Generic
Ponatinib Hydrochloride
5 brands available in the market
At a glance
Ponatinib Hydrochloride is a kinase inhibitor used for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), particularly in patients resistant or intolerant to dasatinib or nilotinib, and those with the T315I mutation.
Description
Ponatinib is a kinase inhibitor that inhibits the tyrosine kinase activity of ABL and T315I mutant ABL. It also inhibits the activity of additional kinases including VEGFR, PDGFR, FGFR, EPH receptors, SRC family, KIT, RET, TIE2, and FLT3. It inhibits the in vitro viability of cells expressing native or mutant BCR-ABL and reduces tumor size in animal models.
Indications
- Chronic Myeloid Leukemia (CML) - chronic, accelerated, or blast phase (dasatinib/nilotinib-resistant or intolerant, or T315I mutation)
- Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) - dasatinib-resistant or intolerant, or T315I mutation
Therapeutic class
Tyrosine Kinase Inhibitor
Pharmacological class
BCR-ABL Tyrosine Kinase Inhibitor
Pharmacology
Ponatinib inhibits the tyrosine kinase activity of ABL and T315I mutant ABL. It also inhibits additional kinases including VEGFR, PDGFR, FGFR, EPH receptors, SRC family, KIT, RET, TIE2, and FLT3. It inhibits in vitro viability of cells expressing native or mutant BCR-ABL and reduces tumor size in animal models.
Mechanism of action
Prevents cancer cell growth by inhibiting ABL tyrosine kinase and BCR-ABL signaling pathways.
Dosage
Adult Dose (Oral):
- Recommended starting dose: 45 mg once daily
- CP-CML patients with major cytogenetic response: Consider dose reduction to 15 mg
- With strong CYP3A inhibitors: Consider starting dose 30 mg
- Renal impairment (CrCl >50 mL/min): No dose adjustment; CrCl <50 mL/min or ESRD: Caution
- Hepatic impairment: Caution
Administration
- May be taken with or without food
- Take at the same time each day
- Swallow tablet whole
Missed dose
If you miss a dose, take it as soon as you remember; skip if it's almost time for next dose; do not double the dose.
Side effects
Serious Adverse Reactions (>2%):
- Pneumonia
- Pancreatitis
- Abdominal pain
- Atrial fibrillation
- Pyrexia
- Myocardial infarction
- Peripheral arterial occlusive disease
- Anemia
- Angina pectoris
- Decreased platelets
- Febrile neutropenia
- Hypertension
- Coronary artery disease
- Congestive heart failure
- Cerebrovascular accident
- Sepsis
- Cellulitis
- Acute kidney injury
- Urinary tract infection
- Increased lipase
Precautions & warnings
- Myelosuppression: Thrombocytopenia, neutropenia, anemia; CBC every 2 weeks for first 3 months, then monthly
- Arterial occlusion (myocardial infarction, stroke, retinal arterial occlusion): Manage cardiovascular risk; interrupt if occurs
- Venous thromboembolism: Monitor; interrupt if thromboembolism occurs
- Hypertension: Monitor and manage blood pressure at each clinic visit
- Congestive heart failure: Monitor for symptoms; consider discontinuation if serious
- Hepatotoxicity: Monitor liver function tests
- Severe hemorrhage: Interrupt and evaluate
- Hepatitis B reactivation: Test before initiating treatment
Contraindications
- Hypersensitivity to ponatinib or any excipient
Drug interactions
- Strong CYP3A4 inhibitors (clarithromycin, itraconazole, ketoconazole, ritonavir, grapefruit juice): Reduce dose to 30 mg
- Strong CYP3A4 inducers (carbamazepine, phenytoin, rifampicin): Avoid
Food interactions
It is not known whether it is safe to consume alcohol with Ponatinib.
Use in pregnancy
Use in Pregnancy: No adequate data in pregnant women; use only when clearly necessary; inform of potential risk to the fetus.
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: Unknown if ponatinib is excreted in human milk; discontinue breastfeeding.
Pediatric use
Safety and efficacy not established in patients under 18 years.
Geriatric use
Elderly patients (>65) are more likely to experience adverse reactions.
Renal / hepatic impairment
Renal Impairment: CrCl >50 mL/min: Safe; CrCl <50 mL/min or ESRD: Caution; consult your doctor.
Hepatic Impairment: Caution; consult your doctor.
Overdose effects
Overdose (up to 540 mg reported): QT prolongation, fatigue, pneumonia, sepsis; treatment: stop ponatinib, observe, supportive care.
Storage conditions
Store in a cool and dry place below 30°C; do not use if exposed to temperatures >40°C; keep out of reach of children.
Chemical structure
Ponatinib Hydrochloride