Ivosidenib (Tibsovo) inhibits the enzyme isocitrate dehydrogenase-1 (IDH1). It is used in the treatment of acute myeloid leukemia in adults older than 75 years of age who have comorbid conditions or in who intensive chemotherapy can not be given.
Ivosidenib Uses:
-
Acute myeloid leukemia (newly diagnosed):
- It is used in the treatment of newly diagnosed acute myeloid leukemia (AML) in adults more than 75 years of age with comorbidities that prohibits the use of intensive induction chemotherapy.
- It is used in patients with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an approved test.
-
AML (relapsed/refractory):
- It is used in management of relapsed or refractory AML in adults with a susceptible IDH-1 mutation as detected by a recommended test.
Ivosidenib (Tibsovo) Dose in Adults:
Note:
- isocitrate dehydrogenase-1 (IDH1) mutation status should be confirmed in the blood or bone marrow prior to therapy initiation.
- IDH-1 mutation may present during treatment and at relapse, therefore patients without IDH1 mutation at diagnosis should be retested at relapse.
Ivosidenib (Tibsovo) Dose in the treatment of newly diagnosed acute myeloid leukemia:
- It is given 500 mg once a day. It should be continued for a minimum of 6 months and then until disease progression or unacceptable toxicity occurs.
Ivosidenib (Tibsovo) Dose in the treatment of relapsed/ refractory acute myeloid leukemia:
- It is given Orally 500 mg once a day and is continued for a minimum of 6 months and then until disease progression or unacceptable toxicity occurs.
-
Dosage adjustment for concomitant strong CYP3A4 inhibitors:
- Consider alternate therapies, if concomitant use of a strong CYP3A4 inhibitor cannot be avoided. Reduce the ivosidenib dose to 250 mg once a day.
- After the strong CYP3A4 inhibitor has been stopped, increase the ivosidenib dose (after at least 5 half-lives of the CYP3A4 inhibitor) to the recommended dose of 500 mg once a day.
-
Missed dose:
- If a dose is not administered at the usual time, give the dose as soon as possible and at least 12 hours prior to the next scheduled dose and return to the normal dosing schedule the following day.
- Do not administer 2 doses within 12 hours. If a dose is vomited, don't give the replacement dose and wait until the next scheduled dose is due.
Ivosidenib (Tibsovo) use in children:
Not indicated.
Ivosidenib Pregnancy Category: N
- In animal reproduction studies, adverse events were noted.
- Studies have shown that fetal harm is possible.
Use of Ivosidenib while breastfeeding
- It is unknown if breast milk secretes it.
- Due to the possibility of serious adverse reactions in breastfed infants, it is not recommended that you breastfeed for at least one month following the last dose.
Ivosidenib (Tibsovo) Dose in Kidney Disease:
Note: Renal function may be estimated using the MDRD formula.
- eGFR ≥30 mL/minute/1.73 m²:
- No dose adjustment necessary.
- eGFR <30 mL/minute/1.73 m²:
- There are no dose adjustments necessary.
- Risks versus potential benefits in patients with preexisting severe renal impairment should be assessed.
- ESRD requiring dialysis:
- The dose adjustments are not studied in ESRD.
- Risks versus potential benefits in patients with preexisting ESRD requiring dialysis should be clinically assessed.
Ivosidenib (Tibsovo) Dose in Liver disease:
- Mild or moderate impairment (Child-Pugh class A or B):
- No dose adjustment is necessary.
- Severe impairment (Child-Pugh class C):
- There are no dosage adjustments provided in the manufacturer's labeling (which has not been studied)given by the manufacturer.
- Risks versus potential benefits in patients with preexisting severe hepatic impairment should be assessed.
Common Side Effects of Ivosidenib (Tibsovo):
-
Cardiovascular:
- Edema
- Prolonged QT Interval On ECG
- Chest Pain
- Hypotension
-
Central Nervous System:
- Fatigue
- Dizziness
- Headache
- Neuropathy
-
Dermatologic:
- Skin Rash
- Pruritis
-
Endocrine & Metabolic:
- Decreased Serum Potassium
- Decreased Serum Sodium
- Decreased Serum Magnesium
- Increased Uric Acid
- Decreased Serum Calcium
- Decreased Serum Phosphate
- Weight Loss
-
Gastrointestinal:
- Diarrhea
- Decreased Appetite
- Nausea
- Abdominal Pain
- Stomatitis
- Constipation
- Vomiting
- Dyspepsia
-
Hematologic & Oncologic:
- Decreased Hemoglobin
- Leukocytosis
- Differentiation Syndrome
-
Hepatic:
- Increased Serum Alkaline Phosphatase
- Increased Serum Aspartate Aminotransferase
- Increased Serum Bilirubin
- Increased Serum Alanine Aminotransferase
-
Neuromuscular & Skeletal:
- Arthralgia
- Myalgia
-
Renal:
- Increased Serum Creatinine
-
Respiratory:
- Dyspnea
- Cough
- Pleural Effusion
-
Miscellaneous:
- Fever
Less Common Side Effects Of Ivosidenib (Tibsovo):
-
Hematologic & Oncologic:
- Tumor Lysis Syndrome
-
Cardiovascular:
- Facial Edema
- Orthostatic Hypotension
- Peripheral Edema
-
Central Nervous System:
- Ataxia
- Reversible Posterior Leukoencephalopathy Syndrome
-
Dermatologic:
- Acneiform Eruption
- Dermal Ulcer
- Exfoliation Of Skin
- Urticaria
-
Endocrine & Metabolic:
- Hypovolemia
-
Gastrointestinal:
- Esophageal Pain
- Rectal Pain
-
Neuromuscular & Skeletal:
- Asthenia
-
Respiratory:
- Oropharyngeal Pain
Contraindications to Ivosidenib (Tibsovo):
- Manufacturers do not have to approve any contraindications.
Warnings and precautions
-
Differentiation syndrome: [US Boxed Warning]
- Some patients who were treated with ivosidenib experienced symptoms of differentiation syndrome, which can be fatal if it is not treated.
- Dyspnea and fever are some of the symptoms. Hypotension, multi-organ dysfunction, and renal dysfunction may also be present.
- If differentiation syndrome is clinically suspected. You should start corticosteroids and continue hemodynamic monitoring until the symptoms resolve.
- Differentiation syndrome refers to rapid proliferation and differentiation (or myeloid cell) of myeloid cells. It can be fatal.
- The symptoms of differentiation syndrome include a noninfectious increase in TLC, pulmonary embolism, pneumonitis and rash.
- Most patients with differentiation syndrome are cured after receiving corticosteroid or ivosidenib interruption.
- It was present from one day to twelve weeks after the initiation of ivosidenib therapy. It can be concomitant or not with leukocytosis.
- If you suspect differentiation syndrome, dexamethasone 10mg IV once every 12 hours or an equivalent dose should be administered. Hemodynamic monitoring should also be initiated and maintained until improvement.
- Concomitant non-infectious leukocytosis or hydroxyurea treatment should be started as soon as clinically indicated.
- After the resolution of symptoms, you should reduce your intake of corticosteroids or hydroxyurea.
- For a minimum period of three days, corticosteroids must be taken. If hydroxyurea and corticosteroid treatment are stopped too soon, symptoms of differentiation syndrome may recur.
- Stop ivosidenib therapy if severe symptoms continue for more than two days after the initiation of corticosteroids.
-
Gastrointestinal toxicities:
- There have been reports of mild diarrhea, nausea, vomiting, constipation and abdominal pain.
-
Guillain Barre syndrome:
- Guillain Barre syndrome has been reported in a few patients who were treated with ivosidenib.
- You should monitor for any new symptoms or signs of motor or sensory neuropathy (eg bilateral or unilateral weakness, sensory alterations or paresthesias or difficulty breathing).
- If GBS is confirmed, discontinue treatment.
-
Extension of QT
- QT (QTc), prolongation, and ventricular arrhythmias may occur in patients treated with ivosidenib. Some patients had a QTc interval of 500 msec or more than 60 msec.
- Ventricular fibrillation is a rare condition.
- Patients with a baseline QTc greater than 450 msec, or with a history or significant cardiovascular disease, were excluded from the clinical trial.
- The risk of QTc interval prolongation may be increased by concurrent use of ivosidenib and antiarrhythmics, fluoroquinolones or triazole antifungals.
- Monitor electrolytes and ECG. Patients with congenital long QTc syndrome or heart failure, patients taking electrolyte abnormalities, and patients who are taking medication known to prolong the QTc interval may need frequent, strict monitoring.
- If the QTc rises to >480 msec, but 500msec, Ivosidenib should not be taken.
- Stop treatment if the QTc rises to greater than 500 msec. Then, reduce the dose of ivosidenib.
- Patients who experience QTc prolongation and signs or symptoms of life-threatening arrhythmia should be forced to stop taking ivosidenib.
-
Tumor lysis syndrome
- Acute myeloid leukemia therapy may lead to tumor lysis syndrome. Maintain adequate fluid intake and monitor blood chemistry and renal function as needed.
Ivosidenib: Drug Interaction
|
Risk Factor C (Monitor therapy) |
|
|
Bosentan |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
CYP3A4 Inducers (Moderate) |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
CYP3A4 Substrates (High risk with Inducers) |
Ivosidenib may decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Deferasirox |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Erdafitinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Erdafitinib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Fingolimod |
May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias (including TdP) with a continuous overnight ECG when fingolimod is combined with QT prolonging drugs. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Fosaprepitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Larotrectinib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Palbociclib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
QT-prolonging Agents (Indeterminate Risk - Avoid) |
May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
QT-prolonging Agents (Indeterminate Risk - Caution) |
May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Sarilumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Siltuximab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Simeprevir |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Tocilizumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Risk Factor D (Consider therapy modification) |
|
|
Amiodarone |
QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Amiodarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Amisulpride |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Amisulpride. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. |
|
Azithromycin (Systemic) |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Azithromycin (Systemic). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. |
|
Chloroquine |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Clofazimine |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clofazimine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
CloZAPine |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of CloZAPine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. |
|
CYP3A4 Inhibitors (Moderate) |
May increase the serum concentration of Ivosidenib. Management: Avoid use of moderate CYP3A4 inhibitors with ivosidenib whenever possible. If combined, monitor for increased ivosidenib toxicities. Drugs listed as exceptions are discussed in further detail in separate drug interaction monographs. Exceptions: Crizotinib; Dronedarone; Erythromycin (Systemic); Fluconazole; Nilotinib; Ribociclib. |
|
CYP3A4 Inhibitors (Strong) |
May increase the serum concentration of Ivosidenib. Management: Avoid use of a strong CYP3A4 inhibitor with ivosidenib whenever possible. When combined use is required, reduce the ivosidenib dose to 250 mg once daily. Drugs listed as exceptions are discussed in further detail in separate drug interaction monographs. Exceptions: Clarithromycin; Saquinavir; Voriconazole. |
|
Dabrafenib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). |
|
Dasatinib |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Dasatinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. |
|
Doxepin-Containing Products |
QT-prolonging Agents (Highest Risk) may enhance the QTcprolonging effect of Doxepin-Containing Products. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. |
|
Dronedarone |
Ivosidenib may enhance the QTc-prolonging effect of Dronedarone. Dronedarone may increase the serum concentration of Ivosidenib. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Droperidol |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Droperidol. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. |
|
Encorafenib |
May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. |
|
Escitalopram |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Escitalopram. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. |
|
Estrogen Derivatives (Contraceptive) |
Ivosidenib may decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Consider alternative methods of contraception (ie, non-hormonal) in patients receiving ivosidenib. |
|
Flecainide |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flecainide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. |
|
Gadobenate Dimeglumine |
QT-prolonging Agents (Highest Risk) may enhance the QTcprolonging effect of Gadobenate Dimeglumine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Gemifloxacin |
QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Gemifloxacin. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Gilteritinib |
May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. If use is necessary, monitor for QTc interval prolongation and arrhythmias. |
|
Halofantrine |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Halofantrine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Haloperidol |
QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Inotuzumab Ozogamicin |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Inotuzumab Ozogamicin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Levofloxacin-Containing Products (Systemic) |
QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Levofloxacin-Containing Products (Systemic). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Lofexidine |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Lofexidine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Lorlatinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. |
|
Methadone |
QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Methadone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Midostaurin |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Midostaurin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
MiFEPRIStone |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. |
|
OLANZapine |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of OLANZapine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. |
|
Ondansetron |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Osimertinib |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Osimertinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. |
|
Pentamidine (Systemic) |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Pilsicainide |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pilsicainide. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Progestins (Contraceptive) |
Ivosidenib may decrease the serum concentration of Progestins (Contraceptive). Management: Consider alternative methods of contraception (ie, non-hormonal) in patients receiving ivosidenib. |
|
Propafenone |
May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
QT-prolonging Class IA Antiarrhythmics (Highest Risk) |
QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
QT-prolonging Class III Antiarrhythmics (Highest Risk) |
QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Class III Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Dronedarone. |
|
QT-prolonging Miscellaneous Agents (Highest Risk) |
QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) |
Ivosidenib may enhance the QTcprolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Ivosidenib. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Nilotinib; Ribociclib. |
|
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) |
Ivosidenib may enhance the QTcprolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Ivosidenib. Management: Avoid using strong CYP3A4 inhibitors together with ivosidenib if possible. If the combination must be used, reduce the ivosidenib dose to 250 mg once daily. Exceptions: Clarithromycin. |
|
RisperiDONE |
QT-prolonging Agents (Highest Risk) may enhance the CNS depressant effect of RisperiDONE. QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of RisperiDONE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Sodium Stibogluconate |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sodium Stibogluconate. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Stiripentol |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. |
|
Vemurafenib |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Vemurafenib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. |
|
Ziprasidone |
May enhance the QTc-prolonging effect of Ivosidenib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. |
|
Risk Factor X (Avoid combination) |
|
|
Citalopram |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Citalopram. |
|
Clarithromycin |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clarithromycin. |
|
Conivaptan |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
CYP3A4 Inducers (Strong) |
May decrease the serum concentration of Ivosidenib. |
|
Domperidone |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Domperidone. |
|
Entrectinib |
May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). |
|
Fexinidazole [INT] |
May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). |
|
Flupentixol |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flupentixol. |
|
Fusidic Acid (Systemic) |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Idelalisib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Itraconazole |
May increase the serum concentration of Ivosidenib. Ivosidenib may decrease the serum concentration of Itraconazole. |
|
Ketoconazole (Systemic) |
May increase the serum concentration of Ivosidenib. Ivosidenib may decrease the serum concentration of Ketoconazole (Systemic). |
|
Lefamulin |
May enhance the QTc-prolonging effect of QT-prolonging CYP3A4 Substrates. Management: Do not use lefamulin tablets with QT-prolonging CYP3A4 substrates. Lefamulin prescribing information lists this combination as contraindicated. |
|
Moxifloxacin (Systemic) |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Moxifloxacin (Systemic). |
|
Nilotinib |
May enhance the QTc-prolonging effect of Ivosidenib. Nilotinib may increase the serum concentration of Ivosidenib. |
|
Pimozide |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pimozide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. |
|
Piperaquine |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Piperaquine. |
|
Posaconazole |
May increase the serum concentration of QT-prolonging CYP3A4 Substrates. Such increases may lead to a greater risk for proarrhythmic effects and other similar toxicities. |
|
Probucol |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Probucol. |
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QT-prolonging Kinase Inhibitors (Highest Risk) |
May enhance the QTc-prolonging effect of other QT-prolonging Kinase Inhibitors (Highest Risk). |
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QUEtiapine |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QUEtiapine. |
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Ribociclib |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ribociclib. |
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Sparfloxacin |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sparfloxacin. |
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Thioridazine |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Thioridazine. |
Monitoring parameters:
- IDH1 mutation status in the blood or bone marrow (prior therapy initiation).
- Monitoring blood counts and serum chemicals at baseline should be done at least once a week for the first month.
- Then, every other week thereafter for the second month. Finally, monthly for the duration.
- For the first month, creatine phosphokinase is taken weekly.
- Monitor ECG at least once a week for the first three weeks, and then every other month for the remainder of therapy.
- If the QTc interval is prolonged, more frequent monitoring may be necessary.
- Pay attention to the symptoms and signs of differentiation syndrome.
- If you suspect differentiation syndrome, monitor your hemodynamic status.
- You should monitor for symptoms such as tumor lysis syndrome or the onset of new symptoms or signs of motor or sensory neuropathy.
- You must ensure compliance.
How to administer Ivosidenib (Tibsovo)?
Oral: Administer at the same time each day, either with or without food (do not administer with a high-fat meal). Do not split, crush, or chew tablets.
Mechanism of action of Ivosidenib (Tibsovo):
- Ivosidenib, an oral small-molecule inhibitor for the mutant isocitrate hydrogenase 1 enzyme (IDH1) is available as an oral treatment.
- Suspected IDH1 mutations may lead to higher levels of 2-hydroxyglutarate (2 HG) in leukemia cells.
- 2-HG inhibits alpha ketoglutarate-dependent enzymes and results in impaired hematopoietic development. Ivosidenib reduced intracellular 2-HG levels, decreased blast counts and induced differentiation in AML IDH1-mutated blood samples.
- This resulted in an increase of mature myeloid cell percentages.
- IDH1 mutations are found in between 6% and 10% of patients with acute myeloidleukemia.
Onset:
- Maximal inhibition of 2-hydroxyglutarate: By day 14.
- The median time to response: 1.9 months; range: 0.8 to 4.7 months.
- The median time to complete remission: 2.8 months; range: 0.9 to 8.3 months.
Duration:
- The median duration of response: 6.5 months
- The median duration of complete remission: 9.3 months.
Absorption:
- Rapid.
Protein binding:
- 92% to 96%
Metabolism:
- It has hepatic metabolism, and primarily metabolized via CYP3A4 with minor contributions via the N-dealkylation and hydrolytic pathways.
Bioavailability:
- A high-fat meal (~900 to 1,000 calories, 500 to 600 fat calories, 250 carbohydrate calories, and 150 protein calories) increased ivosidenib C by 98% (90% CI: 79%, 119%) and AUC by ~25%.
Half-life elimination:
- 93 hours
Time to peak:
- approximately by 3 hours
Excretion:
- Feces: 77% (67% as unchanged drug).
- Via urine: 17% (10% as unchanged drug)
International Brand Names of Ivosidenib:
- Tibsovo
Ivosidenib Brand Names in Pakistan:
No brands available in Pakistan.
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