Givinostat

Acknowledgment
This article consists of drug labeling information developed under U.S. FDA guidance and excerpted from DailyMed. It was not reviewed by the MedLink Neurology Editorial Board. For the latest FDA-approved information about this drug, visit Drugs@FDA.com.

Highlights

Indications and usage
Givinostat (Duvyzat®) is a histone deacetylase inhibitor indicated for the treatment of Duchenne muscular dystrophy in patients 6 years of age and older.
Dosage and administration
	• Obtain and evaluate baseline platelet counts and triglycerides before initiation of givinostat. Do not initiate givinostat in patients with a platelet count less than 150 x 10^9/L.
	• The dosage of givinostat is based on the patient’s body weight.
	• Administer orally twice daily with food.
	• Dosage modifications may be needed for decreased platelet counts, diarrhea, increased triglycerides, or QTc prolongation.
Dosage forms and strengths
Oral suspension: 8.86 mg/mL givinostat.
Note: Givinostat was first approved by the U.S. FDA in 2024.

Contraindications
None
Warnings and precautions
	• Hematological changes. Givinostat can cause dose-related thrombocytopenia and other signs of myelosuppression, including anemia and neutropenia. Monitor platelets; dosage adjustment or discontinuation may be needed.
	• Increased triglycerides. An increase in triglycerides can occur; dosage modification may be needed. Discontinuation may be needed.
	• Gastrointestinal disturbances. Adjust dosage if moderate or severe diarrhea occurs. Antiemetics or antidiarrheal medications may be considered during treatment with givinostat. Discontinue givinostat if the symptoms persist.
	• QTc prolongation. Avoid the use of givinostat in patients who are at an increased risk for ventricular arrhythmias.
Adverse reactions
Most common adverse reactions (10% or greater in givinostat-treated patients) are diarrhea, abdominal pain, thrombocytopenia, nausea/vomiting, hypertriglyceridemia, and pyrexia.
To report suspected adverse reactions, contact ITF Therapeutics, LLC. at 1-833-582-4312 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drug interactions
	• Closely monitor when givinostat 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.
	• Avoid concomitant use with other drugs that prolong the QTc interval; monitor ECG if concomitant use cannot be avoided.
Use in specific populations
	• Pregnancy. Based on animal data, givinostat may cause fetal harm.
	• Hepatic impairment. Exposure to givinostat is expected to be increased
See Patient counseling information and medication guide available in the DAILYMED drug label information.

Indications and usage

Givinostat is indicated for the treatment of Duchenne muscular dystrophy in patients 6 years of age and older.

Dosage and administration

Recommended evaluation and testing before initiation of givinostat

Obtain and evaluate baseline platelet counts and triglycerides before initiation of givinostat. Do not initiate givinostat in patients with a platelet count less than 150 x 109/L. Monitor platelet counts and triglycerides as recommended during treatment to determine if dosage modifications are needed.

In addition, in patients with underlying cardiac disease or taking concomitant medications that cause QT prolongation, obtain ECGs when initiating treatment with givinostat, during concomitant use, and as clinically indicated.

Recommended dosage

The recommended dosage of givinostat is based on body weight and is administered orally twice daily with food (see Table 1).

Table 1. Recommended Dosage in Patients 6 Years of Age and Older for the Treatment of Duchenne Muscular Dystrophy

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
* Based on actual body weight

Dosage modifications for adverse reactions

Decrease in platelets, diarrhea, increase in triglycerides. Givinostat may cause adverse reactions, which may necessitate a dosage modification (see Table 2) if the following occur:

• Platelet count less than 150 x 109/L verified in two assessments 1 week apart
or
• Moderate or severe diarrhea
or
• Fasting triglycerides greater than 300 mg/dL verified by two assessments 1 week apart

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

Table 2. Dosage Modifications for Adverse Reactions in Patients 6 Years of Age and Older for the Treatment of Duchenne Muscular Dystrophy

	First dosage modification*		Second dosage modification†
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
* If the adverse reaction(s) persist after the first dosage modification, proceed to the second dosage modification. † If the adverse reaction(s) persist after the second dosage modification, givinostat should be discontinued. ‡ Based on actual body weight

QTc interval prolongation. Withhold givinostat if the QTc interval is more than 500 ms or the change from baseline is more than 60 ms.

Preparation and administration instructions

See the Instructions for use for further details.

	• Before use, shake the givinostat 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 givinostat.
	• Administer orally with the provided graduated oral syringe.

Missed dose

If a dose is missed, patients should not take double or extra doses.

Dosage forms and strengths

Oral suspension: 8.86 mg/mL givinostat as a white to off-white or faintly pink, peach-cream flavored suspension.

Contraindications

None.

Warnings and precautions

Hematological changes

Givinostat can cause dose-related thrombocytopenia and other signs of myelosuppression, including decreased hemoglobin and neutropenia.

In Study 1, thrombocytopenia occurred in 33% of patients treated with givinostat compared to no patients on placebo. The maximum decrease in platelets occurred within the first 2 months of therapy and remained low throughout the course of therapy. In a few patients, thrombocytopenia was associated with bleeding events, including epistaxis, hematoma, or contusions. Low platelet counts resulted in givinostat dose reduction in 28% of patients. Patients with baseline platelet counts below the lower limit of normal were excluded from the study.

Decreased hemoglobin and decreased neutrophils were also observed in patients treated with givinostat compared to placebo.

Monitor blood counts every 2 weeks for the first 2 months of treatment, then monthly for the first 3 months, and every 3 months thereafter. Modify the dosage of givinostat for confirmed thrombocytopenia. Treatment should be permanently discontinued if the abnormalities worsen despite dose modification. If a patient develops signs or symptoms of thrombocytopenia, obtain a platelet count as soon as possible and hold dosing until the platelet count is confirmed.

Increased triglycerides

Givinostat can cause elevations in triglycerides. In Study 1, hypertriglyceridemia occurred in 23% of patients treated with givinostat (one of whom had familial hypertriglyceridemia) compared to 7% of patients on placebo. High triglycerides (ie, levels greater than 300 mg/dL) resulted in discontinuation and led to dosage modification in 2% and 8%, respectively, of patients treated with givinostat.

Monitor triglycerides at 1 month, 3 months, 6 months, and then every 6 months thereafter. Modify the dosage if fasting triglycerides are verified more than 300 mg/dL. Treatment with givinostat should be discontinued if triglycerides remain elevated despite adequate dietary intervention and dosage adjustment.

Gastrointestinal disturbances

Gastrointestinal disturbances, including diarrhea, nausea, vomiting, and abdominal pain, were common adverse reactions in givinostat clinical trials in Duchenne muscular dystrophy. In Study 1, diarrhea was reported in 37% of patients treated with givinostat (with one severe case reported) compared to 20% of patients on placebo. Diarrhea usually occurred within the first few weeks of initiation of treatment with givinostat.

Vomiting and nausea, sometimes severe and usually occurring within the first 2 months of treatment, occurred in 32% of patients treated with givinostat compared to 18% of patients on placebo. Abdominal pain occurred in 34% of patients treated with givinostat compared to 25% of patients on placebo. One case of abdominal pain was serious.

Antiemetics or antidiarrheal medications may be considered during treatment with givinostat. Fluid and electrolytes should be replaced as needed to prevent dehydration. Modify the dosage of givinostat in patients with moderate or severe diarrhea, and treatment should be discontinued if significant symptoms persist.

QTc prolongation

Givinostat can cause prolongation of the QTc interval. Avoid use of givinostat in patients who are at an increased risk for ventricular arrhythmias (including torsades de pointes), such as those with congenital long QT syndrome, coronary artery disease, electrolyte disturbance, or concomitant use of other medicinal products known to cause QT prolongation. Obtain ECGs before initiating treatment with givinostat in patients with underlying cardiac disease or in patients who are taking concomitant medications that cause QT prolongation.

Adverse reactions

The following clinically significant adverse reactions are described below and elsewhere in the labeling:

	• Hematological changes
	• Increased triglycerides
	• Gastrointestinal disturbances
	• QTc prolongation

Clinical trials experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In controlled and uncontrolled trials in patients with confirmed Duchenne muscular dystrophy, 222 male patients aged 6 years and older were treated with givinostat, including 210 patients treated for 6 or more months, 187 patients for 12 or more months, and 105 patients for 24 or more months.

The safety profile of givinostat is based on a double-blind, placebo-controlled, 18-month study in a total of 179 ambulant patients with Duchenne muscular dystrophy aged 6 years or older on concomitant steroid treatment (Study 1). The dosage in Study 1 was weight-based. Patients were excluded from the study if they had the following abnormalities at the screening visit: platelet, white blood cell, or hemoglobin counts less than the lower limit of normal, triglycerides greater than 300 mg/dL (3.42 mmol/L) in fasting condition, or had a baseline-corrected QT interval, Fridericia’s correction (QTcF) of longer than 450 msec (mean of three consecutive readings 5 minutes apart) or a history of additional risk factors for torsades de pointes (eg, heart failure, hypokalemia, or family history of long QT syndrome). Overall, 2% of patients discontinued the study because of adverse reactions.

Adverse reactions reported in more than 5% of givinostat-treated patients at a frequency at least 5% greater than that of the placebo group are presented in Table 3 below.

Table 3. Adverse Reactions Reported in More Than 5% of Givinostat-Treated Patients and at Least 5% Greater than Placebo in Study 1

Adverse reaction	Givinostat (N=118) %	Placebo (N=61) %
Diarrhea	37%	20%
Abdominal pain	34%	25%
Thrombocytopenia*	33%	0%
Nausea/Vomiting	32%	18%
Hypertriglyceridemia	23%	7%
Pyrexia	13%	8%
Myalgia	9%	3%
Rash	9%	2%
Arthralgia	8%	2%
Fatigue	8%	0%
Constipation	7%	2%
Decreased appetite	7%	0%
* Thrombocytopenia includes decreased platelet count and thrombocytopenia

Less common adverse reactions in Study 1. Adverse reactions of hypothyroidism or thyroid-stimulating hormone increased in 5% of patients treated with givinostat compared to 2% of patients who received placebo.

Drug interactions

Effect of givinostat on other drugs

CYP3A4 sensitive substrates. Givinostat is a weak intestinal CYP3A4 inhibitor. Closely monitor when givinostat 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. Closely monitor when givinostat is used in combination with drugs known as sensitive substrates of the OCT2 transporter, for which a small change in substrate plasma concentration may lead to serious toxicities.

Effect of other drugs on givinostat

Drugs that prolong the QTc interval. Avoid concomitant use of givinostat with other products 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. Withhold givinostat if the QTc interval is longer than 500 ms or the change from baseline is longer than 60 ms.

Givinostat causes QTc interval prolongation. Concomitant use of givinostat 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 arrhythmias, and sudden death.

Use in specific populations

Pregnancy

Risk summary. Givinostat is indicated for the treatment of Duchenne muscular dystrophy, which is a disease of predominantly young male patients. Therefore, there are no adequate data available to assess the use of givinostat 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% to 4% and 15% to 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 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 four times that in humans at the maximum recommended human dose.

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 those in humans at the maximum recommended human dose.

Lactation

Risk summary. There are no human or animal data to assess the effect of givinostat or its metabolites on milk production, the presence of givinostat in milk, or the effects on the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for givinostat and any potential adverse effects on the breastfed infant from givinostat or from the underlying maternal condition.

Females and males of reproductive potential

No human data are available on the effect of givinostat on reproductive potential.

Animal studies indicate possible adverse effects on reproduction.

Pediatric use

The safety and effectiveness of givinostat in children aged 6 years and older have been established. Safety and effectiveness in pediatric patients below the age of 6 years have not been established.

Juvenile animal data. In a study in juvenile male and female rats, givinostat was orally administered at doses of 0, 10, 20, or 40 mg/kg on postnatal days 7 to 27, doses of 0, 15, 30, or 60 mg/kg/day on postnatal days 28 to 48, and doses of 0, 15, 45, or 90 mg/kg/day on postnatal days 49 to 92. Adverse effects on behavior (increased locomotor activity and decreased auditory startle prepulse inhibition) were observed at the high dose at the end of the dosing period. Adverse effects on locomotor activity, but not prepulse inhibition, were observed at the end of the recovery period, primarily at the mid and high doses. Persistent decreases in bone density were observed at all doses tested. A no-effect dose for adverse effects on postnatal development was not identified; the lowest dose tested was associated with plasma exposures (AUC) less than that in humans at the maximum recommended human dose.

Geriatric use

Duchenne muscular dystrophy is largely a disease of children and young adults; therefore, there is no experience with givinostat in geriatric patients with Duchenne muscular dystrophy.

Hepatic impairment

A dedicated clinical study was not conducted to evaluate the pharmacokinetics of givinostat in subjects with hepatic impairment, and no recommendation for dosage adjustment can be made for patients with hepatic impairment. Because givinostat is eliminated mainly through hepatic metabolism, hepatic impairment is expected to increase the exposure of givinostat.

Clinical pharmacology

Mechanism of action

Givinostat is a histone deacetylase inhibitor. The precise mechanism by which givinostat exerts its effect in patients with Duchenne muscular dystrophy is unknown.

Pharmacodynamics

Muscle fat fraction as assessed by MR spectroscopy. The percentage of fat fraction present in the vastus lateralis muscles of the thigh was measured in Study 1 using magnetic resonance spectroscopy. At 18 months, for patients with vastus lateralis muscles fat fraction baseline in the range of 5% to 30%, a mean increase (absolute difference from baseline levels) of vastus lateralis muscles fat fraction was 7.48% in the givinostat-treated patients compared to a 10.89% increase in patients who received placebo.

Cardiac electrophysiology. The largest mean increase in QTc interval of 13.6 ms (upper confidence interval of 17.1 ms) occurred 5 hours after administration of givinostat 265.8 mg to healthy subjects (approximately five times the 53.2 mg dose recommended for patients with Duchenne muscular dystrophy weighing 60 kg or more).

Pharmacokinetics

Givinostat exhibits linear kinetics within the studied dose range. Systemic exposure to givinostat was dose-proportional across the therapeutic dose range. Steady-state concentrations are achieved within 5 to 7 days after twice-daily dosing. An accumulation of less than two-fold was observed for givinostat after twice-daily administration.

Absorption. Absolute bioavailability was not determined. The time to maximum plasma concentrations is about 2 to 3 hours after oral administration.

Effect of food. A high-fat standard meal resulted in an increase in the exposure (about 40% increase in area under the plasma concentration-time curve [AUC] and about 23% increase in maximum plasma concentration [Cmax]) and a delay in time to maximum concentration (Tmax) from 2 to 3 hours.

Distribution. Givinostat is approximately 96% bound to human plasma proteins and is slightly partitioned into red blood cells (blood to plasma ratio = 1.3).

Elimination. In plasma, the apparent elimination half-life of givinostat is about 6 hours.

Metabolism. In vitro studies with human enzymatic preparations together with animal metabolism showed that givinostat is extensively metabolized, forming several metabolites. Cytochrome P450 enzymes and uridine diphosphate glucuronosyltransferase are not involved in the main metabolic reactions. Four major metabolites, which are not active with respect to the efficacy of givinostat, have been characterized in humans and preclinical species.

Excretion. The elimination of givinostat is likely dependent on metabolism, followed by renal and biliary excretion of the resulting metabolites, as suggested by the mass balance study in the rat. Urinary excretion of givinostat in humans is minimal (less than 3% of the dose).

Specific populations. The population PK analyses show that the PK of givinostat can be affected by body weight, whereas age has no effect on the pharmacokinetics of givinostat.

Patients with hepatic impairment. The pharmacokinetics and safety of givinostat have not been studied in patients with hepatic impairment. Givinostat is highly metabolized; therefore, the impact of hepatic impairment on the exposure of givinostat cannot be excluded.

Patients with renal impairment. The pharmacokinetics and safety of givinostat have not been studied in patients with renal impairment. However, renal impairment is not expected to impact the exposure of givinostat because renal excretion is not a significant route of givinostat elimination.

Drug interaction studies.

In vitro. Givinostat is not a substrate of cytochrome P450 enzymes and uridine diphosphate glucuronosyltransferase. Therefore, coadministration of drugs that are inducers or inhibitors of major metabolizing enzymes will not significantly affect the systemic exposure of givinostat.

Givinostat and its metabolites ITF2374, ITF2375, ITF2440, and ITF2563 were investigated as inhibitors of the main cytochrome P450 subfamilies, and the results indicated that no inhibition is expected of CYP1A2, 2C9, 2C19, 2D6, 2B6, 2C8, and 3A4. Givinostat showed induction of CYP1A2, 2B6, and CYP3A4.

In vitro studies indicate that givinostat is a substrate of the intestinal transporters: P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Givinostat showed the potential to inhibit the intestinal transporter P-gp (MDR1) and BCRP based on in vitro results. However, these interactions are not expected to be clinically meaningful.

In vivo. A weak inhibition of the renal uptake transporter OCT2 by givinostat was seen in clinical trials by creatinine (OCT2 substate) measurements.

A clinical drug interaction study was conducted in healthy volunteers to assess the effects of coadministration of givinostat with other drugs, and results indicated that:

	• Givinostat has a weak inhibition of the intestinal CYP3A4 enzyme based on the exposure of a CYP3A4 substrate, midazolam,
	• Givinostat does not likely inhibit P-gp transporters based on the exposure of dabigatran
	• Strong P-gp inhibitors have a weak effect on givinostat based on exposure of clarithromycin, which had an increase in Cmax by about 40% without a significant change of AUC.

The effect of BCRP inhibitors on givinostat PK was not studied in a clinical study. However, the effect of BCRP inhibitors on givinostat PK is expected to be smaller than P-gp inhibitors based on the comparison of the two transporters mediated efflux ratios determined in the in vitro cell models.

Nonclinical toxicology

Carcinogenesis, mutagenesis, impairment of fertility

Carcinogenesis. Studies to assess the carcinogenic potential of givinostat have not been conducted.

Mutagenesis. Givinostat was positive in a bacterial reverse mutation (Ames) assay, and negative in an in vitro mammalian cell (mouse lymphoma) mutation assay, an in vitro chromosomal aberration assay in mammalian (human lymphocytes) cells, and an in vivo gene mutation assay (with Pig-a endpoints) in Big Blue transgenic rats.

Impairment of fertility. Oral administration of givinostat (0, 40, 80, or 160 mg/kg) before and throughout mating in male and female rats and continuing to gestation day 7 in females resulted in no adverse effects on fertility. However, there was an increase in corpora lutea at the mid and high doses and increased pre- and postimplantation loss at all doses. A no-effect dose for adverse effects on early embryonic development was not identified; plasma exposures (AUC) at the lowest dose tested were lower than those in humans at the maximum recommended human dose of 53.2 mg twice daily.

Clinical studies

The effectiveness of givinostat for the treatment of Duchenne muscular dystrophy was evaluated in a randomized, double-blind, placebo-controlled 18-month study (Study 1; NCT02851797). A total of 179 patients were randomized 2:1 to receive either givinostat (n = 118) or placebo (n = 61). A weight-based dose regimen was applied. The study included male patients 6 years of age and older with a confirmed diagnosis of Duchenne muscular dystrophy who were ambulatory and on a stable dosage of corticosteroids. At baseline, patients had a mean age of 9.8 years, 90% were White, 3% were Asian, 3% were Black.

The primary endpoint was the change from baseline to Month 18 in four-stair climb (4SC) time for givinostat compared to placebo. The 4SC is a measure of muscle function that tests the time it takes to climb four stairs. A secondary efficacy endpoint was change from baseline to Month 18 in physical function as assessed by the North Star Ambulatory Assessment.

The primary analysis population was based on a prespecified range of baseline muscle fat fraction as determined by MR spectroscopy. Patients treated with givinostat showed statistically significantly less decline in the four-stair climb compared to placebo (see Table 4). Patients treated with givinostat experienced less worsening on the North Star Ambulatory Assessment compared to placebo, which was nominally significant but not statistically significant based on the prespecified multiplicity adjustment.

Table 4. Change from Baseline to Month 18 on 4SC Compared to Placebo*

	Mean baseline 4SC (seconds)	Mean change from baseline	Treatment difference from placebo (95% CI)	p-value
Givinostat (n = 81 )	3.39	1.25	-1.78 (-3.46, -0.11)	0.037
Placebo (n = 39 )	3.48	3.03	-1.78 (-3.46, -0.11)	0.037
* Givinostat or placebo was administered in addition to a stable dose of corticosteroids throughout the study.

How supplied/storage and handling

How supplied

Givinostat oral suspension is a white to off-white or faintly pink, peach-cream flavored suspension. It is supplied in an amber polyethylene terephthalate bottle closed with a high-density polyethylene child-resistant, screw cap with low-density polyethylene syringe adapter, containing 140 mL of oral suspension (NDC 11797-110-01). Each mL contains 8.86 mg of givinostat.

Givinostat is supplied in a carton, NDC 11797-110-02, containing:

	• One bottle containing 140 mL of oral suspension
	• One 5 mL graduated oral syringe
	• Prescribing information and Instructions for use

The Medication Guide is available at https://itftherapeutics.com/documents/Medication-Guide.pdf.

Storage and handling

Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F). Do not freeze. Store upright.

Discard any unused givinostat remaining after 60 days of first opening of the bottle.

Patient counseling information

Advise the patient to read the FDA-approved patient labeling.

Administration instructions. Instruct patients or caregivers to:

	• Shake givinostat oral suspension well before measuring out each dose.
	• Administer using the provided graduated oral syringe to measure the appropriate volume of suspension corresponding to the prescribed dose for the patient.
	• Take givinostat with food.
	• Discard any unused givinostat oral suspension remaining after 60 days of first opening the bottle.

Hematological changes. Inform patients and caregivers that givinostat can cause hematological changes, including a decrease in platelet counts (thrombocytopenia), anemia, and a decrease in neutrophils (neutropenia). Advise patients to notify their healthcare provider if they have any signs or symptoms of these adverse reactions (eg, easy bruising, excessive bleeding from cuts, blood in the stool, fatigue). Instruct patients to adhere to the testing recommended to monitor for these adverse reactions. Inform patients that their dosage may need to be changed or their treatment may need to be stopped depending on the results of their test for platelet counts.

Increased triglycerides. Inform patients and caregivers that givinostat can cause an increase in triglycerides. Instruct patients to adhere to the testing recommended to monitor for this adverse reaction. Inform patients that their dosage may need to be changed or their treatment may need to be stopped depending on the results of their test for triglycerides.

Gastrointestinal disturbances. Inform patients and caregivers that givinostat can cause diarrhea and vomiting, which may require medication for treatment. Advise patients to maintain hydration if diarrhea or vomiting occurs and contact their healthcare provider if the symptoms persist or become moderate to severe. Inform patients that their dosage may need to be changed or their treatment may need to be stopped depending on the severity of diarrhea.

QTc prolongation. Inform patients and caregivers that givinostat can cause prolongation of the QTc interval. Instruct patients to notify their healthcare provider if they have or develop any symptoms of significant QTc prolongation (eg, dizziness, lightheadedness, syncope) or new cardiac issues and before taking any over-the-counter (eg, diphenhydramine), herbal (eg, echinacea), or prescription medications (eg, antibiotics).

Medication guide

See the Medication guide section of the DAILYMED drug label information.

Cite this article