Introduction
Fintepla (fenfluramine hydrochloride) is an oral solution approved by the FDA for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome in patients aged 2 years and older. It represents a significant advancement in the management of these treatment-resistant epileptic encephalopathies.
Mechanism of Action
Fintepla's precise mechanism of action in seizure control is not fully elucidated but is believed to involve multiple pathways. The drug and its active metabolite, norfenfluramine, act as potent agonists at serotonin 5-HT receptors, particularly 5-HT2A and 5-HT2C subtypes. This serotonergic activity is thought to modulate neuronal excitability and inhibit seizure activity. Additionally, fenfluramine may influence sigma-1 receptor activity, potentially contributing to its anticonvulsant effects.
Indications
- Treatment of seizures associated with Dravet syndrome in patients 2 years of age and older
- Treatment of seizures associated with Lennox-Gastaut syndrome in patients 2 years of age and older
Dosage and Administration
Initial dosage: 0.1 mg/kg twice daily Titration: Increase by 0.1 mg/kg twice daily at weekly intervals Maintenance dosage: 0.35 mg/kg twice daily (maximum 26 mg/day) Maximum dosage: 0.7 mg/kg twice daily (maximum 54 mg/day) for Dravet syndrome; 0.4 mg/kg twice daily (maximum 34 mg/day) for Lennox-Gastaut syndrome Special populations:- Hepatic impairment: Use not recommended in severe impairment
- Renal impairment: No dosage adjustment needed for mild to moderate impairment; use with caution in severe impairment
- Geriatric patients: Use with caution due to increased potential for cardiac complications
Pharmacokinetics
Absorption: Rapid and complete with Tmax of approximately 2 hours Distribution: Extensive tissue distribution; protein binding ~50% Metabolism: Extensive hepatic metabolism via CYP1A2, CYP2B6, and CYP2D6 to active metabolite norfenfluramine Elimination: Terminal half-life ~20 hours; primarily renal excretion (~50%) with fecal elimination (~Contraindications
- Hypersensitivity to fenfluramine or any component of the formulation
- History of pulmonary arterial hypertension
- Use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI use
Warnings and Precautions
Boxed Warning: Valvular heart disease and pulmonary arterial hypertension- Requires cardiac monitoring via echocardiogram at baseline, every 6 months during treatment, and 3-6 months after discontinuation
- Discontinue if echocardiogram demonstrates valvular abnormalities
- Somnolence and sedation: May impair mental/physical abilities
- Suicidal behavior and ideation: Monitor for emergence or worsening of depression
- Decreased appetite and weight loss: Monitor weight regularly
- Increased blood pressure: Monitor periodically
- Serotonin syndrome: Risk particularly with concomitant serotonergic drugs
- Glaucoma: Monitor intraocular pressure in patients at risk
Drug Interactions
Major interactions:- MAOIs: Contraindicated due to risk of serotonin syndrome
- Other serotonergic drugs (SSRIs, SNRIs, triptans): Increased serotonin syndrome risk
- CYP1A2, CYP2B6, CYP2D6 inhibitors/inducers: May alter fenfluramine exposure
- CNS depressants: Additive sedative effects
- Drugs that prolong QT interval: Potential additive effects
Adverse Effects
Most common adverse reactions (≥10%):- Decreased appetite
- Somnolence/sedation
- Diarrhea
- Fatigue
- Pyrexia
- Upper respiratory tract infection
- Vomiting
- Constipation
- Decreased weight
- Valvular heart disease
- Pulmonary arterial hypertension
- Suicidal behavior and ideation
- Serotonin syndrome
- Vision problems
Monitoring Parameters
- Echocardiogram: Baseline, every 6 months during treatment, 3-6 months post-discontinuation
- Weight: Regular monitoring, especially in pediatric patients
- Mental status: Monitor for depression, suicidal thoughts, behavioral changes
- Blood pressure: Periodic monitoring
- Intraocular pressure: In patients at risk for glaucoma
- Clinical signs of serotonin syndrome
- Seizure frequency and severity
Patient Education
- Take exactly as prescribed; do not discontinue abruptly
- Understand the boxed warning regarding cardiac monitoring requirements
- Report any chest pain, shortness of breath, or heart palpitations immediately
- Be aware of potential sedation and avoid driving/operating machinery until effects are known
- Monitor for mood changes, depression, or suicidal thoughts
- Maintain regular weight monitoring, especially in children
- Inform all healthcare providers about Fintepla use
- Keep medication out of reach of children
- Use provided dosing syringe for accurate measurement
References
1. FDA prescribing information: Fintepla (fenfluramine) oral solution 2. Lagae L, Sullivan J, Knupp K, et al. Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial. Lancet. 2020;394(10216):2243-2254. 3. Nabbout R, Mistry A, Zuberi S, et al. Fenfluramine for treatment-resistant seizures in patients with Dravet syndrome receiving stiripentol-inclusive regimens: a randomized clinical trial. JAMA Neurol. 2020;77(3):300-308. 4. Cross JH, Auvin S, Falip M, et al. Expert opinion on the management of Lennox-Gastaut syndrome: treatment algorithms and practical considerations. Front Neurol. 2017;8:505. 5. ClinicalTrials.gov: Study of ZX008 (Fenfluramine HCl) in Children and Young Adults With Lennox-Gastaut Syndrome
This information is intended for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for personalized medical guidance.