依鲁替尼Ibrutinix(伊布替尼ibrutinib)

[Ibrutinix(ibrutinib) indications for ibrutinib].

Ibrutinix(ibrutinib) is indicated for the treatment of patients with lymphoma with sleeve cells (MCL).

[Ibrutinib Ibrutinix (ibrutinib) Specification

This product is a capsule with specifications of 140mg/120 tablets.

【Irutinib Ibrutinix(ibrutinib) Dosage】.

The recommended dose is 560mg (4 tablets) once daily.

[Precautions for Ibrutinib Ibrutinix (ibrutinib)].

[ibrutinib Ibrutinix Clinical Studies].
Mechanism of action:
Ibrutinib Ibrutinib is a small – molecule inhibitor of BTK.Ibrutinib forms covalent bonds with cysteine residues in the active site of BTK, leading to inhibition of BTK enzyme activity.BTK is a signalling molecule in the B-cell antigen receptor (BCR) and cytokine receptor pathways.BTK acts by signalling through the B-cell surface receptor resulting in the inhibition of B – cell pathways required for transaction, chemotaxis, and adhesion. Non-clinical studies have shown that ibrutinib inhibits malignant B-cell proliferation and survival in vivo as well as cell migration and substrate adhesion in vitro.
In patients with recurrent B-cell lymphoma > 90% occupation of the BTK active site in peripheral studies monocytes was observed at ibrutinib doses ≥ 2.5 mg/kg/day (≥ 175 mg/day vs. mean body weight of 70 kg) up to 24 hours.

[Erlotinib Ibrutinix Precautions].
5.1 Haemorrhage
5% of patients with MCL had Grade 3 or higher bleeding events (subdural haematoma, gastrointestinal bleeding, and haematuria). Overall, bleeding events including bruising of any grade occurred in 48% of MCL patients treated with 560 mg daily.
The mechanisms of bleeding events are not well understood.
Consider the benefit-risk of ibrutinib in patients requiring antiplatelet or anticoagulant therapy.
The benefit-risk of considering not using ibrutinib for at least 3 to 7 days before and after surgery is dependent on the type of surgery and the risk of bleeding [see Clinical Studies (14.1)].
5.2 Infection
Treatment with IMBRUVICA has been associated with fatal and non – fatal infections. At least 25% of patients with MCL had National Cancer Institute Common Terminology for Adverse Events (CTCAE) grade 3 or greater infections [see Adverse Reactions (6)]. Monitor patients with fever and infection and timely evaluation.
5.3 Bone Marrow Suppression
Treatment-emergent grade 3 or 4 whole blood cytopenias were reported in 41% of patients. These included neutropenia (29%), thrombocytopenia (17%) and anaemia (9%). Monitor complete blood counts monthly.
5.4 Nephrotoxicity
Treatment with IMBRUVICA has been associated with fatal and severe cases. 67% of patients treated-experienced an increase in creatinine levels to 1.5 times the upper limit of normal and 9% of patients 1.5 to 3 times the upper limit of normal. Monitor creatinine levels regularly. Maintain hydration.
5.5 Second Primary Malignancy
Patients with MCL treated with IMBRUVICA have had other malignancies (5%), including skin cancer (4%), and other cancers (1%).
5.6 Embryo-fetal toxicity
Based on findings in animals, IMBRUVICA can cause fetal harm when given to pregnant women. In rats exposed as MCL patients receiving ibrutinib at a dose of 560 mg per day reported teratogenicity of Ibrutinib at exposure. Reduced fetal weight was observed at lower exposures. Women are advised to avoid becoming pregnant when taking Ibrutinib. Patients should be advised of the potential hazard to the fetus if this drug is used during pregnancy or if the patient becomes pregnant while taking this drug [see Use in Specific Populations (8.1)].

[Irutinib Ibrutinix adverse reactions and contraindications].
The following adverse reactions are discussed in more detail in other sections of the insert:
● Bleeding [see Warnings and Precautions (5.1)].
●Infection [see Warnings and Precautions (5.2)
● bone marrow suppression [see Warnings and Precautions (5.3)
● nephrotoxicity [see Warnings and Precautions (5.4)
● second primary malignancy [see Warnings and Precautions (5.5)
Because clinical trials are conducted under widely varying circumstances, the rate of adverse reactions observed in clinical trials is not directly comparable to the incidence in clinical trials of another drug and may not reflect the incidence observed in practice.

[ibrutinib Ibrutinix for pregnant women
It is not known if ibrutinib is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Ibrutinib, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

[Ibrutinix Ibrutinix Children’s Medication].
The safety and effectiveness of IMBRUVICA in pediatric patients have not been established.