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Fenfluramine: Drug information

Fenfluramine: Drug information
(For additional information see "Fenfluramine: Pediatric drug information" and see "Fenfluramine: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Valvular heart disease and pulmonary arterial hypertension

There is an association between serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine, and valvular heart disease and pulmonary arterial hypertension. Echocardiogram assessments are required before, during, and after treatment with fenfluramine. The benefits vs the risks of initiating or continuing fenfluramine must be considered, based on echocardiogram findings. Because of the risks of valvular heart disease and pulmonary arterial hypertension, fenfluramine is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the FINTEPLA REMS.

Brand Names: US
  • Fintepla
Pharmacologic Category
  • Antiseizure Agent, Miscellaneous;
  • Serotonin 5HT-2 Receptor Agonist
Dosing: Adult
Dravet syndrome–associated seizures

Dravet syndrome–associated seizures:

Patients not taking stiripentol : Oral: Initial: 0.1 mg/kg twice daily; may increase based on response and tolerability after 7 days to 0.2 mg/kg twice daily; may further increase based on response and tolerability after 7 days to 0.35 mg/kg twice daily. Maximum dose: 26 mg/day. Note: If a more rapid titration is warranted, the dose may be increased every 4 days (only in patients not receiving concomitant stiripentol).

Patients taking stiripentol: Oral: Initial: 0.1 mg/kg twice daily; may increase based on response and tolerability after 7 days to 0.15 mg/kg twice daily; may further increase based on response and tolerability after 7 days to 0.2 mg/kg twice daily. Maximum dose: 17 mg/day.

Lennox-Gastaut syndrome–associated seizures

Lennox-Gastaut syndrome–associated seizures:

Patients not taking stiripentol: Oral: Initial: 0.1 mg/kg twice daily; Day 7: Increase as tolerated to 0.2 mg/kg twice daily; Day 14: Increase as tolerated to 0.35 mg/kg twice daily. Maximum dose: 26 mg/day. Note: If a more rapid titration is warranted, the dose may be increased every 4 days (only in patients not receiving concomitant stiripentol).

Patients taking stiripentol: Oral: Initial: 0.1 mg/kg twice daily; Day 7: Increase as tolerated to 0.15 mg/kg twice daily; Day 14: Increase as tolerated to 0.2 mg/kg twice daily. Maximum dose: 17 mg/day.

Discontinuation of therapy: Withdraw gradually to minimize the potential of increased seizure frequency.

Dosage adjustment for concomitant therapy : Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

eGFR ≥30 mL/minute/1.73 m2: No dosage adjustments are necessary.

eGFR 15 to 29 mL/minute/1.73 m2:

Patients not receiving stiripentol: Maximum dose: 20 mg/day.

Patients receiving stiripentol plus clobazam: Maximum dose: 17 mg/day.

eGFR <15 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Adult

Mild impairment (Child-Pugh class A):

Patients not receiving stiripentol: Maximum dose: 20 mg/day.

Patients receiving stiripentol plus clobazam: Maximum dose: 13 mg/day.

Moderate impairment (Child-Pugh class B):

Patients not receiving stiripentol: Maximum dose: 20 mg/day.

Patients receiving stiripentol plus clobazam: Use is not recommended.

Severe impairment (Child-Pugh class C):

Patients not receiving stiripentol: Maximum dose: 17 mg/day.

Patients receiving stiripentol plus clobazam: Use is not recommended.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Fenfluramine: Pediatric drug information")

Note: Prior to initiation, obtain an echocardiogram assessment to rule out valvular heart disease and pulmonary arterial hypertension.

Dravet syndrome–associated seizures

Dravet syndrome–associated seizures:

Children ≥2 years and Adolescents:

Patients not taking stiripentol: Oral: Initial: 0.1 mg/kg/dose twice daily; may increase based on response and tolerability after 7 days to 0.2 mg/kg/dose twice daily; may further increase based on response and tolerability after 7 days to 0.35 mg/kg/dose twice daily. Maximum daily dose: 26 mg/day. Note: If a more rapid titration is warranted, the dose may be increased every 4 days (only in patients not receiving concomitant stiripentol).

Patients taking stiripentol: Oral: Initial: 0.1 mg/kg/dose twice daily; may increase based on response and tolerability after 7 days to 0.15 mg/kg/dose twice daily; may further increase based on response and tolerability after 7 days to 0.2 mg/kg/dose twice daily. Maximum daily dose: 17 mg/day.

Lennox-Gastaut syndrome–associated seizures

Lennox- Gastaut syndrome–associated seizures:

Children ≥2 years and Adolescents:

Patients not taking stiripentol: Oral: Initial: 0.1 mg/kg/dose twice daily for 1 week; on day 7, increase as tolerated to 0.2 mg/kg/dose twice daily for 1 week; then on day 14 increase as tolerated to the recommended maintenance dose of 0.35 mg/kg/dose twice daily. Maximum daily dose: 26 mg/day. Note: If a more rapid titration is warranted, the dose may be increased every 4 days (only in patients not receiving concomitant stiripentol).

Patients taking stiripentol: Oral: Initial: 0.1 mg/kg/dose twice daily for 1 week; on day 7, increase as tolerated to 0.15 mg/kg/dose twice daily for 1 week; then on day 14 increase as tolerated to the recommended maintenance dose of 0.35 mg/kg/dose twice daily. Maximum daily dose: 17 mg/day.

Discontinuation of therapy: Gradually decrease the dose to discontinue; abrupt discontinuation may result in increased seizure frequency or status epilepticus.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Children ≥2 years and Adolescents:

eGFR ≥30 mL/minute/1.73 m2: No dosage adjustments are necessary.

eGFR 15 to 29 mL/minute/1.73 m2:

Patients not receiving stiripentol: Maximum daily dose: 20 mg/day.

Patients receiving stiripentol: Maximum daily dose: 17 mg/day.

eGFR <15 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Pediatric

Children ≥2 years and Adolescents: Mild to severe impairment: Use is not recommended.

Adverse Reactions (Significant): Considerations
Blood pressure increased

Increased blood pressure has been reported; hypertensive crisis has also been observed in adults receiving fenfluramine, including patients without a history of hypertension; there were no cases of hypertensive crisis in patients receiving fenfluramine for Dravet syndrome or Lennox-Gastaut syndrome in trials up to 3 years duration.

Pulmonary arterial hypertension

Pulmonary hypertension (arterial) has been associated with fenfluramine when previously marketed at higher doses for weight loss in adults (and withdrawn from the market in 1997). In current trials of fenfluramine for Dravet syndrome or Lennox-Gastaut syndrome up to 3 years duration, there were no reports of pulmonary arterial hypertension (PAH) in patients receiving fenfluramine (Ref).

Mechanism: Unclear; however, serotonin receptor 5HT-2 agonist activity promotes both vasoconstriction and remodeling of pulmonary vasculature, resulting in a thickening of the medial layer and a narrowing of the lumen of the pulmonary artery (Ref).

Onset: Delayed; based on a retrospective trial of previous case reports of PAH associated with fenfluramine-derivatives for weight loss, the median onset of symptoms was 4.5 years in patients with a median duration of therapy of 6 months (Ref).

Risk factors:

Based on previous data when fenfluramine was used as an appetite suppressant for weight loss:

• Family history of pulmonary hypertension (Ref)

• Duration of use (>3 to 6 months) (Ref)

Serotonin syndrome

Serotonin syndrome may occur, particularly when used in combination with other serotonergic agents or agents that impair metabolism of serotonin. The diagnosis of serotonin syndrome is made based on the Hunter Serotonin Toxicity Criteria (Ref) and may result in a spectrum of symptoms, such as anxiety, agitation, confusion, delirium, hyperreflexia, muscle rigidity, myoclonus, tachycardia, tachypnea, and tremor. Severe cases may cause hyperthermia, significant autonomic instability (ie, rapid and severe changes in blood pressure and pulse), coma, and seizures (Ref).

Mechanism: Dose-related; overstimulation of serotonin receptors by serotonergic agents (Ref).

Onset: Rapid; onset of serotonin syndrome is typically within hours of exposure but delays of ≥24 hours have been reported (Ref).

Risk factors:

• Concurrent use of drugs that increase serotonin synthesis, block serotonin reuptake, and/or impair serotonin metabolism

Valvular heart disease

Fenfluramine has been associated with valvular heart disease when previously marketed at higher doses for weight loss in adults, and this concern led to its withdrawal from the US market in 1997 (Ref). In current trials in patients receiving fenfluramine for Dravet syndrome, trace aortic insufficiency and mitral valve insufficiency, considered to be within the normal physiologic range, have commonly been observed; no cases of valvular heart disease were observed in studies for Dravet syndrome or Lennox-Gastaut syndrome up to 3 years duration (Ref).

Mechanism: Dose-related; likely due to activation of serotonin 5HT-2B receptors; 5HT-2B receptors are abundantly expressed on aortic and mitral valves, and these receptors are known to stimulate mitogenesis (Ref).

Onset: Varied; cases have been reported within months to years after drug discontinuation (Ref).

Risk factors:

Based on previous data when fenfluramine was used as an appetite suppressant for weight loss:

• High doses (Ref)

• Duration of use (≥3 months) (Ref)

• Coadministration with other medications known to be 5HT-2B receptor agonists (Ref)

Weight loss

Fenfluramine causes decreased appetite and significant weight loss (≥7% from baseline); during open-label extension studies, approximately half of patients resumed expected measured increases in weight.

Mechanism: Dose-related (likely); as a derivative of amphetamine, it is believed the anorectic effect is mediated through its serotonergic effects, leading to increased 5-HT in the brain and resulting in decreased appetite (Ref).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in children, adolescents, and adults and may include rates with concurrent antiseizure medications.

>10%:

Cardiovascular: Aortic insufficiency (18% to 23%; including aortic regurgitation) (Lagae 2020) (table 1), increased blood pressure (8% to 13%) (table 2), mitral valve insufficiency (18% to 23%; including mitral regurgitation and mitral stenosis) (Ennezat 2021; Lagae 2020) (table 3)

Fenfluramine: Adverse Reaction: Aortic Insufficiency

Drug (Fenfluramine)

Placebo

Dose

Indication

Number of Patients (Fenfluramine)

Number of Patients (Placebo)

Source

Comments

23%

13%

0.7 mg/kg/day

Dravet syndrome

40

40

Lagae 2020

Trace and within the normal physiological range

18%

13%

0.2 mg/kg/day

Dravet syndrome

39

40

Lagae 2020

Fenfluramine: Adverse Reaction: Increased Blood Pressure

Drug (Fenfluramine)

Placebo

Dose

Indication

Number of Patients (Fenfluramine)

Number of Patients (Placebo)

13%

5%

0.2 mg/kg/day

Dravet syndrome

39

84

8%

5%

0.7 mg/kg/day

Dravet syndrome

40

84

Fenfluramine: Adverse Reaction: Mitral Valve Insufficiency

Drug (Fenfluramine)

Placebo

Dose

Indication

Number of Patients (Fenfluramine)

Number of Patients (Placebo)

Source

Comments

23%

13%

0.7 mg/kg/day

Dravet syndrome

40

40

Lagae 2020

Trace and within the normal physiological range

18%

13%

0.2 mg/kg/day

Dravet syndrome

39

40

Lagae 2020

Endocrine & metabolic: Weight loss (2% to 13%) (table 4)

Fenfluramine: Adverse Reaction: Weight Loss

Drug (Fenfluramine)

Placebo

Dose

Indication

Number of Patients (Fenfluramine)

Number of Patients (Placebo)

13%

1%

0.2 mg/kg/day

Dravet syndrome

39

84

5%

1%

0.7 mg/kg/day

Dravet syndrome

40

84

8%

2%

0.7 mg/kg/day

Lennox-Gastaut syndrome

87

87

2%

2%

0.2 mg/kg/day

Lennox-Gastaut syndrome

89

87

Gastrointestinal: Decreased appetite (20% to 38%) (table 5), diarrhea (11% to 31%), sialorrhea (≤13%), vomiting (8% to 14%)

Fenfluramine: Adverse Reaction: Decreased Appetite

Drug (Fenfluramine)

Placebo

Dose

Indication

Number of Patients (Fenfluramine)

Number of Patients (Placebo)

38%

8%

0.7 mg/kg/day

Dravet syndrome

40

84

23%

8%

0.2 mg/kg/day

Dravet syndrome

39

84

36%

12%

0.7 mg/kg/day

Lennox-Gastaut syndrome

87

87

20%

12%

0.2 mg/kg/day

Lennox-Gastaut syndrome

89

87

Nervous system: Asthenia (≤24%), drooling (≤13%), drowsiness (≤26%), fatigue (≤24%), lethargy (≤26%), malaise (≤24%), sedated state (≤26%)

Respiratory: Upper respiratory tract infection (7% to 21%)

Miscellaneous: Fever (15%)

1% to 10%:

Cardiovascular: Increased heart rate (3% to 5%)

Dermatologic: Skin rash (8%)

Endocrine & metabolic: Dehydration (5%), increased serum prolactin (5%)

Gastrointestinal: Constipation (3% to 10%), gastroenteritis (3% to 8%)

Genitourinary: Urinary incontinence (3% to 5%), urinary tract infection (5%)

Hematologic & oncologic: Bruise (5%)

Nervous system: Abnormal behavior (8%; stereotypy: 5%), abnormal gait (≤10%), ataxia (≤10%), balance impairment (≤10%), chills (5%), falling (10%), headache (8%), hypoactivity (5%), hypotonia (8%), insomnia (5%), irritability (3% to 8%), mood changes (negativism: 5%), status epilepticus (3%), tremor (3%)

Respiratory: Rhinitis (3% to 8%)

Frequency not defined:

Cardiovascular: Heart valve disease (when previously marketed at higher doses for weight loss in adults), hypertensive crisis

Respiratory: Pulmonary hypertension (arterial; when previously marketed at higher doses for weight loss in adults)

Postmarketing: Nervous system: Aggressive behavior

Contraindications

Hypersensitivity to fenfluramine or any component of the formulation; concomitant use with or within 14 days of monoamine oxidase inhibitors.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).

• Ocular effects: May cause mild pupillary dilation, which, in susceptible individuals, can lead to an episode of angle-closure glaucoma. Consider discontinuing fenfluramine in patients with acute decreases in visual acuity or ocular pain.

• Suicidal ideation: Pooled analysis of trials involving various antiseizure medications (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify health care provider immediately if symptoms occur.

Other warnings/precautions:

• REMS program:Counsel patients about the risks, signs and symptoms, and required monitoring for valvular heart disease and pulmonary arterial hypertension.

• Withdrawal: Antiseizure medications should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Oral, as hydrochloride:

Fintepla: 2.2 mg/mL (30 mL, 360 mL) [gluten free; contains ethylparaben, methylparaben; cherry flavor]

Generic Equivalent Available: US

No

Pricing: US

Solution (Fintepla Oral)

2.2 mg/mL (per mL): $64.41

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

Oral: Administer with or without food using the provided calibrated oral syringe (3 mL or 6 mL); do not use a household teaspoon or tablespoon (overdosage may occur).

Enteral: May be administered via gastric and nasogastric feeding tubes.

Administration: Pediatric

Oral: May be administered without regard to meals using provided oral syringe; do not use a household teaspoon (overdosage may occur). May also be administered via gastric or nasogastric tube.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Fintepla: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/212102s013lbl.pdf#page=30

Use: Labeled Indications

Dravet syndrome–associated seizures: Treatment of seizures associated with Dravet syndrome in patients ≥2 years of age.

Lennox-Gastaut syndrome–associated seizures: Treatment of seizures associated with Lennox-Gastaut syndrome in patients ≥2 years of age.

Metabolism/Transport Effects

Substrate of CYP1A2 (major), CYP2B6 (major), CYP2C19 (minor), CYP2C9 (minor), CYP2D6 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Broccoli: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Cannabis: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

CloBAZam: May increase the serum concentration of Fenfluramine. Management: Limit the fenfluramine dose to a maximum daily dosage of 0.2 mg/kg twice daily (17 mg/day) when used in combination with stiripentol and clobazam. Risk D: Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

CYP1A2 Inhibitors (Strong): May increase the serum concentration of Fenfluramine. Management: Limit fenfluramine dose to 20 mg/day without concurrent stiripentol or to 17 mg/day with concomitant stiripentol and clobazam when used with a strong CYP1A2 inhibitor. Risk D: Consider therapy modification

CYP2D6 Inhibitors (Strong): May increase the serum concentration of Fenfluramine. Management: Limit fenfluramine dose to 20 mg/day without concurrent stiripentol or to 17 mg/day with concomitant stiripentol and clobazam when used with a strong CYP2D6 inhibitor. Risk D: Consider therapy modification

CYP3A4 Inducers (Strong): May decrease the serum concentration of Fenfluramine. Management: Avoid concurrent use of strong CYP3A4 inducers with fenfluramine when possible. If combined use cannot be avoided, consider increasing the fenfluramine dose, but do not exceed the fenfluramine maximum daily dose. Risk D: Consider therapy modification

Cyproheptadine: Fenfluramine may enhance the CNS depressant effect of Cyproheptadine. Cyproheptadine may diminish the therapeutic effect of Fenfluramine. Risk C: Monitor therapy

Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy

DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Fexinidazole: May decrease the serum concentration of CYP2B6 Substrates (High risk with Inducers). Management: Avoid concomitant use of fexinidazole and CYP2B6 substrates when possible. If combined, monitor for reduced efficacy of the CYP2B6 substrate. Risk D: Consider therapy modification

Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification

Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification

Linezolid: Fenfluramine may enhance the serotonergic effect of Linezolid. This could result in serotonin syndrome. Risk X: Avoid combination

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lorcaserin (Withdrawn From US Market): May enhance the serotonergic effect of Serotonergic Agents (Moderate Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification

Methylene Blue: Fenfluramine may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Monoamine Oxidase Inhibitors (Antidepressant): Fenfluramine may enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid combination

Monoamine Oxidase Inhibitors (Type B): Fenfluramine may enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid combination

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

RifAMPin: May decrease the serum concentration of Fenfluramine. Management: Avoid concurrent use of rifampin with fenfluramine when possible. If combined use cannot be avoided, consider increasing the fenfluramine dose, but do not exceed the fenfluramine maximum daily dose. Risk D: Consider therapy modification

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Serotonergic Agents (High Risk): Fenfluramine may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy

Serotonergic Agents (Moderate Risk, Miscellaneous): Fenfluramine may enhance the serotonergic effect of Serotonergic Agents (Moderate Risk, Miscellaneous). This could result in serotonin syndrome. Risk C: Monitor therapy

Stiripentol: May increase the serum concentration of Fenfluramine. Management: If coadministered with stiripentol and clobazam, initate fenfluramine at 0.1 mg/kg twice daily, then on day 7 increase fenfluramine to 0.15 mg/kg twice daily, and on day 14 increase fenfluramine to 0.2 mg/kg twice daily. Max dose 17 mg/day. Risk D: Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification

Pregnancy Considerations

Information related to inadvertent maternal use of fenfluramine in pregnancy is available from previous reports when used to treat obesity (Jones 2002; Vial 1992). Fenfluramine is associated with an increased risk of pulmonary arterial hypertension, which has also been reported following exposure in pregnancy (Bonnin 2005).

Data collection to monitor pregnancy and infant outcomes following exposure to antiseizure drugs is ongoing. Patients exposed to fenfluramine during pregnancy are encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry (888-233-2334 or http://www.aedpregnancyregistry.org).

Breastfeeding Considerations

It is not known if fenfluramine is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.

Monitoring Parameters

Echocardiogram to evaluate for valvular heart disease and pulmonary arterial hypertension (baseline, every 6 months during treatment, 3 to 6 months after discontinuing); weight (baseline, then regularly during treatment); growth in pediatric patients (regularly during treatment); BP (baseline, then periodically during treatment); signs/symptoms of serotonin syndrome, such as mental status changes (eg, agitation, hallucinations, delirium, coma), autonomic instability (eg, tachycardia, labile BP, diaphoresis), neuromuscular changes (eg, tremor, rigidity, myoclonus), GI symptoms (eg, nausea, vomiting, diarrhea), and/or seizures.

Mechanism of Action

The mechanisms by which fenfluramine exerts its therapeutic effects in the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome are unknown. Fenfluramine and the metabolite, norfenfluramine, increase extracellular levels of serotonin through interaction with serotonin transporter proteins, and exhibit agonist activity at serotonin 5HT-2 receptors.

Pharmacokinetics (Adult Data Unless Noted)

Note: Pharmacokinetic parameters in pediatric patients are reported to be similar to those in healthy adult subjects.

Distribution: Vz/F: 11.9 L/kg.

Protein binding: 50%.

Metabolism: 75% is metabolized primarily by CYP1A2, CYP2B6, and CYP2D6 to active metabolite norfenfluramine; CYP2C9, CYP2C19, and CYP2D6 are involved to a minor extent. Norfenfluramine is deaminated and oxidized to inactive metabolites.

Bioavailability: ~68% to 74%.

Half-life elimination: 20 hours.

Time to peak: 3 to 5 hours.

Excretion: Urine: >90% (<25% as unchanged drug or active metabolite); feces: <5%.

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: In patients with severe renal impairment (eGFR <30 mL/minute/1.73 m2, Cmax and AUC of fenfluramine increased by 20% and 88%, respectively, and Cmax and AUC of norfenfluramine increased by 13% and 21%, respectively, following a single 0.35 mg/kg dose. Has not been studied in eGFR <15 mL/minute/1.73 m2.

Hepatic function impairment: In patients with mild, moderate, or severe hepatic impairment (Child-Pugh class A, B, and C), AUC of fenfluramine increased by 95%, 113%, and 185%, respectively, and Cmax of fenfluramine increased by 19%, 16%, and 29%, respectively, compared to patients with normal hepatic function, following a single 0.35 mg/kg/dose. AUC of norfenfluramine increased by 18% in mild hepatic impairment and 4% in moderate hepatic impairment, but decreased by 11% in severe hepatic impairment and Cmax of norfenfluramine decreased by 21%, 36%, and 45% in patients with mild, moderate, and severe hepatic impairment, respectively, compared to patients with normal hepatic function, following a single 0.35 mg/kg/dose. The combined molar AUC of fenfluramine and norfenfluramine increased by 55%, 56%, and 82%, and the combined molar Cmax of fenfluramine and norfenfluramine increased by 7.5%, 1.3%, and 8% in patients with mild, moderate, and severe hepatic impairment, respectively, compared to patients with normal hepatic function, following a single 0.35 mg/kg/dose.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AT) Austria: Fintepla;
  • (DE) Germany: Fintepla;
  • (FR) France: Fenfluramine;
  • (GB) United Kingdom: Fintepla;
  • (IE) Ireland: Fintepla;
  • (IT) Italy: Fintepla;
  • (NO) Norway: Fintepla;
  • (PL) Poland: Fintepla;
  • (PR) Puerto Rico: Fintepla;
  • (PT) Portugal: Fintepla
  1. Abenhaim L, Moride Y, Brenot F, et al. Appetite-suppressant drugs and the risk of primary pulmonary hypertension. International Primary Pulmonary Hypertension Study Group. N Engl J Med. 1996;335(9):609-616. doi:10.1056/NEJM199608293350901 [PubMed 8692238]
  2. Andrejak M, Tribouilloy C. Drug-induced valvular heart disease: an update. Arch Cardiovasc Dis. 2013;106(5):333-339. doi:10.1016/j.acvd.2013.02.003 [PubMed 23769407]
  3. Bartlett D. Drug-induced serotonin syndrome. Crit Care Nurse. 2017;37(1):49-54. doi:10.4037/ccn2017169 [PubMed 28148614]
  4. Bonnin M, Mercier FJ, Sitbon O, et al. Severe pulmonary hypertension during pregnancy: mode of delivery and anesthetic management of 15 consecutive cases. Anesthesiology. 2005;102(6):1133-1137. doi:10.1097/00000542-200506000-00012 [PubMed 15915025]
  5. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120. doi:10.1056/NEJMra041867. Erratum in: N Engl J Med. 2007;356(23):2437. Erratum in: N Engl J Med. 2009;361(17):1714. [PubMed 15784664]
  6. Dempsie Y, MacLean MR. Pulmonary hypertension: therapeutic targets within the serotonin system. Br J Pharmacol. 2008;155(4):455-462. doi:10.1038/bjp.2008.241 [PubMed 18536742]
  7. Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: Simple and accurate diagnostic decision rules for serotonin toxicity. QJM. 2003;96(9):635-642. doi:10.1093/qjmed/hcg109 [PubMed 12925718]
  8. Fintepla (fenfluramine) [prescribing information]. Smyrna, GA: UCB Inc; March 2023.
  9. Fintepla (fenfluramine) [prescribing information]. Smyrna, GA: UCB Inc; December 2023.
  10. Jones KL, Johnson KA, Dick LM, Felix RJ, Kao KK, Chambers CD. Pregnancy outcomes after first trimester exposure to phentermine/fenfluramine. Teratology. 2002;65(3):125-130. doi:10.1002/tera.10023 [PubMed 11877776]
  11. Lagae L, Sullivan J, Knupp K, et al; FAiRE DS Study Group. Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial. Lancet. 2019;394(10216):2243-2254. doi:10.1016/S0140-6736(19)32500-0 [PubMed 31862249]
  12. Rothman RB, Baumann MH. Serotonergic drugs and valvular heart disease. Expert Opin Drug Saf. 2009;8(3):317-329. doi:10.1517/14740330902931524 [PubMed 19505264]
  13. Sachdev M, Miller WC, Ryan T, Jollis JG. Effect of fenfluramine-derivative diet pills on cardiac valves: a meta-analysis of observational studies. Am Heart J. 2002;144(6):1065-1073. doi:10.1067/mhj.2002.126733 [PubMed 12486432]
  14. Schoonjans AS, Lagae L, Ceulemans B. Low-dose fenfluramine in the treatment of neurologic disorders: experience in Dravet syndrome. Ther Adv Neurol Disord. 2015;8(6):328-338. doi:10.1177/1756285615607726 [PubMed 26600876]
  15. Souza R, Humbert M, Sztrymf B, et al. Pulmonary arterial hypertension associated with fenfluramine exposure: report of 109 cases. Eur Respir J. 2008;31(2):343-348. doi:10.1183/09031936.00104807. Erratum in: Eur Respir J. 2008;31(4):912. [PubMed 17959632]
  16. Sun-Edelstein C, Tepper SJ, Shapiro RE. Drug-induced serotonin syndrome: a review. Expert Opin Drug Saf. 2008;7(5):587-596. doi:10.1517/14740338.7.5.587 [PubMed 18759711]
  17. Vial T, Robert E, Carlier P, Bertolotti E, Brun A. First-trimester in utero exposure to anorectics: a French collaborative study with special reference to dexfenfluramine. Int J Risk Saf Med. 1992;3(4):207-214. doi:10.3233/JRS-1992-3404 [PubMed 23511002]
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