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Ivosidenib Dosage

Medically reviewed by Drugs.com. Last updated on March 20, 2020.

Applies to the following strengths: 250 mg

Usual Adult Dose for Acute Myeloid Leukemia

500 mg orally once daily until disease progression or unacceptable toxicity; for patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response

Comments:
-NOTE: Select patients for the treatment of AML based on the presence of IDH1 mutations in the blood or bone marrow. Patients without IDH1 mutations at diagnosis should be retested at relapse because a mutation in IDH1 may emerge during therapy and at relapse.

Use: For the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test

Usual Geriatric Dose for Acute Myeloid Leukemia

75 years or older:
500 mg orally once daily until disease progression or unacceptable toxicity; for patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response

Comments:
-NOTE: Select patients for the treatment of AML based on the presence of IDH1 mutations in the blood or bone marrow. Patients without IDH1 mutations at diagnosis should be retested at relapse because a mutation in IDH1 may emerge during therapy and at relapse.

Use: For the treatment of adult patients with newly-diagnosed AML with a susceptible IDH1 mutation as detected by an FDA-approved test who are 75 years older or who have comorbidities that preclude use of intensive induction chemotherapy.

Renal Dose Adjustments

-Mild (CrCl 60 to less than 90 mL/min) or moderate (CrCl 30 to less than 60 mL/min): No adjustment recommended.
-Severe renal impairment (CrCl less than 30 mL/min): Data not available

Liver Dose Adjustments

-Mild hepatic impairment (total bilirubin less than or equal to the upper limit of normal [ULN] and aspartate aminotransferase [AST] greater than ULN or total bilirubin 1 to 1.5 x ULN and any AST): No adjustment recommended.
-Moderate hepatic impairment (total bilirubin 1.5 to 3.0 x ULN and any value for AST), or severe hepatic impairment (total bilirubin greater than 3 x ULN and any value for AST): Data not available

Dose Adjustments

DIFFERENTIATION SYNDROME:
-If differentiation syndrome is suspected, administer systemic corticosteroids and initiate hemodynamic monitoring until symptom resolution and for a minimum of 3 days.
-Interrupt therapy if severe signs and/or symptoms persist for more than 48 hours after initiation of systemic corticosteroids. Resume therapy when signs and symptoms improve to Grade 2 or less.

NONINFECTIOUS LEUKOCYTOSIS (white blood cell [WBC] count greater than 25 x 10(9)/L or an absolute increase in total WBC of greater than 15 x 10(9)/L from baseline):
-Initiate treatment with hydroxyurea, as per standard institutional practices, and leukapheresis if clinically indicated.
-Taper hydroxyurea only after leukocytosis improves or resolves.
-Interrupt therapy if leukocytosis is not improved with hydroxyurea, and then resume therapy at 500 mg daily when leukocytosis has resolved.

QTC INTERVAL GREATER THAN 480 MSEC TO 500 MSEC:
-Monitor and supplement electrolyte levels as clinically indicated.
-Review and adjust concomitant medications with known QTc interval-prolonging effects.
-Interrupt therapy.
-Restart therapy at 500 mg once daily after the QTc interval returns to less an or equal to 480 msec.
-Monitor ECGs at least weekly for 2 weeks following resolution of QTc prolongation.
QTC INTERVAL GREATER THAN 500 MSEC:
-Monitor and supplement electrolyte levels as clinically indicated.
-Review and adjust concomitant medications with known QTc interval-prolonging effects.
-Interrupt therapy.
-Resume therapy at a reduced dose of 250 mg once daily when QTc interval returns to within 30 msec of baseline or less than or equal to 480 msec.
-Monitor ECGs at least weekly for 2 weeks following resolution of QTc prolongation.
-Consider re-escalating the dose to 500 mg daily if an alternative etiology for QTc prolongation can be identified.
QTC INTERVAL PROLONGATION WITH SIGNS/SYMPTOMS OF LIFE-THREATENING ARRHYTHMIA:
-Discontinue therapy permanently.

GUILLAIN-BARRE SYNDROME:
-Discontinue therapy permanently.

OTHER GRADE 3 OR HIGHER TOXICITY CONSIDERED TO BE RELATED TO TREATMENT:
-Interrupt therapy until toxicity resolves to Grade 2 or lower.
-Resume therapy at 250 mg once daily; may increase to 500 mg once daily if toxicities resolve to Grade 1 or lower.
-If Grade 3 or higher toxicity recurs, discontinue therapy.

DOSE MODIFICATION FOR USE WITH STRONG CYP450 3A4 INHIBITORS
-If a strong CYP450 3A4 inhibitor must be coadministered, reduce the dose of this drug to 250 mg once daily.
-If the strong CYP450 3A4 inhibitor is discontinued, increase the dose of this drug (after at least 5 half-lives of the strong CYP450 3A4 inhibitor) to the recommended dose of 500 mg once daily.

Precautions

US BOXED WARNINGS:
-Patients treated with this drug have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain, or peripheral edema, hypotension, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.

CONTRAINDICATIONS:
-None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:
-This drug may be taken with or without food; however, it should not be administered with a high fat meal because of an increase in drug concentration.
-Do not split or crush tablets.
-Administer this drug about the same time each day.
-If a dose is vomited, do not administer a replacement dose; wait until the next scheduled dose is due.
-If a dose is missed or not taken at the usual time, administer the dose as soon as possible and at least 12 hours prior to the next scheduled dose. Return to the normal schedule the following day. Do not administer 2 doses within 12 hours.

Storage requirements:
-Store at 20C to 25C (68F to 77F); excursions permitted between 15C to 30C (59F to 86F).

Monitoring:
-Assess blood counts and blood chemistries prior to the initiation of therapy, at least once weekly for the first month, once every other week for the second month, and once monthly for the duration of therapy.
-Monitor blood creatine phosphokinase weekly for the first month of therapy.
-Monitor electrocardiograms (ECGs) at least once weekly for the first 3 weeks of therapy and then at least once monthly for the duration of therapy. Manage any abnormalities promptly.

Patient advice:
-Read the approved patient labeling the first time you get this drug and also when you get a refill.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Frequently Asked Questions