Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

FINTEPLA (NDA-212102)

(FENFLURAMINE HYDROCHLORIDE)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

Download Data

Expand all

10/15/2025 (SUPPL-17)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

. . .

Clinical Considerations

Disease-associated Maternal and/or Embryofetal Risk

Epilepsy, with or without exposure to antiepileptic drugs, has been associated with several adverse outcomes during pregnancy, including preeclampsia, preterm labor, antepartum and postpartum hemorrhage, placental abruption, poor fetal growth, prematurity, fetal death, and maternal mortality. The risk of maternal or fetal injury may be greatest for patients with untreated or poorly controlled convulsive seizures. Women with epilepsy who become pregnant should not abruptly discontinue antiepileptic drugs, including FINTEPLA, due to the risk of status epilepticus or severe seizures, which may be life-threatening [see Warnings and Precautions (5.6)].

. . .

04/08/2025 (SUPPL-16)

Approved Drug Label (PDF)

Boxed Warning

Additions and/or revisions underlined:

WARNING: VALVULAR HEART DISEASE and PULMONARY ARTERIAL HYPERTENSION

FINTEPLA can cause valvular heart disease and pulmonary arterial hypertension [see Warnings and Precautions (5.1)].

Echocardiogram assessments are required before, during, and after treatment with FINTEPLA. The benefits versus the risks of initiating or continuing FINTEPLA must be considered, based on echocardiogram findings [see Dosage and Administration (2.1, 2.6) and Warnings and Precautions (5.1)].

Because of the risks of valvular heart disease and pulmonary arterial hypertension, FINTEPLA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the FINTEPLA REMS [see Warnings and Precautions (5.2)].

5 Warnings and Precautions

5.1 Valvular Heart Disease and Pulmonary Arterial Hypertension

 

Additions and/or revisions underlined:

FINTEPLA can cause valvular heart disease (VHD) and pulmonary arterial hypertension (PAH). There is a known association between serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine (the active ingredient in FINTEPLA), and valvular heart disease and pulmonary arterial hypertension. Although no patients receiving FINTEPLA developed valvular heart disease or pulmonary arterial hypertension in clinical trials for DS and LGS of up to 3 years in duration, cases of valvular heart disease and pulmonary arterial hypertension have been reported during use of FINTEPLA in the postmarketing setting [see Boxed Warning and Adverse Reactions (6.1)].

Because of this risk, cardiac monitoring is required prior to starting treatment, during treatment, and after treatment with FINTEPLA concludes. Cardiac monitoring via echocardiogram can identify evidence of valvular heart disease and pulmonary arterial hypertension prior to a patient becoming symptomatic, aiding in early detection of these conditions.

…

12/11/2023 (SUPPL-13)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2         Postmarketing Experience

(Newly added subsection)

The following adverse reactions have been identified during postapproval use of FINTEPLA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. 

Psychiatric disorders: aggression

01/03/2023 (SUPPL-6)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

Data

(Additions and/or revisions underlined)

Animal Data

Oral administration of fenfluramine (0, 4.5, 8.6, or 34.6 mg/kg/day) to pregnant rats during organogenesis resulted in decreased fetal body weights and marked increases in fetal malformations (external, visceral, and skeletal) at the highest dose tested, which was associated with maternal toxicity. At the no-effect dose (8.6 mg/kg/day) for adverse effects on embryofetal development in rats, maternal plasma exposures (AUC) of fenfluramine and norfenfluramine (the major metabolite) were approximately 2 and 5 times, respectively, those in humans at the maximum recommended human dose (MRHD) of 26 mg/day.

Oral administration of fenfluramine (0, 4.3, 8.6, 13.0 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in increased embryofetal mortality at all doses and increases in fetal malformations (external and skeletal) at the highest dose tested, which was associated with maternal toxicity…

Oral administration of fenfluramine (0, 4.3, 8,6, or 34.6 mg/kg/day) to female rats throughout gestation and lactation resulted in marked increases in stillborn pups and neonatal offspring deaths at the highest dose tested and delayed growth and reflex development during the pre- weaning period at all doses. Maternal body weight gain was decreased at all doses during pregnancy and at the two highest doses during lactation. A no-effect dose for adverse effects on pre- and postnatal development in rats was not determined. At the lowest dose tested in rats (4.3 mg/kg/day), maternal plasma exposures of fenfluramine and norfenfluramine were approximately 0.5 and 3 times, respectively, those in humans at the MRHD.

8.4         Pediatric Use

Juvenile Animal Data

(Additions and/or revisions underlined)

Oral administration of fenfluramine (0, 3.0, 7, 8, or 17.3 mg/kg/day) to young rats for 10 weeks starting on postnatal day 7 resulted in reduced body weight and neurobehavioral changes (decreased locomotor activity and learning and memory deficits) at all doses tested.

Neurobehavioral effects persisted after dosing was discontinued. Bone size was decreased at the mid and high doses; brain size was decreased at the highest dose. Partial or complete recovery was seen for these endpoints. A no-effect dose for postnatal developmental toxicity was not identified. The lowest dose tested (3.0 mg/kg/day) was associated with plasma fenfluramine exposures (AUC) less than that in humans at the maximum recommended human dose (MRHD) of 26 mg/day and norfenfluramine (metabolite) exposures (AUC) approximately 2 times that in humans at the MRHD.

8.7 Hepatic Impairment

(Additions and/or revisions underlined)

Combined molar exposures of fenfluramine and norfenfluramine were increased in subjects with various degrees of hepatic impairment (Child-Pugh Class A, B, and C), necessitating a dosage adjustment in these patients [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)].

03/25/2022 (SUPPL-3)

Approved Drug Label (PDF)

5 Warnings and Precautions

Additions and/or revisions underlined:

5.1 Valvular Heart Disease and Pulmonary Arterial Hypertension

Because of the association between serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine (the active ingredient in FINTEPLA), and valvular heart disease (VHD) and pulmonary arterial hypertension (PAH), cardiac monitoring is required prior to starting treatment, during treatment, and after treatment with FINTEPLA concludes. Cardiac monitoring via echocardiogram can identify evidence of valvular heart disease and pulmonary arterial hypertension prior to a patient becoming symptomatic, aiding in early detection of these conditions. In clinical trials for DS and LGS of up to 3 years in duration, no patient receiving FINTEPLA developed valvular heart disease or pulmonary arterial hypertension [see Boxed Warning and Adverse Reactions (6.1)].

Monitoring

Prior to starting treatment, patients must undergo an echocardiogram to evaluate for valvular heart disease and pulmonary arterial hypertension.

Echocardiograms should be repeated every 6 months, and once 3-6 months post-treatment with FINTEPLA.

The prescriber must consider the benefits versus the risks of initiating or continuing treatment with FINTEPLA if any of the following signs are observed via ECHO:

• Valvular abnormality or new abnormality via echocardiogram.

• VHD as indicated by mild or greater aortic regurgitation or moderate or greater mitral regurgitation, with additional characteristics of VHD (e.g., valve thickening or restrictive valve motion).

• PAH as indicated by elevated right heart/pulmonary artery pressure (PASP > 35 mm Hg).

FINTEPLA is available only through a restricted program under a REMS [see Warnings and Precautions (5.2)].

5.3 Decreased Appetite and Decreased Weight

Additions and/or revisions underlined:

FINTEPLA can cause decreases in appetite and weight. In placebo-controlled studies for DS (Study 1 and Study 2 combined), approximately 37% of patients treated with FINTEPLA reported, as an adverse reaction, decreased appetite and approximately 9% reported decreased weight, as compared to 8% and 1%, respectively, of patients on placebo. In the placebo- controlled study for LGS (Study 3), approximately 28% of patients treated with FINTEPLA reported, as an adverse reaction, decreased appetite and approximately 5% reported decreased weight, as compared to 15% and 2%, respectively, of patients on placebo [see Adverse Reactions (6.1)]. By the end of the controlled studies, 19% (Studies 1 and 2 combined) of DS patients and 7% (Study 3) of LGS patients treated with FINTEPLA had a measured decrease in weight of 7% or greater from their baseline weight, compared to 2% (Study 1 and 2) and 0% (Study 3) of patients on placebo. This measured decrease in weight appeared to be dose-related. In the controlled studies for DS, 26% of patients on FINTEPLA 0.7 mg/kg/day (Study 1), 19% of patients on FINTEPLA 0.4 mg/kg/day in combination with stiripentol (Study 2), and 13% of patients taking FINTEPLA 0.2 mg/kg/day (Study 1) experienced at least a 7% decrease in weight from baseline. In the controlled study for LGS, 9% of patients on FINTEPLA 0.7 mg/kg/day (Study 3) and 6% of patients on FINTEPLA 0.2 mg/kg/day (Study 3) experienced at least a 7% decrease in weight from baseline. Approximately half of the patients with LGS and most patients with DS resumed the expected measured increases in weight during the open-label extension studies. Given the frequency of these adverse reactions, the growth of pediatric patients treated with FINTEPLA should be carefully monitored …

5.4 Somnolence, Sedation, and Lethargy

Additions and/or revisions underlined:

FINTEPLA can cause somnolence, sedation, and lethargy. In controlled studies for DS (Study 1 and Study 2 combined), the incidence of somnolence, sedation, and lethargy was 25% in patients treated with FINTEPLA, compared with 11% of patients on placebo. In the controlled study for LGS (Study 3), the incidence of somnolence, sedation, and lethargy was 19% in patients treated with FINTEPLA, compared with 16% of patients on placebo. In general, these effects may diminish with continued treatment [see Adverse Reactions (6.1)] …

5.8 Increase in Blood Pressure

Additions and/or revisions underlined:

FINTEPLA can cause an increase in blood pressure [see Adverse Reactions (6.1)]. Rare cases of significant elevation in blood pressure, including hypertensive crisis, has been reported in adult patients treated with fenfluramine, including patients without a history of hypertension. In clinical trials of up to 3 years in duration, no pediatric or adult patient receiving FINTEPLA developed a hypertensive crisis. Monitor blood pressure in patients treated with FINTEPLA.

6 Adverse Reactions

Additions and/or revisions to bulleted line listing underlined:

• Valvular Heart Disease and Pulmonary Arterial Hypertension [see Warnings and Precautions (5.1)]

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

In controlled and uncontrolled trials in patients with Dravet syndrome (DS), 341 patients were treated with FINTEPLA, including 312 patients treated for more than 6 months, 284 patients treated for more than 1 year, and 138 patients treated for more than 2 years.

In controlled and uncontrolled trials in patients with Lennox-Gastaut syndrome (LGS), 262 patients were treated with FINTEPLA, including 219 patients treated for more than 6 months, 172 patients treated for more than 1 year, and 127 patients treated for more than 2 years.

Dravet Syndrome

In placebo-controlled trials of patients with DS taking concomitant standard of care AEDs, 122 patients were treated with FINTEPLA and 84 patients received placebo [see Clinical Studies (14.1)]. The duration of treatment in these trials was 16 weeks (Study 1) or 17 weeks (Study 2) …

Table 2: Adverse Reactions in 5% or More of Patients Treated with FINTEPLA and Greater Than Placebo in Placebo-Controlled Trials for Dravet Syndrome (Study 1 and 2)

Newly added information:

Lennox-Gastaut Syndrome

In the placebo-controlled trial of patients with LGS taking concomitant standard of care AEDs (Study 3), 176 patients were treated with FINTEPLA and 87 patients received placebo [see Clinical Studies (14.2)]. The duration of treatment in this trial was 16 weeks. The mean age was

13.7 years (range 2 to 35 years) and 29% of patients were at least 18 years of age, 45% of patients were female, and 79% were White. All patients were receiving at least one other AED.

The rates of discontinuation as a result of any adverse reaction were 6% and 5% for patients treated with FINTEPLA 0.7 mg/kg/day and 0.2 mg/kg/day, respectively, compared to 1% for patients on placebo. The most frequent adverse reactions leading to discontinuation in the patients treated with any dose of FINTEPLA were seizure (2%) and somnolence (2%).

The common adverse reactions that occurred in patients treated with FINTEPLA (incidence at least 10% and greater than placebo) were diarrhea; decreased appetite; fatigue; somnolence; vomiting.

Table 3 lists the adverse reactions that were reported in 5% or more of patients treated with FINTEPLA and at a rate greater than those on placebo during the titration and maintenance phases of Study 3.

Table 3: Adverse Reactions in 5% or More of Patients Treated with FINTEPLA and Greater Than Placebo in the Placebo-Controlled Trial for Lennox Gastaut Syndrome (Study 3) Newly added table; please refer to label for complete information.

Additions and/or revisions underlined:

Echocardiographic Safety Assessments of Valvular Heart Disease and Pulmonary Arterial Hypertension

Valvular heart disease and pulmonary arterial hypertension were evaluated in the placebo-controlled and open-label extension studies via echocardiography for up to 3 years in duration for 341 DS patients and 263 LGS patients [see Warnings and Precautions (5.1)]. Screening for valvular heart disease assessed for mild or greater aortic regurgitation or moderate or greater  mitral regurgitation, and assessed for additional characteristics of VHD (e.g., valve thickening or restrictive valve motion).

In these clinical studies, two patients with LGS exhibited mild aortic regurgitation (AR) but neither patient had any cardiac signs or symptoms or evidence of valvular structural changes. Neither patient had VHD. The rates of mild AR are consistent with those seen in the screening period prior to treatment (3 patients in LGS and 1 patient in DS clinical trials).

7 Drug Interactions

Additions and/or revisions underlined:

7.1 Effect of Other Drugs on FINTEPLA

CYP2B6, or CYP3A Inducers

Coadministration of FINTEPLA with strong CYP1A2, CYP2B6, or CYP3A inducers will decrease fenfluramine plasma concentrations, which may lower the efficacy of FINTEPLA [see Clinical Pharmacology (12.3)].

It is recommended to avoid coadministration of strong CYP1A2, CYP2B6 or CYP3A inducers. If coadministration of a strong CYP1A2, CYP2B6, or CYP3A inducer with FINTEPLA is necessary, monitor the patient for reduced efficacy and consider increasing the dosage of FINTEPLA as needed; however, do not exceed the maximum daily dosage of FINTEPLA [see Dosage and Administration (2.2)].

If a strong CYP1A2, CYP2B6, or CYP3A inducer is discontinued during maintenance treatment with FINTEPLA, consider gradual reduction in the FINTEPLA dosage to the dose administered prior to initiating the inducer [see Warnings and Precautions (5.6)].

Strong CYP1A2 or CYP2D6 Inhibitors

Coadministration of FINTEPLA with strong CYP1A2 or CYP2D6 inhibitors will increase fenfluramine plasma concentrations [see Clinical Pharmacology (12.3)]. If FINTEPLA is coadministered with strong CYP1A2 or CYP2D6 inhibitors, the maximum daily dosage of FINTEPLA is 20 mg [see Dosage and Administration (2.3)].

If a strong CYP1A2 or CYP2D6 inhibitor is discontinued during maintenance treatment with FINTEPLA, consider gradual increase in the FINTEPLA dosage to the dose recommended without CYP1A2 or CYP2D6 inhibitors; however, do not exceed the maximum daily dosage of FINTEPLA [see Dosage and Administration (2.2)].

If FINTEPLA is coadministered with stiripentol and a strong CYP1A2 or CYP2D6 inhibitor, do not exceed the maximum daily dosage of FINTEPLA of 17 mg [see Dosage and Administration (2.3)].

is coadministered with stiripentol plus clobazam, the maximum daily dosage of FINTEPLA is

0.2 mg/kg twice daily (maximum daily dosage of 17 mg) [see Dosage and Administration (2.2)].

7.3 Serotonergic Drugs

… Concomitant use of FINTEPLA is contraindicated within 14 days of taking MAOIs. Use FINTEPLA with caution in patients taking other medications that increase serotonin.

8 Use in Specific Populations

8.1 Pregnancy

Risk Summary

Additions and/or revisions underlined:

There are no data on FINTEPLA use in pregnant women. Available data from epidemiologic studies with fenfluramine or dexfenfluramine are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. FINTEPLA can cause decreased appetite and decreased weight [see Warnings and Precautions (5.3)]; monitor for adequate weight gain during pregnancy. In animal studies, administration of fenfluramine throughout organogenesis (rat and rabbit) or throughout gestation and lactation (rat) resulted in adverse effects on development (fetal malformations, embryofetal and offspring mortality and growth impairment) in the presence of maternal toxicity at clinically relevant maternal plasma levels of fenfluramine and its major active metabolite (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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.

Newly added information:

Data

Animal Data

Oral administration of fenfluramine (0, 5, 10, or 40 mg/kg/day) to pregnant rats during organogenesis resulted in decreased fetal body weights and marked increases in fetal malformations (external, visceral, and skeletal) at the highest dose tested, which was associated with maternal toxicity. At the no-effect dose (10 mg/kg/day) for adverse effects on embryofetal development in rats, maternal plasma exposures (AUC) of fenfluramine and norfenfluramine (the major metabolite) were approximately 2 and 5 times, respectively, those in humans at the maximum recommended human dose (MRHD) of 26 mg/day.

Oral administration of fenfluramine (0, 5, 10, 15 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in increased embryofetal mortality at all doses and increases in fetal malformations (external and skeletal) at the highest dose tested, which was associated with maternal toxicity. A no-adverse-effect dose for adverse effects on embryofetal development in rabbits was not identified. At the lowest dose tested in rabbits (5 mg/kg/day), maternal plasma exposures of fenfluramine and norfenfluramine were lower than those in humans at the MRHD.

Oral administration of fenfluramine (0, 5, 10, or 40 mg/kg/day) to female rats throughout gestation and lactation resulted in marked increases in stillborn pups and neonatal offspring deaths at the highest dose tested and delayed growth and reflex development during the pre- weaning period at all doses. Maternal body weight gain was decreased at all doses during pregnancy and at the two highest doses during lactation. A no-effect dose for adverse effects on pre- and postnatal development in rats was not determined. At the lowest dose tested in rats (5 mg/kg/day), maternal plasma exposures of fenfluramine and norfenfluramine were approximately 0.5 and 3 times, respectively, those in humans at the MRHD.

Newly added subsection:

8.3 Females and Males of Reproductive Potential

Infertility

In animal studies, oral administration of fenfluramine resulted in adverse reproductive effects in males and females at clinically relevant doses in the presence of parental toxicity [see Nonclinical Toxicology (13.1)].

8.4 Pediatric Use

Additions and/or revisions underlined:

The safety and effectiveness of FINTEPLA for the treatment of seizures associated with DS and LGS have been established in patients 2 years of age and older.

Use of FINTEPLA for the treatment of seizures associated with DS in patients 2 years of age and older is supported by two randomized, double-blind, placebo-controlled trials in 202 patients 2 to 18 years of age. Use of FINTEPLA for the treatment of seizures associated with LGS is supported by a randomized, double-blind, placebo-controlled study in 263 patients aged 2 to 35 years, including 187 patients less than 18 years [see Boxed Warning, Warnings and Precautions (5), Adverse Reaction (6.1), and Clinical Studies (14)].

FINTEPLA can cause decreases in appetite and weight. The growth of pediatric patients treated with FINTEPLA should be carefully monitored.

Safety and effectiveness in patients less than 2 years of age have not been established.

Juvenile Animal Data

… The lowest dose tested (3.5 mg/kg/day) was associated with plasma fenfluramine exposures (AUC) less than that in humans at the maximum recommended human dose (MRHD of 26 mg/day) and norfenfluramine (metabolite) exposures (AUC) approximately 2 times that in humans at the MRHD.

8.5 Geriatric Use

Additions and/or revisions underlined:

Clinical studies of FINTEPLA for the treatment of DS or LGS did not include patients 65 years of age and over to determine whether they respond differently from younger patients …

8.6 Renal Impairment

Additions and/or revisions underlined:

In patients with estimated glomerular filtration rate (eGFR) 15 to 29 mL/min/1.73m2, do not exceed the maximum daily dosage of FINTEPLA of 20 mg. In patients with eGFR 15 to 29 ml/min/1.73m2 and concomitant stiripentol use, do not exceed the maximum daily dosage of FINTEPLA of 17 mg [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)]. FINTEPLA has not been studied in patients with eGFR < 15 mL/min/1.73m2.

8.1 Pregnancy

Risk Summary

Additions and/or revisions underlined:

There are no data on FINTEPLA use in pregnant women. Available data from epidemiologic studies with fenfluramine or dexfenfluramine are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. FINTEPLA can cause decreased appetite and decreased weight [see Warnings and Precautions (5.3)]; monitor for adequate weight gain during pregnancy. In animal studies, administration of fenfluramine throughout organogenesis (rat and rabbit) or throughout gestation and lactation (rat) resulted in adverse effects on development (fetal malformations, embryofetal and offspring mortality and growth impairment) in the presence of maternal toxicity at clinically relevant maternal plasma levels of fenfluramine and its major active metabolite (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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.

Newly added information:

Data

Animal Data

Oral administration of fenfluramine (0, 5, 10, or 40 mg/kg/day) to pregnant rats during organogenesis resulted in decreased fetal body weights and marked increases in fetal malformations (external, visceral, and skeletal) at the highest dose tested, which was associated with maternal toxicity. At the no-effect dose (10 mg/kg/day) for adverse effects on embryofetal development in rats, maternal plasma exposures (AUC) of fenfluramine and norfenfluramine (the major metabolite) were approximately 2 and 5 times, respectively, those in humans at the maximum recommended human dose (MRHD) of 26 mg/day.

Oral administration of fenfluramine (0, 5, 10, 15 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in increased embryofetal mortality at all doses and increases in fetal malformations (external and skeletal) at the highest dose tested, which was associated with maternal toxicity. A no-adverse-effect dose for adverse effects on embryofetal development in rabbits was not identified. At the lowest dose tested in rabbits (5 mg/kg/day), maternal plasma exposures of fenfluramine and norfenfluramine were lower than those in humans at the MRHD.

Oral administration of fenfluramine (0, 5, 10, or 40 mg/kg/day) to female rats throughout gestation and lactation resulted in marked increases in stillborn pups and neonatal offspring deaths at the highest dose tested and delayed growth and reflex development during the pre- weaning period at all doses. Maternal body weight gain was decreased at all doses during pregnancy and at the two highest doses during lactation. A no-effect dose for adverse effects on pre- and postnatal development in rats was not determined. At the lowest dose tested in rats (5 mg/kg/day), maternal plasma exposures of fenfluramine and norfenfluramine were approximately 0.5 and 3 times, respectively, those in humans at the MRHD.

Newly added subsection:

8.3 Females and Males of Reproductive Potential

Infertility

In animal studies, oral administration of fenfluramine resulted in adverse reproductive effects in males and females at clinically relevant doses in the presence of parental toxicity [see Nonclinical Toxicology (13.1)].

8.4 Pediatric Use

Additions and/or revisions underlined:

The safety and effectiveness of FINTEPLA for the treatment of seizures associated with DS and LGS have been established in patients 2 years of age and older.

Use of FINTEPLA for the treatment of seizures associated with DS in patients 2 years of age and older is supported by two randomized, double-blind, placebo-controlled trials in 202 patients 2 to 18 years of age. Use of FINTEPLA for the treatment of seizures associated with LGS is supported by a randomized, double-blind, placebo-controlled study in 263 patients aged 2 to 35 years, including 187 patients less than 18 years [see Boxed Warning, Warnings and Precautions (5), Adverse Reaction (6.1), and Clinical Studies (14)].

FINTEPLA can cause decreases in appetite and weight. The growth of pediatric patients treated with FINTEPLA should be carefully monitored.

Safety and effectiveness in patients less than 2 years of age have not been established.

Juvenile Animal Data

… The lowest dose tested (3.5 mg/kg/day) was associated with plasma fenfluramine exposures (AUC) less than that in humans at the maximum recommended human dose (MRHD of 26 mg/day) and norfenfluramine (metabolite) exposures (AUC) approximately 2 times that in humans at the MRHD.

8.5 Geriatric Use

Additions and/or revisions underlined:

Clinical studies of FINTEPLA for the treatment of DS or LGS did not include patients 65 years of age and over to determine whether they respond differently from younger patients …

8.6 Renal Impairment

Additions and/or revisions underlined:

In patients with estimated glomerular filtration rate (eGFR) 15 to 29 mL/min/1.73m2, do not exceed the maximum daily dosage of FINTEPLA of 20 mg. In patients with eGFR 15 to 29 ml/min/1.73m2 and concomitant stiripentol use, do not exceed the maximum daily dosage of FINTEPLA of 17 mg [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)]. FINTEPLA has not been studied in patients with eGFR < 15 mL/min/1.73m2.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions and/or revisions underlined:

What is the most important information I should know about FINTEPLA?

FINTEPLA can cause serious side effects, including:

1. Decreased appetite and decreased weight. Decreased appetite and decreased weight are both serious and common side effects of FINTEPLA in people with Dravet syndrome (DS) or Lennox-Gastaut syndrome (LGS) …

2. Sleepiness, sedation, and lack of energy (lethargy). These are both serious and common side effects of FINTEPLA in people with Dravet syndrome (DS) or Lennox-Gastaut syndrome (LGS) …

What is FINTEPLA?

• FINTEPLA is a prescription medicine used to treat the seizures associated with Dravet syndrome (DS) and Lennox- Gastaut syndrome (LGS) in patients 2 years of age and older.

What are the possible side effects of FINTEPLA?

FINTEPLA may cause serious side effects, including:

The most common side effects of FINTEPLA when used to treat Dravet syndrome (DS) include:

Newly added:

• decreased appetite                                                            

• increased blood pressure

• decreased weight

Newly added information:

The most common side effects of FINTEPLA when used to treat Lennox-Gastaut syndrome (LGS) include:

• diarrhea    

• sleepiness

• tiredness    

• decreased appetite

• vomiting