Iclusig Dosage

Generic name: ponatinib hydrochloride 15mg
Dosage form: tablet, film coated
Drug classes: BCR-ABL tyrosine kinase inhibitors, Multikinase inhibitors, VEGF/VEGFR inhibitors

Medically reviewed by Drugs.com. Last updated on Nov 10, 2022.

Recommended Dosage

CP-CML

The recommended starting dosage is 45 mg orally once daily with a reduction to 15 mg orally once daily upon achievement of ≤1% BCR-ABL1IS. Patients with loss of response can re-escalate the dose of Iclusig to a previously tolerated dosage of 30 mg or 45 mg orally once daily. Continue Iclusig until loss of response at the re-escalated dose or unacceptable toxicity.

Consider discontinuing Iclusig if hematologic response has not occurred by 3 months.

AP-CML, BP-CML, and Ph+ ALL

The optimal dose of Iclusig has not been identified.

The recommended starting dosage of Iclusig is 45 mg orally once daily. Consider reducing the dose of Iclusig for patients with accelerated phase (AP) CML who have achieved a major cytogenetic response. Continue Iclusig until loss of response or unacceptable toxicity.

Consider discontinuing Iclusig if response has not occurred by 3 months.

Administration

Advise patients of the following:

Iclusig may be taken with or without food.
Swallow tablets whole. Do not crush, break, cut or chew tablets.
If a dose is missed, take the next dose at the regularly scheduled time the next day.

Dosage Modifications for Adverse Reactions

Recommended dosage modifications of Iclusig for adverse reactions are provided in Table 1 and recommended dose reductions of Iclusig for adverse reactions are presented in Table 2.

Table 1: Recommended Dosage Modifications for Iclusig for Adverse Reactions
Adverse Reaction	Severity	Iclusig Dosage Modifications
Based on CTCAE v5.0: Grade 1 mild, Grade 2 moderate, Grade 3 severe, Grade 4 life-threatening ULN = Upper Limit of Normal for the lab; AOE = Arterial Occlusive Event; VTE = Venous Thromboembolic Event; ANC = absolute neutrophil count
AOE: cardiovascular or cerebrovascular [see Warnings and Precautions (5.1)]	Grade 1	Interrupt Iclusig until resolved, then resume at same dose.
	Grade 2	Interrupt Iclusig until Grade 0 or 1, then resume at next lower dose. Discontinue Iclusig if recurrence.
	Grade 3 or 4	Discontinue Iclusig.
AOE: peripheral vascular and other or VTE [see Warnings and Precautions (5.1, 5.2)]	Grade 1	Interrupt Iclusig until resolved, then resume at same dose.
	Grade 2	Interrupt Iclusig until Grade 0 or 1, then resume at same dose. If recurrence, interrupt Iclusig until Grade 0 or 1, then resume at next lower dose.
	Grade 3	Interrupt Iclusig until Grade 0 or 1, then resume at next lower dose. Discontinue Iclusig if recurrence.
	Grade 4	Discontinue Iclusig.
Heart Failure [see Warnings and Precautions (5.3)]	Grade 2 or 3	Interrupt Iclusig until Grade 0 or 1, then resume at next lower dose. Discontinue Iclusig if recurrence.
Heart Failure [see Warnings and Precautions (5.3)]	Grade 4	Discontinue Iclusig.
Hepatotoxicity [see Warnings and Precautions (5.4)]	AST or ALT greater than 3 times ULN	Interrupt Iclusig until Grade 0 or 1, then resume at next lower dose.
Hepatotoxicity [see Warnings and Precautions (5.4)]	AST or ALT at least 3 times ULN concurrent with bilirubin greater than 2 times ULN and alkaline phosphatase less than 2 times ULN	Discontinue Iclusig.
Pancreatitis and Elevated Lipase [see Warnings and Precautions (5.6)]	Serum lipase greater than 1 to 1.5 times ULN	Consider interrupting Iclusig until resolution, then resume at same dose.
	Serum lipase greater than 1.5 to 2 times ULN, 2 to 5 times ULN and asymptomatic, or asymptomatic radiologic pancreatitis	Interrupt Iclusig until Grade 0 or 1 (less than 1.5 times ULN), then resume at next lower dose.
	Serum lipase greater than 2 to 5 times ULN and symptomatic, symptomatic Grade 3 pancreatitis, or serum lipase greater than 5 times ULN and asymptomatic	Interrupt Iclusig until complete resolution of symptoms and after recovery of lipase elevation Grade 0 or 1, then resume at next lower dose.
	Symptomatic pancreatitis and serum lipase greater than 5 times ULN	Discontinue Iclusig.
Myelosuppression [see Warnings and Precautions (5.13)]	ANC less than 1 × 109/L or Platelets less than 50 × 109/L	Interrupt Iclusig until ANC at least 1.5 × 109/L and platelet at least 75 × 109/L, then resume at same dose. If recurrence, interrupt Iclusig until resolution, then resume at next lower dose.
Other Non-hematologic Adverse Reactions [see Warnings and Precautions (5.5, 5.8, 5.10, 5.11, 5.12)]	Grade 1	Interrupt Iclusig until resolved, then resume at same dose.
	Grade 2	Interrupt Iclusig until Grade 0 or 1, then resume at same dose. If recurrence, interrupt Iclusig until Grade 0 or 1, then resume at next lower dose.
	Grade 3 or 4	Interrupt Iclusig until Grade 0 or 1, then resume at next lower dose. Discontinue Iclusig if recurrence.

Table 2: Recommended Dose Reductions for Iclusig for Adverse Reactions
Dose Reduction	Dosage for Patients with CP-CML	Dosage for Patients with AP-CML, BP-CML, and Ph+ ALL
First	30 mg orally once daily	30 mg orally once daily
Second	15 mg orally once daily	15 mg orally once daily
Third	10 mg orally once daily	Permanently discontinue Iclusig in patients unable to tolerate 15 mg orally once daily.
Subsequent Reduction	Permanently discontinue Iclusig in patients unable to tolerate 10 mg orally once daily.

Dosage Modification for Coadministration of Strong CYP3A Inhibitors

Avoid coadministration of Iclusig with strong CYP3A inhibitors. If coadministration of a strong CYP3A inhibitor cannot be avoided, reduce the dosage of Iclusig as recommended in Table 3.

After the strong CYP3A inhibitor has been discontinued for 3 to 5 elimination half-lives, resume the Iclusig dosage that was tolerated prior to initiating the strong CYP3A inhibitor [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

Table 3: Recommended Iclusig Dosage for Coadministration of Strong CYP3A Inhibitors
Current Iclusig Dosage	Recommended Iclusig Dosage with a Strong CYP3A Inhibitor
45 mg orally once daily	30 mg orally once daily
30 mg orally once daily	15 mg orally once daily
15 mg orally once daily	10 mg orally once daily
10 mg orally once daily	Avoid coadministration of Iclusig with a strong CYP3A inhibitor

Dosage for Patients with Hepatic Impairment

Reduce the starting dose of Iclusig from 45 mg orally once daily to 30 mg orally once daily in patients with pre-existing hepatic impairment (Child-Pugh A, B, or C) [see Use in Specific Populations (8.6)].