Rydapt

In combination w/ standard daunorubicin & cytarabine induction & high-dose cytarabine consolidation chemotherapy, & for patients in complete response followed by Rydapt single agent maintenance therapy, for adult patients w/ newly diagnosed AML who are FLT3 mutation +ve. As monotherapy for treatment of adult patients w/ aggressive systemic mastocytosis (ASM), systemic mastocytosis w/ associated haematological neoplasm (SM-AHN), or mast cell leukaemia (MCL).

AML 50 mg bd (approx 12-hr intervals) dosed on days 8-21 of induction & consolidation chemotherapy cycles. Patient in complete response Dose every day as single agent maintenance therapy until relapse for up to 12 cycles of 28 days each. ASM, SM-AHN & MCL 100 mg bd (approx 12-hr intervals). Continue treatment as long as clinical benefit is observed or until unacceptable toxicity occurs.

Should be taken with food: Swallow whole w/ water. Do not open/crush/chew.

Hypersensitivity. Concomitant use w/ potent CYP3A4 inducers (eg, rifampicin, St. John's wort, carbamazepine, enzalutamide, phenytoin).

Risk of neutropenia & infections; cardiac dysfunction eg, CHF & transient decreases in left ventricular ejection fraction (LVEF); increased frequency of QTc prolongation; ILD & pneumonitis. Regularly monitor WBC counts, especially at treatment initiation. Monitor for signs & symptoms of infection. Assess LVEF when clinically indicated (at baseline & during treatment). Caution in patients at risk of QTc prolongation (eg, due to concomitant medicinal products &/or electrolyte disturbances). Consider interval assessments of QT by ECG if Rydapt is taken concurrently w/ medicinal products that can prolong QT interval. Monitor for pulmonary symptoms indicative of ILD or pneumonitis. Caution when concomitantly prescribing w/ strong CYP3A4 inhibitors eg, antifungals (eg, ketoconazole), certain antivirals (eg, ritonavir), macrolide antibiotics (eg, clarithromycin) & nefazodone. Contains macrogolglycerol hydroxystearate & 14 vol % ethanol anhydrous. Minor influence on ability to drive & use machines. Limited clinical experience in patients w/ severe renal impairment & no data available in patients w/ ESRD. Insufficient efficacy data in patients w/ severe hepatic impairment. Can cause foetal harm. Not recommended during pregnancy or in women of childbearing potential not using contraception. Sexually active women of childbearing potential should have a pregnancy test w/in 7 days prior to starting treatment, & should use effective contraception during treatment & for at least 4 mth after stopping treatment. Discontinue breast-feeding during treatment & for at least 4 mth after stopping treatment. Should not be used in combination w/ intensive paed AML combination chemotherapy regimens (including anthracyclines, fludarabine & cytarabine) because of the risk of prolonged haematological recovery. Should be used in elderly ≥60 yr only if eligible to receive intensive induction chemotherapy w/ adequate performance status & w/o significant comorbidities. Not recommended in patients w/ acute promyelocytic leukaemia.

AML: Device-related infection; febrile neutropenia, petechiae, lymphopenia; hypersensitivity; insomnia; headache; hypotension; epistaxis, laryngeal pain, ILD/pneumonitis, dyspnoea; nausea, vomiting, stomatitis, upper abdominal pain, haemorrhoids; dermatitis exfoliative, hyperhidrosis; back pain, arthralgia; pyrexia; decreased Hb & ANC, increased ALT & AST, hypokalaemia, hyperglycaemia, hypernatraemia, prolonged ECG QT & aPTT. URTI; hyperuricaemia; syncope, tremor; eyelid oedema; sinus tachycardia, HTN, pericardial effusion; pleural effusion, nasopharyngitis, acute resp distress syndrome; anorectal/abdominal discomfort; dry skin, keratitis; bone pain, pain in extremity, neck pain; catheter-related thrombosis; hypercalcaemia, increased wt. ASM, SM-AHN & MCL: UTI, URTI; headache, dizziness; dyspnoea, cough, pleural effusion, epistaxis; nausea, vomiting, diarrhoea, constipation; peripheral oedema, fatigue, pyrexia; hyperglycaemia (non-fasting), decreased absolute lymphocyte & ANC, increased total bilirubin, lipase, AST, ALT, amylase, & prolonged ECG QT. Pneumonia, sepsis, bronchitis, oral herpes, cystitis, sinusitis, erysipelas, herpes zoster; febrile neutropenia; hypersensitivity; disturbance in attention, tremor; vertigo; hypotension, haematoma; oropharyngeal pain, ILD/pneumonitis; dyspepsia, GI haemorrhage; asthenia, chills, oedema; increased wt; contusion, fall.

Decreased exposure w/ strong CYP3A4 inducers (eg, carbamazepine, rifampicin, enzalutamide, phenytoin, St. John's wort). Increased exposure w/ strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole). Medicinal products w/ narrow therapeutic range that are substrates of CYP2B6 (eg, bupropion or efavirenz), CYP1A2 (eg, tizanidine), CYP2E1 (eg, chlorzoxazone), & BCRP (eg, rosuvastatin or atorvastatin) may need dose adjustment to maintain optimal exposure when administered concomitantly w/ midostaurin. Increased absorption (AUC) & reduced peak conc (C_max) w/ standard & high-fat meal.

Targeted Cancer Therapy

L01EX10 - midostaurin ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.

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