Fenfluramine

Medically reviewed by Drugs.com. Last updated on Sep 2, 2024.

Pronunciation

(fen FLUR a meen)

Index Terms

• Fenfluramine hydrochloride
• Fintepla

Dosage Forms

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]

Brand Names: U.S.

• Fintepla

Pharmacologic Category

• Anticonvulsant, Miscellaneous
• Serotonin 5HT-2 Receptor Agonist

Pharmacology

The mechanisms by which fenfluramine exerts its therapeutic effects in the treatment of seizures associated with Dravet 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.

Distribution

V_z/F: 11.9 L/kg.

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.

Excretion

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

Time to Peak

4 to 5 hours.

Half-Life Elimination

20 hours.

Protein Binding

50%.

Use: Labeled Indications

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

Contraindications

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

Dosing: Adult

Dravet syndrome–associated seizures: 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. If not on stiripentol, increase to 0.35 mg/kg twice daily. Maximum dose: 26 mg/day. If receiving concurrent stiripentol, may increase to 0.2 mg/kg twice daily. Maximum dose: 17 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).

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: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Dravet syndrome: Children ≥2 years and Adolescents: Oral: Initial: 0.1 mg/kg/dose twice daily; may increase based on clinical response and tolerability after 7 days to 0.2 mg/kg/dose twice daily. After 7 days, if not receiving concurrent stiripentol, may further increase to 0.35 mg/kg/dose twice daily; maximum dose: 13 mg/dose twice daily; may increase dose every 4 days if more rapid titration is warranted. For dosing in patients receiving concurrent stiripentol or other interacting drugs, consult drug interactions database.

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.

Administration

Oral: Administer with or without food using the provided calibrated oral syringe (3 mL or 6 mL).

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

Storage

Store 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). 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.

Drug Interactions

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

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

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

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

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

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

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

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

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

Cannabis: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. 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. Consider therapy modification

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

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

Dabrafenib: May decrease the serum concentration of CYP2B6 Substrates (High risk with Inducers). Monitor therapy

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

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

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

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. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

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. Consider therapy modification

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

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

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

Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2B6 Substrates (High risk with Inducers). Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

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

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

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

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

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

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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. Consider therapy modification

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

Oxitriptan: 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. Monitor therapy

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. 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 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. Consider therapy modification

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

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

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

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

RifAMPin: May decrease the serum concentration of Fenfluramine. Management: Consider increasing the fenfluramine dose when used together with rifampin, but do not exceed the fenfluramine maximum daily dosage [0.35 mg/kg twice daily (26 mg/day)]. Monitor therapy

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

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

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

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

Stiripentol: 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. 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. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Aortic insufficiency (≤23%), increased blood pressure (8% to 13%), mitral valve insufficiency (≤23%)

Endocrine & metabolic: Weight loss (5% to 13%, dose-related)

Gastrointestinal: Decreased appetite (23% to 38%), diarrhea (15% to 31%), sialorrhea (≤13%)

Nervous system: Drooling (≤13%), drowsiness (≤26%), fatigue (≤15%), lethargy (≤26%), malaise (≤15%), sedated state (≤26%)

Neuromuscular & skeletal: Asthenia (≤15%)

Respiratory: Upper respiratory tract infection (5% to 21%)

Miscellaneous: Fever (5% to 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%), vomiting (5% to 10%)

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%), mood changes (negativism: 5%), status epilepticus (3%)

Neuromuscular & skeletal: Tremor (3%)

Otic: Otic infection (3% to 8%)

Respiratory: Bronchitis (3%), croup (3% to 5%), rhinitis (3% to 8%)

Frequency not defined:

Cardiovascular: Heart valve disease, hypertensive crisis

Nervous system: Serotonin syndrome, suicidal ideation, suicidal tendencies

Ophthalmic: Angle-closure glaucoma, mydriasis

Respiratory: Pulmonary hypertension (arterial)

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).

• Decreased appetite and weight: Has been associated with dose-related decreases in appetite and weight. Monitor growth of pediatric patients closely. Consider modifying dose if weight decreases.

• Hypertension: May elevate BP and cause hypertension. Hypertensive events, including hypertensive crisis, have been observed in patients with or without evidence of preexisting hypertension. Assess BP before treatment and monitor periodically.

• 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.

• Pulmonary arterial hypertension: [US Boxed Warning]: There is an association between serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine, 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 pulmonary arterial hypertension, fenfluramine is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the FINTEPLA REMS.

• Serotonin syndrome: Potentially life-threatening serotonin syndrome (SS) may occur with fenfluramine, particularly when used in combination with other serotonergic agents (eg, serotonin–norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, bupropion, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, St John's wort, tryptophan) or agents that impair metabolism of serotonin (eg, monoamine oxidase inhibitors, which are contraindicated with fenfluramine). Monitor patients closely for signs of SS 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. Discontinue treatment (and any concomitant serotonergic agent) immediately if signs/symptoms arise.

• Suicidal ideation: Pooled analysis of trials involving various antiepileptics (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.

• Valvular heart disease: [US Boxed Warning]: There is an association between serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine, and valvular heart disease. 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, fenfluramine is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the FINTEPLA REMS.

Disease-related concerns:

• Hepatic impairment: Use is not recommended in patients with hepatic impairment.

• Renal impairment: Use is not recommended in moderate or severe renal impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• REMS program: [US Boxed Warning]: Fenfluramine is available only through a restricted Risk Evaluation and Mitigation Strategy (REMS) program. Prescribers and pharmacies must enroll in the Fintepla REMS program; enrollment and additional information are available at 1-877-964-3649 or at www.FinteplaREMS.com. Counsel patients about the risks, signs and symptoms, and required monitoring for valvular heart disease and pulmonary arterial hypertension.

• Withdrawal: Anticonvulsants 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.

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).

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 antiepileptic 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).

Patient Education

What is this drug used for?

• It is used to help control certain kinds of seizures.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Not hungry

• Weight loss

• Fatigue

• Feeling tired or weak

• Diarrhea

• Constipation

• Drooling

• Common cold symptoms

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Heart valve problems and high blood pressure in the lungs like shortness of breath; swelling in the arms or legs; chest pain; fast or abnormal heartbeat; change in color of skin or lips to a bluish color; passing out; or feeling very dizzy, tired, or weak.

• High blood pressure like severe headache or dizziness, passing out, or change in eyesight

• Change in balance

• Trouble walking

• Red eyes

• Vision changes

• Eye pain

• Severe eye irritation

• Seeing halos or bright colors around lights

• Severe upset stomach

• Throwing up

• Falls

• Ear pain

• Depression like thoughts of suicide, anxiety, agitation, irritability, panic attacks, mood changes, behavioral changes, or confusion

• Serotonin syndrome like dizziness, severe headache, agitation, sensing things that seem real but are not, fast heartbeat, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Frequently asked questions

• How long does it take Fintepla to work?
• Is Fintepla a controlled substance?
• What type of epilepsy is Diacomit used to treat?
• How is Fintepla injected/administered?

Further information

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