Dosage & administration
500 mg orally once daily with or without food until disease progression or unacceptable toxicity (
The recommended dosage of TIBSOVO is 500 mg taken orally once daily until disease progression or unacceptable toxicity
Start TIBSOVO administration on Cycle 1 Day 1 in combination with azacitidine 75 mg/m2subcutaneously or intravenously once daily on Days 1-7 (or Days 1-5 and 8-9) of each 28-day cycle
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Tibsovo prescribing information
Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal.
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 study AG120-C-009, 15% (11/71) patients with newly diagnosed AML treated with TIBSOVO plus azacitidine experienced differentiation syndrome
In the monotherapy clinical trial AG120-C-001, 25% (7/28) of patients with newly diagnosed AML and 19% (34/179) of patients with relapsed or refractory AML treated with TIBSOVO experienced differentiation syndrome
In the monotherapy clinical trial AG120-C-001, 11% (2/19) of patients with relapsed or refractory MDS treated with TIBSOVO experienced differentiation syndrome
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 hemodynamic monitoring until improvement
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In AML, the safety population reflects exposure to TIBSOVO at 500 mg daily in combination with azacitidine or as monotherapy in patients in Studies AG120-C-009 (N=71) and AG120-C-001 (N=213), respectively
The safety of TIBSOVO was evaluated in AML patients treated in combination with azacitidine, in Study AG120-C-009
Common (≥ 5%) serious adverse reactions in patients who received TIBSOVO in combination with azacitidine included differentiation syndrome (8%).
Fatal adverse reactions occurred in 4% of patients who received TIBSOVO in combination with azacitidine, due to differentiation syndrome (3%) and one case of cerebral ischemia.
Adverse reactions leading to discontinuation of TIBSOVO in ≥2% of patients were differentiation syndrome (3%) and pulmonary embolism (3%).
The most common (>5%) adverse reactions leading to dose interruption of TIBSOVO were neutropenia (25%), electrocardiogram QT prolonged (7%), and thrombocytopenia (7%).
Adverse reactions leading to dose reduction of TIBSOVO included electrocardiogram QT prolonged (8%), neutropenia (8%), and thrombocytopenia (1%).
The most common adverse reactions and laboratory abnormalities observed in Study AG120-C-009 are shown in Tables 2 and 3.
| TIBSOVO + Azacitidine N=71 | Placebo + Azacitidine N=73 | |||
|---|---|---|---|---|
| Body System Adverse Reaction | All Grades n (%) | Grade ≥3 n (%) | All Grades n (%) | Grade ≥3 n (%) |
Gastrointestinal disorders | ||||
| Nausea | 30 (42) | 2 (3) | 28 (38) | 3 (4) |
| VomitingGrouped term includes vomiting and retching. | 29 (41) | 0 | 20 (27) | 1 (1) |
Investigations | ||||
| Electrocardiogram QT prolonged | 14 (20) | 7 (10) | 5 (7) | 2 (3) |
Psychiatric Disorders | ||||
| Insomnia | 13 (18) | 1 (1) | 9 (12) | 0 |
Blood system and lymphatic system disorders | ||||
| Differentiation SyndromeDifferentiation syndrome can be associated with other commonly reported events such as peripheral edema, leukocytosis, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonia, pericardial effusion, rash, fluid overload, tumor lysis syndrome, and creatinine increased. | 11 (15) | 7 (10) | 6 (8) | 6 (8) |
| LeukocytosisGrouped term includes leukocytosis, white blood cell count increased. | 9 (13) | 0 | 1 (1) | 0 |
Vascular disorders | ||||
| HematomaGrouped term includes hematoma, eye hematoma, catheter site hematoma, oral mucosa hematoma, spontaneous hematoma, application site hematoma, injection site hematoma, periorbital hematoma. | 11 (15) | 0 | 3 (4) | 0 |
| HypertensionGrouped term includes blood pressure increased, essential hypertension, and hypertension. | 9 (13) | 3 (4) | 6 (8) | 4 (5) |
Musculoskeletal and connective tissue disorders | ||||
| ArthralgiaGrouped term includes pain in extremity, arthralgia, back pain, musculoskeletal stiffness, cancer pain, and neck pain. | 21 (30) | 3 (4) | 6 (8) | 1 (1) |
Respiratory, thoracic and mediastinal disorders | ||||
| DyspneaGrouped term includes dyspnea, dyspnea exertional, hypoxia, respiration failure. | 14 (20) | 2 (3) | 11 (15) | 4 (5) |
Nervous system disorders | ||||
| Headache | 8 (11) | 0 | 2 (3) | 0 |
| TIBSOVO + Azacitidine N=71 | Placebo + Azacitidine N=73 | |||
|---|---|---|---|---|
| Parameter | All Grades n (%) | Grade ≥ 3 n (%) | All Grades n (%) | Grade ≥ 3 n (%) |
Hematology Parameters | ||||
| Leukocytes decreased | 46 (65) | 39 (55) | 47 (64) | 42 (58) |
| Platelets decreased | 41 (58) | 30 (42) | 52 (71) | 42 (58) |
| Hemoglobin decreased | 40 (56) | 33 (46) | 48 (66) | 42 (58) |
| Neutrophils decreased | 18 (25) | 16 (23) | 25 (35) | 23 (32) |
| Lymphocytes increased | 17 (24) | 1 (1) | 7 (10) | 1 (1) |
Chemistry Parameters | ||||
| Glucose increased | 40 (56) | 9 (13) | 34 (47) | 8 (11) |
| Phosphate decreased | 29 (41) | 7 (10) | 25 (34) | 9 (12) |
| Aspartate Aminotransferase increased | 26 (37) | 0 | 17 (23) | 0 |
| Magnesium decreased | 25 (35) | 0 | 19 (26) | 0 |
| Alkaline Phosphatase increased | 23 (32) | 0 | 21 (29) | 0 |
| Potassium increased | 17 (24) | 2 (3) | 9 (12) | 1 (1) |
The safety profile of single-agent TIBSOVO was studied in 28 adults with newly diagnosed AML treated with 500 mg daily
Common (≥ 5%) serious adverse reactions included differentiation syndrome (18%), electrocardiogram QT prolonged (7%), and fatigue (7%). There was one case of posterior reversible encephalopathy syndrome (PRES).
Common (≥ 10%) adverse reactions leading to dose interruption included electrocardiogram QT prolonged (14%) and differentiation syndrome (11%). Two (7%) patients required a dose reduction due to electrocardiogram QT prolonged. One patient each required permanent discontinuation due to diarrhea and PRES.
The most common adverse reactions reported in the trial are shown in Table 4.
| TIBSOVO (500 mg daily) N=28 | ||
|---|---|---|
| Body System Adverse Reaction | All Grades n (%) | Grade ≥ 3 n (%) |
Gastrointestinal disorders | ||
| Diarrhea | 17 (61) | 2 (7) |
| Nausea | 10 (36) | 2 (7) |
| Abdominal painGrouped term includes abdominal pain, upper abdominal pain, abdominal discomfort, and abdominal tenderness. | 8 (29) | 1 (4) |
| Constipation | 6 (21) | 1 (4) |
| Vomiting | 6 (21) | 1 (4) |
| MucositisGrouped term includes aphthous ulcer, esophageal pain, esophagitis, gingival pain, gingivitis, mouth ulceration, mucosal inflammation, oral pain, oropharyngeal pain, proctalgia, and stomatitis. | 6 (21) | 0 |
| Dyspepsia | 3 (11) | 0 |
General disorders and administration site conditions | ||
| FatigueGrouped term includes asthenia and fatigue. | 14 (50) | 4 (14) |
| EdemaGrouped term includes edema, face edema, fluid overload, fluid retention, hypervolemia, peripheral edema, and swelling face. | 12 (43) | 0 |
Metabolism and nutrition disorders | ||
| Decreased appetite | 11 (39) | 1 (4) |
Blood system and lymphatic system disorders | ||
| LeukocytosisGrouped term includes leukocytosis, hyperleukocytosis, and increased white blood cell count. | 10 (36) | 2 (7) |
| Differentiation SyndromeDifferentiation syndrome can be associated with other commonly reported events such as peripheral edema, leukocytosis, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonia, pericardial effusion, rash, fluid overload, tumor lysis syndrome, and creatinine increased. | 7 (25) | 3 (11) |
Musculoskeletal and connective tissue disorders | ||
| ArthralgiaGrouped term includes arthralgia, back pain, musculoskeletal stiffness, neck pain, and pain in extremity. | 9 (32) | 1 (4) |
| MyalgiaGrouped term includes myalgia, muscular weakness, musculoskeletal pain, musculoskeletal chest pain, musculoskeletal discomfort, and myalgia intercostal. | 7 (25) | 1 (4) |
Respiratory, thoracic, and mediastinal disorders | ||
| DyspneaGrouped term includes dyspnea, dyspnea exertional, hypoxia, and respiratory failure. | 8 (29) | 1 (4) |
| CoughGrouped term includes cough, productive cough, and upper airway cough syndrome. | 4 (14) | 0 |
Investigations | ||
| Electrocardiogram QT prolonged | 6 (21) | 3 (11) |
| Weight decreased | 3 (11) | 0 |
Nervous system disorders | ||
| Dizziness | 6 (21) | 0 |
| NeuropathyGrouped term includes burning sensation, lumbosacral plexopathy, neuropathy peripheral, paresthesia, and peripheral motor neuropathy. | 4 (14) | 0 |
| Headache | 3 (11) | 0 |
Skin and subcutaneous tissue disorders | ||
| Pruritus | 4 (14) | 1 (4) |
| RashGrouped term includes dermatitis acneiform, dermatitis, rash, rash maculo-papular, urticaria, rash erythematous, rash macular, rash pruritic, rash generalized, rash papular, skin exfoliation, and skin ulcer. | 4 (14) | 1 (4) |
Changes in selected post-baseline laboratory values that were observed in patients with newly diagnosed AML are shown in Table 5.
| TIBSOVO (500 mg daily) N=28 | ||
|---|---|---|
| Parameter | All Grades n (%) | Grade ≥ 3 n (%) |
| Hemoglobin decreased | 15 (54) | 12 (43) |
| Alkaline phosphatase increased | 13 (46) | 0 |
| Potassium decreased | 12 (43) | 3 (11) |
| Sodium decreased | 11 (39) | 1 (4) |
| Uric acid increased | 8 (29) | 1 (4) |
| Aspartate aminotransferase increased | 8 (29) | 1 (4) |
| Creatinine increased | 8 (29) | 0 |
| Magnesium decreased | 7 (25) | 0 |
| Calcium decreased | 7 (25) | 1 (4) |
| Phosphate decreased | 6 (21) | 2 (7) |
| Alanine aminotransferase increased | 4 (14) | 1 (4) |
The safety profile of single-agent TIBSOVO was studied in 179 adults with relapsed or refractory AML treated with 500 mg daily
The median duration of exposure to TIBSOVO was 3.9 months (range 0.1 to 39.5 months). Sixty-five patients (36%) were exposed to TIBSOVO for at least 6 months and 16 patients (9%) were exposed for at least 1 year.
Serious adverse reactions (≥ 5%) were differentiation syndrome (10%), leukocytosis (10%), and electrocardiogram QT prolonged (7%). There was one case of progressive multifocal leukoencephalopathy (PML).
The most common adverse reactions leading to dose interruption were electrocardiogram QT prolonged (7%), differentiation syndrome (3%), leukocytosis (3%) and dyspnea (3%). Five out of 179 patients (3%) required a dose reduction due to an adverse reaction.
Adverse reactions leading to a dose reduction included electrocardiogram QT prolonged (1%), diarrhea (1%), nausea (1%), decreased hemoglobin (1%), and increased transaminases (1%).
Adverse reactions leading to permanent discontinuation included Guillain-Barré syndrome (1%), rash (1%), stomatitis (1%), and creatinine increased (1%).
The most common adverse reactions reported in the trial are shown in Table 6.
| TIBSOVO (500 mg daily) N=179 | ||
|---|---|---|
| Body System Adverse Reaction | All Grades n (%) | Grade ≥ 3 n (%) |
General disorders and administration site conditions | ||
| FatigueGrouped term includes asthenia and fatigue. | 69 (39) | 6 (3) |
| EdemaGrouped term includes peripheral edema, edema, fluid overload, fluid retention, and face edema. | 57 (32) | 2 (1) |
| Pyrexia | 41 (23) | 2 (1) |
| Chest painGrouped term includes angina pectoris, chest pain, chest discomfort, and non-cardiac chest pain | 29 (16) | 5 (3) |
Blood system and lymphatic system disorders | ||
| LeukocytosisGrouped term includes leukocytosis, hyperleukocytosis, and increased white blood cell count. | 68 (38) | 15 (8) |
| Differentiation SyndromeDifferentiation syndrome can be associated with other commonly reported events such as peripheral edema, leukocytosis, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonia, pericardial effusion, rash, fluid overload, tumor lysis syndrome, and creatinine increased. | 34 (19) | 23 (13) |
Musculoskeletal and connective tissue disorders | ||
| ArthralgiaGrouped term includes arthralgia, back pain, musculoskeletal stiffness, neck pain, and pain in extremity. | 64 (36) | 8 (4) |
| MyalgiaGrouped term includes myalgia, muscular weakness, musculoskeletal pain, musculoskeletal chest pain, musculoskeletal discomfort, and myalgia intercostal. | 33 (18) | 1 (1) |
Gastrointestinal disorders | ||
| Diarrhea | 60 (34) | 4 (2) |
| Nausea | 56 (31) | 1 (1) |
| MucositisGrouped term includes aphthous ulcer, esophageal pain, esophagitis, gingival pain, gingivitis, mouth ulceration, mucosal inflammation, oral pain, oropharyngeal pain, proctalgia, and stomatitis. | 51 (28) | 6 (3) |
| Constipation | 35 (20) | 1 (1) |
| VomitingGrouped term includes vomiting and retching. | 32 (18) | 2 (1) |
| Abdominal painGrouped term includes abdominal pain, upper abdominal pain, abdominal discomfort, and abdominal tenderness. | 29 (16) | 2 (1) |
Respiratory, thoracic, and mediastinal disorders | ||
| DyspneaGrouped term includes dyspnea, respiratory failure, hypoxia, and dyspnea exertional. | 59 (33) | 16 (9) |
| CoughGrouped term includes cough, productive cough, and upper airway cough syndrome. | 40 (22) | 1 (<1) |
| Pleural effusion | 23 (13) | 5 (3) |
Investigations | ||
| Electrocardiogram QT prolonged | 46 (26) | 18 (10) |
Skin and subcutaneous tissue disorders | ||
| RashGrouped term includes dermatitis acneiform, dermatitis, rash, rash maculo-papular, urticaria, rash erythematous, rash macular, rash pruritic, rash generalized, rash papular, skin exfoliation, and skin ulcer. | 46 (26) | 4 (2) |
Metabolism and nutrition disorders | ||
| Decreased appetite | 33 (18) | 3 (2) |
| Tumor lysis syndrome | 14 (8) | 11 (6) |
Nervous system disorders | ||
| Headache | 28 (16) | 0 |
| NeuropathyGrouped term includes ataxia, burning sensation, gait disturbance, Guillain-Barré syndrome, neuropathy peripheral, paresthesia, peripheral sensory neuropathy, peripheral motor neuropathy, and sensory disturbance. | 21 (12) | 2 (1) |
Vascular disorders | ||
| HypotensionGrouped term includes hypotension and orthostatic hypotension. | 22 (12) | 7 (4) |
Changes in selected post-baseline laboratory values that were observed in patients with relapsed or refractory AML are shown in Table 7.
| TIBSOVO (500 mg daily) N=179 | ||
|---|---|---|
| Parameter | All Grades n (%) | Grade ≥ 3 n (%) |
| Hemoglobin decreased | 108 (60) | 83 (46) |
| Sodium decreased | 69 (39) | 8 (4) |
| Magnesium decreased | 68 (38) | 0 |
| Uric acid increased | 57 (32) | 11 (6) |
| Potassium decreased | 55 (31) | 11 (6) |
| Alkaline phosphatase increased | 49 (27) | 1 (1) |
| Aspartate aminotransferase increased | 49 (27) | 1 (1) |
| Phosphate decreased | 45 (25) | 15 (8) |
| Creatinine increased | 42 (23) | 2 (1) |
| Alanine aminotransferase increased | 26 (15) | 2 (1) |
| Bilirubin increased | 28 (16) | 1 (1) |
The safety of TIBSOVO was evaluated in 19 adults with relapsed or refractory MDS treated with 500 mg daily in AG120-C-001
Serious adverse reactions in ≥ 5% included differentiation syndrome (11%), fatigue (5%), and rash (5%).
Permanent discontinuation of TIBSOVO due to an adverse reaction occurred in 5% of patients. The adverse reaction which resulted in permanent discontinuation of TIBSOVO was fatigue.
Adverse reactions leading to dosage interruption of TIBSOVO occurred in 16% of patients. Adverse reactions which required dosage interruption in ≥ 5% were differentiation syndrome, leukocytosis, and rash.
Dose reductions of TIBSOVO due to an adverse reaction occurred in 16% of patients. Adverse reactions which required a dose reduction in ≥ 5% included differentiation syndrome, fatigue, and rash.
The most common (≥ 25%) adverse reactions, including laboratory abnormalities, were creatinine increased, hemoglobin decrease, arthralgia, albumin decreased, aspartate aminotransferase increased, fatigue, diarrhea, cough, sodium decreased, mucositis, decreased appetite, myalgia, phosphate decreased, pruritus, and rash.
Table 8 summarizes the adverse reactions in AG120-C-001.
| TIBSOVO (500 mg daily) N=19 | ||
|---|---|---|
| Body System Adverse Reaction | All Grades % | Grade 3 or 4 % |
Musculoskeletal and connective tissue disorders | ||
| ArthralgiaGrouped term includes arthralgia, back pain, pain in extremity, flank pain, joint swelling, and neck pain. | 42 | 16 |
| MyalgiaGrouped term includes myalgia, muscle spasms, muscle discomfort, and musculoskeletal chest pain. | 26 | 0 |
General disorders and administration site conditions | ||
| FatigueGrouped term includes fatigue and asthenia. | 37 | 11 |
Respiratory, thoracic, and mediastinal disorders | ||
| Cough | 32 | 0 |
| DyspneaGrouped term includes dyspnea and dyspnea exertional. | 21 | 0 |
Gastrointestinal disorders | ||
| Diarrhea | 32 | 0 |
| MucositisGrouped term includes oropharyngeal pain, gingivitis, mouth ulceration, stomatitis. | 26 | 5 |
| Constipation | 16 | 0 |
| Nausea | 16 | 0 |
Skin and subcutaneous tissue disorders | ||
| Pruritus | 26 | 0 |
| RashGrouped term includes rash, catheter site erythema, and urticaria. | 26 | 0 |
Metabolism and nutrition disorders | ||
| Decreased appetite | 26 | 0 |
Blood system and lymphatic system disorders | ||
| LeukocytosisGrouped term includes leukocytosis, hyperleukocytosis, and white blood cell count increased. | 16 | 5 |
| Differentiation Syndrome | 11 | 0 |
Nervous system disorders | ||
| Headache | 16 | 0 |
Vascular disorders | ||
| Hypertension | 16 | 16 |
Investigations | ||
| Electrocardiogram QT prolonged | 11 | 0 |
Table 9 summarizes laboratory abnormalities in AG120-C-001.
| TIBSOVOLaboratory abnormality is defined as new or worsened by at least one grade from baseline, or if baseline is unknown. N=19 | ||
|---|---|---|
| Laboratory Abnormality | All Grades % | Grade 3 or 4 % |
| Creatinine increased | 95 | 5 |
| Hemoglobin decreased | 42 | 32 |
| Albumin decreased | 37 | 0 |
| Aspartate Aminotransferase increased | 37 | 5 |
| Sodium decreased | 32 | 5 |
| Phosphate decreased | 26 | 5 |
| Alanine Aminotransferase increased | 21 | 5 |
| Bilirubin increased | 21 | 0 |
| Magnesium decreased | 21 | 0 |
| Alkaline Phosphatase increased | 16 | 0 |
| Potassium increased | 16 | 0 |
The safety of TIBSOVO was studied in patients with previously treated, locally advanced or metastatic cholangiocarcinoma in Study AG120-C-005
Serious adverse reactions occurred in 34% of patients receiving TIBSOVO. Serious adverse reactions in ≥2% of patients in the TIBSOVO arm were pneumonia, ascites, hyperbilirubinemia, and jaundice cholestatic.
Fatal adverse reactions occurred in 4.9% of patients receiving TIBSOVO, including sepsis (1.6%) and pneumonia, intestinal obstruction, pulmonary embolism, and hepatic encephalopathy (each 0.8%).
TIBSOVO was permanently discontinued in 7% of patients. The most common adverse reactions leading to permanent discontinuation was acute kidney injury (1.6%).
Dose interruptions due to adverse reactions occurred in 29% of patients treated with TIBSOVO. The most common (>2%) adverse reactions leading to dose interruption were hyperbilirubinemia, alanine aminotransferase increased, aspartate aminotransferase increased, ascites, and fatigue.
Dose reductions of TIBSOVO due to an adverse reaction occurred in 4.1% of patients. Adverse reactions leading to dose reduction were electrocardiogram QT prolonged (3.3%) and neuropathy peripheral (0.8%).
The most common adverse reactions (≥15%) were fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, vomiting, anemia, and rash.
Adverse reactions and laboratory abnormalities observed in Study AG120-C-005 are shown in Tables 10 and 11.
| TIBSOVO (500 mg daily) N=123 | Placebo N=59 | |||
|---|---|---|---|---|
| Body System Adverse Reaction | All Grades n (%) | Grade ≥ 3 n (%) | All Grades n (%) | Grade ≥ 3 n (%) |
General disorders and administration site conditions | ||||
| FatigueGrouped term includes asthenia and fatigue. | 53 (43) | 4 (3) | 18 (31) | 3 (5) |
Gastrointestinal disorders | ||||
| Nausea | 51 (41) | 3 (2) | 17 (29) | 1 (2) |
| Diarrhea | 43 (35) | 0 | 10 (17) | 0 |
| Abdominal painGrouped term includes abdominal pain, abdominal pain upper, abdominal discomfort, abdominal pain lower, epigastric discomfort, abdominal tenderness, and gastrointestinal pain. | 43 (35) | 3 (2) | 13 (22) | 2 (3) |
| Ascites | 28 (23) | 11 (9) | 9 (15) | 4 (7) |
| VomitingGrouped term includes vomiting and retching. | 28 (23) | 3 (2) | 12 (20) | 0 |
Respiratory, thoracic, and mediastinal disorders | ||||
| CoughGrouped term includes cough and productive cough. | 33 (27) | 0 | 5 (9) | 0 |
Metabolism and nutrition disorders | ||||
| Decreased appetite | 30 (24) | 2 (2) | 11 (19) | 0 |
Blood and lymphatic system disorders | ||||
| Anemia | 22 (18) | 8 (7) | 3 (5) | 0 |
Skin and subcutaneous tissue disorders | ||||
| RashGrouped term includes rash, rash maculo-papular, erythema, rash macular, dermatitis exfoliative generalized, drug eruption, and drug hypersensitivity. | 19 (15) | 1 (1) | 4 (7) | 0 |
Nervous system disorders | ||||
| Headache | 16 (13) | 0 | 4 (7) | 0 |
| Neuropathy peripheralGrouped term includes neuropathy peripheral, peripheral sensory neuropathy, and paresthesia. | 13 (11) | 0 | 0 | 0 |
Investigations | ||||
| Electrocardiogram QT prolonged | 12 (10) | 2 (2) | 2 (3) | 0 |
| TIBSOVO (500 mg daily) N=123 | Placebo N=59 | |||
|---|---|---|---|---|
| Parameter | All Grades n (%) | Grade ≥ 3 n (%) | All Grades n (%) | Grade ≥ 3 n (%) |
| AST increased | 41 (34) | 5 (4) | 14 (24) | 1 (2) |
| Bilirubin increased | 36 (30) | 15 (13) | 11 (19) | 2 (3) |
| Hemoglobin decreased | 48 (40) | 8 (7) | 14 (25) | 0 |
Indications and Usage, Relapsed or Refractory MDS (TIBSOVO is indicated for the treatment of adult patients with relapsed or refractory myelodysplastic syndromes (MDS) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test [see Dosage and Administration (2.1), Clinical Pharmacology (12.1)and Clinical Studies (14.3)] . | 10/2023 |
Dosage and Administration, Patient Selection (Select patients for treatment with TIBSOVO based on the presence of IDH1 mutations [see Clinical Studies (14.1, 14.2, 14.3, 14.4)]. Information on FDA-approved tests for the detection of IDH1 mutations in AML, MDS, and cholangiocarcinoma is available at http://www.fda.gov/CompanionDiagnostics. | 10/2023 |
Dosage and Administration, Recommended Dosage (The recommended dosage of TIBSOVO is 500 mg taken orally once daily until disease progression or unacceptable toxicity [see Clinical Studies (14.1, 14.2, 14.3, 14.4)] .For patients with AML or MDS without disease progression or unacceptable toxicity, continue TIBSOVO for a minimum of 6 months to allow time for clinical response.
Newly Diagnosed AML (Combination Regimen) Start TIBSOVO administration on Cycle 1 Day 1 in combination with azacitidine 75 mg/m2subcutaneously or intravenously once daily on Days 1-7 (or Days 1-5 and 8-9) of each 28-day cycle [see Clinical Studies (14.1)] . Refer to the Prescribing Information for azacitidine for additional dosing information. | 10/2023 |
TIBSOVO is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for patients with a susceptible IDH1 mutation as detected by an FDA-approved test with:
- In combination with azacitidine or as monotherapy for the treatment of newly diagnosed AML in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy ().
1.1 Newly Diagnosed Acute Myeloid LeukemiaTIBSOVO is indicated in combination with azacitidine or as monotherapy for the treatment of newly diagnosed acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy
[see Dosage and Administration (2.1), Clinical Pharmacology (12.1)and Clinical Studies (14.1)].
- For the treatment of adult patients with relapsed or refractory AML ().
1.2 Relapsed or Refractory Acute Myeloid LeukemiaTIBSOVO is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test
[see Dosage and Administration (2.1), Clinical Pharmacology (12.1)and Clinical Studies (14.2)].
- For the treatment of adult patients with relapsed or refractory myelodysplastic syndromes ().
1.3 Relapsed or Refractory Myelodysplastic SyndromesTIBSOVO is indicated for the treatment of adult patients with relapsed or refractory myelodysplastic syndromes (MDS) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test[see Dosage and Administration (2.1), Clinical Pharmacology (12.1)and Clinical Studies (14.3)].
- For the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma who have been previously treated ().
1.4 Locally Advanced or Metastatic CholangiocarcinomaTIBSOVO is indicated for the treatment of adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma with an isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test
[see Dosage and Administration (2.1), Clinical Pharmacology (12.1), and Clinical Studies (14.4)].
500 mg orally once daily with or without food until disease progression or unacceptable toxicity (
The recommended dosage of TIBSOVO is 500 mg taken orally once daily until disease progression or unacceptable toxicity
- Administer TIBSOVO with or without food.
- Do not administer TIBSOVO with a high-fat meal[see Warnings and Precautions (5.2)and Clinical Pharmacology (12.3)].
- Do not split, crush, or chew TIBSOVO tablets.
- Administer TIBSOVO tablets orally about the same time each day.
- If a dose of TIBSOVO is vomited, do not administer a replacement dose; wait until the next scheduled dose is due.
- If a dose of TIBSOVO is missed or not taken at the usual time, administer the dose as soon as possible and at least 12 hours prior to the next scheduled dose. Return to the normal schedule the following day. Do not administer 2 doses within 12 hours.
Start TIBSOVO administration on Cycle 1 Day 1 in combination with azacitidine 75 mg/m2subcutaneously or intravenously once daily on Days 1-7 (or Days 1-5 and 8-9) of each 28-day cycle
Tablets: 250 mg as a blue oval-shaped film-coated tablet debossed "IVO" on one side and "250" on the other side.
Lactation: Advise women not to breastfeed (
There are no data on the presence of ivosidenib or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed children, advise women not to breastfeed during treatment with TIBSOVO and for 1 month after the last dose.