Tibsovo

As monotherapy for adults w/ locally advanced or metastatic cholangiocarcinoma w/ IDH1 R132 mutation who were previously treated by at least 1 prior line of systemic therapy. In combination w/ azacitidine for adults w/ newly diagnosed AML w/ isocitrate dehydrogenase-1 (IDH1) R132 mutation who are not eligible to receive standard induction chemotherapy.

AML 500 mg once daily. Start on cycle 1 day 1 w/ azacitidine SC/IV at 75 mg/m², once daily on days 1-7 of each 28-day cycle. Treatment duration: Min of 6 cycles. Cholangiocarcinoma 500 mg once daily. Concomitant use w/ moderate or strong CYP3A4 inhibitors 250 mg once daily. Increase to 500 mg if moderate or strong CYP3A4 inhibitor is discontinued.

Should be taken on an empty stomach: Swallow whole.

Hypersensitivity. Congenital long QT syndrome. Familial history of sudden death or polymorphic ventricular arrhythmia. QT/QTc interval >500 msec, regardless of the correction method. Concomitant administration of strong CYP3A4 inducers or dabigatran.

Permanently discontinue treatment if patients develop QTc interval prolongation w/ signs or symptoms of life-threatening arrhythmia. Discontinue treatment if grade 3 (3^rd time) or grade 4 toxicity recurs. Interrupt treatment if severe signs/symptoms of differentiation syndrome persist for >48 hr after initiation of systemic corticosteroids & resume treatment when signs/symptoms are moderate or lower & upon improvement in patient's clinical condition; leukocytosis has not improved after initiation of hydroxycarbamide; QTC interval is >480-500 msec & monitor ECG every 24 hr until QTc interval returns to w/in 30 msec of baseline or ≤480 msec; ≥grade 3 adverse reaction occurs until resolves to ≤grade 1 or baseline. Consider placing patient under continuous electrocardiographic monitoring in case of QTc interval prolongation >550 msec until QTc returns to values <500 msec. Patients who have albumin levels below normal range or are underwt. Administer systemic corticosteroids & initiate hemodynamic monitoring until symptom resolution & for min of 3 days if differentiation syndrome is suspected. Perform ECG prior to treatment initiation, at least wkly during 1st 3 wk & mthly thereafter if QTc interval remains ≤480 msec. Closely monitor patients w/ CHF or electrolyte abnormalities & periodically monitor ECGs & electrolytes during treatment. Avoid concomitant use w/ medicinal products known to prolong QTc interval & moderate or strong CYP3A4 inhibitors; if suitable alternative is not possible, closely monitor for QTc interval prolongation & perform ECG prior to co-administration w/ wkly monitoring for at least 3 wk then as clinically indicated. Avoid grapefruit or grapefruit juice during treatment. Assess CBC & blood chemistries prior to treatment initiation, at least once wkly for the 1st mth, once every other wk for the 2nd mth, & at each medical visit for the duration of therapy. Monitor for loss of antifungal efficacy if use of itraconazole or ketoconazole cannot be avoided. Avoid use in patients w/ rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. Minor influence on ability to drive & use machines. Severe renal impairment (eGFR <30 mL/min/1.73 m²). Hepatic impairment. Women of childbearing potential should have pregnancy test prior to starting treatment & avoid becoming pregnant during therapy; should use effective contraception, as well as their male partners, during treatment & for at least 1 mth after the last dose. Use barrier method of contraception. Not recommended for use during pregnancy & in women of childbearing potential not using effective contraception. Discontinue breastfeeding during treatment & for at least 1 mth after the last dose. Childn & adolescents <18 yr. Elderly ≥85 yr.

Headache; peripheral neuropathy; vomiting; prolonged ECG QT. Newly diagnosed AML in combination w/ azacitidine: Differentiation syndrome, leukocytosis, thrombocytopenia, neutropenia; insomnia; dizziness; extremity & back pain, arthralgia. Leukopenia; oropharyngeal pain. Previously treated, locally advanced or metastatic cholangiocarcinoma: Anemia; decreased appetite; ascites, diarrhoea, nausea, abdominal pain; rash; fatigue; increased AST & blood bilirubin. Cholestatic jaundice, hyperbilirubinemia; fall; increased ALT, decreased WBC & platelet count.

Decreased plasma conc w/ strong CYP3A4 inducers eg, carbamazepine, phenobarb, phenytoin, rifampicin, St. John's wort (Hypericum perforatum). Increased AUC w/ itraconazole. Increased plasma conc w/ moderate (eg, aprepitant, ciclosporin, diltiazem, erythromycin, fluconazole, grapefruit & grapefruit juice, isavuconazole, verapamil) & strong (eg, clarithromycin, itraconazole, ketoconazole, posaconazole, ritonavir, voriconazole) CYP3A4 inhibitors. Prolonged QTc interval w/ anti-arrhythmics, fluoroquinolones, 5-HT3 receptor antagonists, triazole antifungals). May alter systemic exposure to active substances predominantly transported by P-gp (eg, dabigatran). May increase systemic exposure to OAT3 (eg, benzylpenicillin, furosemide) or OATP1B1/1B3 (eg, atorvastatin, pravastatin, rosuvastatin) substrates. May decrease systemic exposure to CYP3A4 (alfentanil, ciclosporin, everolimus, fentanyl, pimozide, quinidine, sirolimus, tacrolimus), CYP2B6 (cyclophosphamide, ifosfamide, methadone), CYP2C8 (paclitaxel, pioglitazone, repaglinide), CYP2C9 (phenytoin, warfarin), enzyme substrates w/ narrow therapeutic index; CYP2C19 substrate (eg, omeprazole); uridine diphosphate glucuronosyltransferases enzyme substrates (eg, lamotrigine, raltegravir). May decrease systemic conc of hormonal contraceptives.

Targeted Cancer Therapy

L01XM02 - ivosidenib ; Belongs to the class of isocitrate dehydrogenase (IDH) inhibitors. Used in the treatment of cancer.

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