TAFINLAR CAPSULES*
Manufacturer DetailsGLAXO SMITH KLINE INC
Refer Glaxo Smith Kline
Compositions:
Dabrafenib- mg capsules,
Dabrafenib- mg capsules,
| Strength | Rate | Packing Style |
|---|---|---|
| mg | 0.00 | unit capsules |
List of Related Indications:
- Patients with Unrescetable or Metastatic Melaloma with BRAF V600ZE mutation
List Of Drugs:
- Dabrafenib- (Tafinlar)- @- (May 2013)-Chemotherapeutic Agents
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
Avoid concurrent administration of strong inhibitors of CYP3A4 or CYP2C8.
Avoid concurrent administration of strong inducers of CYP3A4 or CYP2C8.
Concomitant use with agents that are sensitive substrates of CYP3A4, CYP2C8,
CYP2C9, CYP2C19, or CYP2B6 may result in loss of efficacy of these agents.
Indication:
TAFINLAR(dabrafenib) capsules, for oral use
Initial U.S. Approval: 2013
RECENT MAJOR CHANGES
Indications and Usage (1.2)
01/2014
Dosage and Administration (2.1-2.3)
01/2014
Warnings and Precautions (5-5.9, 5.11)
01/2014
Drug Name- Tafinlar
Active Ingredient - Dabrafenib
To treat patients with melanoma whose tumors pexpress BRAF V600E gene mutations
Indication-
Tumors
Approved by FDA on 29-5-2013 (Ref- FDA approved List- 2013)
Proprietary Name- TAFINLAR CAPSULES*
Established Name- Dabrafenib
Applicant- GLAXOSMITHKLINE LLC
Indication- For the treatment of patients with unresectable or metastatic melaloma
with BRAF V600ZE mutation as detected by an FDA approved test
Approval Date- May 29,2013
Approved by US FDA (Ref- FDA approved list- 2013)
Adverse Reaction:
Most common adverse reactions (.20%) for TAFINLAR as a single agent are
hyperkeratosis, headache, pyrexia, arthralgia, papilloma, alopecia, and
palmar-plantar erythrodysesthesia syndrome. (
. Most common adverse reactions (.20%) for TAFINLAR in combination
with trametinib are pyrexia, chills, fatigue, rash, nausea, vomiting, diarrhea,
abdominal pain, peripheral edema, cough, headache, arthralgia, night sweats,
decreased appetite, constipation, and myalgia.
Contra-Indications:
CONTRAINDICATIONS
None.
WARNINGS AND PRECAUTIONS
New primary malignancies, cutaneous and non-cutaneous, can occur when
TAFINLAR is administered as a single agent or in combination with trametinib.
Monitor patients for new malignancies prior to initiation of therapy,
while on therapy, and following discontinuation of TAFINLAR or the
combination therapy.
Tumor Promotion in BRAF Wild-Type Melanoma: Increased cell proliferation
can occur with BRAF inhibitors.
Hemorrhage: Major hemorrhagic events can occur in patients receiving
TAFINLAR in combination with trametinib. Monitor for signs and symptoms
of bleeding.
. Venous Thromboembolism: Deep vein thrombosis and pulmonary embolism
can occur in patients receiving TAFINLAR in combination with trametinib.
Cardiomyopathy: Assess LVEF before treatment with TAFINLAR in
combination with trametinib, after one month of treatment, then every
2 to 3 months thereafter.
Ocular Toxicities: Perform ophthalmologic evaluation for any visual
disturbances.
Serious Febrile Reactions: Incidence and severity of pyrexia are increased
with TAFINLAR in combination with trametinib.
Serious Skin Toxicity: Monitor for skin toxicities and for secondary infections.
Discontinue for intolerable Grade 2, or Grade 3 or 4 rash not improving within
3 weeks despite interruption of TAFINLAR.
Hyperglycemia: Monitor serum glucose levels in patients with pre-existing
diabetes or hyperglycemia.
Glucose-6-Phosphate Dehydrogenase Deficiency: Closely monitor for
hemolytic anemia.
Embryofetal Toxicity: Can cause fetal harm. Advise females of reproductive
potential of potential risk to a fetus. TAFINLAR may render hormonal
contraceptives less effective and an alternative method of contraception
should be used.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
TAFINLAR is a kinase inhibitor indicated as a single agent for the treatment of patients
with unresectable or metastatic melanoma with BRAF V600E mutation as detected
by an FDA-approved test.
TAFINLAR in combination with trametinib is indicated for the treatment of patients
with unresectable or metastatic melanoma with BRAF V600E or V600K mutations
as detected by an FDA-approved test. The use in combination is based on the
demonstration of durable response rate. Improvement in disease-related
symptoms or overall survival has not been demonstrated for TAFINLAR in
combination with trametinib.
Limitation of Use: TAFINLAR is not indicated for treatment of patients with wild-type
BRAF melanoma.
DOSAGE AND ADMINISTRATION
Confirm the presence of BRAF V600E mutation in tumor specimens prior to
initiation of treatment with TAFINLAR as a single agent.
Confirm the presence of BRAF V600E or V600K mutation in tumor specimens
prior to initiation of treatment with TAFINLAR in combination with trametinib.
The recommended dose of TAFINLAR is 150 mg orally twice daily as a
single agent or in combination with trametinib 2 mg orally once daily.
Take TAFINLAR at least 1 hour before or at least 2 hours after a meal.
DOSAGE FORMS AND STRENGTHS
Capsules: 50 mg, 75 mg.
Patient Information:
PATIENT COUNSELING INFORMATION
See FDA-approved patient labeling (Medication Guide).
Inform patients of the following:
Evidence of BRAF V600E mutation in the tumor specimen is necessary
to identify patients for whom treatment with TAFINLAR as a single agent
is indicated and evidence of BRAF V600E or V600K mutation in tumor
specimens is necessary to identify patients for whom treatment with
TAFINLAR in combination with trametinib is indicated
TAFINLAR increases the risk of developing new primary cutaneous and
non-cutaneous malignancies. Advise patients to contact their doctor
immediately for any new lesions, changes to existing lesions on their skin,
or signs and symptoms of other malignancies
TAFINLAR administered in combination with trametinib increases the risk
of intracranial and gastrointestinal hemorrhage. Advise patients to contact
their healthcare provider to seek immediate medical attention for signs or
symptoms of unusual bleeding or hemorrhage
TAFINLAR administered in combination with trametinib increases the risks
of pulmonary embolism and deep venous thrombosis.
Advise patients to seek immediate medical attention for sudden onset of
difficulty breathing, leg pain, or swelling
TAFINLAR administered in combination with trametinib can cause
cardiomyopathy. Advise patients to immediately report any signs or
symptoms of heart failure to their healthcare provider
TAFINLAR can cause visual disturbances; TAFINLAR administered in
combination with trametinib can lead to blindness. Advise patients to
contact their healthcare provider if they experience any changes
in their vision
TAFINLAR, administered as a single agent and in combination with
trametinib can cause pyrexia including serious febrile reactions.
Inform patients that the incidence and severity of pyrexia are increased
when TAFINLAR is given in combination with trametinib. Instruct patients
to contact their doctor if they develop fever while taking TAFINLAR
TAFINLAR in combination with trametinib can cause serious skin toxicities
which may require hospitalization. Advise patients to contact their
healthcare provider for progressive or intolerable rash
TAFINLAR can impair glucose control in diabetic patients resulting in
the need for more intensive hypoglycemic treatment. Advise patients
to contact their doctor to report symptoms of severe hyperglycemia
TAFINLAR may cause hemolytic anemia in patients with
glucose-6-phosphate dehydrogenase (G6PD) deficiency. Advise patients
with known G6PD deficiency to contact their doctor to report signs
or symptoms of anemia or hemolysis
TAFINLAR can cause fetal harm if taken during pregnancy. Instruct female
patients to use non-hormonal, highly effective contraception during treatment
and for 2 weeks after discontinuation of treatment with TAFINLAR as a single
agent, or for 4 months after discontinuation of treatment with TAFINLAR
in combination with trametinib. Advise patients to contact their doctor if
they become pregnant, or if pregnancy is suspected, while taking
TAFINLAR
Nursing infants may experience serious adverse reactions if the mother is
taking TAFINLAR during breastfeeding. Advise breastfeeding mothers to
discontinue nursing while taking TAFINLAR
Male patients are at an increased risk for impaired spermatogenesis
TAFINLAR should be taken either at least 1 hour before or at least 2 hours
after a meal
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Dabrafenib is an inhibitor of some mutated forms of BRAF kinases with in vitro IC50
values of 0.65, 0.5, and 1.84 nM for BRAF V600E, BRAF V600K, and BRAF V600D
enzymes, respectively.
Dabrafenib also inhibits wild-type BRAF and CRAF kinases with IC50 values of
3.2 and 5.0 nM, respectively, and other kinases such as SIK1, NEK11,
and LIMK1 at higher concentrations.
2. Pharmacokinetics
Absorption: After oral administration, median time to achieve peak plasma
concentration (Tmax) is 2 hours. Mean absolute bioavailability of oral
dabrafenib is 95%.
Following a single dose, dabrafenib exposure (Cmax and AUC) increased
in a dose-proportional manner across the dose 26 range of 12 to 300 mg,
but the increase was less than dose-proportional after repeat twice-daily
dosing.
After repeat twice-daily dosing of 150 mg, the mean accumulation ratio was
0.73 and the inter-subject variability (CV%) of AUC at steady-state was 38%.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Pregnancy Category D.
Risk Summary: Based on its mechanism of action, TAFINLAR can cause fetal harm
when administered to a pregnant woman. Dabrafenib was teratogenic and
embryotoxic in rats at doses
2. Nursing Mothers
It is not known whether this drug is present in human milk. Because many drugs
are present in human milk and because of the potential for serious adverse
reactions from TAFINLAR in nursing infants, a decision should be made
whether to discontinue nursing or discontinue the drug, taking into account
the importance of the drug to the mother.
3. Pediatric Use
The safety and effectiveness of TAFINLAR have not been established in
pediatric patients.
4. Geriatric Use
One hundred and twenty-six (22%) of 586 patients in clinical trials of TAFINLAR
administered as a single agent and 40 (21%) of the 187 patients receiving
TAFINLAR in Trial 1 were .65 years of age. No overall differences in the
effectiveness or safety of TAFINLAR were observed in the elderly in Trial 1
Across all clinical trials of TAFINLAR administered in combination with trametinib,
there was an insufficient number of patients aged 65 years and over to determine
whether they respond differently from younger patients.
In Trial 2, 11 patients (20%) were 65 years of age and older, and 2 patients (4%)
were 75 years of age and older.
