Summary
Commonly reported side effects of ponatinib include: arterial thrombosis, venous thrombosis, cardiac failure, congestive heart failure, pleural effusion, bone marrow depression, conjunctival irritation, dizziness, dyspnea, eye pain, fluid retention, gastrointestinal hemorrhage, headache, hyperesthesia, hypertension, increased serum alanine aminotransferase, increased serum aspartate aminotransferase, increased serum lipase, paresthesia, peripheral edema, peripheral neuropathy, and xerophthalmia. Other side effects include: acute myocardial infarction, pancreatitis, severe bone marrow depression, supraventricular tachycardia, blurred vision, coronary artery disease, hemorrhage, hyperuricemia, and tachyarrhythmia. Continue reading for a comprehensive list of adverse effects.
Applies to ponatinib: oral tablets.
Warning
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Vascular Occlusion
- Arterial and venous occlusions and thromboembolic events, including fatal MI, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and requirement for urgent revascularization procedures, occurred in ≥27% of patients receiving ponatinib in phase 1 and 2 studies.1 25 (See Vascular Occlusion under Cautions.)
- Vascular occlusive events observed in patients with or without cardiovascular risk factors, including patients ≤50 years of age.1
- If vascular occlusion occurs, interrupt or discontinue ponatinib immediately.1 Consider whether the benefit of restarting ponatinib therapy outweighs the risks.1
-
Heart Failure
- Serious or fatal heart failure observed.1
- Monitor cardiac function.1
- If new or worsening heart failure occurs, interrupt therapy or discontinue ponatinib.1 (See Heart Failure under Cautions.)
-
Hepatic Toxicity
- Severe or fatal hepatotoxicity, including acute hepatic failure and fulminant hepatic failure, observed.1 (See Hepatic Effects under Cautions.)
- Monitor liver function tests prior to initiation of therapy and at least monthly thereafter or as clinically indicated.1
- If hepatotoxicity occurs, interrupt therapy, reduce dosage, or discontinue ponatinib.1 (See Hepatic Effects under Cautions.)
Side effects include:
Hypertension, arterial ischemia, cardiac failure, abdominal pain, constipation, nausea, diarrhea, vomiting, oral mucositis, GI hemorrhage, febrile neutropenia, sepsis, pneumonia, urinary tract infection, upper respiratory tract infection, nasopharyngitis, cellulitis, headache, peripheral neuropathy, dizziness, pleural effusion, cough, dypsnea, rash and related conditions, dry skin, arthralgia, myalgia, pain in extremity, back pain, muscle spasms, bone pain, fatigue/asthenia, pyrexia, thrombocytopenia, anemia, neutropenia, leukopenia, lymphopenia, peripheral edema, pain, chills, decreased appetite, decreased weight, insomnia.
For Healthcare Professionals
Applies to ponatinib: oral tablet.
General
-A safety analysis showed a significant increase in grade 3 or greater adverse reactions (thrombocytopenia, neutropenia, rash, elevated ALT/AST, pancreatitis, elevated lipase) with an increase in dose intensity.[Ref]
Cardiovascular
-Very common (10% or more): Hypertension (74%), elevated blood pressure (68%), arterial ischemia (42%), arterial occlusion (35%), hemorrhage (28%), arrhythmia (19%), heart failure/left ventricular dysfunction (15%)
-Common (1% to 10%): Venous thromboembolism, atrial fibrillation, myocardial infarction, myocardial ischemia, congestive cardiac failure, coronary artery disease, angina pectoris, decreased ejection fraction, acute coronary syndrome, atrial flutter, peripheral arterial occlusive disease, peripheral ischemia, peripheral artery stenosis, intermittent claudication, deep vein thrombosis, hot flush, flushing, palpitations, poor peripheral circulation, splenic infarction
-Uncommon (0.1% to 1%): Hypertensive crisis, renal artery stenosis, cardiac discomfort
Frequency not reported: Ischemic cardiomyopathy, coronary arteriospasm[Ref]
Dermatologic
-Very common (10% or more): Rash and related conditions (63%), dry skin (42%), pruritus (13%), alopecia (11%), cellulitis (11%), erythema (10%)
-Common (1% to 10%): Folliculitis, skin exfoliation, night sweats, hyperhidrosis, petechia, ecchymosis, skin pain, exfoliative dermatitis, hyperkeratosis, skin hyperpigmentation[Ref]
Hematologic
-Very common (10% or more): Leukopenia (63%), myelosuppression (59%), neutropenia (59%), febrile neutropenia (25%), anemia (52%), thrombocytopenia (49%), lymphopenia (32%)
-Common (1% to 10%): Pancytopenia[Ref]
Endocrine
-Very common (10% or more): Increased glucose (54%), decreased glucose (13%)
-Common (1% to 10%): Hypothyroidism[Ref]
Gastrointestinal
-Very common (10% or more): Constipation (53%), abdominal pain (48%), increased lipase (42%), nausea (34%), diarrhea (29%), vomiting (27%), oral mucositis (23%), increased amylase (18%)
-Common (1% to 10%): GI hemorrhage, pancreatitis, gastroesophageal reflux disease, stomatitis, dyspepsia, abdominal distention, abdominal discomfort, dry mouth
-Frequency not reported: GI fistula, GI perforation[Ref]
Other
-Very common (10% or more): Asthenia/fatigue (49%), pyrexia (40%), peripheral edema (25%), pain (60%), chills (13%), sepsis (13%)
-Common (1% to 10%): Effusions (pericardial, pleural, ascites), influenza-like illness, peripheral swelling, non-cardiac chest pain, face edema, malaise[Ref]
Nervous system
-Very common (10% or more): Headache (43%), peripheral neuropathy (24%), dizziness (16%)
-Common (1% to 10%): Cranial neuropathy, cerebrovascular accident, cerebral infarction, lethargy, migraine, hyperesthesia, hypoesthesia, paresthesia, transient ischemic attack
-Uncommon (0.1% to 1%): Cerebral artery stenosis, cerebral hemorrhage, intracranial hemorrhage
-Postmarketing reports: Reversible posterior leukoencephalopathy syndrome/posterior reversible encephalopathy syndrome (RPLS/PRES)[Ref]
Hepatic
-Very common (10% or more): Increased ALT (41%), increased alkaline phosphatase (40%), increased AST (35%), hepatotoxicity (29%), decreased albumin (27%), increased bilirubin (13%)
-Common (1% to 10%): Increased gamma-glutamyltransferase
-Uncommon (0.1% to 1%): Hepatic failure, jaundice
-Frequency not reported: Acute liver failure[Ref]
Metabolic
-Very common (10% or more): Decreased phosphorus (33%), decreased calcium (30%), decreased appetite (31%), fluid retention (31%), decreased sodium (27%), increased creatinine (21%), decreased bicarbonate (19%), increased potassium (19%), decreased potassium (18%), decreased weight (13%), increased calcium (12%), increased sodium (10%)
-Common (1% to 10%): Hypertriglyceridemia, dehydration, increased blood cholesterol
-Uncommon (0.1% to 1%): Tumor lysis syndrome[Ref]
Musculoskeletal
-Very common (10% or more): Arthralgia (33%), myalgia (24%), pain in extremity (23%), back pain (21%), bone pain (14%), muscle spasms (14%), musculoskeletal pain (11%)
-Common (1% to 10%): Neck pain, musculoskeletal chest pain[Ref]
Respiratory
-Very common (10% or more): Cough (22%), dyspnea (20%), pleural effusion (19%), nasopharyngitis (18%), pneumonia (16%), upper respiratory tract infection (14%)
-Common (1% to 10%): Epistaxis, dysphonia, pulmonary hypertension, pulmonary embolism[Ref]
Genitourinary
-Very common (10% or more): Urinary tract infection (14%)
-Common (1% to 10%): Hyperuricemia[Ref]
Psychiatric
-Very common (10% or more): Insomnia (13%)
-Common (1% to 10%): Confusional state, erectile dysfunction[Ref]
Ocular
-Very common (10% or more): Ocular toxicities (14%; conjunctival irritation, corneal erosion/abrasion, dry eye, conjunctivitis, conjunctival hemorrhage, hyperemia, eye pain)
-Common (1% to 10%): Blurred vision, periorbital edema, eyelid edema, visual impairment, retinal toxicities (macular edema, retinal vein occlusion/thrombosis, retinal artery occlusion, retinal hemorrhage)
-Uncommon (0.1% to 1%): Vision loss[Ref]
