Overview

• Generic Name: Fenfluramine
• Brand Names: Fintepla (current), Pondimin (previously)
• Drug Class: Serotonergic agent, anorectic (appetite suppressant)

Chemical Information

• Chemical Formula: C12H16F3N
• Molecular Weight: 231.26 g/mol

Indications

• Dravet Syndrome: Used as an adjunctive treatment for seizures in patients with Dravet Syndrome.
• Appetite Suppressant: Previously used for weight loss (withdrawn due to adverse effects).

Mechanism of Action

• Serotonin Release: Promotes the release of serotonin and inhibits its reuptake, leading to increased serotonin levels in the brain.
• Interaction with Receptors: Modulates various serotonin receptors, contributing to its therapeutic and adverse effects.

Pharmacokinetics

• Absorption: Well absorbed from the gastrointestinal tract.
• Peak Plasma Time: Approximately 3-4 hours after oral administration.
• Distribution: Widely distributed throughout the body.
• Protein Binding: Moderate (50-60%).
• Metabolism: Metabolized primarily in the liver.
• Elimination Half-life: Approximately 20 hours.
• Excretion: Primarily excreted in urine.

Dosage Forms

• Oral Solution: 2.2 mg/mL (Fintepla)
• Tablets: Previously available in various strengths (Pondimin).

Dosage

• Dravet Syndrome:
  • Starting dose: 0.1 mg/kg twice daily.
  • Maintenance dose: Up to 0.35 mg/kg twice daily, based on clinical response and tolerability.

Side Effects

• Common: Decreased appetite, fatigue, diarrhea, drowsiness, weight loss.
• Serious: Valvular heart disease, pulmonary hypertension, serotonin syndrome.

Contraindications

• Hypersensitivity: Known hypersensitivity to fenfluramine or any of its components.
• Cardiac Issues: Patients with a history of heart valve disease or pulmonary hypertension.

Drug Interactions

• MAO Inhibitors: Increased risk of serotonin syndrome.
• Other Serotonergic Drugs: Concurrent use with other serotonergic drugs can increase the risk of serotonin syndrome.

Monitoring

• Cardiac Health: Regular echocardiograms to monitor for heart valve abnormalities.
• Serotonin Syndrome: Monitor for symptoms of serotonin syndrome, especially when used with other serotonergic agents.
• Growth and Development: Monitor weight and growth in pediatric patients.

Special Considerations

• Pregnancy: Not recommended due to potential risks; Category X (when used as an appetite suppressant).
• Breastfeeding: Caution advised as it is unknown if fenfluramine is excreted in human milk.
• Pediatric Use: Approved for use in children with Dravet Syndrome under specific dosing guidelines.
• History of Use: Previously used for weight loss but withdrawn due to association with heart valve disease and pulmonary hypertension.

Storage

• Oral Solution: Store at room temperature, away from light and moisture.

Patient Counseling Information

• Compliance: Importance of taking medication as prescribed.
• Side Effects: Educate about common side effects and when to seek medical attention.
• Cardiac Monitoring: Importance of regular cardiac monitoring and reporting any cardiac symptoms.

Research and Development

• Ongoing Studies: Research continues to explore the efficacy and safety of fenfluramine in other seizure disorders and neurological conditions.

Regulatory Status

• FDA Approval: Approved in 2020 for the treatment of seizures associated with Dravet syndrome (Fintepla).
• Historical Withdrawal: Withdrawn from the market in 1997 for use as an appetite suppressant due to safety concerns.