Alectinib- Alecensa (Dec 2015)- Anti-Cancer drugDrug Name:
Alectinib- Alecensa (Dec 2015)- Anti-Cancer drug
List Of Brands:
Indication Type Description:
Dosages/ Overdosage Etc
Pregnancy and lactation
No pharmacokinetic interactions with alectinib requiring dosage adjustment have
been identified .
ALECENSA® (alectinib) capsules, for oral use
Initial U.S. Approval: 2015
NEW MOLECULAR ENTITY AND NEW THERAPEUTIC BIOLOGICAL
PRODUCTS APPROVED FOR 2015
Certain drugs are classified as New molecular Emtities- NME- for FDA review
Many of these products contain active moieties that have not been approved
by FDA previously, either as a single ingredient or as part of a combination
products; these products frequently provide important new therapies for the
Some drugs are characterized as NMEs for administrative purposes ,but
nonetheless contain certain active moieties in products that have been
previously approved by FDA. For example, CDER classifies biological
products submitted in an application under section 351(a) of the Public
Service Act as NME for purposes of FDA review, regardless of whether
the agency previously approved a related active moiety in a different
FDAs classification of a drug as an -NME- for review purposes is distinct
from FDAs determination of whether a drug is a - New Chemical Entity or - NCE-
within the meaning of the Federal Food,Drug, and Cosmetic Act
Drug Name - Alectinib
Active Ingredient- Alecensa
Date of approval - 12/11/2015
FDA-approved use - To treat ALK- positive Lung Cancer
Approved by US FDA on 12/11/2015- (Ref- FDA approved List- 2015)
The most common adverse reactions (incidence .20%) were
fatigue, constipation, edema and myalgia.
WARNINGS AND PRECAUTIONS
Hepatotoxicity: Monitor liver laboratory tests every 2 weeks
during the first 2 months of treatment, and then periodically during
treatment. In case of severe ALT, AST,or bilirubin elevations, withhold,
then reduce dose, or permanently discontinue ALECENSA.
Interstitial Lung Disease (ILD)/Pneumonitis:
Occurred in 0.4% of patients. Immediately withhold ALECENSA in patients
diagnosed with ILD/pneumonitis and permanently discontinue
if no other potential causes of ILD/pneumonitis have been identified.
Bradycardia: Monitor heart rate and blood pressure regularly.
If symptomatic, withhold ALECENSA then reduce dose, or permanently
Severe Myalgia and Creatine Phosphokinase (CPK) Elevation:
Occurred in 1.2% and 4.6% of patients, respectively.
Assess CPK every 2 weeks during the first month of treatment and
in patients reporting unexplained muscle pain, tenderness, or weakness.
In case of severe CPK elevations, withhold, then resume or reduce dose.
Embryo-Fetal Toxicity: ALECENSA can cause fetal harm.
Advise females of reproductive potential of the potential risk to a fetus and
to use effective contraception.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
ALECENSA 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.
DOSAGE AND ADMINISTRATION
600 mg orally twice daily. Administer ALECENSA with food. )
DOSAGE FORMS AND STRENGTHS
Capsules: 150 mg
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Inform patients of the following:
Inform patients of the signs and symptoms of bilirubin and hepatic transaminase
Advise patients to contact their healthcare provider immediately for signs or
symptoms of bilirubin and hepatic transaminase elevations
Interstitial Lung Disease (ILD)/Pneumonitis
Inform patients of the risks of severe ILD/pneumonitis.
Advise patients to contact their healthcare provider immediately to report new or
worsening respiratory symptoms
Inform patients that symptoms of bradycardia including dizziness, lightheadedness,
and syncope can occur while taking ALECENSA.
Advise patients to contact their healthcare provider to report these symptoms and to
inform their healthcare provider about the use of any heart or blood pressure
Severe Myalgia/CPK elevation
Inform patients of signs and symptoms of myalgia, including unexplained and/or
persistent muscle pain, tenderness, or weakness. Advise patients to contact their
healthcare provider immediately to report new or worsening symptoms of muscle
pain or weakness
Inform patients of the signs and symptoms of photosensitivity. Advise patients to
avoid prolonged sun exposure 368 while taking ALECENSA and for at least 7 days
after study drug discontinuation and to use proper protection from the sun.
Advise patients to use a broad spectrum ultraviolet A (UVA)/ultraviolet B (UVB)
sunscreen and lip balm (SPF .50) to help protect against potential sunburn
ALECENSA can cause fetal harm if taken during pregnancy. Advise a pregnant woman
of the potential risk to a fetus
Advise females of reproductive potential to use effective contraception during
treatment with ALECENSA and for at least 1 week after the last dose of ALECENSA.
Advise patients to inform their healthcare provider of a known or suspected pregnancy
Advise male patients with female partners of reproductive potential to use effective
contraception during treatment with ALECENSA and for 3 months after the last dose
Advise women not to breastfeed during treatment with ALECENSA and for one week
after the last dose
Instruct patients to take ALECENSA twice a day. Advise patients to take ALECENSA with
food and to swallow ALECENSA capsules whole
Advise patients that if a dose of ALECENSA is missed or if the patient vomits after takin
a dose of ALECENSA, patients should be advised not to take an extra dose,
but to take the next dose at the regular time
Genentech USA, Inc.
A Member of the Roche Group ALECENSAR is a registered trademark of
1 DNA Way Chugai Pharmaceutical Co., Ltd., Tokyo, Japan
South San Francisco, CA 94080-4990 .
1. Mechanism of Action
Alectinib is a tyrosine kinase inhibitor that targets ALK and RET.
In nonclinical studies, alectinib inhibited ALK phosphorylation and ALK-mediated
activation of the downstream signaling proteins STAT3 and AKT, and decreased
tumor cell viability in multiple cell lines harboring ALK fusions, amplifications,
or activating mutations. The major active metabolite of alectinib, M4, showed
similar in vitro potency and activity
The pharmacokinetics of alectinib and its major active metabolite M4 have been
characterized in patients with ALK-positive NSCLC and healthy subjects.
In patients with ALK-positive NSCLC, the geometric mean (coefficient of variation %)
steady-state maximal concentration (Cmax,ss) for alectinib was 665 ng/mL (44%)
and for M4 was 246 ng/mL (45%) with peak to trough concentration ratio of 1.2.
The geometric mean steady-state area under the curve from 0 to 12 hours
(AUC0-12h,ss) for alectinib was 7,430 ng*h/mL (46%) and for M4 was 2,810 ng*h/mL
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
Based on animal studies and its mechanism of action, ALECENSA can cause fetal harm
when administered to a pregnant woman
There are no available data on ALECENSA use in pregnant women.
Advise pregnant women of the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects and
miscarriage in clinically-recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
There are no data on the presence of alectinib or its metabolites in human milk, the
effects of alectinib on the breast-fed infant, or its effects on milk production.
Because of the potential for serious adverse reactions in breast-fed infants from
alectinib, advise a lactating woman not to breastfeed during treatment with ALECENSA
and for 1 week after the final dose.
4 Pediatric Use
The safety and effectiveness of ALECENSA in pediatric patients have not been established.
5. Geriatric Use
Clinical studies of ALECENSA did not include sufficient number of subjects aged 65 and
older to determine whether they respond differently from younger subjects.