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PONATINIB INCYTE is a brand name for Ponatinib. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Ponatinib Incyte is indicated in adult patients with • chronic phase, accelerated phase, or blast phase chronic myeloid leukaemia (CML) who are resistant to dasatinib or nilotinib; who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have…
Verbatim from this product's MHRA label. Tap a section to expand.
Therapy should be initiated by a physician experienced in the diagnosis and treatment of patients with leukaemia. Haematologic support such as platelet transfusion and haematopoietic growth factors can be used during treatment if clinically indicated.
Before starting treatment with ponatinib, the cardiovascular status of the patient should be assessed, including history and physical examination, and cardiovascular risk factors should be actively managed. Cardiovascular status should continue to be monitored and medical and supportive therapy for conditions that contribute to cardiovascular risk should be optimised during treatment with ponatinib.
Posology The recommended starting dose is 45 mg of ponatinib once daily. For the standard dose of 45 mg once daily, a 45 mg film-coated tablet is available. Treatment should be continued as long as the patient does not show evidence of disease progression or unacceptable toxicity.
Patients should be monitored for response according to standard clinical guidelines. Discontinuing ponatinib should be considered if a complete haematologic response has not occurred by 3 months (90 days). The risk of arterial occlusive events is likely to be dose-related.
e. 1). If dose reduction is undertaken, close monitoring of response is recommended. In patients with loss of response the dose of Ponatinib can be re-escalated to a previously tolerated dosage of 30 mg or 45 mg orally once daily. Ponatinib should be continued until loss of response at the re-escalated dose or unacceptable toxicity.
Management of toxicities Dose modifications or interruption of dosing should be considered for the management of haematological and non-haematological toxicities. In the case of severe adverse reactions, treatment should be withheld.
For patients whose adverse reactions are resolved or attenuated in severity, Ponatinib may be restarted and escalation of the dose back to the daily dose used prior to the adverse reaction may be considered, if clinically appropriate.
For a dose of 30 mg or 15 mg once daily, 15 mg and 30 mg film-coated tablets are available. 0 x 109/L) and thrombocytopenia (platelet < 50 x 109/L) that are unrelated to leukaemia are summarized in Table 1. 5 x 109/L and platelet ≥ 75 x 109/L *ANC = absolute neutrophil count Arterial occlusion and venous thromboembolism In a patient suspected of developing an arterial occlusive event or a venous thromboembolism, Ponatinib should be immediately interrupted.
0%). Serious arterial cardiovascular, cerebrovascular, and peripheral vascular occlusive adverse reactions (treatment-emergent frequencies) occurred in 10%, 7%, and 9% of Ponatinib treated patients, respectively. Serious venous occlusive reactions (treatment-emergent frequencies) occurred in 5% of patients.
Arterial cardiovascular, cerebrovascular, and peripheral vascular occlusive adverse reactions (treatment-emergent frequencies) occurred in 13%, 9%, and 11% of Ponatinib treated patients, respectively. Overall arterial occlusive adverse reactions have occurred in 25% of Ponatinib treated patients from the PACE phase 2 trial with a minimum 64 months follow up, with serious adverse reactions occurring in 20% of patients.
Some patients experienced more than one type of event. Venous thromboembolic reactions (treatment-emergent frequencies) occurred in 6% of patients. The incidence of thromboembolic events is higher in patients with Ph+ ALL or BP-CML than those with AP CML or CP CML.
No venous occlusive events were fatal. After a minimum follow-up of 64 months, the rates of adverse reactions resulting in discontinuation were 20% in CP-CML, 11% in AP-CML, 15% in BP-CML and 9% in Ph+ ALL. 5% of patients (45 mg cohort).
3% of Ponatinib treated patients (45 mg cohort), respectively. Of the 94 patients in the 45 mg cohort, 1 patient experienced a venous thromboembolic reaction (Grade 1 retinal vein occlusion). Tabulated list of adverse reactions The frequencies of adverse reactions are based on 449 CML and Ph+ALL patients exposed to ponatinib in the PACE phase 2 trial and the 94 CML patients exposed to ponatinib (45 mg starting dose) in the OPTIC phase 2 trial.
1 for information on the main characteristics of participants in the trials. Adverse reactions reported in all CML and Ph+ ALL patients are listed by system organ class and by frequency in Table 4. Frequency categories are very common (≥ 1/10), common (≥ 1/100 to < 1/10) and uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), and not known (cannot be estimated from the available data).
Important adverse reactions Myelosuppression Ponatinib is associated with severe (National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 or 4) thrombocytopenia, neutropenia, and anaemia. Most of the patients with grade 3 or 4 platelet count decreased, anaemia or neutropenia, developed it within the first 3 months of treatment.
The frequency of these events is greater in patients with accelerated phase CML (AP-CML), blast phase CML (BP-CML), or Ph+ ALL than in chronic phase CML (CP-CML). A complete blood count should be performed every 2 weeks for the first 3 months and then monthly or as clinically indicated.
2). Arterial occlusion Arterial occlusions, including fatal myocardial infarction, stroke, retinal arterial occlusions associated in some cases with permanent visual impairment or vision loss, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, renal artery stenosis (associated with worsening, labile or treatment-resistant hypertension), and the need for urgent revascularization procedures have occurred in Ponatinib- treated patients.
Patients with and without cardiovascular risk factors, including patients age 50 years or younger, experienced these events. Arterial occlusion adverse events were more frequent with increasing age and in patients with history of ischaemia, hypertension, diabetes, or hyperlipidaemia.
1). 8). Some patients experienced more than 1 type of event. 8). In these patients, alternative treatment options should also be considered before starting treatment with ponatinib. Before starting treatment with ponatinib, the cardiovascular status of the patient should be assessed, including history and physical examination, and cardiovascular risk factors should be actively managed.
Cardiovascular status should continue to be monitored and medical and supportive therapy for conditions that contribute to cardiovascular risk should be optimised during treatment with ponatinib. Monitoring for evidence of arterial occlusion should be performed and if decreased vision or blurred vision occurs, an ophthalmic examination (including fundoscopy) should be performed.
1.
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8) after the event is resolved. Hypertension may contribute to risk of arterial occlusive events. Ponatinib treatment should be temporarily interrupted if hypertension is not medically controlled. Pancreatitis Recommended modifications for pancreatic adverse reactions are summarized in Table 2.
0 x IULN Ponatinib should be discontinued and symptomatic) *IULN = institution upper limit of normal Hepatic toxicity Dose interruption or discontinuation may be required as described in Table 3. Table 3 Recommended dose modifications for hepatic toxicity Elevation of liver transaminase > 3 × ULN* Persistent grade 2 (longer than 7 days) Grade 3 or higher Occurrence at 45 mg: • Ponatinib should be interrupted and hepatic function should be monitored • Ponatinib should be resumed at 30 mg after recovery to ≤ Grade 1 (< 3 × ULN), or recovery to pre-treatment grade Occurrence at 30 mg: • Ponatinib should be interrupted and resumed at 15 mg after recovery to ≤ Grade 1, or recovery to pre-treatment grade Occurrence at 15 mg: • Ponatinib should be discontinued Elevation of AST or ALT ≥ 3 × ULN concurrent with an elevation of bilirubin > 2 × ULN and alkaline phosphatase < 2 × ULN Ponatinib should be discontinued *ULN = Upper Limit of Normal for the lab Elderly patients Of the 732 patients in the PACE and OPTIC clinical studies of Ponatinib, 191 (26%) were ≥ 65 years of age.
Compared to patients < 65 years, […]
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Table 4 Adverse reactions observed in previously treated CML and Ph+ ALL patients – frequency reported by incidence of treatment emergent events System organ class Frequency Adverse reactions Very common upper respiratory tract infection Infections and infestations Common pneumonia, sepsis, folliculitis, cellulitis, herpes zoster Very common anaemia, platelet count decreased, neutrophil count decreased Blood and lymphatic system disorders Common pancytopenia, febrile neutropenia, white blood cell count decreased, lymphocyte count decreased, myelosuppression Endocrine disorders Common hypothyroidisma Very common decreased appetite, hypertriglyceridaemia, hypercholesterolaemia Metabolism and nutrition disorders Common dehydration, fluid retention, hypocalcaemia, hyperglycaemia, hyperuricaemia, hypophosphataemia, hypokalaemia, weight decreased, hyponatraemia, dyslipidaemia, glucose tolerance impaired, low density lipoprotein increased, weight increase, tumour lysis syndrome Very common insomnia Psychiatric disorders Common anxiety Very common headache, dizziness Common cerebrovascular accident, cerebral infarction, neuropathy peripheral, lethargy, migraine, hyperaesthesia, hypoaesthesia, paraesthesia, transient ischaemic attack, facial nerve disorder, carotid artery stenosis Nervous system disorders Uncommon cerebral artery stenosis, cerebral haemorrhage, haemorrhage intracranial, posterior reversible encephalopathy syndrome * System organ class Frequency Adverse reactions Common vision blurred, dry eye, periorbital oedema, eyelid oedema, conjunctivitis, visual impairment, eye pain, retinal vein occlusion Eye disorders Uncommon retinal vein thrombosis, retinal artery occlusion Common cardiac failure, myocardial infarction, cardiac failure congestive, coronary artery disease, angina pectoris, pericardial effusion, atrial fibrillation, ejection fraction decreased, acute coronary syndrome, atrial flutter, left ventricular dysfunction, left ventricular hypertrophy, sinus bradycardia, tachycardia, n-terminal prohormone brain natriuretic peptide increased, angina unstable, myocardial ischaemia, supraventricular extrasystoles, ventricular extrasystoles, electrocardiogram qt prolonged, cardiac failure chronic, brain natriuretic peptide increased Cardiac disorders Uncommon cardiac discomfort, ischemic cardiomyopathy, arteriospasm coronary Very common hypertension Common peripheral arterial occlusive disease, peripheral ischaemia, peripheral artery stenosis, intermittent claudication, deep vein thrombosis, hot flush, flushing, […]
Ponatinib should be interrupted immediately in case of arterial occlusion. 8). 8). Monitoring for evidence of thromboembolism should be performed. Ponatinib should be interrupted immediately in case of thromboembolism. 8). Retinal venous occlusions associated in some cases with permanent visual impairment or vision loss have occurred in Ponatinib-treated patients.
If decreased vision or blurred vision occurs, an ophthalmic examination (including fundoscopy) should be performed. Hypertension Hypertension may contribute to risk of arterial thrombotic events, including renal artery stenosis. During Ponatinib treatment, blood pressure should be monitored and managed at each clinic visit and hypertension should be treated to normal.
2). In the event of significant worsening, labile or treatment-resistant hypertension, treatment should be interrupted and evaluation for renal artery stenosis should be considered. Treatment-emergent hypertension (including hypertensive crisis) occurred in Ponatinib-treated patients.
Patients may require urgent clinical intervention for hypertension associated with confusion, headache, chest pain, or shortness of breath. Aneurysms and artery dissections The use of VEGF pathway inhibitors in patients with or without hypertension may promote the formation of aneurysms and/or artery dissections.
Before initiating Ponatinib, this risk should be carefully considered in patients with risk factors such as hypertension or history of aneurysm. Congestive heart failure Fatal and serious heart failure or left ventricular dysfunction occurred in Ponatinib- treated patients, including events related to prior vascular occlusive events.
Patients should be monitored for signs or symptoms consistent with heart failure and they should be treated as clinically indicated, including interruption of Ponatinib. 8). Pancreatitis and serum lipase Ponatinib is associated with pancreatitis.
The frequency of pancreatitis is greater in the first 2 months of use. Check serum lipase every 2 weeks for the first 2 months and then periodically thereafter. Dose interruption or reduction may be required. 2). Caution is recommended in patients with a history of pancreatitis or alcohol abuse.
Patients with severe or very severe hypertriglyceridemia should be appropriately managed to reduce the risk of pancreatitis. Hepatotoxicity Ponatinib may result in elevation in ALT, AST, bilirubin, and alkaline phosphatase. Most patients who had an event of hepatotoxicity had their first event […]