Ivosidenib

Ivosidenib is a prescription medication used for the treatment of newly diagnosed, relapsed or refractory acute myeloid leukemia and cholangiocarcinoma.

• Ivosidenib is available under the following different brand names: Tibsovo

Common side effects of Ivosidenib include:

• fatigue
• increased white blood cell count
• joint pain
• diarrhea
• shortness of breath
• swelling
• nausea
• inflammation and ulceration of the mucous membranes lining the digestive tract
• electrocardiogram QT prolonged
• rash
• fever
• cough
• constipation

Serious side effects of Ivosidenib include:

• pneumonia
• ascites
• hyperbilirubinemia
• jaundice cholestatic
• sepsis
• pneumonia
• intestinal obstruction
• pulmonary embolism
• hepatic encephalopathy

Rare side effects of Ivosidenib include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 250 mg

Newly-diagnosed acute myeloid leukemia (AML)

Adult dosage

• Combination regimen
  • 500 mg orally every day until disease progression or unacceptable toxicity
  • For patients without disease progression or unacceptable toxicity, continue for a minimum of 6 months to allow time for clinical response
  • Start Ivosidenib on Cycle 1 Day 1 in combination with azacitidine 75 mg/m2 SC/IV every day on Days 1-7 (or Days 1-5 and 8-9) of each 28-day cycle
• Monotherapy
  • 500 mg orally every day until disease progression or unacceptable toxicity
  • For patients without disease progression or unacceptable toxicity, continue for a minimum of 6 months to allow time for clinical response

Relapsed or refractory AML

Adult dosage

• 500 mg orally every day
• Continue until disease progression or unacceptable toxicity; treat for a minimum of 6 months to allow time for clinical response

Cholangiocarcinoma

Adult dosage

• 500 mg orally every day
• Continue until disease progression or unacceptable toxicity

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Ivosidenib has severe interactions with the following drugs:
  • doravirine
  • fostemsavir
  • isavuconazonium sulfate
  • lonafarnib
  • lorlatinib
  • mavacamten
  • pacritinib
• Ivosidenib has serious interactions with at least 421 other drugs.
• Ivosidenib has moderate interactions with at least 75 other drugs.
• Ivosidenib has minor interactions with the following drugs:
  • acetazolamide
  • anastrozole
  • cyclophosphamide
  • larotrectinib

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Ivosidenib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Ivosidenib?”

Cautions

• In a clinical trial, patients with relapsed or refractory AML treated with ivosidenib experienced differentiation syndrome
• Patients can develop QT (QTc) prolongation and ventricular arrhythmias; 9% of 258 patients treated with Ivosidenib in clinical trials were found to have a QTc interval greater than 500 msec and 14% had a QTc greater than 60 msec; in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary; monitor electrocardiograms (ECGs) and electrolyte levels
• Guillain-Barré syndrome was reported in the clinical study; monitor for the onset of new signs or symptoms of motor and/or sensory neuropathy such as unilateral or bilateral weakness, sensory alterations, paresthesia, or difficulty breathing
• Differentiation syndrome
  • Differentiation syndrome is associated with the rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal if not treated
  • Patients with newly diagnosed AML treated concomitantly with azacitidine have experienced differentiation syndrome
  • Symptoms of differentiation syndrome include noninfectious leukocytosis, peripheral edema, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonitis, pericardial effusion, rash, fluid overload, tumor lysis syndrome, and increased creatinine
  • If differentiation syndrome is suspected, initiate dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an alternative oral or IV corticosteroid) and hemodynamic monitoring until improvement; if concomitant noninfectious leukocytosis is observed, initiate treatment with hydroxyurea or leukapheresis, as clinically indicated
  • Taper corticosteroids and hydroxyurea after resolution of symptoms and administer corticosteroids for a minimum of 3 days; symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid and/or hydroxyurea treatment
  • If severe signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids, discontinue the therapy until signs and symptoms are no longer severe
• Drug interaction overview
  • Coadministration with strong CYP3A4 inducers is known to decrease Ivosidenib plasma concentrations; avoid the use
  • Strong to moderate CYP3A4 inhibitors
    • Coadministration with strong or moderate CYP3A4 inhibitors increased ivosidenib plasma concentrations, which in turn may increase the risk for QTc interval prolongation
    • Avoid coadministration with strong or moderate CYP3A4 inhibitors; if ivosidenib must be coadministered, decrease the dose
  • Effect of ivosidenib on other drugs
    • Ivosidenib induces CYP3A4 and may induce CYP2C9
    • Coadministration decreases concentrations of sensitive CYP3A4 substrates and may decrease concentrations of sensitive CYP2C9 substrates
    • Use alternative therapies that are not sensitive to CYP3A4 and CYP2C9 substrates during treatment
    • Do not administer with itraconazole or ketoconazole (CYP3A4 substrates) owing to the expected loss of antifungal efficacy
    • May decrease the efficacy of hormonal contraceptives owing to lower systemic exposure; consider other contraception methods
    • If coadministration of sensitive CYP3A4 or CYP2C9 substrates is unavoidable, monitor for loss of therapeutic effect of these drugs
  • QTc prolonging drugs
    • Coadministration with QTc-prolonging drugs may increase the risk for QTc interval prolongation
    • Avoid coadministration of QTc-prolonging drugs or replace them with alternative therapies
    • If coadministration is unavoidable, monitor for increased risk for QTc interval prolongation

Pregnancy and Lactation

• Based on animal embryofetal toxicity studies, fetal harm may occur if it is administered to a pregnant woman
• There are no available data on use in pregnant women to inform a drug-associated risk for major birth defects and miscarriage
• If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the potential risk to the fetus
• Lactation
  • There are no data on the presence of ivosidenib or its metabolites in human milk, its effect on the breastfed child, or milk production because many drugs are excreted in human milk; because of the potential for adverse reactions in breastfed children, advise women not to breastfeed during treatment and for at least 1 month after the last dose