Duchenne muscular dystrophy

Active Ingredient: Givinostat

Indication for Givinostat

Population group: only children (1 year - 12 years old) , adolescents (12 years - 18 years old) , adults (18 - 65 years old)
Therapeutic intent: Curative procedure

Givinostat is indicated for the treatment of Duchenne muscular dystrophy (DMD) in ambulant patients, aged 6 years and older, and with concomitant corticosteroid treatment.

For this indication, competent medicine agencies globally authorize below treatments:

22.2-53.2 mg twice daily based on body weight

For:

Dosage regimens

Regimen A, in the case that patient age in years is ≥ 6 and patient weight is ≥ 15 kg and patient weight is < 20 kg :

Oral, 22.2 milligrams givinostat, 2 times daily.

Regimen B, in the case that patient age in years is ≥ 6 and patient weight is ≥ 20 kg and patient weight is < 40 kg :

Oral, 31 milligrams givinostat, 2 times daily.

Regimen C, in the case that patient age in years is ≥ 6 and patient weight is ≥ 40 kg and patient weight is < 60 kg :

Oral, 44.3 milligrams givinostat, 2 times daily.

Regimen D, in the case that patient age in years is ≥ 6 and patient weight is ≥ 60 kg :

Oral, 53.2 milligrams givinostat, 2 times daily.

Detailed description

Baseline platelet counts and triglycerides should be obtained and evaluated prior to initiation of givinostat. Givinostat should not be initiated in patients with a platelet count less than 150 x 109/l. Platelet counts and triglycerides should be monitored as recommended during treatment to determine if dosage modifications are needed (see dose adjustment instructions below).

In addition, in patients with underlying cardiac disease or taking concomitant medicines that cause QT prolongation, an ECG should be obtained when initiating treatment with givinostat, during concomitant use, and as clinically indicated.

The recommended dose of givinostat is based on body weight and should be administered orally twice daily (see Table 1).

Table 1. Recommended Dosage:

WeightaDosage
15 kg to less than 20 kg22.2 mg twice daily
20 kg to less than 40 kg31 mg twice daily
40 kg to less than 60 kg44.3 mg twice daily
60 kg or more53.2 mg twice daily

a Based on actual body weight

The decision to continue treatment in patients who become non-ambulatory should be taken at the discretion of the physician based on the overall benefit and risk assessment.

Dose adjustment for thrombocytopenia, diarrhoea or hypertriglyceridaemia

A dose reduction (see Table 2) should be applied for patient with:

  • Platelet count <150 x 109/l verified by two assessments one week apart,

or

  • Moderate or severe diarrhoea (more than 4 stools per day),

or

  • Fasting triglycerides >300 mg/dl verified by two assessments one week apart.

Based on the severity of these adverse reactions, treatment interruption prior to dosage modification should be considered.

Table 2. Dosage modifications for adverse reactions:

 First Dosage ModificationbSecond Dosage Modificationc
WeightaDosageDosage
15 kg to less
than 20 kg
17.7 mg twice daily13.3 mg twice daily
20 kg to less
than 40 kg
22.2 mg twice daily17.7 mg twice daily
40 kg to less
than 60 kg
31 mg twice daily26.6 mg twice daily
60 kg or
more
39.9 mg twice daily35.4 mg twice daily

a Based on actual body weight
b If the adverse reaction(s) persist after the first dosage modification, proceed to the second dosage modification.
c If the adverse reaction(s) persist after the second dosage modification, givinostat should be discontinued.

Patients should not take a double or extra dose if a dose is missed.

Active ingredient

Givinostat

Givinostat is a class I and II histone deacetylase (HDAC) inhibitor that modulates the uncontrolled HDAC activity in dystrophic muscles, which contributes to the pathology of Duchenne muscular dystrophy (DMD). Givinostat HDAC inhibition has been shown to reduce muscle fiber damage, chronic muscular inflammation, fibrosis, fat deposition, and to promote mitochondrial biogenesis.

Read more about Givinostat

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