Fintepla, with the generic name fenfluramine, is a recommendation medication primarily indicated for managing seizures linked with Dravet sickness and Lennox-Gastaut disorder (LGS) in paediatrics patients. Marketed under the brand name Fintepla by Zogenix, it received FDA approval in 2020.

Originally, fenfluramine was recognized for its role as an appetite inhibition; however, it was withdrawn from the market in the late 1990s due to concerns regarding heart valve damage and pulmonic hyperpiesis. Nevertheless, when administered at lower doses and with appropriate medical oversight, fenfluramine has demonstrated safety and efficacy in treating specific seizure disorders, leading to its re-approval for epilepsy-related indications.

1.Mechanism of Action

Fenfluramine is believed to exert its anti-seizure effects through the following mechanisms:

Serotonin Reuptake Inhibition: Fenfluramine enhances the release of serotonin while inhibiting its reuptake, a neurotransmitter that plays a crucial role in regulating mood and behavior. By increasing serotonin activity, fenfluramine may help stabilize the neural circuits that contribute to seizure activity.

Enhancement of Serotonergic Activity: In the context of epilepsy, heightened serotonergic activity may assist in encourage the excessive neuronal firing that leads to seizures, although the precise machine in Dravet syndrome and LGS remain under study.

Modulation of Glutamate Release: Fenfluramine may also mitigate the excessive release of glutamate, another neurotransmitter implicated in seizure activity, thereby further supporting its anti-seizure properties.

2.Indications (Uses)

Fenfluramine is recommended for the therapeutics of:

Dravet Syndrome: A rare and severe epilepsy form that manifests within the first year of life, characterized by frequent and prolonged seizures. Dravet syndrome often proves resistant to conventional anti-seizure medications.

Lennox-Gastaut Syndrome (LGS): A severe epilepsy form that typically emerges in childhood, marked by various seizure types, intellectual disabilities, and developmental delays.

Fenfluramine is not authorized for the treatment of other seizure types or epilepsy.

3.Dosage and Administration

Initial Dose: The standard initial dosage of Fintepla for both Dravet syndrome and Lennox-Gastaut syndrome is 0.2 mg/kg/day, divided into two doses administered in the morning and evening.

Titration: The dosage may be increased on a weekly basis, reaching a maximum of 0.8 mg/kg/day, contingent upon the patient’s tolerance and the effectiveness in controlling seizures. The target dosage is generally determined by the individual’s weight.

Administration: Fintepla is provided as an oral solution and can be taken with or without food. It is essential to measure the liquid formulation accurately using the dosing syringe or measuring device supplied.

Maximum Dose: The highest recommended daily dosage for the majority of patients is 0.8 mg/kg/day; however, the specific dosage should be customized according to the patient’s response and tolerability.

4.Pharmacokinetics

Absorption: Fenfluramine is effectively absorbed following oral intake, with peak plasma levels reached within 2 to 3 hours.

 

Distribution: Fenfluramine is extensively distributed throughout the body, including the brain, which is vital for its efficacy in managing seizures.

Metabolism: Fenfluramine undergoes metabolism in the liver, primarily via the cytochrome P450 enzyme system. The principal metabolite, norfenfluramine, also plays a role in its pharmacological effects.

Half-life: The half-life of fenfluramine is approximately 20 hours, while norfenfluramine has a half-life of about 50 hours, indicating a prolonged presence in the body.

Elimination: Fenfluramine and its metabolites are primarily excreted through the kidneys.

5.Side Effects

The administration of Fintepla may lead to several potential side effects. The most frequently observed and significant side effects include:

Common Side Effects

Decreased appetite: While this is less of a concern compared to previous fenfluramine formulations, it may still manifest.

Somnolence (drowsiness): This is a prevalent effect, particularly during the initiation of treatment or when the dosage is increased.

Fatigue: Numerous patients report experiencing a sense of tiredness or diminished energy levels.

Irritability: This symptom may manifest in certain children.

Diarrhea: Some individuals may encounter gastrointestinal issues, including diarrhea.

Serious Side Effects

Cardiovascular Concerns: Fenfluramine, similar to previous formulations, has been linked to significant heart-related conditions, such as valvular heart disease and pulmonary arterial hypertension (PAH). Patients prescribed Fintepla are generally monitored through echocardiograms at the outset and at regular intervals throughout their treatment.

Serotonin Syndrome: Due to its influence on serotonin levels, there exists a risk of hydroxyindole syndrome when Fintepla is combined with other hydroxytryptamine medications, such as selective serotonin uptake inhibitors (SSRIs). mark may include confusion, agitation, increased heart rate, and elevated blood pressure.

Suicidal Thoughts/Behavior: Like other anti-seizure medications, there is a potential risk for suicidal ideation or actions, necessitating close monitoring of patients.

Liver Function: Fenfluramine may lead to liver complications; therefore, liver function tests (LFTs) should be conducted periodically.

Contraindications and Precautions

Cardiac Valvulopathy or Pulmonary Arterial Hypertension: Fintepla is contraindicated in individuals with a history of heart valve disease or pulmonary hypertension due to the potential for worsening these conditions.

Hypersensitivity: Individuals with a known hypersensitivity to fenfluramine or any ingredient in Fintepla should refrain from using this medication.

Pregnancy and Breastfeeding: Fenfluramine is classified as Pregnancy Category C, indicating that its safety during pregnancy has not been thoroughly established. It should only be administered if the potential benefits outweigh the risks. The excretion of fenfluramine in breast milk is unknown. Consulting a healthcare provider before breastfeeding while on Fintepla is recommended.

Elderly: Caution is advised when prescribing to elderly patients, particularly due to their heightened risk of cardiovascular side effects.

7.Drug Interactions

Fintepla has the potential to interact with various medications, particularly those that influence the serotonergic system or are processed by CYP enzymes. Important interactions to consider include:

Serotonergic Medications: The concurrent use of Fintepla with other serotonergic agents (such as antidepressants or migraine treatments like triptans) may heighten the risk of serotonin syndrome.

Other Antiepileptic Drugs: Interactions may occur with additional anti-seizure medications. It is advisable to closely monitor patients when Fintepla is used alongside other seizure treatments.

CYP Enzyme Modulators: As fenfluramine is metabolized by CYP enzymes, especially CYP2D6, medications. Inhibit or induce these enzymes could alter its plasma concentrations.

8.Overdose

Signs of a Fintepla overdose may include:

Severe drowsiness

Lethargy

Reduced appetite

Respiratory difficulties or cardiac complications (in extreme cases)

In instances of overdose, it is crucial to provide supportive care and maintain close observation of the patient. Gastric lavage or the administration of activated charcoal may be appropriate if the overdose has occurred recently.

9.Monitoring Requirements

Patients receiving Fintepla should undergo regular assessments for the following:

Cardiac health: It is recommended to perform periodic echocardiograms to evaluate heart valve function and pulmonary arterial pressure.

Liver health: Liver function tests (LFTs) should be carried out prior to initiating treatment and at regular intervals thereafter.

Seizure management: Consistent follow-up with healthcare providers is essential to evaluate the medication’s effectiveness and make necessary dosage adjustments.

Growth and Development (in pediatric patients): Continuous monitoring of the child’s growth, appetite. Developmental milestones, along with any behavioral changes, is important.

Summary

Fintepla (fenfluramine) is an anticonvulsant medication approved for managing seizures linked to Dravet syndrome and Lennox-Gastaut syndrome in children. It has demonstrated efficacy in decreasing seizure frequency and enhancing the quality of life for affected individuals. Nevertheless, it is associated with certain cardiovascular risks.