Product Information
Registration Status: ActiveSIN15753P
CALQUENCE HARD CAPSULES 100MG is approved to be sold in Singapore with effective from 2019-07-25. It is marketed by ASTRAZENECA SINGAPORE PTE LTD, with the registration number of SIN15753P.
This product contains Acalabrutinib 100mg in the form of CAPSULE. It is approved for ORAL use.
This product is manufactured by AstraZeneca AB in SWEDEN.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Product Reference
Important Note: For generic product, the SPC/PIL provided may not be brand specific.
{{/items}} {{^items}}Description
To date, acalabrutinib has been used in trials studying the treatment of B-All, Myelofibrosis, Ovarian Cancer, Multiple Myeloma, and Hodgkin Lymphoma, among others. As of October 31, 2017 the FDA approved Astra Zeneca's orally administered Calquence (acalabrutinib) medication as a Bruton Tyrosine Kinase (BTK) inhibitor indicated for the treatment of adult patients with Mantle Cell Lymphoma (MCL) who have already received at least one prior therapy, marking the company's first entry into the treatment of blood cancers. Also known as ACP-196, acalabrutinib is also considered a second generation BTK inhibitor because it was rationally designed to be more potent and selective than ibrutinib, theoretically expected to demonstrate fewer adverse effects owing to minimized bystander effects on targets other than BTK. Nevertheless, acalabrutinib was approved under the FDA's accelerated approval pathway, which is based upon overall response rate and faciliates earlier approval of medicines that treat serious conditions or/and that fill an unmet medical need based on a surrogate endpoint. Continued approval for acalabrutinib's currently accepted indication may subsequently be contingent upon ongoing verification and description of clinical benefit in confimatory trials. Furthermore, the FDA granted this medication Priority Review and Breakthrough Therapy designations. It also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. At this time, more than 35 clinical trials across 40 countries with more than 2500 patients are underway or have been completed with regards to further research into better understanding and expanding the therapeutic uses of acalabrutinib [L1009].
Indication
Acalabrutinib is currently indicated for the treatment of adult patients with Mantle Cell Lymphoma (MCL) who have received at least one prior therapy [FDA Label].
Mechanism of Action
Mantle Cell Lymphoma (MCL) is a rare yet aggressive type of B-cell non-Hodgkin lymphoma (NHL) with poor prognosis [A31253, L1008]. Subsequently, relapse is common in MCL patients and ultimately represents disease progression [L1008]. Lymphoma occurs when immune system lymphocytes grow and multiply uncontrollably. Such cancerous lymphocytes may travel to many parts of the body, including the lymph nodes, spleen, bone marrow, blood, and other organs where they can multiply and form a mass(es) called a tumor. One of the main kinds of lymphocytes that can develop into cancerous lymphomas are the body's own B-lymphocytes (B-cells) [L1008]. Bruton Tyrosine Kinase (BTK) is a signalling molecule of the B-cell antigen receptor and cytokine receptor pathways. Such BTK signaling causes the activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion [FDA Label]. Acalabrutinib is a small molecule inhibitor of BTK. Both acalabrutinib and its active metabolite, ACP-5862, act to form a covalent bond with a cysteine residue (Cys481) in the BTK active site, leading to inhibition of BTK enzymatic activity [A31253, L1008]. As a result, acalabrutinib inhibits BTK-mediated activation of downstream signaling proteins CD86 and CD69, which ultimately inhibits malignant B-cell proliferation and survival [L1008]. Whereas ibrutinib is typically recognized as the first-in-class BTK inhibitor [A31253], acalabrutinib is considered a second generation BTK inhibitor primarily because it demonstrates highter selectivity and inhibition of the targeted activity of BTK while having a much greater IC50 or otherwise virtually no inhibition on the kinase activities of ITK, EGFR, ERBB2, ERBB4, JAK3, BLK, FGR, FYN, HCK, LCK, LYN, SRC, and YES1 [A31253]. In effect, acalabrutinib was rationally designed to be more potent and selective than ibrutinib, all the while demonstrating fewer adverse effects - in theory - because of the drug's minimized bystander effects on targets other than BTK.
Pharmacokinetics
- Absorption
- The geometric mean absolute bioavailability of acalabrutinib is 25% with a median time to peak plasma concentrations (Tmax) of 0.75 hours [FDA Label].
- Distribution
- The mean steady-state volume of distribution is approximately 34 L [FDA Label].
- Metabolism
- Acalabrutinib is mainly metabolized by CYP3A enzymes. ACP-5862 is identified to be the major active metabolite in plasma with a geometric mean exposure (AUC) that is about 2-3 times greater than the exposure of acalabrutinib. ACP-5862 is about 50% less potent than acalabrutinib in regards to the inhibition of BTK [FDA Label].
- Elimination
Clearance
Acalabrutinib's mean apparent oral clearance (CL/F) is observed to be 159 L/hr with similar PK between patients and healthy subjects, based on population PK analysis [FDA Label].
Active Ingredient/Synonyms
Acalabrutinib | Acalabrutinib |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.