Palbociclib- Ibrance -@- (Feb 2015 ) - Anti-cancer
Drug Name:Palbociclib- Ibrance -@- (Feb 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:
CYP3A Inhibitors: Avoid concurrent use of IBRANCE with strong CYP3A inhibitors.
If the strong inhibitor cannot be avoided, reduce the IBRANCE dose.
.
CYP3A Inducers: Avoid concurrent use of IBRANCE with strong and moderate
CYP3A inducers.
.
CYP3A Substrates: The dose of sensitive CYP3A4 substrates with narrow
therapeutic indices may need to be reduced when given concurrently
with IBRANCE.
Indication:
IBRANCE® (palbociclib) capsules, for oral use
Initial U.S. Approval: 2015
Proprietary Name- IBRANCE
Established Name- Palbociclib
Applicant- Pfizer Inc
Indication- For the treatment of Postmenopausal Women with Estrogen
Receptor (ER) -Positive, Human Epidermal Growth factor
Receptor 2 (HER2) negative Advanced breast Cancer as Initial
Endocrine-Based Therapy for their Metastatic Disease
Approval Date- 2/3/2015
Approved by U.S.FDA on 30-06-2015 (Ref- FDA approved List- 2015)
SUBSEQUENT APPROVAL-
Indication-
FDA granted accelrated approval to Palbocicib, (IBRANCE, Pfizer. Inc.) for use
in Combination with Letrozole for the treament of Postmenopausal women
with Estrogen Receptor (ER) Positive, Human Epidermal growth factor
2(HER2) -negative advanced cancer as initial Endocrine-based therapy
for their Metastatic Disease
Approval Date- February 3,2015
Approved by U.S.FDA as on 30-06-2015 (Ref- FDA approved List- 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.4
Drug Name - Palbociclib
Active Ingredient- Ibrance
Date of approval - 2/03/2015
FDA-approved use - To treat Advanced (Metastatic) Breast cancer
Approved by US FDA on 2/03/2015- (Ref- FDA approved List- 2015)
LIST OF NEW DRUG APPROVED FROM 01-01-2016 To TILL DATE
BY NEW DRUG DIVISION - DRUG CONTROLLER GENERAL- INDIA
Sr.No Name of Drug Indication Date of Issue
14. Palmociclib Capsules 11-08-2016
75mg/100mg/125mg
" Palbociclib is a kinase inhibitor indicated in combination with
Letrozole for the treatment of postmenopausal women with
estrogen receptor receptor (ER )- Positive, human epidermal
growth factor receptor 2 (HER2) -Negative advanced breast
cancer as initial endocrine-based therapy for their metastatic
disease"
Approved by DCG INDIA (Ref- DCGI approved List- 11-08-2016 To Till Date
Adverse Reaction:
Most common adverse reactions (incidence .10%) were
neutropenia, leukopenia, fatigue, anemia, upper respiratory infection, nausea,
stomatitis, alopecia, diarrhea, thrombocytopenia, decreased appetite, vomiting,
asthenia, peripheral neuropathy, and epistaxis.
Contra-Indications:
CONTRAINDICATIONS
None
WARNINGS AND PRECAUTIONS
Hematologic: Neutropenia may occur. Monitor complete blood count prior to
start of IBRANCE therapy and at the beginning of each cycle, as well as
on Day 14 of the first two cycles, and as clinically indicated.
.
Infections: Monitor for signs and symptoms and withhold dosing as
appropriate.
.
Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of potential
risk to a fetus and to use effective contraception.
Dosages/ Overdosage Etc:
Indication- For the treatment of Postmenopausal Women with Estrogen
Receptor (ER) -Positive, Human Epidermal Growth factor
Receptor 2 (HER2) negative Advanced breast Cancer as Initial
Endocrine-Based Therapy for their Metastatic Disease
SUBSEQUENT APPROVAL-
Indication-
FDA granted accelrated approval to Palbocicib, (IBRANCE, Pfizer. Inc.) for use
in Combination with Letrozole for the treament of Postmenopausal women
with Estrogen Receptor (ER) Positive, Human Epidermal growth factor
2(HER2) -negative advanced cancer as initial Endocrine-based therapy
for their Metastatic Disease
INDICATIONS AND USAGE
IBRANCE is a kinase inhibitor indicated in combination with letrozole for the
treatment of postmenopausal women with estrogen receptor (ER)-positive,
human epidermal growth factor receptor 2 (HER2)-negative advanced breast
cancer as initial endocrine-based therapy for their metastatic disease.
This indication is approved under accelerated approval based on
progression-free survival (PFS). Continued approval for this indication
may be contingent upon verification and description of clinical benefit
in a confirmatory trial.
DOSAGE AND ADMINISTRATION
IBRANCE capsules are taken orally with food in combination with letrozole.
Recommended starting dose: 125 mg once daily taken with food for 21 days
followed by 7 days off treatment.
Dosing interruption and/or dose reductions are recommended based on
individual safety and tolerability.
DOSAGE FORMS AND STRENGTHS
Capsules: 125 mg, 100 mg, and 75 mg
Patient Information:
PATIENT COUNSELING INFORMATION
See FDA-approved patient labeling (Patient Information).
Advise patients to immediately report any signs or symptoms of myelosuppression
or infection, such as fever, chills, dizziness, shortness of breath, weakness or any
increased tendency to bleed and/or to bruise
Advise patients to immediately report any signs or symptoms of pulmonary
embolism, such as shortness of breath, chest pain, tachypnea, and tachycardia
Advise patients to take IBRANCE with food and swallow IBRANCE
capsules whole.
IBRANCE may interact with grapefruit. Patients should not consume
grapefruit products while on treatment with IBRANCE.
Inform patients to avoid strong CYP3A inhibitors and strong CYP3A inducers.
Advise patients to inform their health care providers of all concomitant medications,
including prescription medicines, over-the-counter drugs, vitamins,
and herbal products
If the patient vomits or misses a dose, an additional dose should not be
taken that day. The next prescribed dose should be taken at the usual time
. IBRANCE capsules should be swallowed whole (do not chew, crush or
open them prior to swallowing). No capsule should be ingested
if it is broken, cracked, or otherwise not intact.
Advise females of reproductive potential to use effective contraception during
IBRANCE therapy and for at least two weeks after the last dose.
Advise females to contact their healthcare provider if they become pregnant
, or if pregnancy is suspected, during treatment with IBRANCE
Manufactured by: Novartis Pharmaceuticals Corporation East Hanover,
New Jersey 07936
US License Number 1244
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Palbociclib is an inhibitor of cyclin-dependent kinase (CDK) 4 and 6. Cyclin D1 and
CDK4/6 are downstream of signaling pathways which lead to cellular proliferation.
In vitro, palbociclib reduced cellular proliferation of estrogen receptor (ER)-positive
breast cancer cell lines by blocking progression of the cell from G1 into S phase
of the cell cycle.
Treatment of breast cancer cell lines with the combination of palbociclib and
antiestrogens leads to decreased retinoblastoma protein (Rb) phosphorylatio
resulting in reduced E2F expression and signaling and increased growth arrest
compared to treatment with each drug alone
2. Pharmacokinetics
The pharmacokinetics of palbociclib were characterized in patients with solid tumors
including advanced breast cancer and in healthy subjects.
Absorption
The mean Cmax of palbociclib is generally observed between 6 to 12 hours
(time to reach maximum concentration, Tmax) following oral administration.
The mean absolute bioavailability of IBRANCE after an oral 125 mg dose is 46%.
In the dosing range of 25 mg to 225 mg, the AUC and Cmax increased proportionally
with dose in general.
Steady state was achieved within 8 days following repeated once daily dosing.
With repeated once daily administration, palbociclib accumulated with a median
accumulation ratio of 2.4 (range 1.5-4.2).
Food effect: Palbociclib absorption and exposure were very low in approximately
13% of the population under the fasted condition. Food intake increased the
palbociclib exposure in this small subset of the population, but did not alter
palbociclib exposure in the rest of the population to a clinically relevant extent.
Therefore, food intake reduced the intersubject variability of palbociclib exposure,
which supports administration of IBRANCE with food. Compared to IBRANCE given
under overnight fasted
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
Based on findings in animals and mechanism of action, IBRANCE can cause fetal harm
when administered to a pregnant woman
There are no available human data informing the drug-associated risk.
Advise pregnant women of the potential risk to a fetus.
.
2. Lactation
Risk Summary
There are no data on the presence of palbociclib in human milk, the effects of IBRANCE
on the breastfed child, or the effects of IBRANCE on milk production.
Because many drugs are excreted in human milk and because of the potential
for serious adverse reactions in nursing infants from IBRANCE, advise a nursing
woman to discontinue breastfeeding during treatment with IBRANCE
3. Pediatric Use
The safety and efficacy of IBRANCE in pediatric patients have not been studied.
4. Geriatric Use
Of 84 patients who received IBRANCE in Study 1, 37 patients (44%) were .65 years
of age and 8 patients (10%) were .75 years of age.
No overall differences in safety or effectiveness of IBRANCE were observed
between these patients and younger patients but greater sensitivity of some older
individuals cannot be ruled out.
