TIBSOVO® dosing for acute myeloid leukemia (AML)

Single-agent TIBSOVO offers convenient, once-daily oral dosing and can be taken with or without food¹

500 mg

(2 x 250-mg film-coated tablets)

Tablets not shown at actual size.

Taken orally, once daily until disease progression or unacceptable toxicity

Dosing guidance for TIBSOVO¹

Treatment with TIBSOVO has not been studied in patients with pre‑existing severe renal or hepatic impairment. For patients with pre‑existing severe renal or hepatic impairment, consider the risks and potential benefits before initiating treatment with TIBSOVO.

TIBSOVO should be taken at about the same time each day.

If a dose is missed or not taken at the usual time, patients should take the missed dose as soon as possible and at least 12 hours prior to the next scheduled dose. They should return to the normal schedule the following day. They should not take 2 doses within 12 hours.

If a dose is vomited, patients should not take a replacement dose; they should wait until the next scheduled dose is due.

TIBSOVO tablets should not be split, crushed, or chewed.

TIBSOVO can be taken with or without food but should not be taken with a high-fat meal.^a

Managing adverse reactions to TIBSOVO¹

• Assess blood counts and blood chemistries prior to the initiation of TIBSOVO, at least once weekly for the first month, once every other week for the second month, and once monthly for the duration of therapy
  
• Monitor blood creatine phosphokinase weekly for the first month of therapy
• Obtain an electrocardiogram (ECG) prior to treatment initiation. Monitor ECGs at least once weekly for the first 3 weeks of therapy and then at least once monthly for the duration of therapy. Manage any abnormalities promptly

Differentiation syndrome¹

• Symptoms of differentiation syndrome in patients treated with TIBSOVO included noninfectious leukocytosis, peripheral edema, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonitis, pericardial effusion, rash, fluid overload, tumor lysis syndrome, and creatinine increased
• In the combination clinical trial AG120-C-009, differentiation syndrome occurred as early as 3 days after start of therapy and during the first month on treatment
• In the monotherapy clinical trial AG120-C-001, differentiation syndrome occurred as early as 1 day and up to 3 months after TIBSOVO initiation and has been observed with or without concomitant leukocytosis
• If differentiation syndrome is suspected, initiate dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an alternative oral or IV corticosteroid) and initiate hemodynamic monitoring until symptom resolution and for a minimum of 3 days
• Interrupt TIBSOVO if severe signs and/or symptoms persist for more than 48 hours after initiation with systemic corticosteroids
• Resume TIBSOVO when signs and symptoms improve to Grade ≤2^b
• Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid and/or hydroxyurea treatment

Noninfectious leukocytosis¹

• Initiate treatment with hydroxyurea, as per standard institutional practices, and leukapheresis if clinically indicated
• Taper hydroxyurea only after leukocytosis improves or resolves
• Interrupt TIBSOVO if leukocytosis is not improved with hydroxyurea, and then resume TIBSOVO at 500 mg daily when leukocytosis has resolved

QTc prolongation¹

Of the 71 patients treated with TIBSOVO + azacitidine in the combination therapy clinical trial:

• 14% had a QTc interval >500 msec
• 22% had a >60 msec increase from baseline QTc interval

Of the 258 patients treated with single-agent TIBSOVO in the monotherapy clinical trial:

• 9% had a QTc interval >500 msec
• 14% had a >60 msec increase from baseline QTc interval
• One patient developed ventricular fibrillation attributed to TIBSOVO

QTc interval >480 to 500 msec

• Monitor and supplement electrolyte levels as clinically indicated
• Review and adjust concomitant medications with known QTc interval–prolonging effects
• Interrupt TIBSOVO
• Restart TIBSOVO at 500 mg once daily after the QTc interval returns to ≤480 msec
• Monitor ECGs at least weekly for 2 weeks following resolution of QTc prolongation

QTc interval >500 msec

• Monitor and supplement electrolyte levels as clinically indicated
• Review and adjust concomitant medications with known QTc interval–prolonging effects
• Interrupt TIBSOVO
• Resume TIBSOVO at a reduced dose of 250 mg once daily when QTc interval returns to within 30 msec of baseline or ≤480 msec
• Monitor ECGs at least weekly for 2 weeks following resolution of QTc prolongation
• Consider re-escalating the dose of TIBSOVO to 500 mg daily if an alternative etiology for QTc prolongation can be identified

QTc interval prolongation with signs/symptoms of life-threatening arrhythmia

• Discontinue TIBSOVO permanently

Guillain-Barré syndrome¹

• Discontinue TIBSOVO permanently

Other Grade 3^b adverse reactions¹

TIBSOVO in combination with azacitidine

• Interrupt TIBSOVO until toxicity resolves to Grade 1^b or lower, or baseline, then resume at 500 mg daily (Grade 3 toxicity) or 250 mg daily (Grade 4 toxicity)
• If Grade 3 toxicity recurs (a second time), reduce TIBSOVO dose to 250 mg daily until the toxicity resolves, then resume 500 mg daily
• If Grade 3 toxicity recurs (a third time), or Grade 4 toxicity recurs, discontinue TIBSOVO

TIBSOVO monotherapy

• Interrupt TIBSOVO until toxicity resolves to Grade 2^b or lower
• Resume TIBSOVO at 250 mg once daily; may increase to 500 mg once daily if toxicities resolve to Grade 1 or lower
• If Grade 3 or higher toxicity recurs, discontinue TIBSOVO

^b Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening.

IV, intravenous.

Drug-drug interactions with TIBSOVO¹