TIBSOVO (ivosidenib tablets) safety profile
The most common adverse reactions (≥15%) in patients with advanced mIDH1 cholangiocarcinoma (CCA) were fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, vomiting, anemia, and rash.1
Adverse reactions reported in ≥10% of patients receiving TIBSOVO1
|TIBSOVO (500 mg DAILY)
|General disorders and administration site conditions|
|Fatiguea||53 (43)||4 (3)||18 (31)||3 (5)|
|Nausea||51 (41)||3 (2)||17 (29)||1 (2)|
|Diarrhea||43 (35)||0||10 (17)||0|
|Abdominal painb||43 (35)||3 (2)||13 (22)||2 (3)|
|Ascites||28 (23)||11 (9)||9 (15)||4 (7)|
|Vomitingc||28 (23)||3 (2)||12 (20)||0|
|Respiratory, thoracic, and mediastinal disorders|
|Coughd||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|
|Rashe||19 (15)||1 (1)||4 (7)||0|
|Nervous system disorders|
|Headache||16 (13)||0||4 (7)||0|
|Neuropathy peripheralf||13 (11)||0||0||0|
|Electrocardiogram QT prolonged||19 (15)||1 (1)||4 (7)||0|
a Grouped term includes asthenia and fatigue.
b Grouped term includes abdominal pain, abdominal pain upper, abdominal discomfort, abdominal pain lower, epigastric discomfort, abdominal tenderness, and gastrointestinal pain.
c Grouped term includes vomiting and retching.
d Grouped term includes cough and productive cough.
e Grouped term includes rash, rash maculo-papular, erythema, rash macular, dermatitis exfoliative generalized, drug eruption, and drug hypersensitivity.
f Grouped term includes neuropathy peripheral, peripheral sensory neuropathy, and paraesthesia.
Dose modifications1Dose reductions, interruptions, and discontinuations due to adverse events1
- 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%)
- TIBSOVO was permanently discontinued in 7% of patients
- The most common adverse reaction leading to permanent discontinuation was acute kidney injury (1.6%)
In the ClarIDHy trial, median relative dose intensity was 100% across all patients2
- Relative dose intensity is the amount of medication taken over a specific period of time in relation to what was prescribedg
- There were few occurrences of missed dose modifications, indicating excellent overall compliance
gRelative Dose Intensity (%) was calculated as: [Actual Dose Intensity] / [Planned Dose Intensity]. Planned Dose Intensity (mg/day) is the total daily dose assigned at the study entry, which was 500 mg QD.
Warnings and precautions1
QTc Interval Prolongation: Patients treated with TIBSOVO can develop QT (QTc) prolongation and ventricular arrhythmias. Concomitant use of TIBSOVO with drugs known to prolong the QTc interval (eg, anti-arrhythmic medicines, fluoroquinolones, triazole anti-fungals, 5-HT3 receptor antagonists) and CYP3A4 inhibitors may increase the risk of QTc interval prolongation. Conduct monitoring of electrocardiograms (ECGs) and electrolytes. In patients with congenital long QTc syndrome, congestive heart failure, or electrolyte abnormalities, or in those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary. Interrupt TIBSOVO if QTc increases to greater than 480 msec and less than 500 msec. Interrupt and reduce TIBSOVO if QTc increases to greater than 500 msec. Permanently discontinue TIBSOVO in patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia.
Guillain-Barré Syndrome: Guillain-Barré syndrome can develop in patients treated with TIBSOVO. Monitor patients taking TIBSOVO for onset of new signs or symptoms of motor and/or sensory neuropathy such as unilateral or bilateral weakness, sensory alterations, paresthesias, or difficulty breathing. Permanently discontinue TIBSOVO in patients who are diagnosed with Guillain-Barré syndrome.