Novartis Pharmaceuticals Corporation
East Hanover, New Jersey 07936-1080 © 2015 Novartis 4/15 MAF-1111266
Novartis recently acquired these products from GSK. To ensure a seamless transition, GSK is continuing to provide support for these
products and related programs on behalf of Novartis at this time.
respectively, included: pyrexia (fever) (71%, 69%, 26%), chills
(58%, 50%, 17%), fatigue (53%, 57%, 40%), rash (45%, 43%,
53%), nausea (44%, 46%, 21%), vomiting (40%, 43%, 15%),
diarrhea (36%, 26%, 28%), abdominal pain (33%, 24%, 21%),
peripheral edema (31%, 28%, 17%), cough (29%, 11%, 21%),
headache (29%, 37%, 28%), arthralgia (27%, 44%, 34%), night
sweats (24%, 15%, 6%), decreased appetite (22%, 30%, 19%),
constipation (22%, 17%, 11%) and myalgia (22%, 24%, 23%).
The most common (≥5%) serious adverse reactions in Trial 2 (grades
3 or 4) for TAFINLAR 150 mg twice daily and MEKINIST 2 mg once
daily, TAFINLAR 150 mg twice daily and MEKINIST 1 mg once daily,
and TAFINLAR as a single agent, respectively, included: renal failure
(7%, 0%, 0%), pyrexia (5%, 9%, 0%), back pain (5%, 0%, 2%),
and hemorrhage (5%, 0%, 0%).
Effects of Other Drugs on Dabrafenib. Dabrafenib is primarily
metabolized by CYP2C8 and CYP3A4. Strong inhibitors of CYP3A4
or CYP2C8 may increase concentrations of dabrafenib and strong
inducers of CYP3A4 or CYP2C8 may decrease concentrations of
dabrafenib. Substitution of strong inhibitors or strong inducers
of CYP3A4 or CYP2C8 is recommended during treatment with
TAFINLAR. If concomitant use of strong inhibitors (eg, ketoconazole,
nefazodone, clarithromycin, gemfibrozil) or strong inducers
(eg, rifampin, phenytoin, carbamazepine, phenobarbital, St John’s
wort) of CYP3A4 or CYP2C8 is unavoidable, monitor patients
closely for adverse reactions when taking strong inhibitors or loss
of efficacy when taking strong inducers.
Effects of Dabrafenib on Other Drugs. Dabrafenib induces
CYP3A4 and CYP2C9. Dabrafenib decreased the systemic exposures
of midazolam (a CYP3A4 substrate), S-warfarin (a CYP2C9
substrate), and R-warfarin (a CYP3A4/CYP1A2 substrate). Monitor
international normalized ratio (INR) levels more frequently in patients
receiving warfarin during initiation or discontinuation of dabrafenib.
Coadministration of TAFINLAR with other substrates of these
enzymes, including dexamethasone or hormonal contraceptives, can
result in decreased concentrations and loss of efficacy. Substitute
for these medications or monitor patients for loss of efficacy if use
of these medications is unavoidable.
Effects of the Combination of Dabrafenib with Trametinib.
Coadministration of TAFINLAR 150 mg twice daily and MEKINIST
2 mg once daily resulted in no clinically relevant pharmacokinetic
Across clinical trials of TAFINLAR in combination with MEKINIST
(N=202), the incidence of pyrexia was 57% (116/202).
Withhold TAFINLAR for fever of 101.3ºF or higher. Withhold
MEKINIST for any fever higher than 104ºF. Withhold TAFINLAR, and
MEKINIST if used in combination, for any serious febrile reaction
or fever complicated by hypotension, rigors or chills, dehydration,
or renal failure, and evaluate for signs and symptoms of infection.
Refer to Table 2 of the Prescribing Information for TAFINLAR for
recommended dose modifications. Prophylaxis with antipyretics
may be required when resuming TAFINLAR or MEKINIST.
Serious Skin Toxicity. In Trial 2, the incidence of any skin toxicity
was similar for patients receiving TAFINLAR in combination
with MEKINIST (65% [36/55]) compared with patients receiving
TAFINLAR as a single agent (68% [36/53]). The median time
to onset of skin toxicity in patients treated with TAFINLAR in
combination with MEKINIST was 37 days (range: 1 to 225 days)
and median time to resolution of skin toxicity was 33 days (range:
3 to 421 days). No patient required dose reduction or permanent
discontinuation of TAFINLAR or MEKINIST for skin toxicity.
Across clinical trials of TAFINLAR in combination with MEKINIST
(N=202), severe skin toxicity and secondary infections of the skin
requiring hospitalization occurred in 2.5% (5/202) of patients
treated with TAFINLAR in combination with MEKINIST.
Withhold TAFINLAR, and MEKINIST if used in combination, for
intolerable or severe skin toxicity. TAFINLAR and MEKINIST may
be resumed at lower dose levels in patients with improvement
or recovery from skin toxicity within 3 weeks.
Hyperglycemia. In Trial 2, the incidence of Grade 3 hyperglycemia
based on laboratory values was 5% (3/55) in patients treated with
TAFINLAR in combination with MEKINIST compared with 2% (1/53)
in patients treated with TAFINLAR as a single agent.
Monitor serum glucose levels as clinically appropriate when
TAFINLAR is used in combination with MEKINIST in patients with
pre-existing diabetes or hyperglycemia. Advise patients to report
symptoms of severe hyperglycemia, such as excessive thirst or any
increase in the volume or frequency of urination.
Glucose-6-Phosphate Dehydrogenase Deficiency. TAFINLAR,
which contains a sulfonamide moiety, confers a potential risk
of hemolytic anemia in patients with glucose-6-phosphate
dehydrogenase (G6PD) deficiency. Closely observe patients with
G6PD deficiency for signs of hemolytic anemia.
Embryofetal Toxicity. TAFINLAR and MEKINIST both can cause
fetal harm when administered to a pregnant woman. Advise female
patients of reproductive potential to use highly effective non-hormonal
contraception during treatment with TAFINLAR and MEKINIST in
combination and for 4 months after treatment, since TAFINLAR can
render hormonal contraceptives ineffective. Advise patients to contact
their healthcare provider if they become pregnant, or if pregnancy is
suspected, while taking TAFINLAR and MEKINIST.
Most Common Adverse Reactions. The most common (≥20%)
adverse reactions in Trial 2 (all grades) for TAFINLAR 150 mg twice
daily and MEKINIST 2 mg once daily, TAFINLAR 150 mg twice daily
and MEKINIST 1 mg once daily, and TAFINLAR as a single agent,
GlaxoSmithKline; 2014. 2. MEKINIST [package insert]. Research Triangle Park, NC:
GlaxoSmithKline; 2014. 3. Flaherty K T, Infante JR, Daud A, et al. N Engl J Med.
To learn more, visit TAFINLARMEKINISTHCP.com
Please see additional Important Safety Information for
TAFINLAR and MEKINIST, when used in combination, on
the following pages.
Please see Brief Summary of Prescribing Information
for TAFINLAR and MEKINIST on the following pages.