BRUTINACIB 100 TABLETS ( Each film coated tablet contains Accalabrutinib Maleate 100mg

Indications

• Mantle cell lymphoma (MCL)
• Chronic lymphocytic leukemia (CLL)

Dosage

Children: Refer to specific prescribing information for appropriate dosing.

Adults: Refer to specific prescribing information for appropriate dosing.

Mechanism of action

Acalabrutinib binds covalently to the cysteine residue in the active site of BTK, resulting in the inhibition of BTK activity. This leads to disruption of downstream signaling pathways that promote B-cell proliferation and survival, ultimately inducing apoptosis in malignant B-cells.

Pharmacodynamics

The pharmacodynamics of acalabrutinib involve targeted inhibition of BTK, which plays a critical role in the B-cell receptor signaling pathway. By inhibiting BTK, acalabrutinib decreases the activation of various downstream pathways, including NF-kB, which are responsible for cell survival and proliferation. Clinical studies have demonstrated significant activity against B-cell malignancies, with an associated improvement in overall survival and progression-free survival in treated patients.

Pharmacokinetics

Acalabrutinib is rapidly absorbed, with peak plasma concentrations occurring within approximately 1-3 hours after oral administration. The drug has a bioavailability of around 20%, and its pharmacokinetics are characterized by extensive metabolism primarily via the cytochrome P450 enzyme system (CYP3A4). Its elimination half-life is approximately 2-3 hours, with a clearance rate that may be affected by hepatic function. Acalabrutinib is primarily excreted in feces, with minimal renal excretion of unchanged drug.

Contra-indications

• Hypersensitivity to acalabrutinib or any of its excipients
• Severe hepatic impairment (Child-Pugh Class C)

Adverse effects

• Headache
• Diarrhoea
• Fatigue
• Nausea
• Infection
• Hemorrhage
• Anemia
• Thrombocytopenia
• Neutropenia

Interactions

• Strong CYP3A inhibitors (e.g., ketoconazole, itraconazole) may increase acalabrutinib levels
• Strong CYP3A inducers (e.g., rifampin, carbamazepine) may decrease acalabrutinib levels
• Anticoagulants and antiplatelet agents may increase the risk of bleeding

Precautions

• Monitor for signs of bleeding or infection
• Use caution in patients with a history of bleeding disorders
• Regular blood count monitoring is recommended during treatment
• Assess liver function prior to and during treatment

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Acalabrutinib may cause fetal harm. Women of childbearing potential should use effective contraception during treatment.

Breast-feeding

It is unknown whether acalabrutinib is excreted in human milk. A decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Storage

Store at room temperature (20 to 25 degrees Celsius). Protect from moisture and light.

Formulations

• Capsule: 100 mg