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Dear Readers! I started this blog when my daughter was in the NICU. She had ventriculitis. Her CSF report grew E.coli. But, she was injected Teicoplanin directly into her brain. The doctors made two errors here:

Teicoplanin is for gram-positive bacteria only. It does not treat E.coli.
Teicoplanin is not for intraventricular use. The manufacturer strongly discourage injecting Teicoplanin into the brain.

My daughter bled into the brain. She lived for another two years and ultimately died.

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Ivosidenib (Tibsovo) - Uses, Dose, Side effects, MOA

Ivosidenib is a targeted therapy drug used to treat certain types of cancer. Specifically, it is a small molecule inhibitor of the mutated isocitrate dehydrogenase-1 (IDH1) enzyme. The mutation in IDH1 is found in some types of cancer and leads to an abnormal production of an oncometabolite which can promote the growth and survival of cancer cells.

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:

Before starting the treatment, make sure to check if the patient has the IDH1 mutation in their blood or bone marrow.
If a patient didn't have this mutation when first diagnosed, they should be checked again if the cancer comes back

Ivosidenib (Tibsovo) Dose in the treatment of newly diagnosed acute myeloid leukemia:

For treating newly diagnosed Acute myeloid leukemia, take Ivosidenib by mouth at a dose of 500 mg once every day.
This treatment should be continued for at least 6 months, or longer until the disease gets worse or if there are serious side effects.

Ivosidenib (Tibsovo) Dose in the treatment of relapsed/ refractory acute myeloid leukemia:

For Acute myeloid leukemia (when it comes back or doesn't respond to treatment):

Take Ivosidenib by mouth at 500 mg once every day.
Keep this up for at least 6 months. Continue until the disease gets worse or if there are serious side effects.

If taking strong CYP3A4 inhibitor drugs at the same time:

Try to use other treatments if possible.
If you must use them together, take a lower dose of Ivosidenib at 250 mg once daily.
Once you stop the CYP3A4 inhibitor drug, wait a bit (at least the time it takes for 5 half-lives of the inhibitor), then go back to the usual 500 mg dose of Ivosidenib.

If you forget or miss a dose:

Take it as soon as you remember, but make sure it's at least 12 hours before your next dose.
Go back to your regular schedule the next day.
Don't take 2 doses within 12 hours.
If you throw up a dose, don't take an extra one. Wait until your next regular dose.

Ivosidenib (Tibsovo) use in children:

Not indicated.

Ivosidenib Pregnancy Category: N

In studies with animals, there were some problems when they were given ivosidenib while pregnant.
Taking ivosidenib during pregnancy might harm the baby.

Use of Ivosidenib while breastfeeding

We don't know if ivosidenib is in breast milk.
Because it might harm a nursing baby, the maker of the medicine advises not to breastfeed while taking it and for 1 month after the last dose.

Ivosidenib (Tibsovo) Dose in Kidney Disease:

Note: Renal function may be estimated using the MDRD formula.

If your eGFR (a kidney function test) is 30 or more: You can take the usual dose. No changes needed.
If your eGFR is less than 30: The manufacturer doesn't give specific dose guidance because they haven't studied it. Think about the possible risks and benefits if you have serious kidney problems.
If you have ESRD and need dialysis: Again, the manufacturer hasn't given specific dose advice. Consider the risks and benefits if you're in this situation.

Ivosidenib (Tibsovo) Dose in Liver disease:

If you have mild or moderate liver problems (Child-Pugh class A or B): You can take the usual dose. No changes needed.
If you have severe liver problems (Child-Pugh class C): The manufacturer hasn't given specific dose advice because it hasn't been studied. Think about the possible risks and benefits if you have serious liver issues.

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):

The maker of the medicine hasn't listed any reasons you shouldn't take it.

Warnings and precautions

Warning about Differentiation Syndrome with Ivosidenib:

People taking ivosidenib can get a serious condition called differentiation syndrome. If not treated, it can be deadly.
Symptoms can include: fever, trouble breathing, low oxygen levels, lung problems, fluid buildup around the lungs or heart, quick weight gain, swelling, low blood pressure, and issues with the liver, kidneys, or other organs.
If you think you have this, get treated with corticosteroids and be monitored closely until the symptoms go away.
The cause is a fast increase and change of certain blood cells.
Other symptoms can be a high white blood cell count without infection, fluid in the lungs, inflammation of the lungs, rashes, too much fluid in the body, the breakdown of tumor cells, or increased kidney measures.
Most people got better after being treated with corticosteroids or stopping ivosidenib.
This syndrome can start from the first day to 3 months after starting the drug.
If suspected, take dexamethasone (a type of corticosteroid) and monitor your body's response. If there's a high white blood cell count, treatments like hydroxyurea or leukapheresis might be needed.
Taper off the corticosteroids and hydroxyurea once symptoms go away. Take corticosteroids for at least 3 days. Symptoms might come back if stopped too soon.
If severe symptoms last more than 48 hours even after taking corticosteroids, stop taking ivosidenib until the severe symptoms are gone.

Stomach and Gut Side Effects with Ivosidenib:

Some people have experienced light stomach upset, like feeling sick, throwing up, diarrhea, constipation, mouth sores, and stomach pain.

Guillain-Barré Syndrome with Ivosidenib:

A few people taking ivosidenib got Guillain-Barré syndrome, a nerve condition.
Watch for new signs like weakness in one or both sides of the body, feeling strange sensations, tingling, or trouble breathing.
If diagnosed with Guillain-Barré, stop taking ivosidenib forever.

Heart Issue - QT Prolongation with Ivosidenib:

Some people taking ivosidenib had heart rhythm problems, with longer QT intervals on heart tests (ECGs). A few had serious irregular heartbeats.
People with certain pre-existing heart conditions or a naturally long QT interval weren't part of the study.
Taking ivosidenib with certain other medications can raise the risk of this heart issue. These include some heart drugs, certain antibiotics, fungus treatments, and others.
Check heart rhythms and salt levels in the blood while on this drug. If you have other risks (like a history of heart problems or certain salt imbalances), you might need more checks.
If the QT interval goes up but not too much, stop ivosidenib for a while. If it goes up a lot, stop the drug and then restart at a lower dose.
If someone has a long QT interval with dangerous heart symptoms, they should stop taking ivosidenib for good.

Tumor Lysis Syndrome with Ivosidenib:

When treating acute myeloid leukemia, tumor lysis syndrome might happen. This is when cancer cells break down very fast.
Drink enough water and regularly check blood tests and kidney function to stay safe.

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.
QT-prolonging Kinase Inhibitors (Highest Risk)	May enhance the QTc-prolonging effect of other QT-prolonging Kinase Inhibitors (Highest Risk).
QUEtiapine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QUEtiapine.
Ribociclib	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ribociclib.
Sparfloxacin	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sparfloxacin.
Thioridazine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Thioridazine.

Monitoring parameters:

Check for IDH1 mutation:

Before starting treatment, check for the IDH1 mutation in blood or bone marrow.

Regular Tests:

Blood counts and chemistries:
- At the start.
- Weekly for the first month.
- Every other week for the second month.
- Monthly after that.
Creatine phosphokinase (a muscle enzyme):
- Weekly for the first month.
ECG (heart rhythm):
- Weekly for the first three weeks.
- Monthly after that.
- Even more often if the heart rhythm (QTc interval) becomes irregular.

Watch Out for Symptoms:

Differentiation syndrome (a serious condition):
- Look for its signs/symptoms.
- If suspected, check the patient's vital signs and blood flow closely.
Tumor lysis syndrome (when cancer cells break down):
- Be alert for its signs/symptoms.
Neuropathy (nerve issues):
- Look for new signs or symptoms affecting movement or feeling.

Check if Patient is Following Treatment:

Ensure the patient is taking the medicine as advised.

How to administer Ivosidenib (Tibsovo)?

Timing:

Take the tablet at the same time every day.

Food:

You can take it with or without food. But avoid taking it with a meal that's high in fat.

Handling:

Don't break, crush, or chew the tablet. Just swallow it whole.

Mechanism of action of Ivosidenib (Tibsovo):

What is Ivosidenib?

It's a pill that targets a specific enzyme in certain cancer cells.

How does it work?

Some leukemia cells have a faulty part called IDH1. This fault causes these cells to make too much of a substance called 2-HG.
Too much 2-HG stops blood cells from developing properly.
Ivosidenib works by lowering 2-HG in these cells, which allows them to develop more normally.

Who can benefit from it?

About 6% to 10% of people with a type of cancer called acute myeloid leukemia have this faulty IDH1. They might benefit from this treatment.

How Fast and How Long It Works:

It starts working fast, blocking a substance called 2-hydroxyglutarate by the 14th day.
On average, it takes about 2 months to see a response and about 3 months to see a full response.
The average response lasts about 6.5 months, and a full response lasts about 9.3 months.

How the Body Handles It:

Absorption: It gets into the body quickly.
Spread in the Body: It spreads around in a volume of about 234 liters.
Binding: 92-96% of it sticks to proteins in the blood.
Breakdown: The liver breaks it down, mostly using a process called CYP3A4. Some other minor pathways are also involved.
How Food Affects It: A high-fat meal can increase the amount in the blood quite a bit.
How Long It Lasts: It sticks around for a while, with a half-life of 93 hours.
Peak Level: The highest level in the blood is reached about 3 hours after taking it.

How It Leaves the Body:

Through Stools: About 77% of it exits via feces, and most of it (67%) is unchanged.
Through Urine: 17% goes out with urine, with 10% being unchanged.

International Brand Names of Ivosidenib: