Society of Clinical Oncology hepatitis B virus screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends hepatitis B virus (HBV) screening with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), total Ig or IgG, and antibody to hepatitis B surface antigen (anti-HBs) prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow up.

Mechanism of Action

Ponatinib is a pan-BCR-ABL tyrosine kinase inhibitor with in vitro activity against cells expressing native or mutant BCR-ABL (including T315I); it also inhibits VEGFR, FGFR, PDGFR, EPH, and SRC kinases, as well as KIT, RET, TIE2, and FLT3.

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Plasma concentrations not affected by food.

Distribution: V_d: 1,223 L.

Protein binding: >99% to plasma proteins.

Metabolism: Hepatic; primarily via CYP3A4; CYP2C8, CYP2D6, and CYP3A5 are also involved in metabolism. Phase II metabolism occurs via esterases and/or amidases.

Half-life elimination: ~24 hours (range: 12 to 66 hours).

Time to peak: ≤6 hours.

Excretion: Feces (~87%); urine (~5%).

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Iclusig;
(AR) Argentina: Nibclus | Ponatib | Ponazic | Tokiner;
(AT) Austria: Iclusig;
(AU) Australia: Iclusig;
(BD) Bangladesh: Ponatinix | Ponaxen;
(BE) Belgium: Iclusig;
(BG) Bulgaria: Iclusig;
(BR) Brazil: Iclusig;
(CH) Switzerland: Iclusig;
(CL) Chile: Iclusig;
(CO) Colombia: Iclusig;
(DE) Germany: Iclusig;
(EE) Estonia: Iclusig;
(EG) Egypt: Iclusig;
(ES) Spain: Iclusig;
(FI) Finland: Iclusig;
(FR) France: Iclusig;
(GB) United Kingdom: Iclusig;
(GR) Greece: Iclusig;
(HU) Hungary: Iclusig;
(IE) Ireland: Iclusig;
(IT) Italy: Iclusig;
(JP) Japan: Iclusig;
(KR) Korea, Republic of: Iclusig;
(LB) Lebanon: Iclusig;
(LT) Lithuania: Iclusig;
(LV) Latvia: Iclusig;
(MX) Mexico: Iclusig;
(MY) Malaysia: Iclusig;
(NL) Netherlands: Iclusig;
(NO) Norway: Iclusig;
(PH) Philippines: Iclusig;
(PL) Poland: Iclusig;
(PR) Puerto Rico: Iclusig;
(PT) Portugal: Iclusig;
(QA) Qatar: Iclusig;
(RO) Romania: Iclusig;
(RU) Russian Federation: Iclusig;
(SA) Saudi Arabia: Iclusig;
(SE) Sweden: Iclusig;
(SG) Singapore: Iclusig;
(SI) Slovenia: Iclusig;
(SK) Slovakia: Iclusig;
(TH) Thailand: Iclusig;
(TW) Taiwan: Iclusig

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Armenian SH, Lacchetti C, Barac A, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2017;35(8):893-911. doi:10.1200/JCO.2016.70.5400 [PubMed 27918725]
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Iclusig (ponatinib) [prescribing information]. Lexington, MA: Takeda Pharmaceuticals America Inc; February 2022.
Iclusig (ponatinib) tablets [product monograph]. St-Laurent, Quebec, Canada: Paladin Labs Inc; September 2023.
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Lyon AR, López-Fernández T, Couch LS, et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-4361. doi:10.1093/eurheartj/ehac244 [PubMed 36017568]
Madabhavi I, Sarkar M, Modi M, Kadakol N. Pregnancy outcomes in chronic myeloid leukemia: a single center experience. J Glob Oncol. 2019;5:1-11. doi:10.1200/JGO.18.00211 [PubMed 31584851]
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Peccatori FA, Azim HA Jr, Orecchia R, et al; ESMO Guidelines Working Group. Cancer, pregnancy and fertility: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(suppl 6):vi160-170. doi:10.1093/annonc/mdt199 [PubMed 23813932]
Rambhatla A, Strug MR, De Paredes JG, Cordoba Munoz MI, Thakur M. Fertility considerations in targeted biologic therapy with tyrosine kinase inhibitors: a review. J Assist Reprod Genet. 2021;38(8):1897-1908. doi:10.1007/s10815-021-02181-6 [PubMed 33826052]
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Ponatinib: Drug information