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Iclusig

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Iclusig

Indications
Dosage
How Supplied

INDICATIONS

Iclusig (ponatinib) is a kinase inhibitor indicated for the:

These indications are based upon response rate [see Clinical Studies]. There are no trials verifying an improvement in disease-related symptoms or increased survival with Iclusig.

DOSAGE AND ADMINISTRATION

Recommended Dosing

The optimal dose of Iclusig has not been identified. In clinical trials, the starting dose of Iclusig was 45 mg administered orally once daily. However, 59% of the patients required dose reductions to 30 mg or 15 mg once daily during the course of therapy.

Start dosing with 45 mg once daily. Consider reducing the dose of Iclusig for chronic phase (CP) CML and accelerated phase (AP) CML patients who have achieved a major cytogenetic response.

Consider discontinuing Iclusig if response has not occurred by 3 months (90 days).

Iclusig may be taken with or without food. Tablets should be swallowed whole.

Dose Modifications For Myelosuppression

Suggested dose modifications for neutropenia (ANC* less than 1.0 x 109/L) and thrombocytopenia (platelet less than 50 x 109/L) that are unrelated to leukemia are summarized in Table 1.

Table 1: Suggested Dose Modifications for Myelosuppression

ANC* < 1 x 109/L
or
platelet < 50 x 109/L
First occurrence:
  • Interrupt Iclusig and resume initial 45 mg dose after recovery to ANC ≥ 1.5 x 109/L and platelet ≥ 75 x 109/L
Second occurrence:
  • Interrupt Iclusig and resume at 30 mg after recovery to ANC ≥ 1.5 x 109/L and platelet ≥ 75 x 109/L
Third occurrence:
  • Interrupt Iclusig and resume at 15 mg after recovery to ANC ≥ 1.5 x 109/L and platelet ≥ 75 x 109/L
*ANC = absolute neutrophil count

Dose Modifications For Non-Hematologic Adverse Reactions

If a serious non-hematologic adverse reaction occurs, modify the dose or interrupt treatment. Do not restart Iclusig in patients with arterial or venous occlusive reactions unless the potential benefit outweighs the risk of recurrent arterial or venous occlusions and the patient has no other treatment options. For serious reactions other than arterial or venous occlusion, do not restart Iclusig until the serious event has resolved or the potential benefit of resuming therapy is judged to outweigh the risk.

Hepatic Toxicity

Recommended modifications for hepatic toxicity are summarized in Table 2.

Table 2: Recommended Dose Modifications for Hepatic Toxicity

Elevation of liver transaminase > 3 x ULN* (Grade 2 or higher)

Occurrence at 45 mg:

  • Interrupt Iclusig and monitor hepatic function
  • Resume Iclusig at 30 mg after recovery to ≤ Grade 1 ( < 3 x ULN) Occurrence at 30 mg:
  • Interrupt Iclusig and resume at 15 mg after recovery to ≤ Grade 1 Occurrence at 15 mg:
  • Discontinue Iclusig
Elevation of AST or ALT ≥ 3 x ULN concurrent with an elevation of bilirubin > 2 x ULN and alkaline phosphatase < 2 x ULN Discontinue Iclusig
*ULN = Upper Limit of Normal for the lab

Pancreatitis and Elevation of Lipase

Recommended modifications for pancreatic adverse reactions are summarized in Table 3.

Table 3: Recommended Dose Modifications for Pancreatitis and Elevation of Lipase

Asymptomatic Grade 1 or 2 elevation of serum lipase Consider interruption or dose reduction of Iclusig
Asymptomatic Grade 3 or 4 elevation of lipase ( > 2 x ULN*)
or
asymptomatic radiologic pancreatitis (Grade 2 pancreatitis)
Occurrence at 45 mg:
  • Interrupt Iclusig and resume at 30 mg after recovery to ≤ Grade 1 ( < 1.5 x ULN)
Occurrence at 30 mg:
  • Interrupt Iclusig and resume at 15 mg after recovery to ≤ Grade 1 Occurrence at 15 mg:
  • Discontinue Iclusig
Symptomatic Grade 3 pancreatitis

Occurrence at 45 mg:

  • Interrupt Iclusig and resume at 30 mg after complete resolution of symptoms and after recovery of lipase elevation to < Grade 1
Occurrence at 30 mg:
  • Interrupt Iclusig and resume at 15 mg after complete resolution of symptoms and after recovery of lipase elevation to < Grade 1
Occurrence at 15 mg
  • Discontinue Iclusig
Grade 4 pancreatitis Discontinue Iclusig
*ULN = Upper Limit of Normal for the lab

Dose Modification For Use With Strong CYP3A Inhibitors

The recommended dose should be reduced to 30 mg once daily when administering Iclusig with strong CYP3A inhibitors [see DRUG INTERACTIONS].

Dose Modification For Use In Patients With Hepatic Impairment

The recommended starting dose is 30 mg once daily in patients with hepatic impairment (Child-Pugh A, B, or C) [see Use in Specific Populations, and CLINICAL PHARMACOLOGY].

HOW SUPPLIED

Dosage Forms And Strengths

15 mg and 45 mg round, white, film-coated tablets.

Storage And Handling

Iclusig tablets are available in the following configurations:

Strength NDC Number Description Presentation
15 mg 76189-535-60 round, white, film-coated tablets with debossed “A5” on one side and plain on the other side 60 tablets in a wide-mouth white high density polyethylene (HDPE) bottle with child resistant closures that incorporate an induction heat seal liner
76189-535-80 180 tablets in a wide-mouth white high density polyethylene (HDPE) bottle with child resistant closures that incorporate an induction heat seal liner
45 mg 76189-534-30 round, white, film-coated tablets with debossed “AP4” on one side and plain on the other side 30 tablets in a wide-mouth white high density polyethylene (HDPE) bottle with child resistant closures that incorporate an induction heat seal liner
76189-534-90 90 tablets in a wide-mouth white high density polyethylene (HDPE) bottle with child resistant closures that incorporate an induction heat seal liner

Iclusig tablets should be stored at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30° C (59° to 86° F) [see USP Controlled Room Temperature]. Keep away from children.

Manufactured for: ARIAD Pharmaceuticals, Inc. 26 Landsdowne Street Cambridge, MA 02139-4234. Revised: December 2013

Last reviewed on RxList: 8/7/2014
This monograph has been modified to include the generic and brand name in many instances.

Indications
Dosage
How Supplied
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