Table 3.

Suggested management of pyrexia commonly seen in patients treated with dabrafenib

	Recommended evaluations	Recommended treatment
Uncomplicated, first occurrence	Evaluate patient for signs and symptoms of infection and consider imaging/testing as appropriate Routine laboratory testing should include: –CBC with differential –Blood cultures –Renal function testing	Hold drug until fever resolves Encourage oral hydration Give antipyretic until fever resolves: –Acetaminophen every 6 h –Consider alternating acetaminophen and ibuprofen (ibuprofen should be used cautiously owing to possible renal insufficiency) –Consider a short trial of oral corticosteroids Resume drug at same dose level when fever is resolved Consider fever prophylaxis: –Acetaminophen and/or ibuprofen are reasonable for prophylaxis, but these may not be as effective as prednisone –Prednisone (e.g., 10–20 mg daily); titrate down each week over 2–4 weeks
Uncomplicated, second or subsequent occurrence	Evaluate patient for signs and symptoms of infection and consider imaging/testing as appropriate Routine laboratory testing should include: –CBC with differential –Blood cultures –Renal function testing	Hold drug until fever resolves Encourage oral hydration Give antipyretic until fever resolves: –Acetaminophen every 6 h –Consider alternating acetaminophen and ibuprofen (ibuprofen should be used cautiously owing to possible renal insufficiency) –Consider oral corticosteroids If uncomplicated fever recurs in spite of fever prophylaxis: If acetaminophen or ibuprofen were used for prophylaxis, switch to prednisone If prednisone was used as prophylaxis, use a higher dose of prednisone Once fever resolves, restart at the same dose If uncomplicated fever recurs in spite of a higher dose of steroid prophylaxis (e.g., 40 mg daily), reduce dabrafenib to the next lower dose (e.g. from 150 to 100 mg)
Complicated, first occurrence	Patient should be evaluated immediately by a physician to evaluate the severity of symptoms Evaluate patient for signs and symptoms of infection and consider imaging/testing as appropriate Acute/severe issues (e.g., hypotension, arrhythmia) should be managed aggressively and require hospitalization Routine laboratory testing should include: –CBC with differential –Blood cultures –Renal function testing	Hold drug until fever resolves Encourage oral hydration or provide IV hydration Give antipyretic until fever resolves (see guidelines for uncomplicated fever): –Oral steroids are recommended. A higher dose may be necessary (e.g., prednisone 20–40 mg, depending on the severity of the event). Titrate steroids down over a period of 2 weeks Consider pyrexia prophylaxis. Titrate steroids down slowly (e.g., over 2–4 weeks) Once fever resolves, dose reduce dabrafenib to the next lower dose, e.g., from 150 to 100 mg In patients who experienced severe symptoms (e.g., hypotension, arrhythmia), consider discontinuing dabrafenib permanently
Complicated, second occurrence	Repeat above evaluations for “Complicated, first occurrence”	If severe symptoms recur in spite of dose reduction and pyrexia prophylaxis, consider discontinuing dabrafenib permanently

Adverse events are defined using the common terminology criteria for adverse events. Uncomplicated—temperature <104 °F with no hypotension, dehydration, dizziness, arrhythmia, rigors, or grade 3 related symptoms; complicated—temperature >104 °F with hypotension, dehydration, dizziness, arrhythmia, rigors, and/or grade 3 related symptoms

CBC complete blood count, IV intravenous