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Tafinlar

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Tafinlar

Indications
Dosage
How Supplied

INDICATIONS

BRAF V600E Mutation-Positive Unresectable Or Metastatic Melanoma

TAFINLAR® as a single agent is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test.

BRAF V600E Or V600K Mutation-Positive Unresectable Or Metastatic Melanoma

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. This indication is based on the demonstration of durable response rate [see Clinical Studies]. 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 [see WARNINGS AND PRECAUTIONS].

DOSAGE AND ADMINISTRATION

Patient Selection

Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR as a single agent [see WARNINGS AND PRECAUTIONS]. Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of treatment with TAFINLAR in combination with trametinib. Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.

Recommended Dosing

The recommended dosage regimens of TAFINLAR are:

  • 150 mg orally taken twice daily, approximately 12 hours apart, as a single agent
  • 150 mg orally taken twice daily, approximately 12 hours apart, in combination with trametinib 2 mg orally taken once daily

Continue treatment until disease progression or unacceptable toxicity occurs. Take TAFINLAR as a single agent, or TAFINLAR in combination with trametinib, at least 1 hour before or 2 hours after a meal [see CLINICAL PHARMACOLOGY]. Do not take a missed dose of TAFINLAR within 6 hours of the next dose of TAFINLAR. Do not open, crush, or break TAFINLAR capsule.

When administered in combination with trametinib, take the once-daily dose of trametinib at the same time each day with either the morning dose or the evening dose of TAFINLAR.

Dose Modifications

For New Primary Cutaneous Malignancies: No dose modifications are required.

For New Primary Non-Cutaneous Malignancies: Permanently discontinue TAFINLAR in patients who develop RAS mutation-positive non-cutaneous malignancies. If used in combination with trametinib, no dose modifications are required for trametinib in patients who develop non-cutaneous malignancies.

Table 1: Recommended Dose Reductions

Dose Reductions for TAFINLARWhen Administered as a Single Agent or in Combination With Trametinib
First Dose Reduction 100 mg orally twice daily
Second Dose Reduction 75 mg orally twice daily
Third Dose Reduction 50 mg orally twice daily
Subsequent Modification Permanently discontinue TAFINLAR if unable to tolerate 50 mg orally twice daily
Dose Reductions for Trametinib When Administered in Combination With TAFINLAR
First Dose Reduction 1.5 mg orally once daily
Second Dose Reduction 1 mg orally once daily
Subsequent Modification Permanently discontinue if unable to tolerate trametinib 1 mg orally once daily

Table 2: Recommended Dose Modifications for TAFINLAR as a Single Agent and for TAFINLAR and Trametinib Administered in Combination

Severity of Adverse Reactiona TAFINLARb Trametinib (When Used in Combination)b,c
Febrile drug reaction
  • Fever of 101.3°F to 104°F
Withhold TAFINLAR until fever resolves. Then resume at same or lower dose level. Do not modify the dose of trametinib.
  • Fever higher than 104°F
  • Fever complicated by rigors, hypotension, dehydration, or renal failure
  • Withhold TAFINLAR until fever resolves. Then resume at a lower dose level.
    Or
  • Permanently discontinue TAFINLAR.
Withhold trametinib until fever resolves. Then resume trametinib at same or lower dose level.
Cutaneous
  • Intolerable Grade 2 skin toxicity
  • Grade 3 or 4 skin toxicity
Withhold TAFINLAR for up to 3 weeks.
  • If improved, resume at a lower dose level.
  • If not improved, permanently discontinue.
Withhold trametinib for up to 3 weeks.
  • If improved, resume at a lower dose level.
  • If not improved, permanently discontinue.
Cardiac
  • Asymptomatic, absolute decrease in LVEF of 10% or greater from baseline and is below institutional lower limits of normal (LLN) from pretreatment value
Do not modify the dose of TAFINLAR. Withhold trametinib for up to 4 weeks.
  • If improved to normal LVEF value, resume at a lower dose level.
  • If not improved to normal LVEF value, permanently discontinue.
  • Symptomatic congestive heart failure
  • Absolute decrease in LVEF of greater than 20% from baseline that is below LLN
Withhold TAFINLAR, if improved, then resume at the same dose. Permanently discontinue trametinib.
Venous Thromboembolism
  • Uncomplicated DVT or PE
Do not modify the dose of TAFINLAR. Withhold trametinib for up to 3 weeks.
  • If improved to Grade 0-1, resume at a lower dose level.
  • If not improved, permanently discontinue.
  • Life Threatening PE
Permanently discontinue TAFINLAR. Permanently discontinue trametinib.
Ocular Toxicities
  • Grade 2-3 retinal pigment epithelial detachments (RPED)
Do not modify the dose of TAFINLAR. Withhold trametinib for up to 3 weeks.
  • If improved to Grade 0-1, resume at a lower dose level.
  • If not improved, permanently discontinue.
  • Retinal vein occlusion
Do not modify the dose of TAFINLAR. Permanently discontinue trametinib.
  • Uveitis and Iritis
Withhold TAFINLAR for up to 6 weeks.
  • If improved to Grade 0-1, then resume at the same dose.
  • If not improved, permanently discontinue.
Do not modify the dose of trametinib.
Pulmonary
  • Interstitial lung disease/pneumonitis
Do not modify the dose of TAFINLAR. Permanently discontinue trametinib.
Other
  • Intolerable Grade 2 adverse reactions
  • Any Grade 3 adverse reaction
Withhold TAFINLAR.
  • If improved to Grade 0-1, resume at a lower dose level.
  • If not improved, permanently discontinue.
Withhold trametinib for up to 3 weeks.
  • If improved to Grade 0-1, resume at a lower dose level.
  • If not improved, permanently discontinue.
First occurrence of any Grade 4 adverse reaction
  • Withhold TAFINLAR until adverse reaction improves to Grade 0-1. Then resume at a lower dose level.
    Or
  • Permanently discontinue TAFINLAR.
  • Withhold trametinib until adverse reaction improves to Grade 0-1. Then resume at a lower dose level.
    Or
  • Permanently discontinue trametinib.
  • Recurrent Grade 4 adverse reaction
Permanently discontinue TAFINLAR. Permanently discontinue trametinib.
a National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
b See Table 1 for recommended dose reductions of TAFINLAR and trametinib.
c Refer to Full Prescribing Information for trametinib.

HOW SUPPLIED

Dosage Forms And Strengths

50 mg Capsules: Dark red capsule imprinted with 'GS TEW' and '50 mg'.

75 mg Capsules: Dark pink capsule imprinted with 'GS LHF' and '75 mg'.

Storage And Handling

50 mg Capsules: Dark red capsule imprinted with 'GS TEW' and '50 mg' available in bottles of 120 (NDC 0173-0846-08). Each bottle contains a silica gel desiccant.

75 mg Capsules: Dark pink capsule imprinted with 'GS LHF' and '75 mg' available in bottles of 120 (NDC 0173-0847-08). Each bottle contains a silica gel desiccant.

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

GlaxoSmithKline, Research Triangle Park, NC 27709. Revised: January 2014

Last reviewed on RxList: 1/22/2014
This monograph has been modified to include the generic and brand name in many instances.

Indications
Dosage
How Supplied
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