midostaurin: prescribing and clinical use
Focused clinical detail for use alongside current product information, local policy and patient-specific assessment.
midostaurin: clinical details
Prescribing considerations
- Confirm FLT3-ITD or FLT3-TKD mutation with a validated assay before use for AML.
- Control active serious infection before monotherapy and review promptly if infection develops.
- Use caution with cardiac dysfunction, QT-risk factors, electrolyte disturbance, pulmonary disease, and severe or end-stage renal impairment.
- Review pregnancy potential, contraception and fertility preservation before treatment.
- Acute promyelocytic leukaemia has not been studied and use is not recommended.
- Do not combine with intensive paediatric AML regimens containing anthracyclines, fludarabine and cytarabine because prolonged haematological recovery has occurred.
Contraindications and cautions
- Hypersensitivity to midostaurin or a formulation excipient.
- Concurrent potent CYP3A4 inducers, including rifampicin, carbamazepine, phenytoin, enzalutamide and St John’s wort.
Monitoring
- Full blood count, particularly white-cell and neutrophil counts.
- Clinical evidence of infection.
- Respiratory symptoms suggesting pneumonitis or interstitial lung disease.
- Electrolytes, liver tests, blood glucose and pancreatic enzymes as clinically appropriate.
- ECG when QT prolongation risk is present; correct modifiable electrolyte abnormalities.
- Cardiac function, including left ventricular ejection fraction when clinically indicated.
- Treatment toxicity when strong CYP3A4 inhibition cannot be avoided.
Clinical pharmacology
Midostaurin is a multikinase inhibitor of FLT3, mutant KIT and several other receptor and serine/threonine kinases. It is extensively metabolised through CYP3A4 and has two pharmacologically active metabolites.
Formulation and product differences
- The selected UK product is a soft capsule that must be swallowed intact.
- The formulation contains ethanol and macrogolglycerol hydroxystearate; the latter may cause stomach discomfort and diarrhoea.
- The ethanol content warrants consideration in pregnancy and in people with liver disease, epilepsy or alcohol-related problems.
midostaurin preparations and strengths
Capsule
Route: Oral
Strengths: 25 mg
midostaurin interactions
Provide the specialist team with a complete list of prescribed, non-prescription and herbal products before starting anything new.
Rifampicin, carbamazepine, phenytoin, enzalutamide and St John’s wort
These potent CYP3A4 inducers substantially reduce midostaurin exposure and must not be used concurrently.
Strong CYP3A4 inhibitors, including ketoconazole, itraconazole, clarithromycin and ritonavir
These can increase midostaurin exposure; alternatives should be considered or toxicity monitored closely.
Medicines that prolong the QT interval
They may add to the risk of abnormal cardiac repolarisation, so ECG assessment may be needed.
Sources
These sources were used to prepare and review this medicine page.
Prepared and reviewed by the iatroX editorial team.