Tafinlar Disease Interactions

Cardiomyopathy/reduction in left ventricular ejection fraction (LVEF) has been reported with the use of dabrafenib. Exercise caution when using this drug in patients at risk of conditions that could impair left ventricular function. It is recommended to assess LVEF by echocardiogram or multigated acquisition (MUGA) scan before initiation of therapy, 1 month after, and then at 2- to 3-month intervals while on treatment. Withhold therapy for symptomatic cardiomyopathy or asymptomatic LV dysfunction of greater than 20% from baseline that is below institutional lower level of normal. Resume therapy at the same dose level upon recovery of cardiac function.

The use of dabrafenib may cause hyperglycemia in patients with a history of diabetes. Care should be exercised when using this drug in diabetic patients. It is recommended to monitor serum glucose levels at the start of therapy and as clinically indicated. Initiate or optimize anti-hyperglycemic medications as appropriate.

Serious febrile reactions and fever of any severity complicated by rigors or chills, hypotension, dehydration, and/or renal failure have been observed with the use of dabrafenib. The incidence and severity of pyrexia are increased when this drug is administered in combination with trametinib. Patients with serious non-infectious febrile events responded well to dose interruption and/or dose reduction and supportive care. It is recommended to withhold therapy for fever of 38.5 degrees Celsius (101.3 degrees Fahrenheit) or higher, for any serious febrile reaction, or fever associated with complications; evaluate for infection. Consider the administration of antipyretics to resolve fever, and as secondary prophylaxis when resuming therapy for patients with prior episode of severe febrile reaction or fever associated with complications. For instances in which antipyretics are insufficient, consider administering corticosteroids. Upon resolution of pyrexia, dose reduction and/or permanent therapy discontinuation may be required.

Dabrafenib contains a sulfonamide moiety. Care should be exercised when using this drug in patients with glucose-6-phosphate dehydrogenase (G6PD) as it may increase the risk of hemolytic anemia. It is recommended to monitor patients with G6PD deficiency for signs of hemolytic anemia during therapy.

The use of dabrafenib may increase the change of hemorrhagic events. Use care when using this drug in patients at risk of bleeding. It is recommended to permanently discontinue treatment for all Grade 4 hemorrhagic events and for any Grade 3 hemorrhagic events that do not improve. Withhold therapy for Grade 3 hemorrhagic events; if improved, resume at the next lower dose level.

The use of dabrafenib may result in severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS, sometimes life-threatening or fatal. Care should be exercised when using this drug in patients at risk of skin toxicities. It is recommended to monitor for new or worsening serious skin reactions and to permanently discontinue treatment for SCARs. Withhold treatment for intolerable or severe skin toxicity and resume at a lower dose upon improvement or recovery within 3 weeks. Permanently discontinue therapy in skin toxicities have not improved within 3 weeks.

The use of dabrafenib may cause uveitis, including iritis and iridocyclitis. Care should be exercised when using this agent in patients at risk of ocular toxicities. During therapy, it is recommended to routinely monitor patients for visual signs and symptoms of uveitis, such as a change in vision, photophobia, and eye pain. Upon examination, if iritis is diagnosed administer ocular therapy, and continue this drug without a dose modification. For severe uveitis or iridocyclitis, interrupt therapy and treat as clinically indicated and permanently discontinue treatment for persistent Grade 2 or greater uveitis of 6 weeks or more. No dose modifications are required if treatment effectively controls ocular inflammation.

The use of certain multikinase inhibitors has been associated with pulmonary toxicity. Serious cases of interstitial lung disease (ILD), including fatal cases and interstitial pneumonitis or pulmonary fibrosis have been reported. Caution is recommended when using these agents in patients with a history of interstitial pneumonitis or pulmonary fibrosis or those patients presenting with acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, permanently discontinue these agents and institute appropriate measures. Immediately withhold treatment in patients diagnosed with ILD/pneumonitis and permanently discontinue therapy if no other potential causes of ILD/pneumonitis have been identified.