Tafinlar For Oral Suspension

— THERAPEUTIC CATEGORIES —
  • CNS cancers
  • Solid tumors
PAGE CONTENTS
  • Jump to Section
  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Tafinlar For Oral Suspension Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Dabrafenib 10mg; tabs for oral susp; berry-flavored.

    Pharmacological Class

    Kinase inhibitor.

    See Also

    How Supplied

    Caps—120; Tabs for oral susp—210

    Manufacturer

    Novartis Pharmaceuticals Corp

    Generic Availability

    NO

    Mechanism of Action

    Dabrafenib is an inhibitor of some mutated forms of BRAF kinases with in vitro IC50 values of 0.65, 0.5, and 1.84 nM for BRAF V600E, BRAF V600K, and BRAF V600D enzymes, respectively. Dabrafenib also inhibits wild-type BRAF and CRAF kinases with IC50 values of 3.2 and 5.0 nM, respectively, and other kinases, such as SIK1, NEK11, and LIMK1 at higher concentrations. Dabrafenib inhibits cell growth of various BRAF V600 mutation-positive tumors in vitro and in vivo.

    Tafinlar For Oral Suspension Indications

    Indications

    In combination with trametinib for the treatment of pediatric patients with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy.

    Limitations of Use

    Not for treatment of colorectal cancer because of known intrinsic resistance to BRAF inhibition. Not for treatment of wild-type BRAF solid tumors.

    Tafinlar For Oral Suspension Dosage and Administration

    Adult

    ≥18yrs: not established.

    Children

    <1yrs or <8kg: not established. Confirm presence of BRAF V600E mutation prior to initiation. Use caps or tabs for oral susp based on the ability to swallow and body weight. Swallow caps whole (do not use caps if <26kg). For oral susp: disperse tabs in water until fully dissolved; may administer via cup, oral dosing syringe, or feeding tube. Take at least 1hr before or 2hrs after a meal. In combination with trametinib (for caps): 1–<18yrs (26–37kg): 75mg twice daily (approx. 12hrs apart); (38–50kg): 100mg twice daily; (≥51kg): 150mg twice daily. In combination with trametinib (tabs for oral susp): 1–<18yrs (8–9kg): 20mg twice daily; (10–13kg): 30mg twice daily; (14–17kg):40mg twice daily; (18–21kg): 50mg twice daily; (22–25kg): 60mg twice daily; (26–29kg): 70mg twice daily; (30–33mg): 80mg twice daily; (34–37kg): 90mg twice daily; (38–41kg): 100mg twice daily; (42–45kg): 110mg twice daily; (46–50kg): 130mg twice daily; (≥51kg): 150mg twice daily. Continue until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

    Tafinlar For Oral Suspension Contraindications

    Not Applicable

    Tafinlar For Oral Suspension Boxed Warnings

    Not Applicable

    Tafinlar For Oral Suspension Warnings/Precautions

    Warnings/Precautions

    See full labeling for trametinib prior to starting combination therapy. Increased incidence of new cutaneous malignancies; perform skin evaluation prior to initiation, every 2 months during therapy, and up to 6 months after discontinuation. Monitor for non-cutaneous malignancies; permanently discontinue if RAS mutation-positive malignancy occurs. Permanently discontinue for all Grade 4 or any persistent Grade 3 hemorrhagic events. Risk of cardiomyopathy with trametinib; assess LVEF prior to initiation, after one month, and then at every 2–3 month intervals during treatment; withhold for symptomatic cardiomyopathy or asymptomatic LV dysfunction of >20% from baseline that is below institutional LLN. Withhold if fever ≥100.4°F, evaluate infection and assess renal function; prophylaxis with antipyretics when resuming or give steroids for subsequent pyrexia. Pre-existing diabetes or hyperglycemia; monitor serum glucose levels. Monitor for uveitis; if occurs, withhold and treat as clinically indicated; permanently discontinue for persistent Grade ≥2 lasting >6wks. G6PD deficiency: monitor for hemolytic anemia. Severe renal or moderate to severe hepatic impairment. Embryo-fetal toxicity. Advise to use effective non-hormonal contraception (females of reproductive potential) or use of condoms (males w. female partners) during and for ≥2wks after last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 2wks after last dose).

    Tafinlar For Oral Suspension Pharmacokinetics

    Absorption

    Median time to peak plasma concentration (Tmax): 2 hours.

    Mean absolute bioavailability: 95% (caps); 76% (tabs for oral susp).

    Distribution

    Plasma protein bound: 99.7%.

    Apparent volume of distribution: 70.3 L.

    Metabolism

    CYP2C8, CYP3A4. 

    Elimination

    Fecal (71%), renal (23%). 

    Half-life: 8 hours.

    Apparent clearance: 17 L/h after a single dose and 34 L/h after twice-daily dosing for 2 weeks.

    Tafinlar For Oral Suspension Interactions

    Interactions

    Avoid concomitant strong CYP3A4 or CYP2C8 inhibitors (eg, ketoconazole, gemfibrozil); if unavoidable, monitor closely. May antagonize effects of CYP3A4, CYP2C8, CYP2C9, CYP2C19, CYP2B6 substrates (eg, midazolam, warfarin, dexamethasone, hormonal contraceptives); consider alternatives or monitor.

    Tafinlar For Oral Suspension Adverse Reactions

    Adverse Reactions

    Hyperkeratosis, headache, pyrexia, arthralgia, papilloma, alopecia, palmar-plantar erythrodysesthesia syndrome; skin toxicity (may be serious). In combination with trametinib: also chills, fatigue, rash, nausea, vomiting, diarrhea, myalgia, dry skin, decreased appetite, edema, hemorrhage, cough, dyspnea, constipation, dermatitis acneiform, abdominal pain, paronychia, musculoskeletal pain.

    Tafinlar For Oral Suspension Clinical Trials

    See Literature

    Tafinlar For Oral Suspension Note

    Not Applicable

    Tafinlar For Oral Suspension Patient Counseling

    See Literature

    Tafinlar For Oral Suspension Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Dabrafenib 10mg; tabs for oral susp; berry-flavored.

    Pharmacological Class

    Kinase inhibitor.

    See Also

    How Supplied

    Caps—120; Tabs for oral susp—210

    Manufacturer

    Novartis Pharmaceuticals Corp

    Generic Availability

    NO

    Mechanism of Action

    Dabrafenib is an inhibitor of some mutated forms of BRAF kinases with in vitro IC50 values of 0.65, 0.5, and 1.84 nM for BRAF V600E, BRAF V600K, and BRAF V600D enzymes, respectively. Dabrafenib also inhibits wild-type BRAF and CRAF kinases with IC50 values of 3.2 and 5.0 nM, respectively, and other kinases, such as SIK1, NEK11, and LIMK1 at higher concentrations. Dabrafenib inhibits cell growth of various BRAF V600 mutation-positive tumors in vitro and in vivo.

    Tafinlar For Oral Suspension Indications

    Indications

    In combination with trametinib, for the treatment of unresectable or metastatic solid tumors in adult and pediatric patients with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options.

    Limitations of Use

    Not for treatment of colorectal cancer because of known intrinsic resistance to BRAF inhibition. Not for treatment of wild-type BRAF solid tumors.

    Tafinlar For Oral Suspension Dosage and Administration

    Adult

    ≥18yrs: use cap form.

    Children

    <1yrs or <8kg: not established. Confirm presence of BRAF V600E mutation prior to initiation. Use caps or tabs for oral susp based on the ability to swallow and body weight. Swallow caps whole (do not use caps if <26kg). For oral susp: disperse tabs in water until fully dissolved; may administer via cup, oral dosing syringe, or feeding tube. Take at least 1hr before or 2hrs after a meal. In combination with trametinib (for caps): 1–<18yrs (26–37kg): 75mg twice daily (approx. 12hrs apart); (38–50kg): 100mg twice daily; (≥51kg): 150mg twice daily. In combination with trametinib (tabs for oral susp): 1–<18yrs (8–9kg): 20mg twice daily; (10–13kg): 30mg twice daily; (14–17kg):40mg twice daily; (18–21kg): 50mg twice daily; (22–25kg): 60mg twice daily; (26–29kg): 70mg twice daily; (30–33mg): 80mg twice daily; (34–37kg): 90mg twice daily; (38–41kg): 100mg twice daily; (42–45kg): 110mg twice daily; (46–50kg): 130mg twice daily; (≥51kg): 150mg twice daily. Continue until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

    Tafinlar For Oral Suspension Contraindications

    Not Applicable

    Tafinlar For Oral Suspension Boxed Warnings

    Not Applicable

    Tafinlar For Oral Suspension Warnings/Precautions

    Warnings/Precautions

    See full labeling for trametinib prior to starting combination therapy. Increased incidence of new cutaneous malignancies; perform skin evaluation prior to initiation, every 2 months during therapy, and up to 6 months after discontinuation. Monitor for non-cutaneous malignancies; permanently discontinue if RAS mutation-positive malignancy occurs. Permanently discontinue for all Grade 4 or any persistent Grade 3 hemorrhagic events. Risk of cardiomyopathy with trametinib; assess LVEF prior to initiation, after one month, and then at every 2–3 month intervals during treatment; withhold for symptomatic cardiomyopathy or asymptomatic LV dysfunction of >20% from baseline that is below institutional LLN. Withhold if fever ≥100.4°F, evaluate infection and assess renal function; prophylaxis with antipyretics when resuming or give steroids for subsequent pyrexia. Pre-existing diabetes or hyperglycemia; monitor serum glucose levels. Monitor for uveitis; if occurs, withhold and treat as clinically indicated; permanently discontinue for persistent Grade ≥2 lasting >6wks. G6PD deficiency: monitor for hemolytic anemia. Severe renal or moderate to severe hepatic impairment. Embryo-fetal toxicity. Advise to use effective non-hormonal contraception (females of reproductive potential) or use of condoms (males w. female partners) during and for ≥2wks after last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 2wks after last dose).

    Tafinlar For Oral Suspension Pharmacokinetics

    Absorption

    Median time to peak plasma concentration (Tmax): 2 hours.

    Mean absolute bioavailability: 95% (caps); 76% (tabs for oral susp).

    Distribution

    Plasma protein bound: 99.7%.

    Apparent volume of distribution: 70.3 L.

    Metabolism

    CYP2C8, CYP3A4. 

    Elimination

    Fecal (71%), renal (23%). 

    Half-life: 8 hours.

    Apparent clearance: 17 L/h after a single dose and 34 L/h after twice-daily dosing for 2 weeks.

    Tafinlar For Oral Suspension Interactions

    Interactions

    Avoid concomitant strong CYP3A4 or CYP2C8 inhibitors (eg, ketoconazole, gemfibrozil); if unavoidable, monitor closely. May antagonize effects of CYP3A4, CYP2C8, CYP2C9, CYP2C19, CYP2B6 substrates (eg, midazolam, warfarin, dexamethasone, hormonal contraceptives); consider alternatives or monitor.

    Tafinlar For Oral Suspension Adverse Reactions

    Adverse Reactions

    Hyperkeratosis, headache, pyrexia, arthralgia, papilloma, alopecia, palmar-plantar erythrodysesthesia syndrome; skin toxicity (may be serious). In combination with trametinib: also chills, fatigue, rash, nausea, vomiting, diarrhea, myalgia, dry skin, decreased appetite, edema, hemorrhage, cough, dyspnea, constipation, dermatitis acneiform, abdominal pain, paronychia, musculoskeletal pain.

    Tafinlar For Oral Suspension Clinical Trials

    See Literature

    Tafinlar For Oral Suspension Note

    Not Applicable

    Tafinlar For Oral Suspension Patient Counseling

    See Literature

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