Ponatinib
ICLUSIG
Pronunciation: poe-NA-ti-nib (eye-KLOO-sig)
“Inclusive Pony tail nibbler”
What it isOral pan-BCR-ABL tyrosine-kinase inhibitor for resistant CML and Ph-positive ALL.
Why this oneIt retains activity against the T315I gatekeeper mutation that defeats most other BCR-ABL inhibitors.
What limits itArterial occlusion, venous thrombosis, heart failure, and hepatotoxicity demand aggressive cardiovascular selection and monitoring.
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Newly diagnosed Ph+ ALL (with chemotherapy) | adults | 30 mg QD | reduce to 15 mg QD upon MRD-negative (≤0.01% BCR::ABL1/ABL1) CR at end of induction; continue up to 20 cycles | 30 mg QD |
| Ph+ ALL monotherapy (no other kinase inhibitors indicated, or T315I-positive) | adults | 45 mg QD | 45 mg QD until loss of response or unacceptable toxicity (optimal dose not identified) | 45 mg QD |
| CP-CML | adults | 45 mg QD | reduce to 15 mg QD upon ≤1% BCR::ABL1IS; may re-escalate to previously tolerated 30 or 45 mg QD on loss of response | 45 mg QD |
| AP-CML and BP-CML | adults | 45 mg QD | 45 mg QD until loss of response or unacceptable toxicity; consider dose reduction in AP-CML on major cytogenetic response | 45 mg QD |
Renal Undefined
Hepatic Monotherapy (CP/AP/BP-CML, Ph+ ALL): reduce starting dose 45→30 mg QD for pre-existing impairment (Child-Pugh A, B, or C). Newly diagnosed Ph+ ALL: no adjustment for Child-Pugh A; monitor closely in B/C
Instructions
- With or without food; swallow tablets whole — do not crush, break, cut, or chew
- Missed dose: take next dose at regularly scheduled time next day
- Consider discontinuing if no response by 3 months (monotherapy indications)
- Toxicity dose reductions: CP-CML 45→30→15→10 mg QD; AP/BP-CML and Ph+ ALL monotherapy 45→30→15 mg QD; newly diagnosed Ph+ ALL 30→15→10 mg QD; discontinue if lowest step not tolerated
- If strong CYP3A inhibitor unavoidable: 45→30, 30→15, 15→10 mg QD (avoid if on 10 mg)
- Withhold ≥1 week before elective surgery; do not give for ≥2 weeks after major surgery and until adequate wound healing
Available strengths
- tab 10, 15, 30, 45 mg
Cautions
- Arterial occlusive events, VTE, heart failure, hepatotoxicity (boxed)
- Hypertension incl. renal artery stenosis — monitor BP; interrupt/reduce/stop if not controlled
- Pancreatitis and lipase elevation — monitor serum lipase
- Peripheral and cranial neuropathy
- Ocular toxicity — comprehensive eye exams at baseline and periodically
- Hemorrhage
- Fluid retention
- Cardiac arrhythmias
- Myelosuppression — CBC every 2 weeks x3 months, then monthly
- Tumor lysis syndrome — hydrate, correct uric acid before starting
- Reversible posterior leukoencephalopathy syndrome
- Impaired wound healing and GI perforation
Adverse reactions
- Single agent (>20%): rash, arthralgia, abdominal pain, fatigue, headache, constipation, hypertension, dry skin, hepatotoxicity, fluid retention/edema, pyrexia, pancreatitis/lipase elevation, nausea, hemorrhage, anemia, arterial occlusive events, cardiac arrhythmias
- Grade 3/4 labs (>20%): decreased platelets, neutrophils, WBC
Pregnancy Can cause fetal harm — adverse developmental effects in rats at exposures below human exposure at 45 mg/day
Lactation Do not breastfeed during treatment and for 1 week after last dose
Cost
| Strength | #/mo | generic $/mo | CostPlus | |
|---|---|---|---|---|
| 10 mg | tab | 30 qd | not offered | |
| 15 mg | tab | 30 qd | not offered | |
| 30 mg | tab | 30 qd | not offered | |
| 45 mg | tab | 30 qd | not offered |
⚠ BOXED WARNINGS
- Arterial occlusive events
- Venous thromboembolic events
- Heart failure
- Hepatotoxicity
Classes and tags
Clinical profile
Legacy pregnancy categoryD
Defining liabilityArterial occlusion and multiorgan toxicity