Iclusig 15 mg Tablets (Ponatinib Hydrochloride)

Adult dose

Newly diagnosed Ph+ ALL: The recommended starting dose of this drug is 30mg orally once daily, reduced to 15 mg orally once daily upon achieving complete remission (CR) with minimal residual disease (MRD)-negative status (≤0.01% BCR::ABL1/ABL1) at the end of induction. Continue this drug in combination with chemotherapy for up to 20 cycles (each cycle is 28 days) until loss of response or unacceptable toxicity occurs. Chronic-phase CML (CP-CML): The recommended starting dose is 45mg orally once daily, reduced to 15 mg orally once daily upon achieving ≤1% BCR::ABL1IS. In patients who lose response, the dose of this drug may be increased again to the previously tolerated dose of 30mg or 45mg orally once daily. Continue this drug at the re-escalated dose until loss of response or unacceptable toxicity occurs. Consider discontinuing this drug if no hematologic response is achieved by 3 months. Accelerated-phase CML (AP-CML), blast-phase CML (BP-CML), and Ph+ ALL: The optimal dose of this drug has not been established. The recommended starting dose is 45mg once daily. Dose reduction of this drug should be considered for patients with accelerated-phase CML who achieve a major cytogenetic response. Continue this drug until loss of response or unacceptable toxicity occurs. If there is no response by 3 months, discontinuation of this drug should be considered. This drug may be taken with or without food. Swallow tablets whole; do not crush, break, cut, or chew them. If a dose is missed, skip that dose and take the prescribed dose at the regularly scheduled time the next day. Dosage modifications for adverse reactions: Arterial occlusive events (AOE): cardiovascular or cerebrovascular — Grade 1: Withhold this drug until resolved, then resume at the same dose. Grade 2: Withhold this drug until Grade 0 or 1, then resume at the next lower dose. If it recurs, discontinue this drug. Grade 3 or 4: Discontinue this drug. Arterial occlusive events (AOE): peripheral vascular and other, or venous thromboembolic events (VTE) — Grade 1: Withhold this drug until resolved, then resume at the same dose. Grade 2: Withhold this drug until Grade 0 or 1, then resume at the same dose. If it recurs, withhold this drug until Grade 0 or 1, then resume at the next lower dose. Grade 3: Withhold this drug until Grade 0 or 1, then resume at the next lower dose. If it recurs, discontinue this drug. Grade 4: Discontinue this drug. Heart failure — Grade 2 or 3: Withhold this drug until Grade 0 or 1, then resume at the next lower dose. If it recurs, discontinue this drug. Grade 4: Discontinue this drug. Hepatotoxicity — AST or ALT greater than 3 times ULN: Withhold this drug until Grade 0 or 1, then resume at the next lower dose. AST or ALT at least 3 times ULN and bilirubin greater than 2 times ULN, with alkaline phosphatase less than 2 times ULN: Discontinue this drug. Pancreatitis and lipase elevation — Serum lipase 1 - 1.5 times ULN: Consider withholding this drug until resolved, then resume at the same dose. Serum lipase 1.5 - 2 times ULN, asymptomatic serum lipase 2 - 5 times ULN, or asymptomatic pancreatitis with radiographic findings: Withhold this drug until Grade 0 or 1 (less than 1.5 times ULN), then resume at the next lower dose. Symptomatic serum lipase 2 - 5 times ULN, symptomatic Grade 3 pancreatitis, or asymptomatic serum lipase greater than 5 times ULN: Withhold this drug until symptoms have completely resolved and lipase elevation has recovered to Grade 0 or 1, then resume at the next lower dose. Asymptomatic pancreatitis and serum lipase greater than 5 times ULN: Discontinue this drug. Myelosuppression — ANC less than 1 x 109/L or platelets less than 50 x 109/L: Withhold this drug until ANC is at least 1.5 x 109/L and platelets are at least 75 x 109/L, then resume at the same dose. If it recurs, withhold this drug until resolved, then resume at the next lower dose. Other non-hematologic adverse reactions — Grade 1: Withhold this drug until resolved, then resume at the same dose. Grade 2: Withhold this drug until Grade 0 or 1, then resume at the same dose. If it recurs, withhold this drug until Grade 0 or 1, then resume at the next lower dose. Grade 3 or 4: Withhold this drug until Grade 0 or 1, then resume at the next lower dose. If it recurs, discontinue this drug. Dose reductions — Patients with AP-CML, BP-CML, CP-CML, and Ph+ ALL receiving monotherapy: First reduction: 30mg orally once daily; second reduction: 15mg orally once daily; subsequent reduction: discontinue this drug permanently if 15mg orally once daily is not tolerated. Dose reductions — Patients with newly diagnosed Ph+ ALL: First reduction: 15mg orally once daily; second reduction: discontinue this drug permanently if 15mg orally once daily is not tolerated. Dosage modification with concomitant use of strong CYP3A inhibitors: Avoid concomitant use of this drug with strong CYP3A inhibitors. If concomitant use with a strong CYP3A inhibitor cannot be avoided, reduce the dose of this drug. After discontinuing the strong CYP3A inhibitor for 3 – 5 times its elimination half-life, resume the dose of this drug that was tolerated before initiating the strong CYP3A inhibitor. Recommended dose of this drug when used concomitantly with a strong CYP3A inhibitor — Current dose 45mg orally once daily: recommended dose 30mg orally once daily. Current dose 30mg orally once daily: recommended dose 15mg orally once daily. Current dose 15mg orally once daily: avoid concomitant use of this drug with a strong CYP3A inhibitor. Dosage modification in patients with hepatic impairment: For patients with CP-CML, AP-CML, BP-CML, and Ph+ ALL receiving monotherapy, reduce the starting dose of this drug from 45mg orally once daily to 30 mg orally once daily in patients with pre-existing hepatic impairment (Child-Pugh A, B, or C). For patients with newly diagnosed Ph+ ALL, no dosage modification is recommended when administering this drug to patients with mild hepatic impairment (Child-Pugh A). Closely monitor patients with moderate or severe hepatic impairment (Child-Pugh B or C) and adjust the dose of this drug if adverse reactions occur.

This medication is used for the treatment of blood cancer and can affect blood and blood vessels. Taking this medication can result in serious issues such as arterial occlusion, which occurs when arteries are blocked. Such issues may present as heart attacks, strokes, or angina, and are especially more likely to occur in older individuals or those with cardiovascular risk factors such as high blood pressure, diabetes, and hyperlipidemia. Additionally, this medication can cause venous thromboembolism, leading to a risk of blood clots in the legs or lungs. Heart failure, which weakens heart function, is also a side effect of this medication; if heart problems arise, symptoms such as shortness of breath or fatigue may occur, requiring caution. It can also cause liver damage, potentially leading to poor liver function or in severe cases, liver failure, so regular liver function tests are advised. This medication can increase blood pressure, therefore patients with hypertension should manage their blood pressure carefully and may need to temporarily stop taking the medication if blood pressure is not controlled. There is a risk of pancreatitis, which is inflammation of the pancreas, so any signs such as abdominal pain or vomiting should be reported immediately. There is potential for peripheral nerve damage, so if there is numbness, sensory abnormalities, or pain, consultation with a physician is necessary. Effects on the eyes may lead to blurred vision or decreased eyesight; hence, immediate examination is required if there is any change in vision. There is an increased risk of bleeding; if bleeding symptoms such as nosebleeds, bruising, or hematuria occur, caution is needed. This medication may cause fluid retention, leading to swelling or difficulty breathing, so symptoms should be monitored. Bone marrow suppression may result in a decrease in blood cell counts, making patients more susceptible to infections and easily fatigued, necessitating regular blood tests. During pregnancy, this medication may be harmful to the fetus, so women who are pregnant or planning to become pregnant should not take it, and effective contraception should be practiced during treatment. Furthermore, there may be interactions with other medications, so patients must inform their doctors or pharmacists of any other medications they are taking. This medication contains lactose, thus patients with lactose intolerance should not take it. Overall, while taking this medication, regular check-ups for cardiovascular, liver, pancreas, and blood tests are essential, and any abnormal symptoms should be reported immediately to healthcare professionals.

Arterial occlusive events, myocardial infarction, peripheral arterial occlusive disease, angina pectoris, cerebrovascular accident, sudden death, hypertension, venous thromboembolic events, deep vein thrombosis, superficial vein thrombosis, embolism, pulmonary embolism, jugular vein thrombosis, retinal vein occlusion, heart failure, increased brain natriuretic peptide, left ventricular hypertrophy, hepatic toxicity, liver failure, elevated alanine aminotransferase, elevated aspartate aminotransferase, elevated gamma-glutamyl transferase, increased bilirubin, elevated alkaline phosphatase, decreased albumin, decreased blood fibrinogen, rash, arthralgia, abdominal pain, headache, constipation, dry skin, fatigue, fluid retention, edema, fever, nausea, pancreatitis, elevated lipase, bleeding, anemia, oral mucositis, peripheral neuropathy, vomiting, paresthesia, cardiac arrhythmia, febrile neutropenia, impaired glucose tolerance, hyperlipidemia, decreased appetite, sepsis, pneumonia, cough, dyspnea, atrial fibrillation, heart failure, alopecia, myalgia, muscle cramps, bone pain, bone marrow suppression, tumor lysis syndrome, reversible posterior leukoencephalopathy syndrome, wound healing impairment, gastrointestinal perforation, hyperthyroidism, optic neuritis, multiple sclerosis, muscle rigidity, atypical pneumonia, fungal pneumonia, Pseudomonas infection, speech disorders, acute kidney injury, hyperbilirubinemia, hyperkalemia, dehydration, severe skin reactions, panniculitis, blister formation, peeling, mucosal involvement, thrombotic microangiopathy, aneurysm, arterial dissection, cerebral infarction, acute coronary syndrome, arterial thrombosis, ischemic stroke, ischemic cerebral infarction, unstable angina, atrial fibrillation, cardiac arrest, ventricular ectopic contractions, syncope, QT interval prolongation, atrial flutter, sinus bradycardia, complete heart block, loss of consciousness, sinoatrial node dysfunction, macular edema, retinal hemorrhage, vitreous floaters, exfoliative dermatitis, pruritus, urticaria, erythematous rash, dermatitis, contact dermatitis, skin irritation, pancytopenia, erythrocytopenia, lymphadenopathy, acute pancreatitis, abdominal tenderness, dyspepsia, erosive gastritis, pain, visual loss, dry eyes, ocular pain, blurred vision, retinal toxicity, retinal hemorrhage, retinal vein occlusion, macular degeneration, decreased platelet count, leukopenia, lymphocytopenia, decreased hemoglobin, increased amylase, decreased calcium, decreased phosphate, decreased potassium, decreased albumin, increased glucose, increased creatinine, decreased sodium, increased potassium, decreased magnesium, insomnia, anxiety, dizziness, chills, soft tissue infection, secondary cancer, hypothyroidism, decreased appetite, weight loss

This medication should be stored in a tightly closed container to protect it from air and moisture. The appropriate storage temperature is room temperature, between 1 degree and 30 degrees Celsius. Avoid extremely hot or cold places, and it is advisable to keep it in a cool place away from direct sunlight.

Appearance

White, biconvex, round, film-coated tablets

Package unit

30 tablets/bottle