Givinostat: prescribing and clinical use
Focused clinical detail for use alongside current product information, local policy and patient-specific assessment.
Givinostat: clinical details
Prescribing considerations
- Initiate and supervise within a specialist Duchenne muscular dystrophy service.
- Pivotal evidence came from ambulant male patients receiving stable corticosteroid treatment; initiation in non-ambulant patients was not studied in that trial.
- Review medicines for QT-prolonging, sensitive CYP3A4-substrate and OCT2-substrate interactions.
Contraindications and cautions
- Hypersensitivity to givinostat or an excipient.
- Hereditary fructose intolerance because the suspension contains sorbitol.
- Avoid in patients at increased risk of ventricular arrhythmia, including congenital long-QT syndrome or important uncorrected electrolyte disturbance.
Monitoring
- Full blood count, particularly platelets.
- Fasting triglycerides.
- ECG when cardiac disease or another QT-prolonging medicine is present.
- Bleeding, diarrhoea, vomiting, dehydration and reduced appetite.
- Consider thyroid testing if clinically indicated because hypothyroidism or raised TSH has been reported.
Clinical pharmacology
Givinostat is an HDAC inhibitor with an incompletely defined mechanism in Duchenne muscular dystrophy. Food increases systemic exposure. It is highly protein-bound and extensively metabolised; unchanged urinary excretion is minimal. It weakly inhibits intestinal CYP3A4 and renal OCT2.
Formulation and product differences
- Peach-cream-flavoured oral suspension supplied with a graduated oral syringe.
- Contains sorbitol and sodium benzoate and is essentially sodium-free.
Givinostat preparations and strengths
Oral suspension
Route: Oral
Strengths: 8.86 mg/mL
Givinostat interactions
Give the specialist and pharmacist a complete medicines list. Important interactions include:
Medicines that prolong the QT interval
Examples include amiodarone, sotalol, ondansetron, azithromycin, clarithromycin, ciprofloxacin, fluconazole, risperidone and some anaesthetics. These can add to the risk of an abnormal heart rhythm.
Sensitive oral CYP3A4 substrates
Givinostat weakly inhibits intestinal CYP3A4, so medicines including tacrolimus, sirolimus, simvastatin, sildenafil or midazolam may require closer toxicity monitoring.
OCT2 substrates
Exposure to sensitive medicines such as metformin or dofetilide may increase because givinostat weakly inhibits OCT2.
Sources
These sources were used to prepare and review this medicine page.
Prepared and reviewed by the iatroX editorial team.