Ponatinib (Iclusig) is a kinase inhibitor that has been approved for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myeloid leukemia (CML).

Side Effects of Ponatinib (Iclusig)

Adverse Reactions with Monotherapy

Dermatological toxicity: Rash and related symptoms (75%), dry skin (42%).

Musculoskeletal reactions: Arthralgia (joint pain) (61%), myalgia (muscle pain) (24%).

Gastrointestinal reactions: Abdominal pain (54%), constipation (42%), nausea (29%), vomiting (19%).

General reactions: Headache (43%), fatigue (44%), fever (26%).

Vascular events: Hypertension (high blood pressure) (42%), arterial occlusive events (31%).

Adverse Reactions with Combination Chemotherapy

Hepatotoxicity (66%), arthralgia (47%), rash (47%).

Headache (45%), fever (44%), abdominal pain (43%).

Severe Adverse Reactions of Ponatinib (Iclusig)

Arterial Occlusive Events (AOEs)

Cardiovascular events: Myocardial infarction, angina pectoris, acute coronary syndrome.

Cerebrovascular events: Stroke, cerebral artery stenosis.

Peripheral vascular events: Severe peripheral vascular disease requiring emergency revascularization.

Monitor for symptoms of vascular events and report warning signs immediately.

Interrupt or permanently discontinue treatment based on the severity of the event.

Decide whether to restart treatment only after evaluating the benefit-risk balance.

Heart Failure

PhALLCON trial data: Occurred in 6% of patients, with 1.2% being severe cases.

Most common manifestations: Left ventricular hypertrophy (5%), left ventricular dysfunction (5%).

Precautions for Ponatinib (Iclusig)

Drug Interactions

Contraindicated concomitant drugs: Strong CYP3A inducers.

Strong CYP3A inhibitors: Dosage adjustment is required if co-administration is necessary.

Administration Guidelines

Swallow the tablet whole; do not chew, crush, or split it. 

May be taken with or without food.

If a dose is missed, take the next scheduled dose on the following day as planned—do not take a double dose.

Clinical Monitoring Protocol

Liver function: Before treatment initiation and at least once monthly thereafter.

Blood pressure: At baseline and as clinically needed.

Serum lipase: Every 2 weeks for the first 2 months, then once monthly thereafter.