Osimertinib- Tagrisso -@- (Nov 2015)- Anti-cancer
Drug Name:Osimertinib- Tagrisso -@- (Nov 2015)- Anti-cancer
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
Strong CYP3A Inhibitors: Avoid concurrent administration with
TAGRISSO if possible. If no alternative exists, the patient should be
closely monitored for signs of toxicity.
Strong CYP3A Inducers: Avoid if possible because concomitant use
may decrease osimertinib plasma concentrations.
Indication:
TAGRISSO. (osimertinib) tablet, 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
patients.
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
product.
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
No.36
Drug Name - Osimertinib
Active Ingredient- Tagrisso
Date of approval - 11/13/2015
FDA-approved use - To treat people patients with non-small lung cancer
Approved by US FDA on 11/13/2015- (Ref- FDA approved List- 2015)
INDICATIONS AND USAGE
TAGRISSO is a kinase inhibitor indicated for the treatment of patients with
metastatic epidermal growth factor receptor (EGFR) T790M mutationpositive
non-small cell lung cancer (NSCLC), as detected by an FDAapproved
test, who have progressed on or after EGFR TKI therapy.
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.
Adverse Reaction:
Most common adverse reactions (.25%) were diarrhea, rash, dry skin, and
nail toxicity.
Contra-Indications:
CONTRAINDICATIONS
None.
WARNINGS AND PRECAUTIONS
Interstitial Lung Disease (ILD)/Pneumonitis: Occurred in 3.3% of
patients. Permanently discontinue TAGRISSO in patients diagnosed
with ILD/Pneumonitis.
QTc Interval Prolongation: Monitor electrocardiograms and electrolytes
in patients who have a history or predisposition for QTc prolongation, or
those who are taking medications that are known to prolong the QTc
interval. Withhold then restart at a reduced dose or permanently
discontinue TAGRISSO.
Cardiomyopathy: Occurred in 1.4% of patients. Assess left ventricular
ejection fraction (LVEF) before treatment and then every 3 months
thereafter.
Embryo-Fetal Toxicity: TAGRISSO can cause fetal harm. Advise
females of potential risk to the fetus and to use effective contraception
during treatment with TAGRISSO and for 6 weeks after final dose.
Advise males to use effective contraception for 4 months, after the last
dose of TAGRISSO.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
TAGRISSO is a kinase inhibitor indicated for the treatment of patients with
metastatic epidermal growth factor receptor (EGFR) T790M mutationpositive
non-small cell lung cancer (NSCLC), as detected by an FDAapproved
test, who have progressed on or after EGFR TKI therapy.
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
Confirm the presence of T790M mutation in tumor specimens prior to
initiation of treatment with TAGRISSO.
80 mg orally once daily, with or without food.
DOSAGE FORMS AND STRENGTHS
Tablets: 80 mg and 40 mg
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Interstitial Lung Disease/Pneumonitis
Inform patients of the risks of severe or fatal ILD, including pneumonitis.
Advise patients to contact their healthcare provider immediately to report new
or worsening respiratory symptoms
QTc Interval Prolongation
Inform patients of symptoms that may be indicative of significant QTc prolongation
including dizziness,lightheadedness, and syncope. Advise patients to report these
symptoms and to inform their physician about the use of any heart or blood pressure
medications
Cardiomyopathy
TAGRISSO can cause cardiomyopathy. Advise patients to immediately report any
signs or symptoms of heart failure to their healthcare provider
.
Embryo-Fetal Toxicity
TAGRISSO can cause fetal harm if taken during pregnancy. Advise pregnant women
of the potential risk to a fetus.
Advise females to inform their healthcare provider if they become pregnant or
if pregnancy is suspected, while taking TAGRISSO .
Females and Males of Reproductive Potential
Advise females of reproductive potential to use effective contraception during
treatment with TAGRISSO and for 6 weeks after the final dose
.
Advise males to use effective contraception during treatment and for 4 months
after the final dose of TAGRISSO
Lactation
Advise women not to breastfeed during treatment with TAGRISSO and for 2 weeks
after the final dose
.
Distributed by: AstraZeneca Pharmaceuticals
LP Wilmington, DE 19850
TAGRISSO is a trademark of the AstraZeneca group of companies cAstraZeneca 2015
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Osimertinib is kinase inhibitor of the epidermal growth factor receptor (EGFR), which
binds irreversibly to certain mutant forms of EGFR (T790M, L858R, and exon
19 deletion) at approximately 9-fold lower concentrations than wild-type.
2. Pharmacokinetics
The area under the plasma concentration-time curve (AUC) and maximal plasma
concentration (Cmax) of osimertinib increased dose proportionally over
20 to 240 mg dose range (i.e., 0.25 to 3 times the recommended dosage)
after oral administration and exhibited linear pharmacokinetics (PK).
Administration of TAGRISSO orally once daily resulted in approximately
3-fold accumulation with steady state exposures achieved after 15 days
of dosing. At steady state, the Cmax to Cmin (minimal concentration) ratio was 1.6-fold.
Absorption
The median time to Cmax of osimertinib was 6 hours (range 3-24 hours).
Following administration of a 20 mg TAGRISSO tablets with a high-fat, high-calorie
meal (containing approximately 58 grams of fat and 1000 calories), the Cmax and
AUC of osimertinib increased by 14% and 19% respectively, compared
to fasting conditions.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
Based on data from animal studies and its mechanism of action, TAGRISSO can cause
fetal harm when administered to a pregnant woman.
There are no available data on TAGRISSO use in pregnant women.
Administration of osimertinib to pregnant rats was associated with embryolethality
and reduced fetal growth at plasma exposures 1.5 times the exposure
at the recommended human dose [see Data].
Advise pregnant women of the potential risk to a fetus.
2. Lactation
Risk Summary
There are no data on the presence of osimertinib in human milk, the effects
of osimertinib on the breastfed infant or on milk production. Administration to rats
during gestation and early lactation was associated with adverse effects, including
reduced growth rates and neonatal death
Because of the potential for serious adverse reactions in breastfed infants from
osimertinib, advise a lactating woman not to breastfeed during treatment with
TAGRISSO and for 2 weeks after the final dose.
].
3. Pediatric Use
The safety and effectiveness of TAGRISSO in pediatric patients have not been established.
4. Geriatric Use
One hundred eighty-seven (45%) of the 411 patients in clinical trials of TAGRISSO
were 65 years of age and older, and 54 patients (13%) were 75 years of age and older.
No overall differences in effectiveness were observed based on age.
Exploratory analysis suggest a higher incidence of Grade 3 and 4 adverse reactions
(32% versus 25%) and more frequent dose modifications for adverse
reactions (23% versus 17%) in patients 65 years or older as compared to those younger than 65 years.
