Formulary
Givinostat: Indications, Dosing, Side Effects and Interactions
Givinostat is a histone deacetylase inhibitor that reduces muscle loss and inflammation in dystrophic muscles, although its exact mechanism of action is...
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Givinostat: Indications, Dosing, Side Effects and Interactions
Givinostat is a histone deacetylase inhibitor that reduces muscle loss and inflammation in dystrophic muscles, although its exact mechanism of action is...
Drug action
Givinostat is a histone deacetylase inhibitor that reduces muscle loss and inflammation in dystrophic muscles, although its exact mechanism of action is unknown.
Indications and dose
**Duchenne muscular dystrophy**
- **Adult** (By Mouth): (body-weight 60 kg and above) 53.2 mg twice daily, for dose adjustments, treatment interruption, or discontinuation due to side-effects-consult product literature.
**Duchenne muscular dystrophy for givinostat**
- **Child 6-17 years (body-weight 10-19 kg)** (By mouth): 22.2 mg twice daily, for dose adjustments, treatment interruption, or discontinuation due to side-effects-consult product literature.
- **Child 6-17 years (body-weight 20-39 kg)** (By mouth): 31 mg twice daily, for dose adjustments, treatment interruption, or discontinuation due to side-effects-consult product literature.
- **Child 6-17 years (body-weight 40-59 kg)** (By mouth): 44.3 mg twice daily, for dose adjustments, treatment interruption, or discontinuation due to side-effects-consult product literature.
- **Child 6-17 years (body-weight 60 kg and above)** (By mouth): 53.2 mg twice daily, for dose adjustments, treatment interruption, or discontinuation due to side-effects-consult product literature.
Cautions
Risk factors for ventricular arrhythmias (e.g congenital long QT syndrome, coronary artery disease, electrolyte disturbances, concomitant use with other drugs known to prolong the QT interval) Cautions, further information ECG monitoring In patients with underlying cardiac disease or using other drugs known to prolong the QT interval, an ECG should be obtained before starting treatment, during concomitant use, and as clinically indicated. M
Contraindications
Platelet count less than 150 x 10 9 cells/litre (do not initiate); QTc interval more than 500 milliseconds
Side effects
Common or very common Appetite decreased; arthralgia; constipation; diarrhoea; fatigue; fever; gastrointestinal discomfort; gastrointestinal disorders; hypertriglyceridaemia; myalgia; nausea; rash; thrombocytopenia; vomiting Frequency not known Hypothyroidism
Interactions
**Severe interactions:**
- Closely monitor when Duvyzat is used in combination with orally administered CYP3A4 sensitive substrates (e.g., alfentanil, tacrolimus, sirolimus, lovastatin, simvastatin, indinavir, sildenafil,...
- Closely monitor when Duvyzat is used in combination with drugs known as a sensitive substrate of the OCT2 transporter (e.g.: metformin, dofetilide) for which a small change in substrate plasma...
**Other interactions (4):**
- Effect of other medicinal products on givinostat pharmacokinetics Avoid concomitant use of Duvyzat with other product(s) with a known potential to prolong the QTc interval.
- Caution is advised when prescribing Duvyzat with medicinal products known to prolong the QTc interval with known or possible risk for torsades de pointes, e.g.
- Effect of givinostat on pharmacokinetics of other medicinal products Givinostat is a weak intestinal CYP3A4 inhibitor.
- Givinostat is a weak inhibitor of the renal uptake transporter OCT2.
Pregnancy
Avoid (toxicity in animal studies). M
Breast feeding
Specialist sources indicate use with caution, especially if breast-feeding a newborn or pre-term infant (no information available). High plasma-protein binding suggests limited excretion into milk. Monitor breast-fed infant for side-effects.
Medicinal forms
Clinical governance
**Author:** MedNext Clinical Team. **Clinical reviewer:** Dr Shameer Deen, MBBS, MS, MRCS. **Sources:** BNF, Indian Pharmacopoeia, CIMS India. **Correction:** Report errors at support@mednext.academy.
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