pixel

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)
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
Fatiguea 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 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
Investigations
Electrocardiogram QT prolonged 19 (15) 1 (1) 4 (7) 0

Dose modifications1

Dose 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 prescribeda
  • There were few occurrences of missed dose modifications, indicating excellent overall compliance

aRelative 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 is 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 (e.g., 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.

Learn about TIBSOVO dosing

References: 1. Tibsovo. Package insert. Servier Pharmaceuticals LLC; 2021. 2. Data on file. Servier Pharmaceuticals, LLC.

 
pixel pixel
cca-efficacy-modal cca-efficacy-modal

CCA, cholangiocarcinoma; ECOG PS, Eastern Cooperative Oncology Group Performance Status; IDH1, isocitrate dehydrogenase-1; mIDH1, mutated IDH1; NGS, next-generation sequencing; QD, once a day; RECIST, Response Evaluation Criteria in Solid Tumors.

References: 1. Tibsovo. Package insert. Servier Pharmaceuticals LLC; 2021. 2. Data on file. Servier Pharmaceuticals, LLC. 3. Zhu AX, Macarulla T, Javle MM, et al. JAMA Oncol. 2021;7(11):1669-1677.

cca-efficacy-modal cca-efficacy-modal

CCA, cholangiocarcinoma; ECOG PS, Eastern Cooperative Oncology Group Performance Status; IDH1, isocitrate dehydrogenase-1; mIDH1, mutated IDH1; NGS, next-generation sequencing; QD, once a day; RECIST, Response Evaluation Criteria in Solid Tumors.

References: 1. Tibsovo. Package insert. Servier Pharmaceuticals LLC; 2021. 2. Data on file. Servier Pharmaceuticals, LLC. 3. Zhu AX, Macarulla T, Javle MM, et al. JAMA Oncol. 2021;7(11):1669-1677.

 

INDICATION

TIBSOVO 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.

Indications & Important Safety Information

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

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 (e.g., 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.