Givinostat
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From MedlinePlus, U.S. National Library of Medicine
Histone Deacetylase Inhibitor
Dosing in kidney impairment
This label has no separate kidney-impairment dosing section. Check warnings and clinical pharmacology in the full label.
Dosing in liver impairment
Hepatic Impairment A dedicated clinical study was not conducted to evaluate the pharmacokinetics of DUVYZAT in subjects with hepatic impairment, and no recommendation for dosage adjustment can be made for patients with hepatic impairment. Because DUVYZAT is eliminated mainly through hepatic metabolism, hepatic impairment is expected to increase the exposure of givinostat [see Clinical Pharmacology ] .
Preparation and administration
Preparation and Administration Instructions See the Instructions for Use for further details. Before use, shake the DUVYZAT suspension for at least 30 seconds by inverting the bottle by 180°. Visually verify the homogeneity of the suspension. Using a graduated oral syringe, measure the appropriate volume of suspension corresponding to the prescribed dose of DUVYZAT.
Administer orally with the provided graduated oral syringe.
| WeightBased on actual body weight | Dosage | Oral Suspension Volume |
|---|---|---|
| 10 kg to less than 20 kg | 22.2 mg twice daily | 2.5 mL twice daily |
| 20 kg to less than 40 kg | 31 mg twice daily | 3.5 mL twice daily |
| 40 kg to less than 60 kg | 44.3 mg twice daily | 5 mL twice daily |
| 60 kg or more | 53.2 mg twice daily | 6 mL twice daily |
| First Dosage ModificationIf the adverse reaction(s) persist after the first dosage modification, proceed to the second dosage modification. | Second Dosage ModificationIf the adverse reaction(s) persist after the second dosage modification, DUVYZAT should be discontinued. | |||
|---|---|---|---|---|
| WeightBased on actual body weight | Dosage | Oral Suspension Volume | Dosage | Oral Suspension Volume |
| 10 kg to less than 20 kg | 17.7 mg twice daily | 2 mL twice daily | 13.3 mg twice daily | 1.5 mL twice daily |
| 20 kg to less than 40 kg | 22.2 mg twice daily | 2.5 mL twice daily | 17.7 mg twice daily | 2 mL twice daily |
| 40 kg to less than 60 kg | 31 mg twice daily | 3.5 mL twice daily | 26.6 mg twice daily | 3 mL twice daily |
| 60 kg or more | 39.9 mg twice daily | 4.5 mL twice daily | 35.4 mg twice daily | 4 mL twice daily |
Drug interactions
Check givinostat against a medication listLabel text (4 paragraphs)
Closely monitor when DUVYZAT is used in combination with an oral CYP3A4 sensitive substrate or a sensitive substrate of the OCT2 transporter, for which a small change in substrate plasma concentration may lead to serious toxicities. ( 7.1 ) Avoid concomitant use with other drugs that prolong the QTc interval; monitor ECG if concomitant use cannot be avoided. ( 7.2 )
7.1 Effect of DUVYZAT on Other Drugs CYP3A4 Sensitive Substrates Givinostat is a weak intestinal CYP3A4 inhibitor [see Clinical Pharmacology (12.3) ] . Closely monitor when DUVYZAT is used in combination with orally administered CYP3A4 sensitive substrates for which a small change in substrate plasma concentration may lead to serious toxicities. OCT2 Sensitive Substrates Givinostat is a weak inhibitor of the renal uptake transporter OCT2 [see Clinical Pharmacology (12.3) ] . Closely monitor when DUVYZAT is used in combination with drugs known as a sensitive substrate of the OCT2 transporter for which a small change in substrate plasma concentration may lead to serious toxicities.
7.2 Effect of Other Drugs on DUVYZAT Drugs that Prolong the QTc Interval Avoid concomitant use of DUVYZAT with other product(s) with a known potential to prolong the QTc interval. If concomitant use cannot be avoided, obtain ECGs when initiating, during concomitant use, and as clinically indicated [see Warnings and Precautions (5.4) ] . Withhold DUVYZAT if the QTc interval is > 500 ms or the change from baseline is > 60 ms [see Dosage and Administration (2.1) ] . DUVYZAT causes QTc interval prolongation [see Clinical Pharmacology (12.2) ] .
Concomitant use of DUVYZAT with other products that prolong the QTc interval may result in a greater increase in the QTc interval and adverse reactions associated with QTc interval prolongation, including Torsade de pointes, other serious arrythmias, and sudden death [see Warnings and Precautions (5.4) ] .
Contraindications
None. None. ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary DUVYZAT is indicated for the treatment of DMD, which is a disease of predominantly young male patients. Therefore, there are no adequate data available to assess the use of DUVYZAT in pregnant women. In animal studies, oral administration of givinostat during organogenesis resulted in decreased fetal body weight and increased structural variations; oral administration during pregnancy and lactation resulted in increased embryofetal and offspring mortality and neurobehavioral changes in the offspring. In the U.S.
general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Oral administration of givinostat (0, 40, 80, or 160 mg/kg/day) to pregnant rats throughout organogenesis resulted in reduced fetal body weight at the highest dose tested and increases in the incidence of skeletal and visceral variations at the mid and high doses. The no-effect dose (40 mg/kg/day) for adverse effects on embryofetal development was associated with maternal plasma exposures (AUC) lower than that in humans at the maximum recommended human dose (MRHD) of 53.2 mg twice daily.
Oral administration of givinostat (0, 40, 80, or 160 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in maternal death at the highest dose tested, resulting in too few fetuses to evaluate. No adverse effects on embryofetal development were observed at the low and mid doses. Plasma exposures (AUC) at the higher no-effect dose (80 mg/kg) for adverse effects on embryofetal development were approximately 4 times that in humans at the MRHD. Oral administration of givinostat (0, 40, 80, or 160 mg/kg/day) to rats throughout pregnancy and lactation resulted in increases in embryofetal mortality, stillbirths, and offspring mortality at the highest dose tested.
When offspring were tested postweaning (postnatal day 49), adverse effects on behavior (decreased open field activity) were observed at all doses. A no-effect dose for adverse developmental effects was not identified; plasma exposures (AUC) at the lowest dose tested were lower than that in humans at the MRHD.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
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