Version July 2025
Differentiation syndrome, which can be fatal, has occurred with revumenib. Signs and symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and renal dysfunction. If differentiation syndrome is suspected, immediately initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.
Dosage guidance:
Safety: Do not initiate revumenib until WBC is <25,000/mm3. Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to treatment. Do not initiate revumenib if QTcF is >450 msec. Dosing presented as BSA-directed dose (mg/m2) and as a fixed dose (mg); use caution.
Clinical considerations: Select patients for therapy based on the presence of a KMT2A translocation in bone marrow cells. Concurrent standard intrathecal chemotherapy prophylaxis is recommended for patients at risk of CNS relapse.
Acute leukemia, relapsed or refractory, KMT2A rearranged:
Children and Adolescents:
Weight <40 kg: Note: Tablets should not be split; multiple tablet strengths may be needed to complete a dose.
BSA-directed dosing:
Patients NOT receiving strong CYP3A4 inhibitors: Oral: 160 mg/m2/dose twice daily.
Patients receiving strong CYP3A4 inhibitors: Oral: 95 mg/m2/dose twice daily.
Fixed dosing (based on BSA):
|
BSA |
Revumenib dosage based on 160 mg/m2/dosea |
Revumenib dosage based on 95 mg/m2/doseb |
|---|---|---|
|
a Patients NOT receiving strong CYP3A4 inhibitors | ||
|
b Patients receiving strong CYP3A4 inhibitors | ||
|
0.4 m2 |
50 mg twice daily |
25 mg twice daily |
|
0.5 m2 |
75 mg twice daily |
50 mg twice daily |
|
0.6 m2 |
100 mg twice daily |
50 mg twice daily |
|
0.7 m2 |
110 mg twice daily |
50 mg twice daily |
|
0.8 m2 |
135 mg twice daily |
75 mg twice daily |
|
0.9 m2 |
135 mg twice daily |
75 mg twice daily |
|
1 m2 |
160 mg twice daily |
100 mg twice daily |
|
1.1 m2 |
185 mg twice daily |
110 mg twice daily |
|
1.2 m2 |
185 mg twice daily |
110 mg twice daily |
|
1.3 m2 |
220 mg twice daily |
135 mg twice daily |
|
1.4 m2 |
220 mg twice daily |
135 mg twice daily |
Weight ≥40 kg:
Patients NOT receiving strong CYP3A4 inhibitors: Oral: 270 mg twice daily.
Patients receiving strong CYP3A4 inhibitors: Oral: 160 mg twice daily.
Dosing adjustment for toxicity:
Children and Adolescents: Oral: Note: Tablets should not be split; multiple tablet strengths may be needed to complete a dose.
|
NOT receiving strong CYP3A4 inhibitor |
Receiving strong CYP3A4 inhibitor | |
|---|---|---|
|
Usual (initial) dose |
160 mg/m2/dose twice daily |
95 mg/m2/dose twice daily |
|
Reduced dose |
95 mg/m2/dose twice daily |
65 mg/m2/dose twice daily |
|
BSA |
Revumenib dosage for 95 mg/m2/dosea |
Revumenib dosage for 65 mg/m2/doseb |
|---|---|---|
|
a Patients NOT receiving strong CYP3A4 inhibitors | ||
|
b Patients receiving strong CYP3A4 inhibitors | ||
|
0.4 m2 |
25 mg twice daily |
25 mg twice daily |
|
0.5 m2 |
50 mg twice daily |
25 mg twice daily |
|
0.6 m2 |
50 mg twice daily |
25 mg twice daily |
|
0.7 m2 |
50 mg twice daily |
50 mg twice daily |
|
0.8 m2 |
75 mg twice daily |
50 mg twice daily |
|
0.9 m2 |
75 mg twice daily |
50 mg twice daily |
|
1 m2 |
100 mg twice daily |
50 mg twice daily |
|
1.1 m2 |
110 mg twice daily |
75 mg twice daily |
|
1.2 m2 |
110 mg twice daily |
75 mg twice daily |
|
1.3 m2 |
135 mg twice daily |
75 mg twice daily |
|
1.4 m2 |
135 mg twice daily |
100 mg twice daily |
|
NOT receiving strong CYP3A4 inhibitor |
Receiving strong CYP3A4 inhibitor | |
|---|---|---|
|
Usual (initial) dose |
270 mg twice daily |
160 mg twice daily |
|
Reduced dose |
160 mg twice daily |
110 mg twice daily |
|
Adverse reaction |
Severity |
Revumenib dosage modification |
|---|---|---|
|
Allergic reaction |
≥ Grade 3 |
Permanently discontinue revumenib. |
|
Differentiation syndrome |
Suspected |
Immediately initiate systemic corticosteroids (eg, dexamethasone 0.25 mg/kg/dose IV every 12 hours, maximum dose: 10 mg/dose) for a minimum of 3 days and until resolution of signs and symptoms. Begin supportive care and hemodynamic monitoring until improvement. |
|
Severe signs and/or symptoms persisting for >48 hours after corticosteroid initiation |
Interrupt revumenib. Begin supportive care and hemodynamic monitoring until improvement. Resume revumenib at the same dose when signs and symptoms improve to ≤ grade 1. | |
|
Life-threatening symptoms such as pulmonary symptoms requiring ventilator support |
Interrupt revumenib. Immediately initiate systemic corticosteroids (eg, dexamethasone 0.25 mg/kg/dose IV every 12 hours, maximum dose: 10 mg/dose) for a minimum of 3 days and until resolution of signs and symptoms. Begin supportive care and hemodynamic monitoring until improvement. Resume revumenib at the same dose when signs and symptoms improve to ≤ grade 1. | |
|
Recurrent differentiation syndrome after tapering corticosteroids |
Restart corticosteroids promptly. | |
|
Electrolyte serum abnormalities |
Potassium 3.6 to 3.9 mEq/L and/or Magnesium 1.7 to 1.9 mg/dL or 0.66 to 0.81 mmol/L |
Supplement potassium and/or magnesium. Continue revumenib. |
|
Potassium ≤3.5 mEq/L and/or Magnesium ≤1.6 mg/dL or ≤0.65 mmol/L |
Supplement potassium and/or magnesium and recheck levels within 24 hours. On recheck of potassium and magnesium levels within 24 hours: • If potassium is >3.5 mEq/L and/or magnesium is >1.6 mg/dL, continue revumenib. • If potassium is <3.5 mEq/L and/or magnesium is <1.6 mg/dL, hold revumenib and continue supplementation. Resume revumenib at the same dose level when the correction is complete. | |
|
Hematologic toxicity (neutropenia or thrombocytopenia) |
Grade 4 |
Interrupt revumenib until recovery to ≤ grade 2 or baseline. Then resume revumenib at the same dose level. |
|
Recurrent grade 4, without attributable cause |
Interrupt revumenib until recovery to ≤ grade 3. Then resume revumenib at the reduced dose level. | |
|
Leukocytosis, noninfectious |
Elevated or rapidly rising leukocyte count |
Initiate treatment with hydroxyurea. Add leukapheresis if clinically indicated. Taper hydroxyurea only after leukocytosis improves or resolves. |
|
QTc prolongation |
QTcF interval >480 msec to 500 msec |
Interrupt revumenib. Check electrolyte levels. Correct hypokalemia and hypomagnesemia. Resume revumenib at the same dose level after the QTcF interval returns to ≤480 msec. |
|
QTcF interval >500 msec (grade 3) or increases by >60 msec from baseline |
Interrupt revumenib. Check electrolyte levels. Correct hypokalemia and hypomagnesemia. Resume revumenib at the reduced dose level after the QTcF interval returns to ≤480 msec. | |
|
QTc interval prolongation with signs/symptoms of life-threatening arrhythmia, torsades de pointes, polymorphic ventricular tachycardia (grade 4) |
Permanently discontinue revumenib. | |
|
Other nonhematologic adverse reactions |
≥ Grade 3 |
Interrupt revumenib until recovery to ≤ grade 1 or baseline. Recovery in ≤7 days: Resume revumenib at the same dose level. If the same ≥ grade 3 toxicity recurs, interrupt revumenib until recovery to ≤ grade 1 or baseline, then resume revumenib at the reduced dose level. Recovery in >7 days: Resume revumenib at the reduced dose level. If the same ≥ grade 3 toxicity recurs, discontinue revumenib. |
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function:
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, there were no clinically significant differences in revumenib pharmacokinetics in patients with CrCl 30 to 89 mL/minute.
CrCl <30 mL/minute: There are no dosage adjustments provided in manufacturer's labeling; effect of severe kidney impairment on revumenib pharmacokinetics is unknown.
Mild (total bilirubin ≤ ULN and AST > ULN or total bilirubin >1 to 1.5 times ULN and any AST) or moderate (total bilirubin >1.5 to 3 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, there were no clinically significant differences in revumenib pharmacokinetics in patients with mild or moderate liver impairment.
Severe hepatic impairment (total bilirubin >3 times ULN and any AST): There are no dosage adjustments provided in the manufacturer's labeling; effect of severe liver impairment on revumenib pharmacokinetics is unknown.
(For additional information see "Revumenib: Drug information")
Dosage guidance:
Safety: Do not initiate revumenib until WBC is <25,000/mm3. Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to treatment. Do not initiate revumenib if QTcF is >450 msec.
Clinical considerations: Select patients for therapy based on the presence of a KMT2A translocation in bone marrow cells. Concurrent standard intrathecal chemotherapy prophylaxis is recommended for patients at risk of CNS relapse.
Acute leukemia, relapsed or refractory, KMT2A rearranged:
Patients ≥40 kg: Oral: 270 mg twice daily (160 mg twice daily with concomitant strong CYP3A4 inhibitors); continue until disease progression or unacceptable toxicity. In patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response (Ref).
Patients <40 kg: Oral: 160 mg/m2/dose twice daily (95 mg/m2/dose twice daily with concomitant strong CYP3A4 inhibitors); continue until disease progression or unacceptable toxicity. In patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response (Ref).
|
BSA |
Revumenib dose administered twice daily (based on 160 mg/m2/dose twice daily) |
Revumenib dose administered twice daily (based on 95 mg/m2/dose twice daily) |
|---|---|---|
|
a Do not cut or split tablets; attain desired dose by combining different tablet strengths if necessary. | ||
|
1.4 m2 |
220 mg twice daily |
135 mg twice daily |
|
1.3 m2 |
220 mg twice daily |
135 mg twice daily |
|
1.2 m2 |
185 mg twice daily |
110 mg twice daily |
|
1.1 m2 |
185 mg twice daily |
110 mg twice daily |
|
1 m2 |
160 mg twice daily |
100 mg twice daily |
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Missed doses: If a dose is missed or not administered at the usual time, administer the dose as soon as possible on the same day 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.
Altered kidney function prior to treatment initiation:
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, there were no clinically significant differences in revumenib pharmacokinetics in patients with CrCl 30 to 89 mL/minute.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (effect of severe kidney impairment on revumenib pharmacokinetics is unknown).
End-stage kidney disease (CrCl <15 mL/minute): There are no dosage adjustments provided in the manufacturer's labeling (effect of end-stage kidney disease on revumenib pharmacokinetics is unknown).
Altered liver function prior to treatment initiation:
Mild (total bilirubin ≤ ULN and AST > ULN or total bilirubin >1 to 1.5 times ULN and any AST) or moderate (total bilirubin >1.5 to 3 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer’s labeling; however, there were no clinically significant differences in revumenib pharmacokinetics in patients with mild or moderate hepatic impairment.
Severe hepatic impairment (total bilirubin >3 times ULN and any AST): There are no dosage adjustments provided in the manufacturer’s labeling (effect of severe hepatic impairment on revumenib pharmacokinetics is unknown).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in children, adolescents, and adults.
>10%:
Cardiovascular: Edema (23%), heart failure (<20%), pericardial effusion (<20%), prolonged QT interval on ECG (29%), syncope (<20%), ventricular tachycardia (<20%)
Dermatologic: Skin rash (<20%)
Endocrine & metabolic: Decreased serum phosphate (25%), decreased serum potassium (24%), hypercholesterolemia (19%), hyperkalemia (<20%), hyperparathyroidism (<20%), hyponatremia (<20%), increased parathyroid hormone (33%), increased serum calcium (15%), increased serum phosphate (50%), increased serum triglycerides (25%)
Gastrointestinal: Abdominal pain (<20%), constipation (23%), decreased appetite (24%), diarrhea (30%; grades 3/4: 4%), dysgeusia (<20%), nausea (51%; grades 3/4: 4%)
Hematologic & oncologic: Differentiation syndrome (29%; grades 3/4: 13%), febrile neutropenia (35%; grades 3/4: 33%), hemorrhage (53%; grades 3/4: 9%)
Hepatic: Increased serum alanine aminotransferase (33%), increased serum alkaline phosphatase (21%), increased serum aspartate aminotransferase (37%)
Hypersensitivity: Hypersensitivity reaction (<20%)
Infection: Infection (41%; including bacterial infection [31%], viral infection [23%], serious infection [24%])
Nervous system: Fatigue (22%), headache (<20%), paresthesia (<20%)
Neuromuscular & skeletal: Musculoskeletal pain (42%)
Ophthalmic: Cataract (<20%)
Renal: Increased serum creatinine (19%), kidney impairment (<20%)
1% to 10%:
Cardiovascular: Thrombosis (10%; serious: 5%)
Hematologic & oncologic: Leukocytosis (8%; grades 3/4: 5%)
Frequency not defined: Respiratory: Respiratory failure
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Differentiation syndrome: Revumenib may cause fatal or life-threatening (grade 3 or 4) differentiation syndrome. Symptoms of differentiation syndrome, including those seen in patients treated with revumenib, include fever, dyspnea, hypoxia, peripheral edema, pleuropericardial effusion, acute kidney failure, and/or hypotension. Differentiation syndrome occurred in nearly one-third of patients who received revumenib at the recommended dose for relapsed or refractory acute leukemia with a KMT2A translocation, including patients with acute myeloid leukemia, mixed-phenotype acute leukemia, and acute lymphoblastic leukemia. The median time to onset of differentiation syndrome was 10 days (range: 3 to 41 days). Some patients experienced >1 differentiation syndrome event. Treatment interruption was required for some patients, and treatment was withdrawn in a small percentage of patients.
• QT prolongation: Revumenib may cause QT (QTc) interval prolongation, including grade 3 events. QTc interval prolongation was reported as an adverse reaction in nearly one-third of patients treated with revumenib at the recommended dose for relapsed or refractory acute leukemia with a KMT2A translocation. The heart rate–corrected QT interval (using Fridericia method; QTcF) was >500 msec in some patients, and the increase from baseline QTcF was >60 msec in nearly one-fifth of patients. Revumenib dose reduction due to QTc interval prolongation was required in some patients. QTc prolongation was reported in all age groups. Concomitant use of revumenib with medications known to prolong the QTc interval may increase the risk of QTc interval prolongation.
Special populations:
• Older adults: QTc prolongation and edema occurred at higher incidences in patients ≥65 years of age treated with revumenib, when compared to patients <65 years of age.
Other warnings/precautions:
• Appropriate use: Select patients for the treatment of acute leukemia based on the presence of a KMT2A translocation in bone marrow cells.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as citrate:
Revuforj: 25 mg, 110 mg
Revuforj: 160 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
No
Tablets (Revuforj Oral)
25 mg (per each): $400.00
110 mg (per each): $790.00
160 mg (per each): $790.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Oral: Tablets: Administer at approximately the same times each day, either in a fasted state or with a low-fat meal (~400 calories, ≤25% fat). Swallow tablet whole, do not cut or chew; multiple tablet strengths may be necessary to achieve dose. If patient has difficulty swallowing, tablets may be crushed and dispersed in 10 mL of water and administered within 2 hours of preparation.
Dispersion instructions (for patients who have difficulty swallowing): Using a pill crusher, thoroughly crush the appropriate number of revumenib tablets for the dose; ensure all large tablet pieces are broken up and the consistency is flour-like. Add 10 mL of water to a small cup, then carefully pour the crushed tablets into the water, ensuring that the entire dose is extracted; do not add the tablets first, followed by water. Swirl the cup every 30 seconds to 1 minute for a total of 5 minutes; the mixture should look cloudy. Administer immediately using an oral syringe; must be administered within 2 hours of preparation. Rinse the cup with room temperature water, rinsing down the sides, and swirl water to make sure any remaining powder is mixed with the water; administer using an oral syringe. Repeat rinse step until entire dose has been administered. Patient should remain sitting up straight or standing for 2 to 3 minutes immediately following dose.
Missed doses: If a dose is missed or not administered at the usual time, administer the dose as soon as possible on the same day and at least 12 hours prior to the next scheduled dose; then return to the normal schedule the following day. Do not administer 2 doses within 12 hours. If dose is vomited, do not repeat the dose.
Oral: Administer at approximately the same times each day, either in a fasted state or with a low-fat meal (~400 calories, ≤25% fat). Swallow tablets whole; do not cut or chew tablets. For patients unable to swallow whole, tablets may be crushed and dispersed in water and administered within 2 hours of preparation.
This medication is not on the NIOSH (2024) list; however, it may meet the criteria for a hazardous drug. Revumenib may cause teratogenicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Store in the original container until dispensed.
Treatment of relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation (FDA approved in ages ≥1 year and adults).
Revuforj may be confused with Revlimid.
Revumenib may be confused with enasidenib, ivosidenib, regorafenib, repotrectinib, ripretinib, ritlectinib, ruxolitinib.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Amiodarone: QT-prolonging Miscellaneous Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Amisulpride (Oral): QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Amisulpride (Oral). 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 greater risk. Risk D: Consider Therapy Modification
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Arsenic Trioxide: QT-prolonging Miscellaneous Agents (Highest Risk) may increase QTc-prolonging effects of Arsenic Trioxide. 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. Risk D: Consider Therapy Modification
Azithromycin (Systemic): QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG (Intravesical): Myelosuppressive Agents may decrease therapeutic effects of BCG (Intravesical). Myelosuppressive Agents may increase adverse/toxic effects of BCG (Intravesical). Risk X: Avoid
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Bedaquiline: QT-prolonging Miscellaneous Agents (Highest Risk) may increase QTc-prolonging effects of Bedaquiline. 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. Risk D: Consider Therapy Modification
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Carbetocin: May increase QTc-prolonging effects of QT-prolonging 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. Risk D: Consider Therapy Modification
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Chloroquine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
ChlorproMAZINE: QT-prolonging Miscellaneous Agents (Highest Risk) may increase QTc-prolonging effects of ChlorproMAZINE. 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. Risk D: Consider Therapy Modification
Cisapride: QT-prolonging Miscellaneous Agents (Highest Risk) may increase QTc-prolonging effects of Cisapride. 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. Risk D: Consider Therapy Modification
Citalopram: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Citalopram. Risk X: Avoid
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Cladribine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk X: Avoid
Clarithromycin: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Clarithromycin. Risk X: Avoid
Clofazimine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
ClomiPRAMINE: May increase QTc-prolonging effects of QT-prolonging 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. Risk D: Consider Therapy Modification
CloZAPine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Miscellaneous Oncologic Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Revumenib. Risk X: Avoid
CYP3A4 Inducers (Strong): May decrease serum concentration of Revumenib. Risk X: Avoid
CYP3A4 Inhibitors (Strong): May increase serum concentration of Revumenib. Management: If combined use is required, decrease revumenib dose for patients weighing 40 kg or more to 160 mg orally twice/day; for patients weighing less than 40 kg to 95 mg/m2 twice daily. Risk D: Consider Therapy Modification
Dabrafenib: May increase QTc-prolonging effects of Revumenib. Dabrafenib may decrease serum concentration of Revumenib. Dabrafenib may also increase concentrations of the M1 metabolite, which may contribute to the QT-prolonging effect of Revumenib. Risk X: Avoid
Dasatinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Delamanid: QT-prolonging Miscellaneous Agents (Highest Risk) may increase QTc-prolonging effects of Delamanid. 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. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Domperidone: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Domperidone. Risk X: Avoid
Doxepin-Containing Products: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Dronedarone: Revumenib may increase QTc-prolonging effects of Dronedarone. Dronedarone may increase serum concentration of Revumenib. Management: Consider alternatives to this combination. If use is necessary, monitor for QTc prolongation and arrhythmias (including torsades de pointes). Patients with other risk factors are likely at greater risk for these potentially life-threatening toxicities. Risk D: Consider Therapy Modification
DroPERidol: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Encorafenib: May increase QTc-prolonging effects of Revumenib. Encorafenib may decrease serum concentration of Revumenib. Encorafenib may also increase concentrations of the M1 metabolite, which may contribute to the QT-prolonging effect of Revumenib. Risk X: Avoid
Entrectinib: May increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk X: Avoid
Escitalopram: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Etelcalcetide: May increase QTc-prolonging effects of QT-prolonging 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. Risk D: Consider Therapy Modification
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Fexinidazole: May increase QTc-prolonging effects of Revumenib. Fexinidazole may decrease serum concentration of Revumenib. Fexinidazole may increase active metabolite exposure of Revumenib. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Fingolimod: May increase QTc-prolonging effects 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. Risk C: Monitor
Flecainide: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Fluorouracil Products: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Fluorouracil Products. 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. Risk D: Consider Therapy Modification
Flupentixol: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Flupentixol. Risk X: Avoid
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Gadobenate Dimeglumine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Gemifloxacin: May increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Gilteritinib: May increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. If use is necessary, monitor for QTc interval prolongation and arrhythmias. Risk D: Consider Therapy Modification
Halofantrine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Haloperidol: QT-prolonging Miscellaneous Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
HydrOXYzine: May increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk C: Monitor
Iboga: May increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Imipramine: May increase QTc-prolonging effects of QT-prolonging 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. Risk D: Consider Therapy Modification
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Inotuzumab Ozogamicin: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Levofloxacin-Containing Products (Systemic): May increase QTc-prolonging effects of QT-prolonging Miscellaneous Agents (Highest Risk). 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. Risk D: Consider Therapy Modification
Levoketoconazole: QT-prolonging Miscellaneous Agents (Highest Risk) may increase QTc-prolonging effects of Levoketoconazole. Risk X: Avoid
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lofexidine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Lonafarnib: May increase QTc-prolonging effects of QT-prolonging 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. Risk D: Consider Therapy Modification
Meglumine Antimoniate: May increase QTc-prolonging effects of QT-prolonging 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. Risk D: Consider Therapy Modification
Methadone: May increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Midostaurin: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Moxifloxacin (Systemic): QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Moxifloxacin (Systemic). Risk X: Avoid
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Mumps- Rubella- or Varicella-Containing Live Vaccines may increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Nilotinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Nilotinib. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
OLANZapine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Ondansetron: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Osimertinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Oxytocin: May increase QTc-prolonging effects of QT-prolonging 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. Risk D: Consider Therapy Modification
Papaverine: QT-prolonging Miscellaneous Agents (Highest Risk) may increase QTc-prolonging effects of Papaverine. 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. Risk D: Consider Therapy Modification
PAZOPanib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of PAZOPanib. Risk X: Avoid
Pentamidine (Systemic): QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pilsicainide: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Pimozide: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk X: Avoid
Piperaquine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Piperaquine. Risk X: Avoid
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Probucol: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Probucol. Risk X: Avoid
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Propafenone: May increase QTc-prolonging effects of QT-prolonging Miscellaneous Agents (Highest Risk). 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. Risk D: Consider Therapy Modification
Propofol: May increase QTc-prolonging effects of QT-prolonging 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. Risk D: Consider Therapy Modification
QT-prolonging Agents (Indeterminate Risk - Avoid): May increase QTc-prolonging effects 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. Risk C: Monitor
QT-prolonging Agents (Indeterminate Risk - Caution): May increase QTc-prolonging effects 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. Risk C: Monitor
QT-prolonging Class IA Antiarrhythmics (Highest Risk): May increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
QT-prolonging Class III Antiarrhythmics (Highest Risk): May increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
QT-Prolonging Inhalational Anesthetics (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging 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. Risk D: Consider Therapy Modification
QT-prolonging Kinase Inhibitors (Highest Risk): May increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May increase QTc-prolonging effects of Revumenib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Revumenib. 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. Risk D: Consider Therapy Modification
QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): Revumenib may increase QTc-prolonging effects of QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk). QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk) may increase serum concentration of Revumenib. Management: Avoid combination is possible. If required, for patients weighing 40 kg or more decrease the revumenib dose to 160 mg orally twice/day, and for patients weighing less than 40 kg decrease to 95 mg/m2 orally twice/day. Monitor ECG more closely. Risk D: Consider Therapy Modification
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May increase QTc-prolonging effects of Revumenib. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Revumenib. Management: Avoid combination is possible. If required, for patients weighing 40 kg or more decrease the revumenib dose to 160 mg orally twice/day, and for patients weighing less than 40 kg decrease to 95 mg/m2 orally twice/day. Monitor ECG more closely. Risk D: Consider Therapy Modification
QUEtiapine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of QUEtiapine. Risk X: Avoid
QuiNINE: QT-prolonging Miscellaneous Agents (Highest Risk) may increase QTc-prolonging effects of QuiNINE. 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. Risk D: Consider Therapy Modification
Quizartinib: May increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ribociclib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Ribociclib. Risk X: Avoid
RisperiDONE: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of RisperiDONE. QT-prolonging Agents (Highest Risk) may increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sertindole: May increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sparfloxacin: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Sparfloxacin. Risk X: Avoid
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor
SUNItinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of SUNItinib. 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 D: Consider Therapy Modification
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Terbutaline: May increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Thioridazine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Thioridazine. Risk X: Avoid
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Toremifene: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Toremifene. 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 D: Consider Therapy Modification
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Vemurafenib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ziprasidone: QT-prolonging Miscellaneous Agents (Highest Risk) may increase QTc-prolonging effects of Ziprasidone. 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. Risk D: Consider Therapy Modification
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Verify pregnancy status within 7 days prior to initiating treatment in patients who could become pregnant.
Patients who could become pregnant and patients with partners who could become pregnant should use effective contraception during therapy and for 4 months after the last revumenib dose.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to revumenib may cause fetal harm.
KMT2A translocation status (in bone marrow cells). Verify pregnancy status within 7 days prior to initiating treatment (in patients who could become pregnant). Monitor blood counts, electrolytes, and liver enzymes prior to treatment initiation and at least monthly thereafter. Monitor ECG prior to treatment initiation and at least once weekly during the first 4 weeks, then at least monthly thereafter (more frequent ECG monitoring may be necessary in patients with congenital long QTc syndrome, heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval). Monitor for signs/symptoms of differentiation syndrome, hypersensitivity, and/or QTc prolongation. Monitor bone growth and development in pediatric patients. Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion(Ref) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Revumenib blocks the interaction of menin with both wild-type lysine methyltransferase 2A (KMT2A) and KMT2A fusion proteins. Binding of KMT2A fusion proteins with menin is involved in KMT2A-rearranged (KMT2Ar) acute leukemias through a leukemogenic transcriptional pathway activation. In nonclinical studies of cells expressing KMT2A fusions, inhibition of the menin-KMT2A interaction with revumenib altered the transcription of multiple genes including differentiation markers and demonstrated antiproliferative and antitumor activity in leukemia cells harboring KMT2A fusion proteins.
Distribution: 78 L.
Protein binding: 90%.
Metabolism: Hepatic; via CYP3A4; active metabolite is M1 (which contributes to effects on QTc, but does not contribute to efficacy at the recommended dosage).
Half-life elimination: 3.6 hours (without concomitant strong CYP3A4 inhibitors); 7.5 hours (with concomitant strong CYP3A4 inhibitors).
Time to peak: Median: 1 hour (without concomitant strong CYP3A4 inhibitors); 2 hours (with concomitant strong CYP3A4 inhibitors).
Excretion: Adults: Feces (~49%; 7% as unchanged drug); Urine (~27%; 7% as unchanged drug).
Clearance: 27 L/hour (without concomitant strong CYP3A4 inhibitors); 7 L/hour (with concomitant strong CYP3A4 inhibitors).
Body weight: Body weight (8 to 146 kg) has a significant effect on revumenib pharmacokinetics, with higher revumenib exposures in patients with lower body weight (<40 kg); this supports BSA-based dosing for patients <40 kg.
