Product Information
Registration Status: ActiveALECENSA HARD CAPSULE 150MG is approved to be sold in Singapore with effective from 2017-04-24. It is marketed by ROCHE SINGAPORE PTE LTD, with the registration number of SIN15220P.
This product contains Alectinib 150mg in the form of CAPSULE. It is approved for ORAL use.
This product is manufactured by Excella GmbH & Co. KG. in ITALY, andDelpharm Milano in GERMANY.
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.
Description
Alectinib is a second generation oral drug that selectively inhibits the activity of anaplastic lymphoma kinase (ALK) tyrosine kinase. It is specifically used in the treatment of non-small cell lung cancer (NSCLC) expressing the ALK-EML4 (echinoderm microtubule-associated protein-like 4) fusion protein that causes proliferation of NSCLC cells. Inhibition of ALK prevents phosphorylation and subsequent downstream activation of STAT3 and AKT resulting in reduced tumour cell viability. Approved under accelerated approval in 2015, alectinib is indicated for use in patients who have progressed on or were not tolerant of crizotinib, which is associated with the development of resistance.
Indication
Alectinib is a kinase inhibitor indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Mechanism of Action
Alectinib is a second generation oral drug that selectively inhibits the activity of anaplastic lymphoma kinase (ALK) tyrosine kinase. It is specifically used in the treatment of non-small cell lung cancer (NSCLC) expressing the ALK-EML4 (echinoderm microtubule-associated protein-like 4) fusion protein that causes proliferation of NSCLC cells. Inhibition of ALK prevents phosphorylation and subsequent downstream activation of STAT3 and AKT resulting in reduced tumour cell viability. Both alectinib and its major active metabolite M4 demonstrate similar in vivo and in vitro activity against multiple mutant forms of ALK.
Pharmacokinetics
- Absorption
- Alectinib reached maximal concentrations at 4 hours following administration of 600 mg twice daily under fed conditions in patients with ALK-positive NSCLC. The absolute bioavailability was 37% in the fed state. A high-fat, high-calorie meal increased the combined exposure of alectinib and its major metabolite M4 by 3.1-fold following oral administration of a single 600 mg dose.
- Distribution
- 4016 L
- Metabolism
- Alectinib is metabolized by CYP3A4 to its major active metabolite M4. M4 is then further metabolized by CYP3A4. Both alectinib and M4 demonstrate similar in vivo and in vitro activity. In vitro studies suggest that alectinib is not a substrate for P-gp while M4 is.
- Elimination
Clearance
The apparent clearance is 81.9L/hr for alectinib and 217 L/hr for M4.
Toxicity
The most common adverse reactions (>5%) associated with alectinib use were fatigue, constipation, edema, and myalgia. Less common effects associated with use were hepatotoxicity, interstitial lung disease (ILD)/pneumonitis, bradycardia, severe myalgia and creatine phosphokinase (CPK) elevation, and embryo-fetal toxicity. Females of reproductive potential are advised to use effective contraception during treatment with alectinib and for 1 week following the final dose.
Active Ingredient/Synonyms
9-ethyl-6,6-dimethyl-8-[4-(morpholin-4-yl)piperidin-1-yl]-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile | Alectinib |
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.