These Highlights Do Not Include All The Information Needed To Use Fintepla Safely And Effectively. See Full Prescribing Information For Fintepla.

Dravet Syndrome

• The initial starting and maintenance dosage for patients with Dravet syndrome is 0.1 mg/kg twice daily, which can be increased weekly based on efficacy and tolerability. Table 1 provides the recommended titration schedule, if needed.
• Patients with Dravet syndrome not on concomitant stiripentol who are tolerating FINTEPLA at 0.1 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 0.35 mg/kg twice daily (maximum daily dosage of 26 mg).
  
  Patients with Dravet syndrome taking concomitant stiripentol plus clobazam who are tolerating FINTEPLA at 0.1 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 0.2 mg/kg twice daily (maximum daily dosage of 17 mg) [see Drug Interactions (7.1)].

Fenfluramine can cause mydriasis and can precipitate angle closure glaucoma. Consider discontinuing treatment with FINTEPLA in patients with acute decreases in visual acuity or ocular pain.

Overdose has not been observed in the FINTEPLA clinical trial program. However, overdose of fenfluramine, the active ingredient in FINTEPLA, has been reported at higher doses than those included in the clinical trial program. Some of the cases were fatal. Events reported after overdose include mydriasis, tachycardia, flushing, tremors/twitching/muscle spasms, agitation/restlessness/anxiety, increased muscle tone/rigor/opisthotonos, respiratory distress or failure, and seizure. Seizure, coma, and cardiorespiratory arrest were reported in most of the fatal overdoses.

There is no available specific antidote to the overdose reactions of FINTEPLA. In the event of overdose, standard medical practice for the management of drug overdosage should be used. An adequate airway, oxygenation, and ventilation should be ensured; monitoring of cardiac rhythm and vital sign measurement is recommended. A certified poison control center should be contacted for updated information on the management of overdose with FINTEPLA.

FINTEPLA oral solution contains 2.2 mg/mL fenfluramine, equivalent to 2.5 mg/mL of the hydrochloride salt.

The active ingredient, fenfluramine hydrochloride, is designated chemically as N-ethyl-α- methyl-3-(trifluoromethyl)phenethylamine hydrochloride.

The structural formula is:

Fenfluramine hydrochloride is a white to off-white crystalline solid. The pKa of fenfluramine is 10.2.

FINTEPLA is a clear, colorless solution, pH 5.

FINTEPLA contains the following inactive ingredients: cherry flavor, citric acid, ethylparaben hydroxyethylcellulose, methylparaben, potassium citrate, sucralose, and water.

FINTEPLA contains no ingredient made from gluten-containing grain (wheat, barley, or rye), and contains not more than 0.1% of carbohydrates, which is solely derived from the cherry flavor.

FINTEPLA oral solution is a clear, colorless, cherry flavored liquid containing 2.2 mg/mL fenfluramine and is supplied in a white plastic bottle with a child resistant closure as follows:

• Carton containing one 360 mL bottle (NDC 43376-322-36)
• Carton containing one 30 mL bottle (NDC 43376-322-30)

Before dispensing, the pharmacist will insert a press-in bottle adapter into the dispensing bottle. The pharmacy will provide 3 mL or 6 mL calibrated oral dosing syringes.

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.

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. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

FINTEPLA is contraindicated in patients with:

• Hypersensitivity to fenfluramine or any of the excipients in FINTEPLA [see Description (11)]
• Concomitant use, or within 14 days of the administration, of monoamine oxidase inhibitors because of an increased risk of serotonin syndrome [see Warnings and Precautions (5.7)]

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

• Valvular Heart Disease and Pulmonary Arterial Hypertension [see Warnings and Precautions (5.1)]
• Decreased Appetite and Decreased Weight [see Warnings and Precautions (5.3)]
• Somnolence, Sedation, and Lethargy [see Warnings and Precautions (5.4)]
• Suicidal Behavior and Ideation [see Warnings and Precautions (5.5)]
• Withdrawal of Antiepileptic Drugs [see Warnings and Precautions (5.6)]
• Serotonin Syndrome [see Warnings and Precautions (5.7)]
• Increase in Blood Pressure [see Warnings and Precautions (5.8)]
• Glaucoma [see Warnings and Precautions (5.9)]

• Dose adjustment is required for patients taking stiripentol plus clobazam. ( 2.2, 2.3, 7.1)
• Strong CYP1A2 or CYP2D6 inhibitors: a dose adjustment is recommended ( 2.3, 7.1)
• Strong CYP1A2, CYP2B6, or CYP3A4 inducers: it is recommended to avoid coadministration with FINTEPLA. If coadministration is necessary, consider a FINTEPLA dosage increase. ( 7.1)

The effectiveness of FINTEPLA for the treatment of seizures associated with DS in patients 2 years of age and older was established in two randomized, double-blind, placebo-controlled trials in patients 2 to 18 years of age.

Study 1 (N=117) compared a 0.7 mg/kg/day and a 0.2 mg/kg/day dose of FINTEPLA with placebo in patients who were not receiving stiripentol (NCT02682927 and NCT02826863). Study 2 (N=85) compared a 0.4 mg/kg/day dose of FINTEPLA with placebo in patients who were receiving stiripentol and either clobazam, valproate, or both (NCT02926898). In both studies, patients had a clinical diagnosis of DS and were inadequately controlled on at least one AED or other antiseizure treatment including vagal nerve stimulation or a ketogenic diet. Both trials had a 6-week baseline period, during which patients were required to have a minimum of 6 convulsive seizures while on stable AED therapy. Convulsive seizures included tonic, clonic, generalized tonic-clonic, tonic-atonic, secondarily generalized tonic-clonic, hemiclonic, and focal with observable motor signs. The baseline period was followed by randomization into a 2- week (Study 1) or 3-week (Study 2) titration period and a subsequent 12-week maintenance period, where the dose of FINTEPLA remained stable.

In Study 1, 98% of patients were taking between 1 and 4 concomitant AEDs. The most frequently used concomitant AEDs (in at least 25% of patients), were valproate (61%), clobazam (59%), and topiramate (25%). In Study 2, 100% of patients were taking between 2 and 4 concomitant AEDs. The most frequently used concomitant AEDs (in at least 25% of patients), were stiripentol (100%), clobazam (94%), and valproate (89%).

The primary efficacy endpoint in both studies was the change from baseline in the frequency of convulsive seizures per 28 days during the combined 14-week (Study 1) or 15-week (Study 2) titration and maintenance periods (i.e., treatment period). The median longest interval between convulsive seizures was also assessed.

In Study 1 and Study 2, the reduction in convulsive seizure frequency per 28 days was statistically significantly greater for all dose groups of FINTEPLA compared to placebo (Table 6). A reduction in convulsive seizures was observed within 3 to 4 weeks of starting FINTEPLA, and the effect remained generally consistent over the 14- or 15-week treatment period.

Figure 1 and Figure 2 display the percentage of patients by category of seizure response from baseline in convulsive seizure frequency (per 28 days) during the treatment period in Study 1 and Study 2, respectively.

Figure 1: Proportion of Patients by Category of Seizure Response for FINTEPLA and Placebo in Patients with Dravet Syndrome (Study 1)

Figure 2: Proportion of Patients by Category of Seizure Response for FINTEPLA and Placebo in Patients with Dravet Syndrome (Study 2)

In Study 1, 3 of 40 (8%) patients in the FINTEPLA 0.7 mg/kg/day group and 3 of 38 (8%) patients in the FINTEPLA 0.2 mg/kg/day group reported no convulsive seizures during the 14-week treatment period, compared to 0 patients in the placebo group. In Study 2, 1 of 43 (2%) patients in the FINTEPLA 0.4 mg/kg/day group reported no convulsive seizures during the 15-week treatment period, compared to 0 patients in the placebo group.

In Study 1 and Study 2, FINTEPLA was associated with a statistically significant longer interval between convulsive seizures compared to placebo (Figure 3).

Figure 3: Median Longest Interval Between Convulsive Seizures in Patients with Dravet Syndrome (Study 1 and Study 2)

In patients with estimated glomerular filtration rate (eGFR) 15 to 29 mL/min/1.73m ², do not exceed the maximum daily dosage of FINTEPLA of 20 mg .In patients with eGFR 15 to 29 ml/min/1.73m ²and concomitant stiripentol use, do not exceed the maximum daily dosage of FINTEPLA of 17 mg [see Dosage and Administration (2.4)and Clinical Pharmacology (12.3)]. FINTEPLA has not been studied in patients with eGFR < 15 mL/min/1.73m ².

Be sure that you read, understand, and follow these instructions before you start using FINTEPLA oral solution and each time you get a refill. There may be new information.

This Instructions for Use contains information on how to take FINTEPLA. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

What is included with FINTEPLA?

The following items are included to prepare and give an oral dose of FINTEPLA:

• 1 bottle of FINTEPLA oral solution (2.2 mg/mL)
• 2 reusable oral syringes

  		1 Bottle of FINTEPLA Oral Solution (2.2 mg/mL)
  	2 Oral Syringes

Call the pharmacist at 1-844-288-5007 if you did not receive the items listed above, or if you need help using them.

Important information about FINTEPLA

• FINTEPLA is an oralmedicine (taken by mouth) and is given 2 times each day. Follow your healthcare provider's instructions for taking or giving doses of FINTEPLA.
• If you have questions about how to prepare or give FINTEPLA, contact your healthcare provider or call your pharmacist.
• Always use the oral syringes provided with FINTEPLA to make sure the right dose is given. If you need a new syringe contact your pharmacist. Do notuse a household teaspoon or tablespoon.

Oral syringes provided with FINTEPLA by the pharmacy.

With FINTEPLA you will receive 2 reusable oral syringes.

Call the pharmacist at 1-844-288-5007 if you have any questions about the syringes provided with FINTEPLA.

How should I store FINTEPLA?

• Store FINTEPLA at room temperature between 68°F to 77°F (20°C to 25°C).
• Do notrefrigerate or freeze.
• Keep the cap tightly closed and the bottle upright.
• Store the FINTEPLA bottle and syringe together in a clean area.
• Throw away (discard) any unused FINTEPLA 3 months after first opening the bottle orif the Discard After date on the package or bottle has passed. Whichever one comes first.
• Keep FINTEPLA and all medicines out of the reach of children.

Manufactured for: UCB, Inc., Smyrna, GA 30080

FINTEPLA ^®is a registered trademark of the UCB Group of Companies. ©2025. All rights reserved.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: 10/2025

The pharmacokinetics of fenfluramine and norfenfluramine were studied in healthy subjects, in pediatric patients with DS, and in pediatric and adult patients with LGS. The steady-state systemic exposure (C _maxand AUC) of fenfluramine was slightly greater than dose proportional over the dose range of 13 to 51.8 mg twice-daily fenfluramine (i.e., 1 to 4 times the maximum recommended dose). In pediatric patients with DS who received FINTEPLA 0.7 mg/kg/day, up to a total daily dose of 26 mg fenfluramine, the geometric mean steady-state fenfluramine (coefficient of variation) C _maxwas 68.0 (41%) ng/mL and AUC _0-24hwas 1390 (44%) ng*h/mL.

FINTEPLA is to be administered orally and may be taken with or without food.

Serotonin syndrome, a potentially life-threatening condition, may occur with FINTEPLA, particularly with concomitant administration of FINTEPLA with other serotonergic drugs, including, but not limited to, selective serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), bupropion, triptans, dietary supplements (e.g., St. John's Wort, tryptophan), drugs that impair metabolism of serotonin (including monoamine oxidase inhibitors [MAOIs], which are contraindicated with FINTEPLA [see Contraindications (4)], dextromethorphan, lithium, tramadol, and antipsychotics with serotonergic agonist activity. Patients should be monitored for the emergence of signs and symptoms of serotonin syndrome, which include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular signs (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). If serotonin syndrome is suspected, treatment with FINTEPLA should be stopped immediately and symptomatic treatment should be started.

Concomitant administration of FINTEPLA and drugs (e.g., SSRIs, SNRIs, TCAs, MAO inhibitors, trazodone, etc.), over-the-counter medications (e.g., dextromethorphan), or herbal supplements (e.g., St. John's Wort) that increase serotonin may increase the risk of serotonin syndrome [see Warnings and Precautions (5.7)]. Concomitant use of FINTEPLA is contraindicated within 14 days of taking MAOIs. Use FINTEPLA with caution in patients taking other medications that increase serotonin.

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)] .

FINTEPLA is indicated for the treatment of seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) in patients 2 years of age and older.

The precise mechanism by which fenfluramine exerts its therapeutic effects in the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome is unknown. Fenfluramine and the metabolite, norfenfluramine, exhibit agonist activity at serotonin 5-HT2 receptors. There is an association between serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine and norfenfluramine, and valvular heart disease and pulmonary arterial hypertension.

Store FINTEPLA at room temperature between 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Do not refrigerate or freeze. Store the bottle and syringe together.

Discard any unused portion 3 months after first opening the bottle or the "Discard After" date on the bottle, whichever is sooner.

FINTEPLA is available only through a restricted distribution program called the FINTEPLA REMS program because of the risk of valvular heart disease and pulmonary arterial hypertension [see Warnings and Precautions (5.1)].

Notable requirements of the FINTEPLA REMS Program include:

• Prescribers must be certified by enrolling in the FINTEPLA REMS program.
• Prescribers must counsel patients receiving FINTEPLA about the risk of valvular heart disease and pulmonary arterial hypertension, how to recognize signs and symptoms of valvular heart disease and pulmonary arterial hypertension, the need for baseline (pretreatment) and periodic cardiac monitoring via echocardiogram during FINTEPLA treatment, and cardiac monitoring after FINTEPLA treatment.
• Patients must enroll in the REMS program and comply with ongoing monitoring requirements [see Warnings and Precautions (5.1)].
• The pharmacy must be certified by enrolling in the REMS program and must only dispense to patients who are authorized to receive FINTEPLA.
• Wholesalers and distributors must only distribute to certified pharmacies.

Further information is available at www.FinteplaREMS.com or by telephone at 1-877-964-3649.

• Decreased Appetite and Decreased Weight: Advise patients that FINTEPLA can cause decreased appetite and decreased weight. ( 5.3)
• Somnolence, Sedation, and Lethargy: Monitor for somnolence and sedation. Advise patients not to drive or operate machinery until they have gained sufficient experience on FINTEPLA. ( 5.4)
• Suicidal Behavior and Ideation: Monitor patients for suicidal behavior and thoughts. ( 5.5)
• Withdrawal of Antiepileptic Drugs: FINTEPLA should be gradually withdrawn to minimize the risk of increased seizure frequency and status epilepticus. ( 5.6)
• Serotonin Syndrome: Advise patients that serotonin syndrome is a potentially life-threatening condition and may occur with FINTEPLA, particularly with concomitant administration of FINTEPLA with other serotonergic drugs. ( 5.7)
• Increase in Blood Pressure: Monitor blood pressure during treatment. ( 5.8)
• Glaucoma: Discontinue therapy in patients with acute decrease in visual acuity or ocular pain. ( 5.9)

• FINTEPLA is to be administered orally and may be taken with or without food. ( 2.2)
• Dravet Syndrome
  • The initial starting and maintenance dosage is 0.1 mg/kg twice daily, which can be increased weekly based on efficacy and tolerability. ( 2.2)
  • The maximum daily maintenance dosage of FINTEPLA is 0.35 mg/kg twice daily (maximum daily dosage of 26 mg). ( 2.2)
• Lennox-Gastaut Syndrome
  • The initial starting dosage is 0.1 mg/kg twice daily, which should be
    
    increased weekly based on tolerability. ( 2.2)
  • The recommended maintenance dosage of FINTEPLA is 0.35 mg/kg twice daily (maximum daily dosage of 26 mg). ( 2.2)
• Dravet Syndrome and Lennox-Gastaut Syndrome
  • Dose adjustment is required in patients taking concomitant stiripentol plus clobazam: the maximum daily maintenance dosage of FINTEPLA is 0.2 mg/kg twice daily (maximum daily dosage of 17 mg). ( 2.2, 2.3, 2.4, 7.1)
• Dosage adjustment is recommended in patients:
  • Taking strong CYP1A2 or CYP2D6 inhibitors ( 2.3, 7.1)
  • With severe renal impairment ( 2.4, 8.6)
  • With mild, moderate, and severe hepatic impairment ( 2.5, 8.7)

The effectiveness of FINTEPLA for the treatment of seizures associated with LGS in patients 2 years of age and older was established in a randomized, double-blind, placebo-controlled study in 263 patients 2 to 35 years of age (Study 3; NCT03355209).

Study 3 compared a 0.7 mg/kg/day and a 0.2 mg/kg/day dose of FINTEPLA with placebo. Patients had a diagnosis of LGS and were inadequately controlled on at least one AED, with or without vagal nerve stimulation and/or ketogenic diet. The study had a 4-week baseline period, during which patients were required to have a minimum of 8 drop seizures while on stable AED therapy. Drop seizures were generalized tonic-clonic, secondarily generalized tonic-clonic, tonic, atonic, or tonic-atonic seizures that were confirmed to result in drops. The baseline period was followed by randomization into a 2-week titration period and a subsequent 12-week maintenance period, where the dose of FINTEPLA remained stable.

In Study 3, 99% of patients were taking between 1 and 4 concomitant AEDs. The most frequently used concomitant AEDs (in at least 25% of patients) were clobazam (45%), lamotrigine (34%), and valproate (56%).

The primary efficacy endpoint in Study 3 was the median percent change from baseline in the frequency of drop seizures per 28 days during the combined 14-week titration and maintenance periods (i.e., treatment period). The proportion of patients who achieve improvement (minimally, much, or very much improved) in the Clinical Global Impression of Change (CGI-I) as assessed by Principal Investigator was a secondary endpoint.

In Study 3, the median percent change from baseline (reduction) in the frequency of drop seizures per 28 days was significantly greater for the 0.7 mg/kg/day dose group of FINTEPLA compared with placebo (Table 7). A reduction in drop seizures was observed within 2 weeks of initiating treatment with FINTEPLA, and the effect remained generally consistent over the 14-week treatment period.

The median percent reduction from baseline in drop seizure frequency per 28 days for the lower dose of FINTEPLA (0.2 mg/kg/day) did not reach statistical significance compared to placebo (Table 7).

Figure 4 displays the percentage of patients by category of reduction from baseline in drop seizure frequency per 28 days during the treatment period in Study 3.

Figure 4: Proportion of Patients by Category of Seizure Response for FINTEPLA and Placebo in Patients with Lennox–Gastaut Syndrome (Study 3)

Numerically greater improvements on the CGI-I by Investigator were observed in patients treated with FINTEPLA compared with placebo.

Oral solution: 2.2 mg/mL fenfluramine as a clear, colorless, cherry flavored liquid.

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

• Pregnancy: Based on animal data, may cause fetal harm ( 8.1)

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.

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 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.

A calibrated measuring device (either a 3 mL or 6 mL oral syringe) will be provided by the pharmacy and is recommended to measure and administer the prescribed dose accurately [see How Supplied/Storage and Handling (16.1)] . A household teaspoon or tablespoon is not an adequate measuring device and should not be used.

Discard any unused FINTEPLA oral solution remaining after 3 months of first opening the bottle or the "Discard After" date on the bottle, whichever is sooner.

FINTEPLA is compatible with commercially available gastric and nasogastric feeding tubes.

When discontinuing FINTEPLA, the dose should be decreased gradually. As with all antiepileptic drugs, abrupt discontinuation should be avoided when possible, to minimize the risk of increased seizure frequency and status epilepticus [see Warnings and Precautions (5.6)].

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Antiepileptic drugs (AEDs), including FINTEPLA, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with an AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, or any unusual changes in mood or behavior.

Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs that did not include FINTEPLA showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.

The increased risk of suicidal thoughts or behavior with AEDs was observed as early as 1 week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.

The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed. Table 3 shows absolute and relative risk by indication for all evaluated AEDs.

The relative risk for suicidal thoughts or behavior was higher in clinical trials in patients with epilepsy than in clinical trials in patients with psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.

Anyone considering prescribing FINTEPLA or any other AED must balance the risk of suicidal thoughts or behaviors with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

As with most AEDs, FINTEPLA should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus. If withdrawal is needed because of a serious adverse reaction, rapid discontinuation can be considered.

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)].

Other central nervous system (CNS) depressants, including alcohol, could potentiate these effects of FINTEPLA. Prescribers should monitor patients for somnolence and sedation and should advise patients not to drive or operate machinery until they have gained sufficient experience on FINTEPLA to gauge whether it adversely affects their ability to drive or operate machinery.

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. Weight should be monitored regularly during treatment with FINTEPLA, and dose modifications should be considered if a decrease in weight is observed.

Prior to starting treatment with FINTEPLA, obtain an echocardiogram assessment to evaluate for valvular heart disease and pulmonary arterial hypertension [see Dosage and Administration (2.6)and Warnings and Precautions (5.1)] .

Cyproheptadine and potent 5-HT1A, 5-HT1D, 5-HT2A, and 5-HT2C serotonin receptor antagonists may decrease the efficacy of FINTEPLA. If cyproheptadine or potent 5--HT1A, 5--HT1D, 5-HT2A, or 5-HT2C serotonin receptor antagonists are coadministered with FINTEPLA, patients should be monitored appropriately.

To evaluate for valvular heart disease and pulmonary arterial hypertension, obtain an echocardiogram assessment every 6 months during treatment with FINTEPLA, and 3 to 6 months after the final dose of FINTEPLA [see Warnings and Precautions (5.1)].

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 Warningand 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.

NDC 43376-322-30

Fintepla ^®

(fenfluramine)

oral solution

2.2 mg/mL

Rx only

For oral use only

Contents 30 mL

NDC 43376-322-30

Fintepla ^®

(fenfluramine)

oral solution

2.2 mg/mL

For oral use only

Attention Pharmacist:

Dispense the enclosed

Medication Guide to each patient

Contents:

One 30 mL bottle

Rx only

NDC 43376-322-36

Fintepla ^®

(fenfluramine)

oral solution

2.2 mg/mL

For oral use only

Rx only

Contents 360 mL

Fintepla ^®

(fenfluramine)

oral solution

2.2 mg/mL

For oral use only

Attention Pharmacist:

Dispense the enclosed

Medication Guide to each

patient

Contents:

One 360 mL bottle

Rx only

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)].

For patients with severe renal impairment (estimated glomerular filtration rate (eGFR) 15 to 29 mL/min/1.73m ²), a maximum total daily dosage of 20 mg without concomitant stiripentol and 17 mg with concomitant stiripentol plus clobazam is recommended [see Use in Specific Populations (8.6)] .

See Table 2for dosage adjustments and recommendations for patients with hepatic impairment [see Use in Specific Populations (8.7)] .

For patients with concomitant use of FINTEPLA with a strong CYP1A2 or CYP2D6 inhibitor, a maximum total daily dosage of 20 mg without concomitant stiripentol and 17 mg with concomitant stiripentol plus clobazam is recommended [see Drug Interactions (7.1)] .

Dravet Syndrome

• The initial starting and maintenance dosage for patients with Dravet syndrome is 0.1 mg/kg twice daily, which can be increased weekly based on efficacy and tolerability. Table 1 provides the recommended titration schedule, if needed.
• Patients with Dravet syndrome not on concomitant stiripentol who are tolerating FINTEPLA at 0.1 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 0.35 mg/kg twice daily (maximum daily dosage of 26 mg).
  
  Patients with Dravet syndrome taking concomitant stiripentol plus clobazam who are tolerating FINTEPLA at 0.1 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 0.2 mg/kg twice daily (maximum daily dosage of 17 mg) [see Drug Interactions (7.1)].

Fenfluramine can cause mydriasis and can precipitate angle closure glaucoma. Consider discontinuing treatment with FINTEPLA in patients with acute decreases in visual acuity or ocular pain.

Overdose has not been observed in the FINTEPLA clinical trial program. However, overdose of fenfluramine, the active ingredient in FINTEPLA, has been reported at higher doses than those included in the clinical trial program. Some of the cases were fatal. Events reported after overdose include mydriasis, tachycardia, flushing, tremors/twitching/muscle spasms, agitation/restlessness/anxiety, increased muscle tone/rigor/opisthotonos, respiratory distress or failure, and seizure. Seizure, coma, and cardiorespiratory arrest were reported in most of the fatal overdoses.

There is no available specific antidote to the overdose reactions of FINTEPLA. In the event of overdose, standard medical practice for the management of drug overdosage should be used. An adequate airway, oxygenation, and ventilation should be ensured; monitoring of cardiac rhythm and vital sign measurement is recommended. A certified poison control center should be contacted for updated information on the management of overdose with FINTEPLA.

FINTEPLA oral solution contains 2.2 mg/mL fenfluramine, equivalent to 2.5 mg/mL of the hydrochloride salt.

The active ingredient, fenfluramine hydrochloride, is designated chemically as N-ethyl-α- methyl-3-(trifluoromethyl)phenethylamine hydrochloride.

The structural formula is:

Fenfluramine hydrochloride is a white to off-white crystalline solid. The pKa of fenfluramine is 10.2.

FINTEPLA is a clear, colorless solution, pH 5.

FINTEPLA contains the following inactive ingredients: cherry flavor, citric acid, ethylparaben hydroxyethylcellulose, methylparaben, potassium citrate, sucralose, and water.

FINTEPLA contains no ingredient made from gluten-containing grain (wheat, barley, or rye), and contains not more than 0.1% of carbohydrates, which is solely derived from the cherry flavor.

FINTEPLA oral solution is a clear, colorless, cherry flavored liquid containing 2.2 mg/mL fenfluramine and is supplied in a white plastic bottle with a child resistant closure as follows:

• Carton containing one 360 mL bottle (NDC 43376-322-36)
• Carton containing one 30 mL bottle (NDC 43376-322-30)

Before dispensing, the pharmacist will insert a press-in bottle adapter into the dispensing bottle. The pharmacy will provide 3 mL or 6 mL calibrated oral dosing syringes.

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.

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. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

FINTEPLA is contraindicated in patients with:

• Hypersensitivity to fenfluramine or any of the excipients in FINTEPLA [see Description (11)]
• Concomitant use, or within 14 days of the administration, of monoamine oxidase inhibitors because of an increased risk of serotonin syndrome [see Warnings and Precautions (5.7)]

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

• Valvular Heart Disease and Pulmonary Arterial Hypertension [see Warnings and Precautions (5.1)]
• Decreased Appetite and Decreased Weight [see Warnings and Precautions (5.3)]
• Somnolence, Sedation, and Lethargy [see Warnings and Precautions (5.4)]
• Suicidal Behavior and Ideation [see Warnings and Precautions (5.5)]
• Withdrawal of Antiepileptic Drugs [see Warnings and Precautions (5.6)]
• Serotonin Syndrome [see Warnings and Precautions (5.7)]
• Increase in Blood Pressure [see Warnings and Precautions (5.8)]
• Glaucoma [see Warnings and Precautions (5.9)]

• Dose adjustment is required for patients taking stiripentol plus clobazam. ( 2.2, 2.3, 7.1)
• Strong CYP1A2 or CYP2D6 inhibitors: a dose adjustment is recommended ( 2.3, 7.1)
• Strong CYP1A2, CYP2B6, or CYP3A4 inducers: it is recommended to avoid coadministration with FINTEPLA. If coadministration is necessary, consider a FINTEPLA dosage increase. ( 7.1)

The effectiveness of FINTEPLA for the treatment of seizures associated with DS in patients 2 years of age and older was established in two randomized, double-blind, placebo-controlled trials in patients 2 to 18 years of age.

Study 1 (N=117) compared a 0.7 mg/kg/day and a 0.2 mg/kg/day dose of FINTEPLA with placebo in patients who were not receiving stiripentol (NCT02682927 and NCT02826863). Study 2 (N=85) compared a 0.4 mg/kg/day dose of FINTEPLA with placebo in patients who were receiving stiripentol and either clobazam, valproate, or both (NCT02926898). In both studies, patients had a clinical diagnosis of DS and were inadequately controlled on at least one AED or other antiseizure treatment including vagal nerve stimulation or a ketogenic diet. Both trials had a 6-week baseline period, during which patients were required to have a minimum of 6 convulsive seizures while on stable AED therapy. Convulsive seizures included tonic, clonic, generalized tonic-clonic, tonic-atonic, secondarily generalized tonic-clonic, hemiclonic, and focal with observable motor signs. The baseline period was followed by randomization into a 2- week (Study 1) or 3-week (Study 2) titration period and a subsequent 12-week maintenance period, where the dose of FINTEPLA remained stable.

In Study 1, 98% of patients were taking between 1 and 4 concomitant AEDs. The most frequently used concomitant AEDs (in at least 25% of patients), were valproate (61%), clobazam (59%), and topiramate (25%). In Study 2, 100% of patients were taking between 2 and 4 concomitant AEDs. The most frequently used concomitant AEDs (in at least 25% of patients), were stiripentol (100%), clobazam (94%), and valproate (89%).

The primary efficacy endpoint in both studies was the change from baseline in the frequency of convulsive seizures per 28 days during the combined 14-week (Study 1) or 15-week (Study 2) titration and maintenance periods (i.e., treatment period). The median longest interval between convulsive seizures was also assessed.

In Study 1 and Study 2, the reduction in convulsive seizure frequency per 28 days was statistically significantly greater for all dose groups of FINTEPLA compared to placebo (Table 6). A reduction in convulsive seizures was observed within 3 to 4 weeks of starting FINTEPLA, and the effect remained generally consistent over the 14- or 15-week treatment period.

Figure 1 and Figure 2 display the percentage of patients by category of seizure response from baseline in convulsive seizure frequency (per 28 days) during the treatment period in Study 1 and Study 2, respectively.

Figure 1: Proportion of Patients by Category of Seizure Response for FINTEPLA and Placebo in Patients with Dravet Syndrome (Study 1)

Figure 2: Proportion of Patients by Category of Seizure Response for FINTEPLA and Placebo in Patients with Dravet Syndrome (Study 2)

In Study 1, 3 of 40 (8%) patients in the FINTEPLA 0.7 mg/kg/day group and 3 of 38 (8%) patients in the FINTEPLA 0.2 mg/kg/day group reported no convulsive seizures during the 14-week treatment period, compared to 0 patients in the placebo group. In Study 2, 1 of 43 (2%) patients in the FINTEPLA 0.4 mg/kg/day group reported no convulsive seizures during the 15-week treatment period, compared to 0 patients in the placebo group.

In Study 1 and Study 2, FINTEPLA was associated with a statistically significant longer interval between convulsive seizures compared to placebo (Figure 3).

Figure 3: Median Longest Interval Between Convulsive Seizures in Patients with Dravet Syndrome (Study 1 and Study 2)

In patients with estimated glomerular filtration rate (eGFR) 15 to 29 mL/min/1.73m ², do not exceed the maximum daily dosage of FINTEPLA of 20 mg .In patients with eGFR 15 to 29 ml/min/1.73m ²and concomitant stiripentol use, do not exceed the maximum daily dosage of FINTEPLA of 17 mg [see Dosage and Administration (2.4)and Clinical Pharmacology (12.3)]. FINTEPLA has not been studied in patients with eGFR < 15 mL/min/1.73m ².

Be sure that you read, understand, and follow these instructions before you start using FINTEPLA oral solution and each time you get a refill. There may be new information.

This Instructions for Use contains information on how to take FINTEPLA. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

What is included with FINTEPLA?

The following items are included to prepare and give an oral dose of FINTEPLA:

• 1 bottle of FINTEPLA oral solution (2.2 mg/mL)
• 2 reusable oral syringes

  		1 Bottle of FINTEPLA Oral Solution (2.2 mg/mL)
  	2 Oral Syringes

Call the pharmacist at 1-844-288-5007 if you did not receive the items listed above, or if you need help using them.

Important information about FINTEPLA

• FINTEPLA is an oralmedicine (taken by mouth) and is given 2 times each day. Follow your healthcare provider's instructions for taking or giving doses of FINTEPLA.
• If you have questions about how to prepare or give FINTEPLA, contact your healthcare provider or call your pharmacist.
• Always use the oral syringes provided with FINTEPLA to make sure the right dose is given. If you need a new syringe contact your pharmacist. Do notuse a household teaspoon or tablespoon.

Oral syringes provided with FINTEPLA by the pharmacy.

With FINTEPLA you will receive 2 reusable oral syringes.

Call the pharmacist at 1-844-288-5007 if you have any questions about the syringes provided with FINTEPLA.

How should I store FINTEPLA?

• Store FINTEPLA at room temperature between 68°F to 77°F (20°C to 25°C).
• Do notrefrigerate or freeze.
• Keep the cap tightly closed and the bottle upright.
• Store the FINTEPLA bottle and syringe together in a clean area.
• Throw away (discard) any unused FINTEPLA 3 months after first opening the bottle orif the Discard After date on the package or bottle has passed. Whichever one comes first.
• Keep FINTEPLA and all medicines out of the reach of children.

Manufactured for: UCB, Inc., Smyrna, GA 30080

FINTEPLA ^®is a registered trademark of the UCB Group of Companies. ©2025. All rights reserved.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: 10/2025

The pharmacokinetics of fenfluramine and norfenfluramine were studied in healthy subjects, in pediatric patients with DS, and in pediatric and adult patients with LGS. The steady-state systemic exposure (C _maxand AUC) of fenfluramine was slightly greater than dose proportional over the dose range of 13 to 51.8 mg twice-daily fenfluramine (i.e., 1 to 4 times the maximum recommended dose). In pediatric patients with DS who received FINTEPLA 0.7 mg/kg/day, up to a total daily dose of 26 mg fenfluramine, the geometric mean steady-state fenfluramine (coefficient of variation) C _maxwas 68.0 (41%) ng/mL and AUC _0-24hwas 1390 (44%) ng*h/mL.

FINTEPLA is to be administered orally and may be taken with or without food.

Serotonin syndrome, a potentially life-threatening condition, may occur with FINTEPLA, particularly with concomitant administration of FINTEPLA with other serotonergic drugs, including, but not limited to, selective serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), bupropion, triptans, dietary supplements (e.g., St. John's Wort, tryptophan), drugs that impair metabolism of serotonin (including monoamine oxidase inhibitors [MAOIs], which are contraindicated with FINTEPLA [see Contraindications (4)], dextromethorphan, lithium, tramadol, and antipsychotics with serotonergic agonist activity. Patients should be monitored for the emergence of signs and symptoms of serotonin syndrome, which include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular signs (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). If serotonin syndrome is suspected, treatment with FINTEPLA should be stopped immediately and symptomatic treatment should be started.

Concomitant administration of FINTEPLA and drugs (e.g., SSRIs, SNRIs, TCAs, MAO inhibitors, trazodone, etc.), over-the-counter medications (e.g., dextromethorphan), or herbal supplements (e.g., St. John's Wort) that increase serotonin may increase the risk of serotonin syndrome [see Warnings and Precautions (5.7)]. Concomitant use of FINTEPLA is contraindicated within 14 days of taking MAOIs. Use FINTEPLA with caution in patients taking other medications that increase serotonin.

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)] .

FINTEPLA is indicated for the treatment of seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) in patients 2 years of age and older.

The precise mechanism by which fenfluramine exerts its therapeutic effects in the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome is unknown. Fenfluramine and the metabolite, norfenfluramine, exhibit agonist activity at serotonin 5-HT2 receptors. There is an association between serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine and norfenfluramine, and valvular heart disease and pulmonary arterial hypertension.

Store FINTEPLA at room temperature between 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Do not refrigerate or freeze. Store the bottle and syringe together.

Discard any unused portion 3 months after first opening the bottle or the "Discard After" date on the bottle, whichever is sooner.

FINTEPLA is available only through a restricted distribution program called the FINTEPLA REMS program because of the risk of valvular heart disease and pulmonary arterial hypertension [see Warnings and Precautions (5.1)].

Notable requirements of the FINTEPLA REMS Program include:

• Prescribers must be certified by enrolling in the FINTEPLA REMS program.
• Prescribers must counsel patients receiving FINTEPLA about the risk of valvular heart disease and pulmonary arterial hypertension, how to recognize signs and symptoms of valvular heart disease and pulmonary arterial hypertension, the need for baseline (pretreatment) and periodic cardiac monitoring via echocardiogram during FINTEPLA treatment, and cardiac monitoring after FINTEPLA treatment.
• Patients must enroll in the REMS program and comply with ongoing monitoring requirements [see Warnings and Precautions (5.1)].
• The pharmacy must be certified by enrolling in the REMS program and must only dispense to patients who are authorized to receive FINTEPLA.
• Wholesalers and distributors must only distribute to certified pharmacies.

Further information is available at www.FinteplaREMS.com or by telephone at 1-877-964-3649.

• Decreased Appetite and Decreased Weight: Advise patients that FINTEPLA can cause decreased appetite and decreased weight. ( 5.3)
• Somnolence, Sedation, and Lethargy: Monitor for somnolence and sedation. Advise patients not to drive or operate machinery until they have gained sufficient experience on FINTEPLA. ( 5.4)
• Suicidal Behavior and Ideation: Monitor patients for suicidal behavior and thoughts. ( 5.5)
• Withdrawal of Antiepileptic Drugs: FINTEPLA should be gradually withdrawn to minimize the risk of increased seizure frequency and status epilepticus. ( 5.6)
• Serotonin Syndrome: Advise patients that serotonin syndrome is a potentially life-threatening condition and may occur with FINTEPLA, particularly with concomitant administration of FINTEPLA with other serotonergic drugs. ( 5.7)
• Increase in Blood Pressure: Monitor blood pressure during treatment. ( 5.8)
• Glaucoma: Discontinue therapy in patients with acute decrease in visual acuity or ocular pain. ( 5.9)

• FINTEPLA is to be administered orally and may be taken with or without food. ( 2.2)
• Dravet Syndrome
  • The initial starting and maintenance dosage is 0.1 mg/kg twice daily, which can be increased weekly based on efficacy and tolerability. ( 2.2)
  • The maximum daily maintenance dosage of FINTEPLA is 0.35 mg/kg twice daily (maximum daily dosage of 26 mg). ( 2.2)
• Lennox-Gastaut Syndrome
  • The initial starting dosage is 0.1 mg/kg twice daily, which should be
    
    increased weekly based on tolerability. ( 2.2)
  • The recommended maintenance dosage of FINTEPLA is 0.35 mg/kg twice daily (maximum daily dosage of 26 mg). ( 2.2)
• Dravet Syndrome and Lennox-Gastaut Syndrome
  • Dose adjustment is required in patients taking concomitant stiripentol plus clobazam: the maximum daily maintenance dosage of FINTEPLA is 0.2 mg/kg twice daily (maximum daily dosage of 17 mg). ( 2.2, 2.3, 2.4, 7.1)
• Dosage adjustment is recommended in patients:
  • Taking strong CYP1A2 or CYP2D6 inhibitors ( 2.3, 7.1)
  • With severe renal impairment ( 2.4, 8.6)
  • With mild, moderate, and severe hepatic impairment ( 2.5, 8.7)

The effectiveness of FINTEPLA for the treatment of seizures associated with LGS in patients 2 years of age and older was established in a randomized, double-blind, placebo-controlled study in 263 patients 2 to 35 years of age (Study 3; NCT03355209).

Study 3 compared a 0.7 mg/kg/day and a 0.2 mg/kg/day dose of FINTEPLA with placebo. Patients had a diagnosis of LGS and were inadequately controlled on at least one AED, with or without vagal nerve stimulation and/or ketogenic diet. The study had a 4-week baseline period, during which patients were required to have a minimum of 8 drop seizures while on stable AED therapy. Drop seizures were generalized tonic-clonic, secondarily generalized tonic-clonic, tonic, atonic, or tonic-atonic seizures that were confirmed to result in drops. The baseline period was followed by randomization into a 2-week titration period and a subsequent 12-week maintenance period, where the dose of FINTEPLA remained stable.

In Study 3, 99% of patients were taking between 1 and 4 concomitant AEDs. The most frequently used concomitant AEDs (in at least 25% of patients) were clobazam (45%), lamotrigine (34%), and valproate (56%).

The primary efficacy endpoint in Study 3 was the median percent change from baseline in the frequency of drop seizures per 28 days during the combined 14-week titration and maintenance periods (i.e., treatment period). The proportion of patients who achieve improvement (minimally, much, or very much improved) in the Clinical Global Impression of Change (CGI-I) as assessed by Principal Investigator was a secondary endpoint.

In Study 3, the median percent change from baseline (reduction) in the frequency of drop seizures per 28 days was significantly greater for the 0.7 mg/kg/day dose group of FINTEPLA compared with placebo (Table 7). A reduction in drop seizures was observed within 2 weeks of initiating treatment with FINTEPLA, and the effect remained generally consistent over the 14-week treatment period.

The median percent reduction from baseline in drop seizure frequency per 28 days for the lower dose of FINTEPLA (0.2 mg/kg/day) did not reach statistical significance compared to placebo (Table 7).

Figure 4 displays the percentage of patients by category of reduction from baseline in drop seizure frequency per 28 days during the treatment period in Study 3.

Figure 4: Proportion of Patients by Category of Seizure Response for FINTEPLA and Placebo in Patients with Lennox–Gastaut Syndrome (Study 3)

Numerically greater improvements on the CGI-I by Investigator were observed in patients treated with FINTEPLA compared with placebo.

Oral solution: 2.2 mg/mL fenfluramine as a clear, colorless, cherry flavored liquid.

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

• Pregnancy: Based on animal data, may cause fetal harm ( 8.1)

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.

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 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.

A calibrated measuring device (either a 3 mL or 6 mL oral syringe) will be provided by the pharmacy and is recommended to measure and administer the prescribed dose accurately [see How Supplied/Storage and Handling (16.1)] . A household teaspoon or tablespoon is not an adequate measuring device and should not be used.

Discard any unused FINTEPLA oral solution remaining after 3 months of first opening the bottle or the "Discard After" date on the bottle, whichever is sooner.

FINTEPLA is compatible with commercially available gastric and nasogastric feeding tubes.

When discontinuing FINTEPLA, the dose should be decreased gradually. As with all antiepileptic drugs, abrupt discontinuation should be avoided when possible, to minimize the risk of increased seizure frequency and status epilepticus [see Warnings and Precautions (5.6)].

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Antiepileptic drugs (AEDs), including FINTEPLA, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with an AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, or any unusual changes in mood or behavior.

Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs that did not include FINTEPLA showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.

The increased risk of suicidal thoughts or behavior with AEDs was observed as early as 1 week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.

The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed. Table 3 shows absolute and relative risk by indication for all evaluated AEDs.

The relative risk for suicidal thoughts or behavior was higher in clinical trials in patients with epilepsy than in clinical trials in patients with psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.

Anyone considering prescribing FINTEPLA or any other AED must balance the risk of suicidal thoughts or behaviors with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

As with most AEDs, FINTEPLA should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus. If withdrawal is needed because of a serious adverse reaction, rapid discontinuation can be considered.

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)].

Other central nervous system (CNS) depressants, including alcohol, could potentiate these effects of FINTEPLA. Prescribers should monitor patients for somnolence and sedation and should advise patients not to drive or operate machinery until they have gained sufficient experience on FINTEPLA to gauge whether it adversely affects their ability to drive or operate machinery.

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. Weight should be monitored regularly during treatment with FINTEPLA, and dose modifications should be considered if a decrease in weight is observed.

Prior to starting treatment with FINTEPLA, obtain an echocardiogram assessment to evaluate for valvular heart disease and pulmonary arterial hypertension [see Dosage and Administration (2.6)and Warnings and Precautions (5.1)] .

Cyproheptadine and potent 5-HT1A, 5-HT1D, 5-HT2A, and 5-HT2C serotonin receptor antagonists may decrease the efficacy of FINTEPLA. If cyproheptadine or potent 5--HT1A, 5--HT1D, 5-HT2A, or 5-HT2C serotonin receptor antagonists are coadministered with FINTEPLA, patients should be monitored appropriately.

To evaluate for valvular heart disease and pulmonary arterial hypertension, obtain an echocardiogram assessment every 6 months during treatment with FINTEPLA, and 3 to 6 months after the final dose of FINTEPLA [see Warnings and Precautions (5.1)].

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 Warningand 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.

NDC 43376-322-30

Fintepla ^®

(fenfluramine)

oral solution

2.2 mg/mL

Rx only

For oral use only

Contents 30 mL

NDC 43376-322-30

Fintepla ^®

(fenfluramine)

oral solution

2.2 mg/mL

For oral use only

Attention Pharmacist:

Dispense the enclosed

Medication Guide to each patient

Contents:

One 30 mL bottle

Rx only

NDC 43376-322-36

Fintepla ^®

(fenfluramine)

oral solution

2.2 mg/mL

For oral use only

Rx only

Contents 360 mL

Fintepla ^®

(fenfluramine)

oral solution

2.2 mg/mL

For oral use only

Attention Pharmacist:

Dispense the enclosed

Medication Guide to each

patient

Contents:

One 360 mL bottle

Rx only

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)].

For patients with severe renal impairment (estimated glomerular filtration rate (eGFR) 15 to 29 mL/min/1.73m ²), a maximum total daily dosage of 20 mg without concomitant stiripentol and 17 mg with concomitant stiripentol plus clobazam is recommended [see Use in Specific Populations (8.6)] .

See Table 2for dosage adjustments and recommendations for patients with hepatic impairment [see Use in Specific Populations (8.7)] .

For patients with concomitant use of FINTEPLA with a strong CYP1A2 or CYP2D6 inhibitor, a maximum total daily dosage of 20 mg without concomitant stiripentol and 17 mg with concomitant stiripentol plus clobazam is recommended [see Drug Interactions (7.1)] .