Peringatan Keamanan

Overdosage of fenfluramine has been reported; in overdose cases, symptoms include agitation, anxiety, restlessness, twitching, tremors/muscle spasms, flushing, tachycardia, mydriasis, increased muscle tone, respiratory distress/failure, seizure, and coma. Some overdosage cases proved fatal, and in most fatal cases, patients experienced seizures, coma, and cardiorespiratory arrest.L14522

There is currently no standard practice for managing fenfluramine overdose. Symptomatic management, including ensuring proper ventilation and monitoring of both cardiac and respiratory functions is recommended.L14522

Fenfluramine

DB00574

small molecule approved illicit investigational withdrawn

Deskripsi

Dravet syndrome is a pediatric encephalopathy that typically manifests within the first year of life following exposure to elevated temperatures. It is characterized by recurrent pharmacoresistant seizures, which increase in frequency and severity with disease progression. Concomitantly with these seizures, patients typically display delayed development and neurocognitive impairment.A214694, A214709, A214712, A214715 Fenfluramine is a serotonergic phenethylamine originally used as an appetite suppressant until concerns regarding cardiotoxicity in obese patients lead to its withdrawal from the market in 1997.A214694, A214718, A11906 Through its ability to modulate neurotransmission, fenfluramine has reemerged as an effective therapy against pharmacoresistant seizures, such as those involved in Dravet syndrome.A214688, A214691, A214700

Fenfluramine was granted initial FDA approval in 1973 prior to its withdrawal; it was granted a new FDA approval on June 25, 2020, for treatment of patients with Dravet syndrome and Lennox-Gastaut syndrome through the restricted FINTEPLA REMS program. It is currently sold under the name FINTEPLA® by Zogenix INC.L14522

Struktur Molekul 2D

Berat 231.2573
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) Fenfluramine has an elimination half-life of 20 hours in healthy subjects.[L14522]
Volume Distribusi Fenfluramine has an apparent volume of distribution of 11.9 L/kg with a coefficient of variation of 16.5% following oral administration in healthy subjects.[L14522]
Klirens (Clearance) Fenfluramine has a mean clearance of 24.8 L/h with a coefficient of variation of 29% in healthy subjects.[L14522]

Absorpsi

Fenfluramine has a steady-state Tmax of between four and five hours and an absolute bioavailability of approximately 68-74%. Fenfluramine administered to pediatric patients at 0.7 mg/kg/day up to 26 mg resulted in a mean Cmax of 68.0 ng/mL with a coefficient of variation of 41%; similarly the AUC0-24 was 1390 (44%) ng\*h/mL.L14522

Metabolisme

Fenfluramine is metabolized primarily in the liver by CYP1A2, CYP2B6, CYP2D6, CYP2C9, CYP2C19, and CYP3A4/5 to yield the major active metabolite norfenfluramine and several other minor inactive metabolites.L14522

Rute Eliminasi

Over 90% of fenfluramine is excreted in urine and less than 5% in feces; unchanged fenfluramine and the major active metabolite norfenfluramine account for less than 25% of the recovered amount.L14522

Interaksi Makanan

1 Data
  • 1. Take with or without food. The absorption is unaffected by food.

Interaksi Obat

1225 Data
Deferasirox The serum concentration of Fenfluramine can be increased when it is combined with Deferasirox.
Peginterferon alfa-2b The serum concentration of Fenfluramine can be increased when it is combined with Peginterferon alfa-2b.
Leflunomide The serum concentration of Fenfluramine can be decreased when it is combined with Leflunomide.
Teriflunomide The serum concentration of Fenfluramine can be decreased when it is combined with Teriflunomide.
Buprenorphine Fenfluramine may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.
Doxylamine Doxylamine may increase the central nervous system depressant (CNS depressant) activities of Fenfluramine.
Dronabinol Dronabinol may increase the central nervous system depressant (CNS depressant) activities of Fenfluramine.
Droperidol Droperidol may increase the central nervous system depressant (CNS depressant) activities of Fenfluramine.
Hydrocodone Fenfluramine may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
Hydroxyzine Hydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Fenfluramine.
Magnesium sulfate The therapeutic efficacy of Fenfluramine can be increased when used in combination with Magnesium sulfate.
Metyrosine Fenfluramine may increase the sedative activities of Metyrosine.
Minocycline Minocycline may increase the central nervous system depressant (CNS depressant) activities of Fenfluramine.
Nabilone Nabilone may increase the central nervous system depressant (CNS depressant) activities of Fenfluramine.
Orphenadrine Fenfluramine may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
Paraldehyde Fenfluramine may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
Perampanel Perampanel may increase the central nervous system depressant (CNS depressant) activities of Fenfluramine.
Pramipexole Fenfluramine may increase the sedative activities of Pramipexole.
Ropinirole Fenfluramine may increase the sedative activities of Ropinirole.
Rufinamide The risk or severity of adverse effects can be increased when Rufinamide is combined with Fenfluramine.
Sodium oxybate Fenfluramine may increase the central nervous system depressant (CNS depressant) activities of Sodium oxybate.
Suvorexant Fenfluramine may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.
Tapentadol Tapentadol may increase the central nervous system depressant (CNS depressant) activities of Fenfluramine.
Thalidomide Fenfluramine may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
Zolpidem Fenfluramine may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
Methadone The risk or severity of adverse effects can be increased when Methadone is combined with Fenfluramine.
Atomoxetine The metabolism of Atomoxetine can be decreased when combined with Fenfluramine.
Dicoumarol The risk or severity of adverse effects can be increased when Fenfluramine is combined with Dicoumarol.
Phenindione The risk or severity of adverse effects can be increased when Fenfluramine is combined with Phenindione.
Phenprocoumon The risk or severity of adverse effects can be increased when Fenfluramine is combined with Phenprocoumon.
4-hydroxycoumarin The risk or severity of adverse effects can be increased when Fenfluramine is combined with 4-hydroxycoumarin.
Coumarin The risk or severity of adverse effects can be increased when Fenfluramine is combined with Coumarin.
Ethyl biscoumacetate The risk or severity of adverse effects can be increased when Fenfluramine is combined with Ethyl biscoumacetate.
Fluindione The risk or severity of adverse effects can be increased when Fenfluramine is combined with Fluindione.
Clorindione The risk or severity of adverse effects can be increased when Fenfluramine is combined with Clorindione.
Diphenadione The risk or severity of adverse effects can be increased when Fenfluramine is combined with Diphenadione.
Tioclomarol The risk or severity of adverse effects can be increased when Fenfluramine is combined with Tioclomarol.
(S)-Warfarin The risk or severity of adverse effects can be increased when Fenfluramine is combined with (S)-Warfarin.
Mirabegron The serum concentration of Fenfluramine can be increased when it is combined with Mirabegron.
Abiraterone The serum concentration of Fenfluramine can be increased when it is combined with Abiraterone.
Mirtazapine The therapeutic efficacy of Fenfluramine can be decreased when used in combination with Mirtazapine.
Cyproterone acetate The metabolism of Fenfluramine can be increased when combined with Cyproterone acetate.
Ethanol Fenfluramine may increase the central nervous system depressant (CNS depressant) activities of Ethanol.
Azelastine Fenfluramine may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
Brimonidine Brimonidine may increase the central nervous system depressant (CNS depressant) activities of Fenfluramine.
Seproxetine The risk or severity of adverse effects can be increased when Fenfluramine is combined with Seproxetine.
Methylene blue Fenfluramine may increase the serotonergic activities of Methylene blue.
Trospium The metabolism of Fenfluramine can be decreased when combined with Trospium.
Disopyramide The metabolism of Fenfluramine can be decreased when combined with Disopyramide.
Biperiden The metabolism of Fenfluramine can be decreased when combined with Biperiden.
Oxybutynin The metabolism of Fenfluramine can be decreased when combined with Oxybutynin.
Solifenacin The metabolism of Solifenacin can be decreased when combined with Fenfluramine.
Zopiclone The risk or severity of adverse effects can be increased when Fenfluramine is combined with Zopiclone.
Caffeine The metabolism of Fenfluramine can be decreased when combined with Caffeine.
Moxifloxacin The metabolism of Fenfluramine can be decreased when combined with Moxifloxacin.
Gatifloxacin The metabolism of Fenfluramine can be decreased when combined with Gatifloxacin.
Simeprevir The metabolism of Fenfluramine can be decreased when combined with Simeprevir.
Lobeglitazone The metabolism of Fenfluramine can be decreased when combined with Lobeglitazone.
Pazufloxacin The metabolism of Fenfluramine can be decreased when combined with Pazufloxacin.
Osilodrostat The metabolism of Fenfluramine can be decreased when combined with Osilodrostat.
Nicardipine The metabolism of Fenfluramine can be decreased when combined with Nicardipine.
Metoprolol The metabolism of Fenfluramine can be decreased when combined with Metoprolol.
Terfenadine The metabolism of Fenfluramine can be decreased when combined with Terfenadine.
Quinine The metabolism of Fenfluramine can be decreased when combined with Quinine.
Celecoxib The metabolism of Fenfluramine can be decreased when combined with Celecoxib.
Darifenacin The metabolism of Fenfluramine can be decreased when combined with Darifenacin.
Chloroquine The metabolism of Fenfluramine can be decreased when combined with Chloroquine.
Delavirdine The metabolism of Fenfluramine can be decreased when combined with Delavirdine.
Tipranavir The metabolism of Fenfluramine can be decreased when combined with Tipranavir.
Perhexiline The metabolism of Fenfluramine can be decreased when combined with Perhexiline.
Fusidic acid The metabolism of Fenfluramine can be decreased when combined with Fusidic acid.
Asunaprevir The metabolism of Fenfluramine can be decreased when combined with Asunaprevir.
Rucaparib The metabolism of Fenfluramine can be decreased when combined with Rucaparib.
Ritonavir The metabolism of Fenfluramine can be decreased when combined with Ritonavir.
Ketoconazole The metabolism of Fenfluramine can be decreased when combined with Ketoconazole.
Cyclosporine The metabolism of Fenfluramine can be decreased when combined with Cyclosporine.
Cholecalciferol The metabolism of Fenfluramine can be decreased when combined with Cholecalciferol.
Cimetidine The metabolism of Fenfluramine can be decreased when combined with Cimetidine.
Terbinafine The metabolism of Fenfluramine can be decreased when combined with Terbinafine.
Primaquine The metabolism of Fenfluramine can be decreased when combined with Primaquine.
Panobinostat The metabolism of Fenfluramine can be decreased when combined with Panobinostat.
Lumefantrine The metabolism of Fenfluramine can be decreased when combined with Lumefantrine.
Sulfaphenazole The metabolism of Fenfluramine can be decreased when combined with Sulfaphenazole.
Phenylbutyric acid The metabolism of Fenfluramine can be decreased when combined with Phenylbutyric acid.
Manidipine The metabolism of Fenfluramine can be decreased when combined with Manidipine.
Rolapitant The metabolism of Fenfluramine can be decreased when combined with Rolapitant.
Rhein The metabolism of Fenfluramine can be decreased when combined with Rhein.
Berotralstat The metabolism of Fenfluramine can be decreased when combined with Berotralstat.
Quinidine The metabolism of Fenfluramine can be decreased when combined with Quinidine.
Bupropion The metabolism of Fenfluramine can be decreased when combined with Bupropion.
Propafenone The metabolism of Fenfluramine can be decreased when combined with Propafenone.
Cinacalcet The metabolism of Fenfluramine can be decreased when combined with Cinacalcet.
Halofantrine The metabolism of Fenfluramine can be decreased when combined with Halofantrine.
Glycerol phenylbutyrate The metabolism of Fenfluramine can be decreased when combined with Glycerol phenylbutyrate.
Botulinum toxin type B The risk or severity of CNS depression can be increased when Botulinum toxin type B is combined with Fenfluramine.
Botulinum toxin type A The risk or severity of CNS depression can be increased when Botulinum toxin type A is combined with Fenfluramine.
Baclofen Baclofen may increase the central nervous system depressant (CNS depressant) activities of Fenfluramine.
Lorazepam The risk or severity of CNS depression can be increased when Lorazepam is combined with Fenfluramine.
Ethchlorvynol The risk or severity of CNS depression can be increased when Ethchlorvynol is combined with Fenfluramine.
Succinylcholine The risk or severity of CNS depression can be increased when Succinylcholine is combined with Fenfluramine.

Target Protein

Sodium-dependent serotonin transporter SLC6A4
5-hydroxytryptamine receptor 1D HTR1D
5-hydroxytryptamine receptor 2C HTR2C
Sigma non-opioid intracellular receptor 1 SIGMAR1
5-hydroxytryptamine receptor 2A HTR2A
5-hydroxytryptamine receptor 2B HTR2B
5-hydroxytryptamine receptor 1A HTR1A

Referensi & Sumber

Synthesis reference: Vincenzo Cannata, Barbara Galbiati, Angelo Spreafico, "Process for manufacturing 1-(3-trifluoromethyl)-phenyl-propan-2-one intermediate in the synthesis of the fenfluramine." U.S. Patent US5811586, issued August, 1965.
Artikel (PubMed)
  • PMID: 2463643
    Fuller RW, Snoddy HD, Robertson DW: Mechanisms of effects of d-fenfluramine on brain serotonin metabolism in rats: uptake inhibition versus release. Pharmacol Biochem Behav. 1988 Jul;30(3):715-21. doi: 10.1016/0091-3057(88)90089-5.
  • PMID: 28073790
    Griffin A, Hamling KR, Knupp K, Hong S, Lee LP, Baraban SC: Clemizole and modulators of serotonin signalling suppress seizures in Dravet syndrome. Brain. 2017 Mar 1;140(3):669-683. doi: 10.1093/brain/aww342.
  • PMID: 32169824
    Martin P, de Witte PAM, Maurice T, Gammaitoni A, Farfel G, Galer B: Fenfluramine acts as a positive modulator of sigma-1 receptors. Epilepsy Behav. 2020 Apr;105:106989. doi: 10.1016/j.yebeh.2020.106989. Epub 2020 Mar 10.
  • PMID: 10498829
    Porter RH, Benwell KR, Lamb H, Malcolm CS, Allen NH, Revell DF, Adams DR, Sheardown MJ: Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells. Br J Pharmacol. 1999 Sep;128(1):13-20.
  • PMID: 29805740
    Rodriguez-Munoz M, Sanchez-Blazquez P, Garzon J: Fenfluramine diminishes NMDA receptor-mediated seizures via its mixed activity at serotonin 5HT2A and type 1 sigma receptors. Oncotarget. 2018 May 4;9(34):23373-23389. doi: 10.18632/oncotarget.25169. eCollection 2018 May 4.
  • PMID: 31116409
    Schoonjans AS, Ceulemans B: An Old Drug for a New Indication: Repurposing Fenfluramine From an Anorexigen to an Antiepileptic Drug. Clin Pharmacol Ther. 2019 Nov;106(5):929-932. doi: 10.1002/cpt.1469. Epub 2019 May 22.
  • PMID: 26822114
    Sourbron J, Schneider H, Kecskes A, Liu Y, Buening EM, Lagae L, Smolders I, de Witte P: Serotonergic Modulation as Effective Treatment for Dravet Syndrome in a Zebrafish Mutant Model. ACS Chem Neurosci. 2016 May 18;7(5):588-98. doi: 10.1021/acschemneuro.5b00342. Epub 2016 Feb 17.
  • PMID: 28428755
    Sourbron J, Smolders I, de Witte P, Lagae L: Pharmacological Analysis of the Anti-epileptic Mechanisms of Fenfluramine in scn1a Mutant Zebrafish. Front Pharmacol. 2017 Apr 6;8:191. doi: 10.3389/fphar.2017.00191. eCollection 2017.
Menampilkan 8 dari 15 artikel.

Contoh Produk & Brand

Produk: 7 • International brands: 6
Produk
  • Fintepla
    Solution • 2.2 mg/1mL • Oral • US • Approved
  • Fintepla
    Solution • 2.2 mg/ml • Oral • EU • Approved
  • Fintepla
    Solution • 2.2 mg/ml • Oral • EU • Approved
  • Fintepla
    Solution • 2.2 mg/ml • Oral • EU • Approved
  • Fintepla
    Solution • 2.2 mg/ml • Oral • EU • Approved
  • Pondimin Tab 20mg
    Tablet • 20 mg / tab • Oral • Canada • Approved
  • Pondimin Tab 20mg
    Tablet • 20 mg • Oral • Canada • Approved
International Brands
  • Adifax
  • Obedrex
  • Ponderax
  • Ponderax PA
  • Pondimin
  • Rotondin

Sekuens Gen/Protein (FASTA)

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