Ponatinib tablets

• Before you start the treatment, read any printed information you have been given by your doctor and the printed manufacturer's leaflet from inside the pack of tablets. These will give you more information about ponatinib and will provide a full list of the side-effects which you may experience from taking it.
• Ponatinib will be prescribed for you by a specialist doctor who is experienced in treating your condition. It is important that you take the tablets exactly as you are told to. It is usual to take one 45 mg tablet daily, although your dose may be different to this. The directions for taking the tablets will be printed on the label of the pack to remind you what your doctor has told you to do, but if you have any concerns or questions, you should contact your doctor or hospital clinic for further advice.
• You can take ponatinib tablets before or after meals. Swallow the tablet whole with a drink of water - do not crush or chew the tablet.
• If you forget to take a dose, make sure that you remember to take your next dose when it is due. Do not take two doses on the same day to make up for a forgotten dose.

Along with their useful effects, most medicines can cause unwanted side-effects although not everyone experiences them. The table below contains some of the most common ones associated with ponatinib. You will find a full list in the manufacturer's information leaflet supplied with your medicine. The unwanted effects often improve as your body adjusts to the new medicine, but speak with your doctor or pharmacist if any of the following continue or become troublesome.

If you experience any other symptoms which you think may be due to the tablets, speak with your doctor or pharmacist.

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 DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS]
• Hypertension [see WARNINGS AND PRECAUTIONS]
• Pancreatitis [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS]
• Increased Toxicity in Newly Diagnosed Chronic Phase CML [see 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]

Clinical Trial Experience

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

Table 6: Serious Adverse Reactions (SAR)

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

Table 8: Incidence of Clinically Relevant Non-Hematologic Laboratory Abnormalities

Read the entire FDA prescribing information for Iclusig (Ponatinib Tablets)