Prescription Drug Information: Tafinlar (Page 2 of 10)

3 DOSAGE FORMS AND STRENGTHS

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.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 New Primary Malignancies

Cutaneous Malignancies

TAFINLAR Monotherapy (Adult): In the pooled safety population [see Adverse Reactions (6.1)] , cutaneous squamous cell carcinomas (cuSCC), and keratoacanthomas occurred in 11% and 4% of patients, respectively. Basal cell carcinoma and new primary melanoma occurred in 4% and 1% of patients, respectively.

TAFINLAR Administered with Trametinib (Adult): In the pooled safety population [see Adverse Reactions (6.1)] , the incidence of cuSCC (including keratoacanthomas) occurred in 2% of patients. Basal cell carcinoma and new primary melanoma occurred in 3% and < 1% of patients, respectively.

TAFINLAR Administered with Trametinib (Pediatric): In the pooled safety population, new primary melanoma occurred in < 1% of patients.

Perform dermatologic evaluations prior to initiation of TAFINLAR, every 2 months while on therapy, and for up to 6 months following discontinuation of TAFINLAR.

Non-Cutaneous Malignancies

Based on its mechanism of action, TAFINLAR may promote the growth and development of malignancies with activation of RAS through mutation or other mechanisms [see Warnings and Precautions (5.2)].

In the pooled adult safety populations of TAFINLAR monotherapy and TAFINLAR administered with trametinib [see Adverse Reactions (6.1)] , non-cutaneous malignancies occurred in 1% of patients.

Monitor patients receiving TAFINLAR for signs or symptoms of non-cutaneous malignancies. Permanently discontinue TAFINLAR for RAS mutation-positive non-cutaneous malignancies [see Dosage and Administration (2.4)].

5.2 Tumor Promotion in BRAF Wild-Type Tumors

In vitro experiments have demonstrated paradoxical activation of MAP-kinase signaling and increased cell proliferation in BRAF wild-type cells which are exposed to BRAF inhibitors. Confirm evidence of BRAF V600E or V600K mutation status prior to initiation of TAFINLAR as a single agent or in combination with trametinib [see Indications and Usage (1.6), Dosage and Administration (2.1)].

5.3 Hemorrhage

Hemorrhage, including major hemorrhage defined as symptomatic bleeding in a critical area or organ, can occur when TAFINLAR is administered with trametinib. Fatal cases have been reported.

TAFINLAR Administered with Trametinib (Adult): In the pooled safety population [see Adverse Reactions (6.1)] , hemorrhagic events occurred in 17% of patients; gastrointestinal hemorrhage occurred in 3% of patients; intracranial hemorrhage occurred in 0.6% of patients; fatal hemorrhage occurred in 0.5% of patients. The fatal events were cerebral hemorrhage and brainstem hemorrhage.

TAFINLAR Administered with Trametinib (Pediatric): In the pooled safety population, hemorrhagic events occurred in 25% of patients; the most common type of bleeding was epistaxis (16%). Serious events of bleeding occurred in 3.6% of patients and included gastrointestinal hemorrhage (1.2%), cerebral hemorrhage (0.6%) uterine hemorrhage (0.6%), post-procedural hemorrhage (0.6%), and epistaxis (0.6%).

Permanently discontinue TAFINLAR for all Grade 4 hemorrhagic events and for any Grade 3 hemorrhagic events that do not improve. Withhold TAFINLAR for Grade 3 hemorrhagic events; if improved, resume TAFINLAR at the next lower dose level.

5.4 Cardiomyopathy

TAFINLAR Administered with Trametinib (Adult): In the pooled safety population [see Adverse Reactions (6.1)] , cardiomyopathy, defined as a decrease in left ventricular ejection fraction (LVEF) ≥ 10% from baseline and below the institutional lower limit of normal (LLN), occurred in 6% of patients. Development of cardiomyopathy resulted in dose interruption or discontinuation of TAFINLAR in 3% and < 1% of patients, respectively. Cardiomyopathy resolved in 45 of 50 patients who received TAFINLAR administered with trametinib.

TAFINLAR Administered with Trametinib (Pediatric): In the pooled safety population, cardiomyopathy, defined as a decrease in LVEF ≥ 10% from baseline and below the institutional LLN, occurred in 9% of patients.

Assess LVEF by echocardiogram or multigated acquisition (MUGA) scan before initiation of TAFINLAR in combination with trametinib, one month after initiation, and then at 2- to 3-month intervals while on treatment. Withhold TAFINLAR for symptomatic cardiomyopathy or asymptomatic LV dysfunction of > 20% from baseline that is below institutional LLN. Resume TAFINLAR at the same dose level upon recovery of cardiac function to at least the institutional LLN for LVEF and absolute decrease ≤ 10% compared to baseline [see Dosage and Administration (2.4)].

5.5 Uveitis

TAFINLAR Monotherapy (Adult): In the pooled safety population [see Adverse Reactions (6.1)] , uveitis occurred in 1% of patients.

TAFINLAR Administered with Trametinib (Adult): In the pooled safety population [see Adverse Reactions (6.1)] , uveitis occurred in 2% of patients.

TAFINLAR Administered with Trametinib (Pediatric): In the pooled safety population, uveitis occurred in 1.2% of patients.

Treatment employed in clinical trials included steroid and mydriatic ophthalmic drops. Monitor patients for visual signs and symptoms of uveitis (e.g., change in vision, photophobia, eye pain). If iritis is diagnosed, administer ocular therapy and continue TAFINLAR without dose modification. If severe uveitis (i.e., iridocyclitis) or if mild or moderate uveitis does not respond to ocular therapy, withhold TAFINLAR and treat as clinically indicated. Resume TAFINLAR at the same or lower dose if improves to Grade 0 or 1. Permanently discontinue TAFINLAR for persistent Grade 2 or greater uveitis of > 6 weeks [see Dosage and Administration (2.4)].

5.6 Serious Febrile Reactions

Serious febrile reactions and fever of any severity complicated by hypotension, rigors or chills, dehydration, or renal failure, can occur with TAFINLAR.

The incidence and severity of pyrexia are increased when TAFINLAR is administered with trametinib compared with TAFINLAR as a single agent [see Adverse Reactions (6.1)].

TAFINLAR Monotherapy (Adult): In the pooled safety population [see Adverse Reactions (6.1)] , fever (serious and non-serious) occurred in 30% of patients. Approximately 13% of these patients experienced 3 or more discrete episodes. Serious febrile reactions and fever of any severity complicated by hypotension, rigors or chills occurred in 6% of patients.

TAFINLAR Administered with Trametinib (Adult): In the pooled safety population [see Adverse Reactions (6.1)] , fever occurred in 58% of patients. Serious febrile reactions and fever of any severity complicated by hypotension, rigors or chills, dehydration or renal failure occurred in 5% of patients. Fever was complicated by hypotension in 4%, dehydration in 3%, syncope in 2%, renal failure in 1%, and severe chills/rigors in < 1% of patients.

TAFINLAR Administered with Trametinib (Pediatric): In the pooled safety population [see Adverse Reactions (6.1)] , pyrexia occurred in 66% of patients.

Withhold TAFINLAR when used as monotherapy, and both TAFINLAR and trametinib when used in combination, if the patient’s temperature is ≥ 100.4°F. In case of recurrence, therapy can also be interrupted at the first symptom of pyrexia [see Adverse Reactions (6.1)]. Fever may be complicated by hypotension, rigors or chills, dehydration, or renal failure. Evaluate for signs and symptoms of infection and monitor serum creatinine and other evidence of renal function during and following severe pyrexia. If appropriate, TAFINLAR, or both TAFINLAR and trametinib when used in combination, may be restarted if the patient has recovered from the febrile reaction for at least 24 hours, either at the same or lower dose [see Dosage and Administration (2.4)]. Administer antipyretics as secondary prophylaxis when resuming TAFINLAR if patient had a prior episode of severe febrile reaction or fever associated with complications. Administer corticosteroids (e.g., prednisone 10 mg daily) for at least 5 days for second or subsequent pyrexia if temperature does not return to baseline within 3 days of onset of pyrexia, or for pyrexia associated with complications, such as dehydration, hypotension, renal failure, or severe chills/rigors, and there is no evidence of active infection.

5.7 Serious Skin Toxicities

Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported during treatment with TAFINLAR administered with trametinib [see Adverse Reactions (6.2)].

TAFINLAR Administered with Trametinib (Adult): In the pooled safety population [see Adverse Reactions (6.1)] , other serious skin toxicity occurred in < 1% of patients.

TAFINLAR Administered with Trametinib (Pediatric): In the pooled safety population, serious adverse events of skin and subcutaneous tissue disorders occurred in 1.8% of patients.

Monitor for new or worsening serious skin reactions. Permanently discontinue TAFINLAR for SCARs [see Dosage and Administration (2.4)]. For other skin toxicities, withhold TAFINLAR for intolerable or severe skin toxicity. Resume TAFINLAR at a lower dose in patients with improvement or recovery from skin toxicity within 3 weeks. Permanently discontinue TAFINLAR if skin toxicity has not improved within 3 weeks [see Dosage and Administration (2.4)].

5.8 Hyperglycemia

TAFINLAR Monotherapy (Adult): In the pooled safety population [see Adverse Reactions (6.1)] , 14% of patients with a history of diabetes that received TAFINLAR required more intensive hypoglycemic therapy. Grade 3 and Grade 4 hyperglycemia occurred in 3% of patients.

TAFINLAR Administered with Trametinib (Adult): In the pooled safety population [see Adverse Reactions (6.1)] , 15% of patients with a history of diabetes who had received TAFINLAR with trametinib required more intensive hypoglycemic therapy. Grade 3 and Grade 4 hyperglycemia occurred in 2% of patients.

TAFINLAR Administered with Trametinib (Pediatric): In the pooled safety population, Grade 3 and Grade 4 hyperglycemia events occurred in < 1% of patients.

Monitor serum glucose levels upon initiation and as clinically appropriate when TAFINLAR is administered in patients with preexisting diabetes or hyperglycemia. Initiate or optimize anti-hyperglycemic medications as clinically indicated.

5.9 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. Monitor patients with G6PD deficiency for signs of hemolytic anemia while taking TAFINLAR.

5.10 Risks Associated with Combination Treatment

TAFINLAR is indicated for use in combination with trametinib. Review the prescribing information for trametinib for information on the serious risks of trametinib prior to initiation of TAFINLAR with trametinib.

5.11 Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) has been observed in the post-marketing setting when TAFINLAR was administered with trametinib. If HLH is suspected, interrupt treatment. If HLH is confirmed, discontinue treatment and initiate appropriate management of HLH.

5.12 Embryo-Fetal Toxicity

Based on findings from animal studies and its mechanism of action, TAFINLAR can cause fetal harm when administered to a pregnant woman. Dabrafenib was teratogenic and embryotoxic in rats at doses three times greater than the human exposure at the recommended adult clinical dose. Advise pregnant women of the potential risk to a fetus. Advise female patients of reproductive potential to use effective non-hormonal contraception, since TAFINLAR can render hormonal contraceptives ineffective, during treatment with TAFINLAR and for 2 weeks after the last dose [see Drug Interactions (7.2), Use in Specific Populations (8.1, 8.3)].

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