Semistauro Special Precautions

Neutropenia and infections: Neutropenia has occurred in patients receiving SEMISTAURO as monotherapy and in combination with chemotherapy (see Adverse Reactions). Severe neutropenia (ANC <0.5 x 10⁹/l) was generally reversible by withholding SEMISTAURO until recovery and discontinuation in the ASM, SM-AHN, and MCL studies.
White blood cell counts (WBCs) should be monitored regularly, especially at treatment initiation.
In patients who develop unexplained severe neutropenia, treatment with SEMISTAURO should be interrupted until ANC is ≥1.0 x 10⁹/l, as recommended in Tables 5 and 6. SEMISTAURO should be discontinued in patients who develop recurrent or prolonged severe neutropenia that is suspected to be related to SEMISTAURO (see Dosage & Administration).
Any active serious infection should be under control prior to starting treatment with SEMISTAURO monotherapy. Patients should be monitored for signs and symptoms of infection, including any device-related infections, and if a diagnosis of infection is made, appropriate treatment must be instituted promptly, including, as needed, the discontinuation of SEMISTAURO.
Cardiac dysfunction: Patients with symptomatic congestive heart failure were excluded from clinical studies. In the ASM, SM-AHN, and MCL studies, cardiac dysfunction such as congestive heart failure (CHF) (including some fatalities) and transient decreases in left ventricular ejection fraction (LVEF) occurred. In the randomised AML study, no difference in CHF was observed between the SEMISTAURO + chemotherapy and placebo + chemotherapy arms. In patients at risk, SEMISTAURO should be used with caution and the patient closely monitored by assessing LVEF when clinically indicated (at baseline and during treatment).
An increased frequency of QTc prolongation was noted in midostaurin-treated patients (see Adverse Reactions), however, a mechanistic explanation for this observation was not found. Caution is warranted in patients at risk of QTc prolongation (e.g. due to concomitant medicinal products and/or electrolyte disturbances). Interval assessments of QT by ECG should be considered if SEMISTAURO is taken concurrently with medicinal products that can prolong QT interval.
Pulmonary toxicity: Interstitial lung disease (ILD) and pneumonitis, in some cases fatal, have occurred in patients treated with SEMISTAURO monotherapy or in combination with chemotherapy. Patients should be monitored for pulmonary symptoms indicative of ILD or pneumonitis, and SEMISTAURO discontinued in patients who experience pulmonary symptoms indicative of ILD or pneumonitis without an infectious aetiology that are ≥Grade 3 (NCI CTCAE).
Embryofoetal toxicity and breast-feeding: Pregnant women should be informed of the potential risk to a foetus; females of reproductive potential should be advised to have a pregnancy test within 7 days prior to starting treatment with SEMISTAURO and to use effective contraception during treatment with SEMISTAURO and for at least 4 months after stopping treatment.
Because of the potential for serious adverse reactions in breast-feeding infants from SEMISTAURO, women should discontinue breast-feeding during treatment with SEMISTAURO and for at least 4months after stopping treatment (see Use in Pregnancy & Lactation).
Severe renal impairment: Caution is warranted when considering the administration of midostaurin in patients with severe renal impairment or end-stage renal disease and patients should be carefully monitored for toxicity (see Pharmacology: Pharmacokinetics under Actions).
Interactions: Caution is required when concomitantly prescribing with midostaurin medicinal products that are strong inhibitors of CYP3A4, such as, but not limited to, antifungals (e.g. ketoconazole), certain antivirals (e.g. ritonavir), macrolide antibiotics (e.g. clarithromycin), and nefazodone because they can increase the plasma concentrations of midostaurin especially when (re-)starting with midostaurin treatment (see Interactions). Alternative medicinal products that do not strongly inhibit CYP3A4 activity should be considered. In situations where satisfactory therapeutic alternatives do not exist, patients should be closely monitored for midostaurin-related toxicity.
Excipients: This medicine contains 109.418 mg of alcohol (ethanol) in each capsule <which is equivalent to 13.23 %w/w>. The amount in each capsule of this medicine is equivalent to less than 2.74 ml beer or 1.10 ml wine. The small amount of alcohol in this medicine will not have any noticeable effects. Alcohol may be harmful in patients with alcohol-related problems, epilepsy, or liver problems, or during pregnancy or breast-feeding.
Effects on ability to drive and use machines: SEMISTAURO has minor influence on the ability to drive and use machines. Dizziness and vertigo have been reported in patients taking SEMISTAURO and should be considered when assessing a patient's ability to drive or use machines.
Use in Children: Paediatric patients: SEMISTAURO should not be used in combination with intensive paediatric AML combination chemotherapy regimens including anthracyclines, fludarabine and cytarabine because of the risk of prolonged haematological recovery (such as prolonged severe neutropenia and thrombocytopenia) (see Dosage & Administration and Pharmacology: Pharmacodynamics under Actions).