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Tibsovo is a brand name for Ivosidenib. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Tibsovo in combination with azacitidine is indicated for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) with an isocitrate dehydrogenase-1 (IDH1) R132 mutation who are not eligible to receive standard induction chemotherapy (see section 5.1). Tibsovo monotherapy is indicated for the…
Verbatim from this product's EMA label. Tap a section to expand.
Treatment should be initiated under the supervision of physicians experienced in the use of anti-cancer medicinal products. Before taking Tibsovo, patients must have confirmation of an IDH1 R132 mutation using an appropriate diagnostic test.
Posology Acute myeloid leukaemia The recommended dose is 500 mg ivosidenib (2 x 250 mg tablets) taken orally once daily on days 1- 28 of each cycle. Ivosidenib should be started on cycle 1 day 1 in combination with azacitidine at 75 mg/m2 of body surface area, intravenously or subcutaneously, once daily on days 1-7 of each 28-day cycle.
The first 3 treatment cycle of azacitidine should be given at 100% of the dose. It is recommended that patients be treated for a minimum of 6 cycles. For the posology and method of administration of azacitidine, please refer to the full product information for azacitidine.
Treatment should be continued until disease progression or until treatment is no longer tolerated by the patient. Cholangiocarcinoma The recommended dose is 500 mg ivosidenib (2 x 250 mg tablets) taken orally once daily. Treatment should be continued until disease progression or until treatment is no longer tolerated by the patient.
Missed or delayed doses If a dose is missed or not taken at the usual time, the tablets should be taken as soon as possible within 12 hours after the missed dose. Two doses should not be taken within 12 hours. The tablets should be taken as usual the following day.
If a dose is vomited, replacement tablets should not be taken. The tablets should be taken as usual the following day. Precautions to be taken prior to administration and monitoring An electrocardiogram (ECG) must be performed prior to treatment initiation.
Heart rate corrected QT (QTc) should be less than 450 msec prior to treatment initiation and, in the presence of an abnormal QT, practitioners should thoroughly reassess the benefit/risk of initiating ivosidenib. In case QTc interval prolongation is between 480 msec and 500 msec, initiation of treatment with ivosidenib should remain exceptional and be accompanied by close monitoring.
An ECG must be performed prior to treatment initiation, at least weekly during the first 3 weeks of therapy and then monthly thereafter if the QTc interval remains ≤ 480 msec. 4). In case of suggestive symptomatology, an ECG should be performed as clinically indicated.
Newly diagnosed acute myeloid leukaemia in combination with azacitidine Summary of the safety profile The most common adverse reactions were vomiting (40%), neutropenia (31%), thrombocytopenia (28%), electrocardiogram QT prolonged (21%), insomnia (19%).
11 The most common serious adverse reactions were differentiation syndrome (8%) and thrombocytopenia (3%). In patients treated with ivosidenib in combination with azacitidine, the frequency of discontinuation of ivosidenib due to adverse reactions was 6%.
Adverse reactions leading to discontinuation were electrocardiogram QT prolonged (1%), insomnia (1%), neutropenia (1%) and thrombocytopenia (1%). The frequency of dose interruption of ivosidenib due to adverse reactions was 35%. The most common adverse reactions leading to dose interruption were neutropenia (24%), electrocardiogram QT prolonged (7%), thrombocytopenia (7%), leukopenia (4%) and differentiation syndrome (3%).
The frequency of dose reduction of ivosidenib due to adverse reactions was 19%. Adverse reactions leading to dose reduction were electrocardiogram QT prolonged (10%), neutropenia (8%) and thrombocytopenia (1%). Tabulated list of adverse reactions The frequencies of adverse reactions are based on Study AG120-C-009 which included 72 patients with newly diagnosed AML randomised to and treated with ivosidenib (500 mg daily) in combination with azacitidine.
0 months). The adverse reaction frequencies are based on all-cause adverse event frequencies, where a proportion of the events for an adverse reaction may have other causes than ivosidenib, such as the disease, other medicinal products or unrelated causes.
Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
8). 2). Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells. Symptoms include: non-infectious leukocytosis, peripheral oedema, pyrexia, dyspnoea, pleural effusion, hypotension, hypoxia, pulmonary oedema, pneumonitis, pericardial effusion, rash, fluid overload, tumour lysis syndrome and creatinine increased.
Patients must be informed of signs and symptoms of differentiation syndrome, be advised to contact their physician immediately if these occur and the need to carry the Patient Alert Card with them at all times. If differentiation syndrome is suspected, administer systemic corticosteroids and initiate hemodynamic monitoring until symptom resolution and for a minimum of 3 days.
2). 7 Taper corticosteroids and hydroxycarbamide only after resolution of symptoms. Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid and/or hydroxycarbamide treatment. Interrupt treatment with Tibsovo if severe signs/symptoms persist for more than 48 hours after the initiation of systemic corticosteroids and resume treatment at 500 mg ivosidenib once daily when the signs/symptoms are moderate or lower and upon improvement in the patient’s clinical condition.
8). 2). 2). In case of suggestive symptomatology, an ECG should be performed as clinically indicated. In case of severe vomiting and/or diarrhoea, an assessment of serum electrolytes abnormalities, especially hypokalaemia and magnesium, must be performed.
Patients should be informed of the risk of QT prolongation, its signs and symptoms (palpitation, dizziness, syncope or even cardiac arrest) and be advised to contact their physician immediately if these occur. Concomitant administration of medicinal products known to prolong the QTc interval, or moderate or strong CYP3A4 inhibitors may increase the risk of QTc interval prolongation and should be avoided whenever possible during treatment with Tibsovo.
1. 5). Congenital long QT syndrome. Familial history of sudden death or polymorphic ventricular arrhythmia. 4).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Concomitant administration of medicinal products known to prolong the QTc interval, or moderate or strong CYP3A4 inhibitors may increase the risk of QTc interval prolongation and should be avoided whenever possible during treatment with Tibsovo.
Patients should be treated with caution and closely monitored for QTc interval prolongation if use of a suitable alternative is not possible. 8). Complete blood count and blood chemistries should be assessed prior to the initiation of Tibsovo, at least once weekly for the first month of treatment, once every other week for the second month, and at each medical visit for the duration of therapy as clinically indicated.
Dose modification for concomitant administration of moderate or strong CYP3A4 inhibitors If use of moderate or strong CYP3A4 inhibitors cannot be avoided, the recommended dose of ivosidenib should be reduced to 250 mg (1 x 250 mg tablet) once daily.
5). 8) • If differentiation syndrome is suspected, administer systemic corticosteroids for a minimum of 3 days and taper only after symptom resolution. Premature discontinuation may result in symptom recurrence. • Initiate haemodynamic monitoring until symptom resolution and for a minimum of 3 days.
• Interrupt Tibsovo if severe signs/symptoms persist for more than 48 hours after initiation of systemic corticosteroids. • Resume treatment at 500 mg ivosidenib once daily when signs/symptoms are moderate or lower and upon improvement in clinical condition.
8) • Initiate treatment with hydroxycarbamide according to institutional standards of care and leukapheresis as clinically indicated. • Taper hydroxycarbamide only after leukocytosis improves or resolves. Premature discontinuation may result in recurrence.
• Interrupt Tibsovo if leukocytosis has not improved after initiation of hydroxycarbamide. • Resume treatment at 500 mg ivosidenib once daily when leukocytosis has resolved. 8) • Monitor and supplement electrolyte levels as clinically indicated.
5). • Interrupt Tibsovo until QTc interval returns to ≤ 480 msec. • Resume treatment at 500 mg ivosidenib once daily after the QTc interval returns to ≤ 480 msec. • Monitor ECGs at least weekly for 3 weeks and as clinically indicated following return of QTc interval to ≤ 480 msec.
8) • Monitor and supplement electrolyte levels as clinically indicated. 5). • Interrupt Tibsovo and monitor ECG every 24 h until QTc interval returns to within 30 […]
Table 2 - Adverse drug reactions reported in patients with newly diagnosed AML treated with ivosidenib in combination with azacitidine in clinical study AG120-C-009 (N=72) System organ class Frequency Adverse reactions Blood and lymphatic system disorders Very common Differentiation syndrome, Leukocytosis, Thrombocytopenia, Neutropenia Common Leukopenia Psychiatric disorders Very common Insomnia Nervous system disorders Very common Headache, Dizziness Common Neuropathy peripheral Gastrointestinal disorders Very common Vomiting1 Common Oropharyngeal pain Musculoskeletal and connective tissue disorders Very common Pain in extremity, Arthralgia, Back pain Investigations Very common Electrocardiogram QT prolonged 1 Grouped term includes vomiting and retching.
Previously treated, locally advanced or metastatic cholangiocarcinoma Summary of the safety profile The most common adverse reactions were fatigue (43%), nausea (42%), abdominal pain (35%), diarrhoea (35%), decreased appetite (24%), ascites (23%), vomiting (23%), anaemia (19%) and rash (15%).
The most common serious adverse reactions were ascites (2%), hyperbilirubinemia (2%), and jaundice cholestatic (2%). 12 In patients treated with ivosidenib, the frequency of treatment discontinuation due to adverse reactions was 2%.
Adverse reactions leading to discontinuation were ascites (1%) and hyperbilirubinemia (1%). The frequency of dose interruption of ivosidenib due to adverse reactions was 16%. The most common adverse reactions leading to dose interruption were hyperbilirubinemia (3%), alanine aminotransferase increased (3%), aspartate aminotransferase increased (3%), ascites (2%) and fatigue (2%).
The frequency of dose reduction of ivosidenib due to adverse reactions was 4%. Adverse reactions leading to dose reduction were electrocardiogram QT prolonged (3%) and neuropathy peripheral (1%). Tabulated list of adverse reactions The frequencies of adverse reactions are based on Study AG120-C-005 which included 123 patients with previously treated, locally advanced or metastatic cholangiocarcinoma, randomised to and treated with 500 mg ivosidenib once daily.
2) months). The adverse reaction frequencies are based on all-cause adverse event frequencies, where a proportion of the events for an adverse reaction may have other causes than ivosidenib, such as the disease, other medicinal products or unrelated causes.
Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
Table 3 - Adverse drug reactions reported in patients with locally advanced or metastatic cholangiocarcinoma treated with ivosidenib in clinical study AG120-C-005 (N=123) System organ class Frequency Adverse reactions Blood and lymphatic system disorders Very common Anaemia Metabolism and nutrition disorders Very common Decreased appetite Nervous system disorders Very common Neuropathy peripheral, Headache Gastrointestinal disorders Very common Ascites, Diarrhoea, Vomiting, Nausea, Abdominal pain Hepatobiliary disorders Common Jaundice cholestatic, Hyperbilirubinemia Skin and subcutaneous tissue disorders Very common Rash1 General disorders and administration site conditions Very common Fatigue Common Fall Investigations Very common Aspartate aminotransferase increased, Blood bilirubin increased Common Electrocardiogram QT prolonged, Alanine aminotransferase increased, White blood cell count decreased, Platelet count decreased 1 Grouped term includes rash, rash maculo-papular, erythema, rash macular, dermatitis exfoliative generalized, drug eruption, and drug hypersensitivity.
Description of selected adverse reactions Differentiation syndrome in patients with acute myeloid leukaemia […]
Patients should be treated with caution and closely monitored for QTc interval prolongation if use of a suitable alternative is not possible. ECG should be performed prior to co-administration, weekly monitoring for at least 3 weeks and then as clinically indicated.
5). If administration of furosemide (an OAT3 substrate) is clinically indicated to manage signs/symptoms of differentiation syndrome, patients should be closely monitored for electrolyte imbalances and QTc interval prolongation. Patients with congestive heart failure or electrolyte abnormalities should be monitored closely, with periodic monitoring of ECGs and electrolytes, during treatment with ivosidenib.
2). Ivosidenib should be used with caution in patients who have either albumin levels below the normal range or are underweight. 73 m2). 2). Hepatic impairment The safety and efficacy of ivosidenib have not been established in patients with moderate and severe hepatic impairment (Child-Pugh classes B and C).
2). 8). 8 CYP3A4 substrates Ivosidenib induces CYP3A4 and it may, therefore, decrease systemic exposure to CYP3A4 substrates. 5). 6). Women of childbearing potential and males with female partners of childbearing potential should use effective contraception during treatment with Tibsovo and for at least 1 month after the last dose.
6). Lactose intolerance Tibsovo contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should avoid this medicinal product. Sodium content This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.