Semistauro

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

AML 50 mg bd on Days 8-21 of induction & consolidation chemotherapy cycles. Patient in complete response Daily dose as single agent maintenance therapy until relapse for up to 12 cycles of 28 days each. ASM, SM-AHN & MCL 100 mg bd.

Should be taken with food: Swallow whole w/ glass of water, do not open/crush/chew.

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

Discontinue use if recurrent or prolonged severe neutropenia develops; pulmonary symptoms indicative of ILD or ≥Grade 3 pneumonitis w/o infectious aetiology is experienced. Interrupt treatment if unexplained severe neutropenia develops or until ANC is ≥1 x 10⁹/L. Not recommended in acute promyelocytic leukaemia. Active serious & device-related infections; symptomatic CHF, patients at risk of QTc prolongation. Regularly monitor WBC prior to initiation. Assess LVEF when clinically indicated at baseline & during treatment. Concurrent use w/ QT interval-prolonging medicinal products. Concomitant use w/ strong CYP3A4 inhibitors eg, antifungals, certain antivirals, macrolides & nefazodone. May affect ability to drive & use machines. Severe hepatic & renal impairment; ESRD. May impair fertility. Women of childbearing potential should use effective contraception during & for at least 4 mth after last dose. Not recommended during pregnancy. Not to be used during lactation & for at least 4 mth after last dose. Not to be used in combination w/ intensive paed AML combination chemotherapy regimens due to risk of prolonged haematological recovery.

Headache; dyspnoea, epistaxis; nausea, vomiting; pyrexia; hyperglycaemia, decreased ANC, increased ALT & AST, prolonged ECG QT. URTI; febrile neutropenia; hypersensitivity; tremor; hypotension; pleural effusion, ILD/pneumonitis; increased wt. AML: Device-related infection; petechiae, lymphopenia; insomnia; laryngeal pain; stomatitis, upper abdominal pain, haemorrhoids; exfoliative dermatitis, hyperhidrosis; back pain, arthralgia; decreased Hb, hypokalaemia, hypernatraemia, prolonged aPTT. Hyperuricaemia; syncope; eyelid oedema; sinus tachycardia, HTN, pericardial effusion; nasopharyngitis, acute resp distress syndrome; anorectal & abdominal discomfort; dry skin, keratitis; bone & neck pain, pain in extremity; catheter-related thrombosis; hypercalcaemia. ASM, SM-AHN & MCL: UTI; dizziness; cough; diarrhoea, constipation; peripheral oedema, fatigue; decreased absolute lymphocyte, increased total bilirubin, lipase & amylase. Pneumonia, sepsis, bronchitis, oral herpes, cystitis, sinusitis, erysipelas, herpes zoster; attention disturbance; vertigo; haematoma; oropharyngeal pain; dyspepsia, GI haemorrhage; asthenia, chills, oedema; 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. Concomitant use w/ narrow therapeutic range substrates of CYP2B6 (eg, bupropion, efavirenz), CYP1A2 (eg, tizanidine), CYP2E1 (eg, chlorzoxazone) & BCRP (eg, rosuvastatin, atorvastatin).

Targeted Cancer Therapy

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

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