Rezlidhia (olutasidenib)

If toxicity occurs, olutasidenib may require dosage reduction, temporary withholding of the dose, or discontinuation. See Table 1 for recommended actions based on adverse reaction type and severity.

Table 1. Dosage Modifications for Adverse Reactions to Olutasidenib.

Adverse Reaction Recommended Action Differentiation syndrome If differentiation syndrome is suspected, withhold olutasidenibuntil signs and symptoms improve. Administer systemic corticosteroids and initiate hemodynamic monitoring until symptom resolution and for a minimum of 3 days. Resume at 150 mg twice daily aft er resolution. If a recurrence is suspected, withhold olutasidenib and institute treatment per above guidance. After symptom resolution, resume at a reduced dosage of 150 mg once daily for a minimum of 7 days, after which it can be increased to 150 mg twi ce daily. Noninfectious leukocytosis Initate treatment with hydroxyurea as per standard practices. Taper hydroxyurea only after leukocytosis improves or resolves. Grade 3 hepatotoxicity Withhold olutasideniband monitor liver function tests twice per week until laboratory values have returned to baseline or grade 1 toxicity. Resume at a reduced dosage of 150 mg once daily and continue monitoring; may increase to 150 mg twice daily if hepa totoxicity resolves to baseline for at least 28 days.If hepatotoxicity (grade 3) recurs at 150 mg once daily, discontinue olutasidenib. Grade 4 hepatotoxicity or AST or ALT Permanently discontinue >3x ULN and total bilirubin >2x ULN olutasidenib. and alkaline phosphatase <2x ULN in the absence of a clear alternative explanation Other grade 3 or higher toxicity Interrupt olutasidenib until considered related to treatment toxicity resolves to grade 2 or lower. Resume at 150 mg once daily; may increase to 150 mg twice daily if toxicities resolved to grade 1 or lower for at least 1 week. If grade 3 or higher toxicity recurs at 150 mg once daily, discontinueolutasidenib.

Olutasidenib is administered orally as a capsule. Swallow whole; do not break, open, or chew the capsules. Olutasidenib should be taken on an empty stomach at least 1 hour before or 2 hours after a meal. Administer the drug at about the same time each day; do not administer 2 doses within 8 hours.

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 8 hours prior to the next scheduled dose. Return to the normal schedule the following day.

Store capsules at 20-25degreesC (excursions permitted between 15-30degreesC).

No dosing information is available for this tab.

Olutasidenib is a cytochrome P-450 (CYP) 3A4 substrate. In vitro studies demonstrate that olutasidenib inducesCYP3A4, CYP2B6, CYP1A2, CYP2C8, and CYP2C9. Olutasidenib does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5.

Olutasidenib is not a substrate of breast cancer resistance protein (BCRP), bile salt export pump (BSEP), multidrug resistance protein (MRP) 2, MRP3, or MRP4. Olutasidenib is an inhibitor of P-glycoprotein (P-gp), BCRP, organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic anion transporter (OAT) 3, organic cation transporter (OCT) 2, multidrug and toxin extrusion (MATE) 1, and MATE2K. Olutasidenib does not inhibit BSEP, MRP2, MRP3, MRP4, or OAT1.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Olutasidenib/Strong And Moderate Cyp3a4 Inducers

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Strong and moderate CYP3A4 inducers may increase the metabolism of olutasidenib by CYP3A4.(1)

CLINICAL EFFECTS: The concurrent use of strong and moderate CYP3A4 inducers and olutasidenib may result in decreased levels and clinical effectiveness of olutasidenib.(1)

PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.

PATIENT MANAGEMENT: Avoid concomitant use of strong and moderate CYP3A4 inducers with olutasidenib.(1)

DISCUSSION: Coadministration of multiple doses of rifampin (a strong CYP3A4 inducer) decreased olutasidenib area-under-curve (AUC) and maximum concentration (Cmax) by 80% and 43%, respectively.(1) Strong and moderate CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, belzutifan, bosentan, carbamazepine, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, encorafenib, enzalutamide, etravirine, fexinidazole, fosphenytoin, ivosidenib, lesinurad, lorlatinib, lumacaftor, mavacamten, mitapivat, mitotane, modafinil, nafcillin, pacritinib, pexidartinib, phenobarbital, phenytoin, primidone, repotrectinib, rifabutin, rifampin, rifapentine, St. John's wort, sotorasib, telotristat, thioridazine, and tovorafenib.(2)

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*None.

• Lactation

• Pregnancy

• Child-pugh class A hepatic impairment
• Child-pugh class B hepatic impairment
• Disease of liver

The most common adverse reactions (occurring in >=20% of patients) are increased AST,increased ALT, increased alkaline phosphatase, increased creatinine, increased lymphocytes, increased bilirubin, increased lipase, increased uric acid, decreased potassium, decreased sodium, nausea, fatigue/malaise, arthralgia, constipation, leukocytosis, dyspnea, pyrexia, rash, mucositis, diarrhea, and transaminitis.

More Frequent

• Elevated serum lipase
• Hyperbilirubinemia
• Hyperuricemia
• Hypokalemia
• Hyponatremia
• Increased alkaline phosphatase
• Increased aspartate transaminase
• Leukocytosis
• Lymphocytosis

Less Frequent

• Cholangitis
• Cholestasis
• Differentiation syndrome

More Frequent

• Arthralgia
• Constipation
• Diarrhea
• Dyspnea
• Fatigue
• Fever
• Malaise
• Nausea
• Skin rash
• Stomatitis

Less Frequent

• Acute abdominal pain
• Anorexia
• Cough
• Edema
• Headache disorder
• Vomiting

No enhanced messaging available.

Safety and effectiveness of olutasidenib have not been established in pediatric patients.

Based on animal embryo-fetal toxicity studies,olutasidenib may cause fetal harm when administered to a pregnant woman. There are no available data onolutasidenib use in pregnant women to evaluate for a drug-associated risk.

In embryo-fetal development studies, oralolutasidenib resulted in embryo-fetal death and altered fetal growth when administered to pregnant rats and rabbits during the period of organogenesis at exposures up to 10 times and 0.7 times, respectively, the human exposure at the recommended daily dose. Advise pregnant women of the potential risk to a fetus.

There are no data on the presence ofolutasidenib or its metabolites in human milk, the effects on the breast-fed child, or the effects on milk production. Because many drugs are excreted in human milk, and due to the potential for adverse reactions in a breast-fed child, advise women not to breast-feed during treatment witholutasidenib and for 2 weeks after the last dose.

The manufacturer makes no specific dosage recommendations for geriatric patients.

Among the 153 patients with relapsed/refractory IDH1-mutated AML treated witholutasidenib in clinical trials, 76% were>=65 years of age and 31% were>=75 years of age. No overall differences in effectiveness were observed between patients >=65 years of age and younger patients. Compared to patients <65 years of age, an increased incidence of hepatotoxicity and hypertension was observed in patients>=65 years of age.