Ponatinib

Ponatinib is a prescription medication used to treat different stages of chronic myeloid leukemia (CML) or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).

• Ponatinib is available under the following different brand names: Iclusig 

Common side effects of Ponatinib include:

• Skin rash,
• Abdominal or stomach pain,
• Tiredness,
• Headache,
• Dry skin,
• Constipation,
• Fever,
• Joint pain, or
• Nausea.

Serious side effects of Ponatinib include:

• Chest pain or heavy feeling,
• Pain spreading to the arm or shoulder.
• Sudden numbness or weakness (especially on one side of the body),
• Problems with vision, speech, or balance.
• Sudden cough, rapid breathing, coughing up blood.
• Easy bruising, unusual bleeding.
• Confusion, severe drowsiness, feeling like you might pass out.
• Fever, chills, flu symptoms, sores in the mouth and throat.
• Irregular heart rate.
• Shortness of breath (even with mild exertion).
• Yellowing skin or eyes.
• Severe pain in the upper stomach spreads to the back.
• Little or no urinating,
• Numbness or tingly feeling around your mouth,
• Overactive reflexes,
• Weak pulse,
• Fainting; or
• Dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, seizure).

Rare side effects of Ponatinib include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 10 mg
• 15 mg
• 30 mg
• 45 mg

Chronic Myeloid Leukemia

Chronic phase (CP) chronic myeloid leukemia (CML)

• 45 mg orally once a day initially
  • Reduce to 15 mg orally once a day upon achievement of below 1 percent BCR-ABL1IS
  • Re-escalate dose to previously tolerated dosage of 30 mg or 45 mg orally once a day in patients with loss of response
  • Continue until loss of response at the re-escalated dose or unacceptable toxicity
  • Consider discontinuing treatment if a response has not occurred within 3 months
  • Accelerated phase (AP) or blast phase (BP) CML
• 45 mg orally once a day
  • Consider reducing the dose for AP-CML in patients who have achieved a major cytogenetic response
  • Continue until loss of response or unacceptable toxicity
  • Consider discontinuing treatment if a response has not occurred within 3 months

Acute Lymphoblastic Leukemia

• 45 mg orally once a day initially
• Continue until loss of response or unacceptable toxicity
• Consider discontinuing treatment if the response has not occurred by 3 months

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Ponatinib has severe interactions with no other drugs.
• Ponatinib has serious interactions with at least 73 other drugs.
• Ponatinib has moderate interactions with at least 118 other drugs.
• Ponatinib has minor interactions with the following drugs:
  • dexlansoprazole
  • efavirenz
  • esomeprazole
  • lansoprazole
  • omeprazole
  • pantoprazole
  • rabeprazole

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Ponatinib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Ponatinib?”

Cautions

• Arterial occlusive events, including fatalities, have occurred
• Serious or severe VTEs have occurred
• Fatal, serious, or severe heart failure events reported
• May cause hepatotoxicity, including liver failure and death; hepatotoxic events reported, include elevations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyl transferase (GGT)
• Severe pancreatitis has occurred
• Peripheral and cranial neuropathy reported; monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness; interrupt, then resume at same or reduced dose or discontinue the drug based on recurrence/severity
• Serious ocular toxicities leading to blindness or blurred vision were reported; conjunctival irritation, corneal erosion or abrasion, dry eye, conjunctivitis, conjunctival hemorrhage, hyperemia, and edema or eye pain cataracts, periorbital edema, blepharitis, glaucoma, eyelid edema, ocular hyperemia, iritis, iridocyclitis, and ulcerative keratitis; conduct comprehensive eye exams at baseline and periodically during treatment
• Fatal and serious hemorrhage events have occurred, interrupting the dose for severe hemorrhage
• Severe myelosuppression (Grade 3 or 4) was observed early, with a median onset time of 1 month (range less than 1-40 months)
• Monitor for fluid retention; interrupt, reduce, or discontinue
• Monitor for symptoms of arrhythmias; monitor for signs and symptoms suggestive of slow heart rate (fainting, dizziness) or rapid heart rate (chest pain, palpitations, or dizziness) and manage patients as clinically indicated; interrupt, then resume at same or reduced dose or discontinue the drug based on recurrence/severity; symptomatic bradycardia and supraventricular tachycardia reported
• Thrombocytopenia, neutropenia, and anemia may require dose interruption or reduction; monitor CBC every 2 weeks for 3 months and then monthly and as clinically indicated; interrupt for ANC below 1000/mm3 or thrombocytopenia below 50,000/mm3
• Serious tumor lysis syndrome developed, and hyperuricemia occurred; ensure adequate hydration and correct high uric acid levels before initiating therapy to decrease the risk for tumor lysis syndrome
• May compromise wound healing or increase the risk for GI perforation; temporarily interrupt therapy in patients undergoing major surgical procedures
• Monitor serum lipase every 2 weeks for the first 2 months and then monthly thereafter or as clinically indicated; consider additional serum lipase monitoring in patients with a history of pancreatitis or alcohol abuse; interrupt, then resume at same or reduced dose or discontinue the drug based on severity; evaluate for pancreatitis when lipase elevation is accompanied by abdominal symptoms
• Can cause fetal harm; advise women of the potential risk to a fetus
• Revere posterior leukoencephalopathy syndrome
• Reversible posterior leukoencephalopathy syndrome (RPLS; also known as posterior reversible encephalopathy syndrome) has been reported; symptoms include hypertension, seizure, headache, decreased alertness, altered mental functioning, vision loss, and other visual and neurological disturbances
• Confirm diagnosis with an MRI
  • Interrupt therapy until resolution; safety of resumption in patients upon resolution of RPLS is unknown
• Hypertension
  • Serious or severe hypertension, including hypertensive crisis, has occurred
  • Urgent clinical intervention may be required for hypertension associated with confusion, headache, chest pain, or shortness of breath
  • Monitor blood pressure at baseline and as clinically indicated and manage hypertension as clinically indicated
  • Interrupt, dose reduce or stop therapy if hypertension is not medically controlled
  • For significant worsening, labile or treatment-resistant hypertension, interrupt therapy and consider evaluating for renal artery stenosis
  • Increased toxicity in newly diagnosed CP-CML
  • Studies showed ponatinib-treated patients with CP-CML have d 2-fold increased risk of serious adverse reaction compared with imatinib
  • Median exposure to treatment was below 6 months
  • Arterial and venous thrombosis and occlusions occurred at least twice as frequently with ponatinib compared with imatinib; ponatinib-treated patients also exhibit greater incidence of myelosuppression, hepatotoxicity, cardiac failure, hypertension, and skin and subcutaneous tissue disorders
  • Ponatinib is not indicated nor recommended for newly diagnosed CP-CML
• Drug interaction overview
  • CYP3A4 substrate
    • Inhibits P-GP, BCRP, and bile salt export pump
  • Strong CYP3A inhibitors
    • Avoid coadministration
    • Strong CYP3A inhibitors increase ponatinib plasma concentrations and toxicities; if unable to avoid, reduce the ponatinib dose
  • Strong CYP3A4 inducers
    • Avoid coadministration unless benefits outweigh risks; monitor for reduced efficacy of ponatinib
    • Strong CYP3A inducers decrease ponatinib plasma concentrations

Pregnancy and Lactation

• Based on findings in animals and their mechanism of action, fetal harm when administered to pregnant females
• No data available on use in pregnant females
• Verify the pregnancy status of females of reproductive potential before initiation
• Contraception
  • Females of reproductive potential: Use effective contraception during treatment and for 3 weeks after the final dose
• Infertility
  • Based on animal data, impair fertility in females of reproductive potential may occur
  • Unknown whether these effects on fertility are reversible
• Lactation
  • There is no data on drug presence in human milk or the effects on breastfed children or milk production
  • Advise females not to breastfeed during treatment and for 6 days following the last dose