Fintepla
fenfluramine · Solution · Oral
Uses
1 INDICATIONS AND USAGE 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. FINTEPLA is indicated for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome in patients 2 years of age and older. ( 1 )
Dosage and administration
2 DOSAGE AND ADMINISTRATION 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 ) 2.1 Assessments Prior to Initiating FINTEPLA 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) ] . 2.2 Dosing Information FINTEPLA is to be administered orally and may be taken with or without food. 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) ]. Lennox-Gastaut Syndrome The initial starting dosage for patients with Lennox-Gastaut syndrome is 0.1 mg/kg twice daily, which should be increased weekly based on tolerability. Table 1 provides the recommended titration schedule. Patients with Lennox-Gastaut syndrome not on concomitant stiripentol who are tolerating FINTEPLA should be titrated to the recommended maintenance dosage of 0.35 mg/kg twice daily (maximum daily dosage of 26 mg). Patients with Lennox-Gastaut syndrome taking concomitant stiripentol plus clobazam who are tolerating FINTEPLA should be titrated to the recommended maintenance dosage of 0.2 mg/kg twice daily (maximum daily dosage of 17 mg) [see Drug Interactions (7.1) ]. Table 1: FINTEPLA Recommended Titration Schedule For patients not on concomitant stiripentol in whom a more rapid titration is warranted, the dose may be increased every 4 days. Without concomitant stiripentol With concomitant stiripentol plus clobazam Weight-based Dosage To calculate the dose volume: Weight (kg) × Weight-based dosage (mg/kg) ÷ 2.2 mg/mL = mL dose to be taken twice daily Maximum Total Daily Dosage For maximum dosage with concomitant use of strong CYP1A2 or CYP2D6 inhibitors, in patients with severe renal impairment, or in patients with hepatic impairment see Dosage and Administration 2.3, 2.4, 2.5. Weight-based Dosage Maximum Total Daily Dosage Initial Dosage For patients with Dravet syndrome, dosage may be increased based on clinical response to the maximum recommended dosage, as needed. 0.1 mg/kg twice daily 26 mg 0.1 mg/kg twice daily 17 mg Day 7 0.2 mg/kg twice daily 26 mg 0.15 mg/kg twice daily 17 mg Day 14 For patients with Lennox-Gastaut syndrome, dosage should be increased as tolerated to the recommended maintenance dosage (i.e., Day 14). 0.35 mg/kg twice daily 26 mg 0.2 mg/kg twice daily 17 mg 2.3 Dosage Modifications for Patients with Concomitant Use of Strong CYP1A2 or CYP2D6 Inhibitors (DS and LGS) 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) ] . 2.4 Dosage Modifications for Patients with Severe Renal Impairment (DS and LGS) 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) ] . 2.5 Dosage Modifications for Patients with Mild, Moderate, and Severe Hepatic Impairment (DS and LGS) See Table 2 for dosage adjustments and recommendations for patients with hepatic impairment [see Use in Specific Populations (8.7) ] . Table 2: FINTEPLA Dosage Modifications and Recommendations for Patients with Hepatic Impairment Hepatic Impairment Classification Without concomitant stiripentol titrate as recommended [see Dosage and Administration (2.2)] With concomitant stiripentol plus clobazam Maximum total daily dosage Maximum total daily dosage Mild (Child-Pugh A) 20 mg 13 mg Moderate (Child-Pugh B) 20 mg Use not recommended Severe (Child-Pugh C) 17 mg Use not recommended 2.6 Assessments During and After Administration of FINTEPLA 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) ].
Dosage forms and strengths
Oral solution: 2.2 mg/mL fenfluramine as a clear, colorless, cherry flavored liquid. Oral solution: 2.2 mg/mL fenfluramine ( 3 )
Contraindications
4 CONTRAINDICATIONS 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) ] Hypersensitivity to fenfluramine or any of the excipients in FINTEPLA ( 4 ) Within 14 days of the administration of monoamine oxidase inhibitors due to an increased risk of serotonin syndrome ( 4 )
Warnings and precautions
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 ) 5.1 Valvular Heart Disease and Pulmonary Arterial Hypertension 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. 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) ]. 5.2 FINTEPLA REMS Program 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. 5.3 Decreased Appetite and Decreased Weight 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.
Side effects
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) ] The most common adverse reactions (incidence at least 10% and greater than placebo) in patients with Dravet syndrome were decreased appetite; somnolence, sedation, lethargy; diarrhea; constipation; abnormal echocardiogram; fatigue, malaise, asthenia; ataxia, balance disorder, gait disturbance; blood pressure increased; drooling, salivary hypersecretion; pyrexia; upper respiratory tract infection; vomiting; decreased weight; fall; status epilepticus. ( 6.1 ) The most common adverse reactions (incidence at least 10% and greater than placebo) in patients with Lennox-Gastaut syndrome were diarrhea; decreased appetite; fatigue; somnolence; vomiting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact UCB, Inc. at 1-844-599-2273 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In controlled and uncontrolled trials in patients with 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). In Study 1 and Study 2, the mean age was 9 years (range 2 to 19 years) and approximately 46% of patients were female and 74% were White. All patients were receiving at least one other AED. In Study 1 and Study 2, the rates of discontinuation as a result of any adverse reaction were 13%, 0%, and 7% for patients treated with FINTEPLA 0.7 mg/kg/day, 0.2 mg/kg/day, and 0.4 mg/kg/day in combination with stiripentol, respectively, compared to 6% for patients on placebo. The most frequent adverse reaction leading to discontinuation in the patients treated with any dose of FINTEPLA was somnolence (3%). The most common adverse reactions that occurred in patients treated with FINTEPLA (incidence at least 10% and greater than placebo) were decreased appetite; somnolence, sedation, lethargy; diarrhea; constipation; abnormal echocardiogram; fatigue, malaise, asthenia; ataxia, balance disorder, gait disturbance; blood pressure increased; drooling, salivary hypersecretion; pyrexia; upper respiratory tract infection; vomiting; decreased weight; fall; status epilepticus. Table 4 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 1 and Study 2. Table 4: 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) Adverse Reaction FINTEPLA Dose Group Combined Placebo Group Patients in placebo groups from Studies 1 and 2 were pooled. Study 1 Study 2 0.2 mg/kg/day 0.7 mg/kg/day 0.4 mg/kg/day 0.4 mg/kg/day was not an intermediate dose. Patients on the 0.4 mg/kg/day dose were also taking concomitant stiripentol plus clobazam, which increases exposure of FINTEPLA. N=39 % N=40 % N=43 % N=84 % Decreased appetite 23 38 49 8 Somnolence, sedation, lethargy 26 25 23 11 Abnormal echocardiogram Consisted of trace and mild mitral regurgitation, and trace aortic regurgitation, which are considered physiologic. 18 23 9 6 Diarrhea 31 15 23 6 Constipation 3 10 7 0 Fatigue, malaise, asthenia 15 10 30 5 Ataxia, balance disorder, gait disturbance 10 10 7 1 Abnormal behavior 0 8 9 0 Blood pressure increased 13 8 0 5 Drooling, salivary hypersecretion 13 8 2 0 Hypotonia 0 8 0 0 Rash 8 8 5 4 Blood prolactin increased 0 5 0 0 Chills 0 5 2 0 Decreased activity 0 5 0 1 Dehydration 0 5 0 0 Insomnia 0 5 5 2 Pyrexia 15 5 21 14 Stereotypy 0 5 0 0 Upper respiratory tract infection 21 5 7 10 Vomiting 10 5 5 8 Weight decreased 13 5 7 1 Croup 5 3 0 1 Ear infection 8 3 9 5 Gastroenteritis 8 3 2 0 Increased heart rate 5 3 0 2 Irritability 0 3 9 2 Rhinitis 8 3 7 2 Tremor 3 3 9 0 Urinary incontinence 5 3 0 0 Decreased blood glucose 0 0 9 1 Bronchitis 3 0 9 1 Contusion 5 0 0 0 Eczema 0 0 5 0 Enuresis 5 0 0 0 Fall 10 0 0 4 Headache 8 0 0 2 Laryngitis 0 0 5 0 Negativism 5 0 0 0 Status epilepticus 3 0 12 2 Urinary tract infection 5 0 5 0 Viral infection 0 0 5 1 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.
Drug interactions
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 ) 7.1 Effect of Other Drugs on FINTEPLA Stiripentol Plus Clobazam Coadministration of FINTEPLA with stiripentol plus clobazam, with or without valproate, increases fenfluramine plasma concentrations [see Clinical Pharmacology (12.3) ]. If FINTEPLA 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) ] . Strong CYP1A2, 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) ]. 7.2 Effects of Serotonin Receptor Antagonists 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. 7.3 Serotonergic Drugs 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.
Use in specific populations
Pregnancy: Based on animal data, may cause fetal harm ( 8.1 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as FINTEPLA, during pregnancy. Encourage women who are taking FINTEPLA during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling the toll-free number 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org. Risk Summary 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 ) . 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. 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) ]. Data 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. A no-adverse-effect dose for adverse effects on embryofetal development in rabbits was not identified. At the lowest dose tested in rabbits (4.3 mg/kg/day), maternal plasma exposures of fenfluramine and norfenfluramine were lower than those in humans at the MRHD. 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. 8.2 Lactation Risk Summary There are no data on the presence of fenfluramine or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for FINTEPLA and any potential adverse effects on the breastfed infant from FINTEPLA or from the underlying maternal condition. 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 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.
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as FINTEPLA, during pregnancy. Encourage women who are taking FINTEPLA during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling the toll-free number 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org. Risk Summary 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 ) . 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. 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) ]. Data 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. A no-adverse-effect dose for adverse effects on embryofetal development in rabbits was not identified. At the lowest dose tested in rabbits (4.3 mg/kg/day), maternal plasma exposures of fenfluramine and norfenfluramine were lower than those in humans at the MRHD. 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.
Pediatric use
8.4 Pediatric Use 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 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.
Geriatric use
8.5 Geriatric Use 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.
Overdosage
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.
Description
11 DESCRIPTION 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. Chemical Structure
Mechanism of action
12.1 Mechanism of Action 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.
How supplied
16.1 How Supplied 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. 16.2 Storage and Handling 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.
Storage
16.2 Storage and Handling 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.
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Administration Information Advise patients who are prescribed FINTEPLA to use the oral dosing syringes provided by the pharmacy [see Dosage and Administration (2.7) and Instructions for Use ] . Instruct patients to discard any unused FINTEPLA 3 months after first opening the bottle or if the "discard after" date on the dispensing bottle has passed, whichever is sooner [see How Supplied/Storage and Handling (16.1) , (16.2) ]. Valvular Heart Disease and Pulmonary Arterial Hypertension Advise patients that cardiac monitoring must be performed using echocardiography to monitor for serious heart valve changes or high blood pressure in the arteries of the lungs [see Warnings and Precautions (5.1) ]. FINTEPLA REMS Program FINTEPLA is available only through a restricted program called the FINTEPLA REMS program [see Warnings and Precautions (5.2) ] . Inform the patient of the following notable requirements: Patients must enroll in the program and comply with ongoing echocardiogram monitoring requirements [see Warnings and Precautions (5.1) ]. FINTEPLA is only prescribed by certified health care providers and only dispensed from certified pharmacies participating in the program. Therefore, provide patients with the telephone number and website for information on how to obtain the product [see Warnings and Precautions (5.2) ]. Decreased Appetite and Decreased Weight Advise patients that decreased appetite is frequent during treatment with FINTEPLA, which can cause decrease in weight [see Warnings and Precautions (5.3) ] . Somnolence, Sedation, and Lethargy Inform patients that FINTEPLA can cause somnolence, sedation, and lethargy. Caution patients about operating hazardous machinery, including motor vehicles, until they are reasonably certain that FINTEPLA does not affect them adversely (e.g., impair judgment, thinking, or motor skills) [see Warnings and Precautions (5.4) ] . Suicidal Thinking and Behavior Counsel patients, their caregivers, and their families that antiepileptic drugs may increase the risk of suicidal thoughts and behavior and advise them to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts of self-harm. Instruct patients, caregivers, and families to report behaviors of concern immediately to healthcare providers [see Warnings and Precautions (5.5) ] . Withdrawal of Antiepileptic Drugs (AEDs) Advise patients not to discontinue use of FINTEPLA without consulting with their healthcare provider. FINTEPLA should normally be gradually withdrawn to reduce the potential for increased seizure frequency and status epilepticus [see Dosage and Administration (2.8) , Warnings and Precautions (5.6) ] . Serotonin Syndrome Inform patients about the risk of serotonin syndrome, which can be life-threatening. Advise patients on the signs and symptoms of serotonin syndrome and that certain over-the-counter medications and herbal supplements can increase this risk [see Warnings and Precautions (5.7) ]. Increase in Blood Pressure Inform patients that FINTEPLA can cause an increase in blood pressure [see Warnings and Precautions (5.8) ]. Glaucoma Inform patients that FINTEPLA can cause mydriasis and can precipitate angle closure glaucoma. Instruct patients to contact their healthcare provider if they have any acute decreases in visual acuity or ocular pain [see Warnings and Precautions (5.9) ]. Pregnancy Registry Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during FINTEPLA therapy. Encourage women who are taking FINTEPLA to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy [see Use in Specific Populations (8.1) ] .
Label text from the FDA structured product label by UCB, Inc. (revised Oct 27, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Fenfluramine in 1 product
Fintepla NDC products (1)
Frequently asked questions
What is Fintepla used for?
1 INDICATIONS AND USAGE 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. FINTEPLA is indicated for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome in patients 2 years of age and older. ( 1 )
What are the side effects of Fintepla?
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… See the full label for the complete list.
Who makes Fintepla?
Fintepla is listed by 1 labeler in the FDA NDC directory, including UCB, Inc..