Genetic Implications:
Pronunciation:
poe-na-ti-nib
Trade Name(s)
Ther. Class.
Pharm. Class.
kinase inhibitors
Inhibits kinases, which are involved in various stages of cell proliferation.
Therapeutic Effect(s):
Decreased progression of leukemia with improved survival.
Absorption: Well absorbed following oral administration, absorption is pH dependant (↑ gastric pH may ↓ absorption).
Distribution: Unknown.
Protein Binding: >99%.
Metabolism and Excretion: Highly metabolized, primarily by CYP3A4; metabolites eliminated in feces (87%) and urine (5%).
Half-life: 24 hr (range 12–66 hr).
TIME/ACTION PROFILE (response as noted by disease markers)
ROUTE | ONSET | PEAK | DURATION |
---|---|---|---|
PO* | unknown | 84 days | unknown |
PO† | unknown | 21 days | 3.2–9.5 mo |
Contraindicated in:
Use Cautiously in:
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
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Drug-Drug
Natural-Natural:
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.
Tablets (contain lactose): 10 mg, 15 mg, 30 mg, 45 mg
Monitor for signs and symptoms of HF (shortness of breath, chest pain, palpitations, dizziness, fainting). Treat symptomatically, consider discontinuation if serious.
Monitor BP and heart rate periodically during therapy. May cause hypertension. Treat hypertension to normalize BP. May require interruption of therapy, dose reduction, or discontinuation.
Assess for bleeding during therapy. Interrupt therapy if severe hemorrhage occurs.
Monitor for signs and symptoms of vascular thrombosis (chest pain, shortness of breath, weakness on one side of the body, speech problems, leg pain, leg swelling). May require interruption or discontinuation of therapy.
Assess skin during therapy. If bullous, blistering, and exfoliative skin conditions, including Stevens-Johnson syndrome/toxic epidermal necrolysis, occur, interrupt or discontinue treatment. Rash may require treatment with corticosteroids or anti-infectives with anti-inflammatory properties; acne treatments may aggravate dry skin and erythema.
Assess for symptoms of PRES (headache, altered mental status, seizures, visual disturbances, hypertension) periodically during therapy. Confirm diagnosis by radiologic procedure. If PRES is suspected or diagnosed, maintain BP control and immediately reduce immunosuppression. Symptoms are usually reversed on reduction or discontinuation of immunosuppression.
Lab Test Considerations:
Obtain CBC and platelet counts every 2 wk for first 3 mo, then monthly or as clinically indicated. If neutropenia (absolute neutrophil count [ANC] <1 × 109 /L) or thrombocytopenia (platelet <50 × 109 /L) occur unrelated to leukemia , hold ponatinib and resume initial 45 mg dose after recovery to ANC <1.5 × 109 /L and platelet <75 × 109 /L. For second occurrence , hold ponatinib and resume at 30 mg dose after recovery to ANC <1.5 × 109 /L and platelet <75 × 109 /L. For third occurrence , hold ponatinib and resume at 15 mg dose after recovery to ANC <1.5 × 109 /L and platelet <75 × 109 /L.
Do not confuse ponatinib with pazopanib.
Caution patient to notify health care professional immediately if symptoms suggestive of a blood clot (chest pain, shortness or breath, weakness on one side of the body, speech problems, leg pain, leg swelling), liver failure (yellowing of eyes or skin, tea-colored urine, drowsiness), HF, pancreatitis (nausea, vomiting, abdominal pain or discomfort), neuropathy, unusual bleeding, easy bruising, fluid retention (leg swelling, abdominal swelling, weight gain, shortness of breath) or fever occurs.
Advise patient to notify health care professional if signs of slow heart rate (fainting, dizziness, chest pain) or signs of rapid heart rate (palpitations, dizziness) occur.
Instruct patient to maintain adequate hydration to minimize risk of tumor lysis syndrome.
Decreased progression of leukemia.