Tafinlar + Mekinist

• the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test. (
  1.2
       
  BRAF V600E or V600K Mutation-Positive Unresectable or Metastatic Melanoma

  TAFINLAR is indicated, in combination with trametinib, for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test

  [see Dosage and Administration (2.1)]

  .
  ,
  2.1
       
  Patient Selection

  Melanoma

  • 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 (5.2), Clinical Studies (14.1)]
    .
  • Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Warnings and Precautions (5.2), Clinical Studies (14.2, 14.3)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.

  NSCLC

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.4)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600E mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.

  ATC

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.5)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600E mutations in ATC is available at: http://www.fda.gov/CompanionDiagnostics.

  Solid Tumors

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.6)]
    . An FDA-approved test for the detection of BRAF V600E mutation in solid tumors other than melanoma and NSCLC is not currently available.

  Low-Grade Glioma

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.7)]
    . An FDA-approved test for the detection of BRAF V600E mutation in LGG is not currently available.
  )
  
• the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection. (
  1.3
       
  Adjuvant Treatment of BRAF V600E or V600K Mutation-Positive Melanoma

  TAFINLAR is indicated, in combination with trametinib, for the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection

  [see Dosage and Administration (2.1)]

  .
  ,
  2.1
       
  Patient Selection

  Melanoma

  • 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 (5.2), Clinical Studies (14.1)]
    .
  • Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Warnings and Precautions (5.2), Clinical Studies (14.2, 14.3)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.

  NSCLC

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.4)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600E mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.

  ATC

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.5)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600E mutations in ATC is available at: http://www.fda.gov/CompanionDiagnostics.

  Solid Tumors

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.6)]
    . An FDA-approved test for the detection of BRAF V600E mutation in solid tumors other than melanoma and NSCLC is not currently available.

  Low-Grade Glioma

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.7)]
    . An FDA-approved test for the detection of BRAF V600E mutation in LGG is not currently available.
  )
• the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test. (
  1.4
       
  BRAF V600E Mutation-Positive Metastatic NSCLC

  TAFINLAR is indicated, in combination with trametinib, for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test

  [see Dosage and Administration (2.1)]

  .
  ,
  2.1
       
  Patient Selection

  Melanoma

  • 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 (5.2), Clinical Studies (14.1)]
    .
  • Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Warnings and Precautions (5.2), Clinical Studies (14.2, 14.3)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.

  NSCLC

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.4)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600E mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.

  ATC

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.5)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600E mutations in ATC is available at: http://www.fda.gov/CompanionDiagnostics.

  Solid Tumors

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.6)]
    . An FDA-approved test for the detection of BRAF V600E mutation in solid tumors other than melanoma and NSCLC is not currently available.

  Low-Grade Glioma

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.7)]
    . An FDA-approved test for the detection of BRAF V600E mutation in LGG is not currently available.
  )
  
• the treatment of patients with locally advanced or metastatic anaplastic thyroid cancer (ATC) with BRAF V600E mutation, as detected by an FDA-approved test, and with no satisfactory locoregional treatment options. (
  1.5
       
  BRAF V600E Mutation-Positive Locally Advanced or Metastatic Anaplastic Thyroid Cancer

  TAFINLAR is indicated, in combination with trametinib, for the treatment of patients with locally advanced or metastatic anaplastic thyroid cancer (ATC) with BRAF V600E mutation, as detected by an FDA-approved test, and with no satisfactory locoregional treatment options

  [see Dosage and Administration (2.1)]

  .
  ,
  2.1
       
  Patient Selection

  Melanoma

  • 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 (5.2), Clinical Studies (14.1)]
    .
  • Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Warnings and Precautions (5.2), Clinical Studies (14.2, 14.3)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.

  NSCLC

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.4)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600E mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.

  ATC

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.5)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600E mutations in ATC is available at: http://www.fda.gov/CompanionDiagnostics.

  Solid Tumors

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.6)]
    . An FDA-approved test for the detection of BRAF V600E mutation in solid tumors other than melanoma and NSCLC is not currently available.

  Low-Grade Glioma

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.7)]
    . An FDA-approved test for the detection of BRAF V600E mutation in LGG is not currently available.
  )
  
• the treatment of adult and pediatric patients 1 year of age and older with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). (
  1.6
       
  BRAF V600E Mutation-Positive Unresectable or Metastatic Solid Tumors

  TAFINLAR is indicated, in combination with trametinib, for the treatment of adult and pediatric patients 1 year of age and older with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options

  [see Dosage and Administration (2.1)]

  . This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DoR)

  [see Clinical Studies (14.6)]

  . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
  ,
  2.1
       
  Patient Selection

  Melanoma

  • 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 (5.2), Clinical Studies (14.1)]
    .
  • Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Warnings and Precautions (5.2), Clinical Studies (14.2, 14.3)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.

  NSCLC

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.4)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600E mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.

  ATC

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.5)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600E mutations in ATC is available at: http://www.fda.gov/CompanionDiagnostics.

  Solid Tumors

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.6)]
    . An FDA-approved test for the detection of BRAF V600E mutation in solid tumors other than melanoma and NSCLC is not currently available.

  Low-Grade Glioma

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.7)]
    . An FDA-approved test for the detection of BRAF V600E mutation in LGG is not currently available.
  )
• the treatment of pediatric patients 1 year of age and older with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy. (
  1.7
       
  BRAF V600E Mutation-Positive Low-Grade Glioma

  TAFINLAR is indicated, in combination with trametinib, for the treatment of pediatric patients 1 year of age and older with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy

  [see Dosage and Administration (2.1)]

  .
  ,
  2.1
       
  Patient Selection

  Melanoma

  • 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 (5.2), Clinical Studies (14.1)]
    .
  • Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Warnings and Precautions (5.2), Clinical Studies (14.2, 14.3)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.

  NSCLC

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.4)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600E mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.

  ATC

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.5)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600E mutations in ATC is available at: http://www.fda.gov/CompanionDiagnostics.

  Solid Tumors

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.6)]
    . An FDA-approved test for the detection of BRAF V600E mutation in solid tumors other than melanoma and NSCLC is not currently available.

  Low-Grade Glioma

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.7)]
    . An FDA-approved test for the detection of BRAF V600E mutation in LGG is not currently available.
  )
  

• The recommended dosage of TAFINLAR in adult patients is 150 mg (two 75 mg capsules) orally twice daily. The recommended dosage for TAFINLAR in pediatric patients is based on body weight. Take TAFINLAR at least 1 hour before or 2 hours after a meal. (
  2

  DOSAGE AND ADMINISTRATION

  • The recommended dosage of TAFINLAR in adult patients is 150 mg (two 75 mg capsules) orally twice daily. The recommended dosage for TAFINLAR in pediatric patients is based on body weight. Take TAFINLAR at least 1 hour before or 2 hours after a meal.

  2.1
       
  Patient Selection

  Melanoma

  • 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 (5.2), Clinical Studies (14.1)]
    .
  • Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Warnings and Precautions (5.2), Clinical Studies (14.2, 14.3)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.

  NSCLC

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.4)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600E mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.

  ATC

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.5)]
    .
  • Information on FDA-approved tests for the detection of BRAF V600E mutations in ATC is available at: http://www.fda.gov/CompanionDiagnostics.

  Solid Tumors

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.6)]
    . An FDA-approved test for the detection of BRAF V600E mutation in solid tumors other than melanoma and NSCLC is not currently available.

  Low-Grade Glioma

  • Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib
    [see Clinical Studies (14.7)]
    . An FDA-approved test for the detection of BRAF V600E mutation in LGG is not currently available.

  2.2
       
  Recommended Dosage

  TAFINLAR Capsules

  Adult Patients

  The recommended dosage for TAFINLAR capsules in adult patients is 150 mg taken orally twice daily

  [see Dosage and Administration (2.3)]

  .

  Pediatric Patients

  The recommended dosage for TAFINLAR capsules in pediatric patients who weigh at least 26 kg is based on body weight (Table 1)

  [see Dosage and Administration (2.3)]

  . A recommended dosage of TAFINLAR capsules has not been established in patients who weigh less than 26 kg.

  Table 1. Recommended Dosage for TAFINLAR Capsules in Pediatric Patients (Weight-based)

  Body Weight	Recommended Dosage
  26 to 37 kg	75 mg orally twice daily
  38 to 50 kg	100 mg orally twice daily
  51 kg or greater	150 mg orally twice daily

  TAFINLAR Tablets for Oral Suspension

  Adult and Pediatric Patients

  The recommended dosage for TAFINLAR tablets for oral suspension for adult and pediatric patients is based on body weight (Table 2)

  [see Dosage and Administration (2.3)]

  .

  Table 2. Recommended Dosage for TAFINLAR Tablets for Oral Suspension in Adult and Pediatric Patients (Weight-based)

  Body Weight	Recommended Dosage
  8 to 9 kg	20 mg twice daily
  10 to 13 kg	30 mg twice daily
  14 to 17 kg	40 mg twice daily
  18 to 21 kg	50 mg twice daily
  22 to 25 kg	60 mg twice daily
  26 to 29 kg	70 mg twice daily
  30 to 33 kg	80 mg twice daily
  34 to 37 kg	90 mg twice daily
  38 to 41 kg	100 mg twice daily
  42 to 45 kg	110 mg twice daily
  46 to 50 kg	130 mg twice daily
  ≥ 51 kg	150 mg twice daily

  Duration of Treatment

  • The recommended duration of treatment for patients with unresectable or metastatic melanoma or solid tumors, metastatic NSCLC, or locally advanced or metastatic anaplastic thyroid cancer is until disease progression or unacceptable toxicity.
  • The recommended duration of treatment in the adjuvant melanoma setting is until disease recurrence or unacceptable toxicity for up to 1 year.
  • The recommended duration of treatment for pediatric patients with LGG is until disease progression or until unacceptable toxicity.

  Combination Therapy with Trametinib

  Refer to the trametinib prescribing information for recommended trametinib dosing information.

  2.3
       
  Administration

  • Take TAFINLAR at the same time each day, approximately 12 hours apart.
  • Do not take a missed dose of TAFINLAR within 6 hours of the next dose of TAFINLAR.
  • If vomiting occurs after TAFINLAR administration, do not take an additional dose. Take the next dose at its scheduled time.

  TAFINLAR Capsules

  • Take TAFINLAR capsules on an empty stomach (at least 1 hour before or 2 hours after a meal)
    [see Clinical Pharmacology (12.3)]
    .
  • Do not open, crush, or break TAFINLAR capsules.

  TAFINLAR Tablets for Oral Suspension

  • Prior to use of the oral suspension, instruct caregivers (and if appropriate, patients) on proper dosing and administration of TAFINLAR tablets for oral suspension.
  • Take the oral suspension on an empty stomach (at least 1 hour before or 2 hours after a meal). Breastfeeding and/or baby formula may be given on demand if a pediatric patient is unable to tolerate the fasting conditions
    [see Clinical Pharmacology (12.3)]
    .
  • Do not swallow whole, chew or crush TAFINLAR tablets for oral suspension.

  Preparation and Administration

  • Prepare the oral suspension with approximately 5 mL of water for 1 to 4 tablets, and approximately 10 mL of water for 5 to 15 tablets in the provided dosing cup.
  • Gently stir the water and prescribed number of tablets with the handle of a teaspoon until the tablets are fully dissolved. It may take at least 3 minutes to fully dissolve the tablets. Once the tablets are dissolved, the oral suspension will be cloudy white.
  • Administer the oral suspension immediately after preparation from a dosing cup, oral syringe or feeding tube (10 French gauge or larger for 1 to 3 tablets; 12 French gauge or larger for 4 to 15 tablets).
  • Discard the oral suspension if not administered within 30 minutes after preparation.

  2.4
       
  Dosage Modifications for Adverse Reactions

  Dose reductions for adverse reactions associated with TAFINLAR are presented in Tables 3 and 4.

  Table 3. Recommended Dosage Reductions for TAFINLAR Capsules for Adverse Reactions

  Recommended Dosage	75 mg orally twice daily	100 mg orally twice daily	150 mg orally twice daily
  First dose reduction	50 mg orally twice daily	75 mg orally twice daily	100 mg orally twice daily
  Second dose reduction	N/A	50 mg orally twice daily	75 mg orally twice daily
  Third dose reduction	N/A	N/A	50 mg orally twice daily
  Subsequent modification	Permanently discontinue if unable to tolerate TAFINLAR capsules 50 mg orally twice daily.

  Table 4. Recommended Dosage Reductions for TAFINLAR Tablets for Oral Suspension for Adverse Reactions

  Body Weight (Recommended dosage)	First Dose Reduction	Second Dose Reduction	Third Dose Reduction
  	Tablets for oral suspension twice daily
  8 to 9 kg (20 mg twice daily)	10 mg twice daily	N/A	N/A
  10 to 13 kg (30 mg twice daily)	20 mg twice daily	10 mg twice daily	N/A
  14 to 17 kg (40 mg twice daily)	30 mg twice daily	20 mg twice daily	10 mg twice daily
  18 to 21 kg (50 mg twice daily)	30 mg twice daily	20 mg twice daily	10 mg twice daily
  22 to 25 kg (60 mg twice daily)	40 mg twice daily	30 mg twice daily	20 mg twice daily
  26 to 29 kg (70 mg twice daily)	50 mg twice daily	40 mg twice daily	20 mg twice daily
  30 to 33 kg (80 mg twice daily)	50 mg twice daily	40 mg twice daily	30 mg twice daily
  34 to 37 kg (90 mg twice daily)	60 mg twice daily	50 mg twice daily	30 mg twice daily
  38 to 41 kg (100 mg twice daily)	70 mg twice daily	50 mg twice daily	30 mg twice daily
  42 to 45 kg (110 mg twice daily)	70 mg twice daily	60 mg twice daily	40 mg twice daily
  46 to 50 kg (130 mg twice daily)	90 mg twice daily	70 mg twice daily	40 mg twice daily
  ≥ 51 kg (150 mg twice daily)	100 mg twice daily	80 mg twice daily	50 mg twice daily

  Dosage modifications for adverse reactions associated with TAFINLAR are presented in Table 5.

  Table 5. Recommended Dosage Modifications for TAFINLAR for Adverse Reactions

  aNational Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. bSee Tables 3 and 4 for recommended dose reductions of TAFINLAR. cDose modifications are not recommended for TAFINLAR when administered with trametinib for the following adverse reactions of trametinib: retinal vein occlusion (RVO), retinal pigment epithelial detachment (RPED), interstitial lung disease/pneumonitis, and uncomplicated venous thromboembolism. Dose modification of TAFINLAR is not required for new primary cutaneous malignancies.
  Severity of Adverse Reactiona	Dosage Modification for TAFINLAR b
  New Primary Malignancies [see Warnings and Precautions (5.1)]
  Non-Cutaneous RAS Mutation-positive Malignancies	Permanently discontinue TAFINLAR.
  Cardiomyopathy [see Warnings and Precautions (5.4)]
  Symptomatic cardiomyopathy Absolute decrease in left ventricular ejection fraction (LVEF) of greater than 20% from baseline that is below the institutional lower limit of normal (LLN)	Withhold TAFINLAR until LVEF improves to at least the institutional LLN and absolute decrease to less than or equal to 10% compared to baseline, then resume TAFINLAR at same dose.
  Uveitis [see Warnings and Precautions (5.5)]
  Uveitis, including iritis and iridocyclitis	For mild or moderate uveitis that does not respond to ocular therapy, or for severe uveitis, withhold TAFINLAR for up to 6 weeks. If improved to Grade 0-1, then resume TAFINLAR at same or lower dose. If not improved, permanently discontinue TAFINLAR.
  Febrile Reactions [see Warnings and Precautions (5.6)]
  Fever of 100.4°F to 104°F (or first symptoms in case of recurrence)	Withhold TAFINLAR until fever resolves, then resume TAFINLAR at same or lower dose.
  Fever higher than 104°F Fever complicated by rigors, hypotension, dehydration, or renal failure	Withhold TAFINLAR until febrile reactions resolve for at least 24 hours, then resume TAFINLAR at lower dose. Or Permanently discontinue TAFINLAR.
  Skin Toxicities [see Warnings and Precautions (5.7)]
  Intolerable Grade 2 Grade 3 or 4	Withhold TAFINLAR for up to 3 weeks. If improved, resume TAFINLAR at lower dose. If not improved, permanently discontinue TAFINLAR.
  Severe cutaneous adverse reactions (SCARs)	Permanently discontinue TAFINLAR.
  Other Adverse Reactionsc, including Hemorrhage [see Warnings and Precautions (5.3)]
  Intolerable Grade 2 Any Grade 3	Withhold TAFINLAR. If improved to Grade 0-1, resume TAFINLAR at lower dose. If not improved, permanently discontinue TAFINLAR.
  First occurrence of any Grade 4	Withhold TAFINLAR until improves to Grade 0-1, then resume TAFINLAR at lower dose. Or Permanently discontinue TAFINLAR.
  Recurrent Grade 4	Permanently discontinue TAFINLAR.

  Refer to the trametinib prescribing information for dose modifications for adverse reactions associated with trametinib.
  )

TAFINLAR Capsules:

• 50 mg: Dark red capsule imprinted with ‘GS TEW’ and ‘50 mg’.
• 75 mg: Dark pink capsule imprinted with ‘GS LHF’ and ‘75 mg’.

TAFINLAR Tablets for Oral Suspension:

• 10 mg: White to slightly yellow, round, biconvex 6 mm tablet debossed with “D” on one side and “NVR” on the other, contains berry flavor.

• Lactation
  : Do not breastfeed. (
  8.2
       
  Lactation

  Risk Summary

  There are no data on the presence of dabrafenib in human milk, or the effects of dabrafenib on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with TAFINLAR and for 2 weeks following the last dose.
  )
  
  
• Females and Males of Reproductive Potential
  : May impair fertility. (
  8.3
       
  Females and Males of Reproductive Potential

  Pregnancy Testing

  Verify pregnancy status in females of reproductive potential prior to initiating TAFINLAR.

  Contraception

  Based on data from animal studies and its mechanism of action, TAFINLAR can cause fetal harm when administered to pregnant women

  [see Use in Specific Populations (8.1

  )].

  Females

  Advise female patients of reproductive potential to use effective contraception during treatment with TAFINLAR and for 2 weeks after the last dose. Counsel patients to use a non-hormonal method of contraception since TAFINLAR can render hormonal contraceptives ineffective

  [see Drug Interactions (7.2)]

  .

  Males

  To avoid potential drug exposure to pregnant partners and female partners of reproductive potential, advise male patients (including those who have had vasectomies) with female partners of reproductive potential to use condoms during treatment with TAFINLAR and for 2 weeks after the last dose.

  Infertility

  Females

  Advise female patients of reproductive potential that TAFINLAR may impair fertility. A reduction in fertility was observed in female rats at dose exposures equivalent to the human exposure at the recommended adult dose. A reduction in the number of corpora lutea was noted in pregnant rats at dose exposures approximately three times the human exposure at the recommended adult dose

  [see Nonclinical Toxicology (13.1)].

  Males

  Advise male patients of the potential risk for impaired spermatogenesis which may be irreversible. Effects on spermatogenesis have been observed in animals treated with dabrafenib at dose exposures up to three times the human exposure at the recommended adult dose

  [see Nonclinical Toxicology (13.1)].
  )