Tafinlar

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 ) 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 a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. b See Tables 3 and 4 for recommended dose reductions of TAFINLAR. c Dose 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 Reaction a 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 Reactions c , 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.

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1 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.