CNS: dizziness, fatigue, headache, weakness, insomnia, POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES), STROKE.
CV: arrhythmias, arterial thrombosis, hypertension, mI, peripheral arterial disease, peripheral edema, VENOUS THROMBOEMBOLISM, HF, pericardial effusion.
Derm: dry skin, rash, ERYTHEMA MULTIFORME, impaired wound healing, STEVENS-JOHNSON SYNDROME.
EENT: blindness, blurred vision, cataracts, dry eye, eye pain, glaucoma, iritis, macular edema, retinal hemorrhage, retinal vein occlusion, ulcerative keratitis.
Endo: hyperglycemia, hypothyroidism.
F and E: hyperkalemia, hypocalcemia, hypokalemia, hyponatremia, hypophosphatemia.
GI: abdominal pain, constipation, diarrhea, hepatotoxicity, nausea, mucositis, ↓ appetite, FISTULA FORMATION, GI PERFORATION, PANCREATITIS.
GU: ↓fertility (females).
Hemat: anemia, bleeding, leukopenia, neutropenia, thrombocytopenia, LYMPHOPENIA.
MS: arthralgia, back pain, bone pain, extremity pain, muscle spasm, myalgia, muscle weakness.
Neuro: peripheral neuropathy.
Resp: pleural effusion.
Misc: fever, TUMOR LYSIS SYNDROME.
Drug-Drug:
- Levels and risk of toxicity may be ↑ by CYP3A4 inhibitors including clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, and voriconazole; concurrent use should be avoided, but if necessary daily dose of ponatinib should not exceed 30 mg.
- Levels and effectiveness may be ↓ by CYP3A4 inducers including carbamazepine, phenytoin and rifampin; avoid concurrent use if possible.
- Levels and effectiveness may be ↑ by drugs that ↑ gastric pH including proton pump inhibitors, H2 blockers and antacids; concurrent use should be avoided if possible.
Natural-Natural Products:
- Levels and effectiveness may be ↓ by St. John's wort; concurrent use should be avoided.
Drug-Food:
- Levels and risk of toxicity may be ↑ by grapefruit juice; concurrent use should be avoided.
Chronic Phase Chronic Myeloid Leukemia
- PO (Adults): 45 mg once daily; ↓ to 15 mg once daily upon achievement of 1% BCR-ABL1I. If loss of response occurs, may then ↑ to 30 mg once daily or 45 mg once daily. Continue until loss of response at re-escalated dose or unacceptable toxicity. Consider discontinuing therapy if hematologic response has not occurred within 3 mo. Concurrent use of strong CYP3A4 inhibitor If current dose 45 mg once daily, ↓ to 30 mg once daily. If current dose 30 mg once daily, ↓ to 15 mg once daily. If current dose 15 mg once daily, ↓ to 10 mg once daily. If current dose 10 mg once daily, avoid concurrent use.
Hepatic Impairment
- PO (Adults): Child-Pugh A, B, or C If current dose 45 mg once daily, ↓ to 30 mg once daily.
Acute Phase Chronic Myeloid Leukemia, Blast Phase Chronic Myeloid Leukemia, or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
- PO (Adults): 45 mg once daily. In patients with acute phase CML, consider ↓ dose upon achievement of major cytogenetic response. Continue until loss of response or unacceptable toxicity. Consider discontinuing therapy if hematologic response has not occurred within 3 mo. Concurrent use of strong CYP3A4 inhibitor If current dose 45 mg once daily, ↓ to 30 mg once daily. If current dose 30 mg once daily, ↓ to 15 mg once daily. If current dose 15 mg once daily, ↓ to 10 mg once daily. If current dose 10 mg once daily, avoid concurrent use.
Hepatic Impairment
- PO (Adults): Child-Pugh A, B, or C If current dose 45 mg once daily, ↓ to 30 mg once daily.
Therapeutic Classification: antineoplastics
Pharmacologic Classification: kinase inhibitors
Absorption: Well absorbed following oral administration, absorption is pH dependant (↑ gastric pH may ↓ absorption).
Distribution: Unknown.
Protein Binding: >99%.
Metabolism/Excretion: Highly metabolized, primarily by CYP3A4; metabolites eliminated in feces (87%) and urine (5%).
Half-life: 24 hr (range 1266 hr).
(response as noted by disease markers)
*For resistant/intolerant chronic phase CML
For accelerated/blast phase CML or Ph+ALL