"The U.S. Food and Drug Administration today approved Gazyva (obinutuzumab) for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia (CLL).
CLL is a blood and bone ma"...
Iclusig (ponatinib) is a kinase inhibitor indicated for the:
- Treatment of adult patients with T315I-positive chronic myeloid leukemia (CML) (chronic phase, accelerated phase, or blast phase) and T315I-positive Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL).
- Treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia or Ph+ ALL for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated.
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
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 CP CML and 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
Table 1: Suggested Dose Modifications for
|ANC* < 1 x 109/L or platelet < 50 x 109/L||First occurrence:
|*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.
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:
|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:
|Symptomatic Grade 3 pancreatitis||Occurrence at 45 mg:
|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].
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:
|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: 1/3/2014
This monograph has been modified to include the generic and brand name in many instances.
Additional Iclusig Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
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