Table of Contents
1. Name of the medicinal product
2. Qualitative and quantitative composition
3. Pharmaceutical form
4. Clinical particulars
4.1 Therapeutic indications
4.2 Posology and method of administration
4.3 Contraindications
4.4 Special warnings and precautions for use
4.5 Interaction with other medicinal products and other forms of interaction
4.6 Fertility, pregnancy and lactation
4.7 Effects on ability to drive and use machines
4.8 Undesirable effects
4.9 Overdose
5. Pharmacological properties
5.1 Pharmacodynamic properties
5.2 Pharmacokinetic properties
5.3 Preclinical safety data
6. Pharmaceutical particulars
6.1 List of excipients
6.2 Incompatibilities
6.3 Shelf life
6.4 Special precautions for storage
6.5 Nature and contents of container
6.6 Special precautions for disposal and other handling
7. Marketing authorisation holder
8. Marketing authorisation number(s)
9. Date of first authorisation/renewal of the authorisation
10. Date of revision of the text
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1. Name of the medicinal product
Iclusig 15 mg film-coated tablets
Iclusig 45 mg film-coated tablets
2. Qualitative and quantitative composition
Each 15 mg film-coated tablet contains 15 mg of ponatinib (as hydrochloride).
Each 45 mg film-coated tablet contains 45 mg of ponatinib (as hydrochloride).
Excipients with known effect
Each 15 mg film-coated tablet contains 40 mg of lactose monohydrate.
Each 45 mg film-coated tablet contains 120 mg of lactose monohydrate
For the full list of excipients, see section 6.1.
3. Pharmaceutical form
Film-coated tablet (tablet).
15 mg tablet: white, biconvex, round film-coated tablet that is approximately 6 mm in diameter, with "A5" debossed on one side.
45 mg tablet: white, biconvex, round film-coated tablet that is approximately 9 mm in diameter, with "AP4" debossed on one side.
4. Clinical particulars
4.1 Therapeutic indications
Iclusig is indicated in adult patients with
• chronic phase, accelerated phase, or blast phase chronic myeloid leukaemia (CML) who are resistant to dasatinib or nilotinib; who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation
• Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) who are resistant to dasatinib; who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation.
4.2 Posology and method of administration
Therapy should be initiated by a physician experienced in the diagnosis and treatment of patients with leukaemia. Haematologic support such as platelet transfusion and haematopoietic growth factors can be used during treatment if clinically indicated.
Before starting treatment with ponatinib, the cardiovascular status of the patient should be assessed and cardiovascular risk factors should be actively managed. Cardiovascular status should continue to be monitored and therapy optimised during treatment with ponatinib.
Posology
The recommended starting dose is 45 mg of ponatinib once daily. For the standard dose of 45 mg once daily, a 45 mg film-coated tablet is available. Treatment should be continued as long as the patient does not show evidence of disease progression or unacceptable toxicity.
Dose adjustments or modifications
Dose modifications should be considered for the management of treatment toxicity. For a dose of 30 mg or 15 mg once daily, 15 mg film-coated tablets are available.
Myelosuppression
Dose modifications for neutropenia (ANC* < 1.0 x 109/L) and thrombocytopenia (platelet < 50 x 109/L) that are unrelated to leukaemia are summarized in Table 1.
Table 1 Dose modifications for myelosuppression
|
ANC* < 1.0 x 109/L
or
platelet < 50 x 109/L
|
First occurrence:
• Withhold Iclusig and resume initial 45 mg dose after recovery to ANC ≥ 1.5 x 109/L and platelet ≥ 75 x 109/L
|
|
Second occurrence:
• Withhold Iclusig and resume at 30 mg after recovery to ANC ≥ 1.5 x 109/L and platelet ≥ 75 x 109/L
|
|
Third occurrence:
• Withhold 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
|
Non-haematological adverse reactions
If a severe non-haematological adverse reaction occurs, treatment should be withheld. After the event is resolved or attenuated in severity, Iclusig may be resumed at the same dose or at a reduced dose according to initial grade of the adverse reaction.
Vascular occlusion
In a patient suspected of developing an arterial or venous occlusive event, Iclusig should be immediately interrupted. A benefit-risk consideration should guide a decision to restart Iclusig therapy (see sections 4.4 and 4.8) after the event is resolved.
Hypertension may contribute to risk of arterial thrombotic events. Iclusig treatment should be temporarily interrupted if hypertension is not medically controlled.
Pancreatitis
Recommended modifications for pancreatic adverse reactions are summarized in Table 2.
Table 2 Dose modifications for pancreatitis and elevation of lipase/amylase
|
Asymptomatic Grade 2 pancreatitis and/or elevation of lipase/amylase
|
Continue Iclusig at the same dose
|
|
Grade 3 or 4 asymptomatic elevation of lipase/amylase ( > 2.0 x IULN*) only
|
Occurrence at 45 mg:
• Withhold Iclus |
