Fenfluramine
Mechanism :
Fenfluramine is a serotonergic drug. It decreases seizures by being an agonist at serotonergic receptors in the brain.
Its exact mechanism in Dravet syndrome is unknown.
Indication :
- Not indicated in children of age less than 2 years.
- >2 years: seizures; Dravet syndrome (Can be use with or without concomitant stiripentol).
Contraindications :
• Hypersensitivity to drug
• If monoamine oxidase inhibitors were used in the past 14 days
• Moderate to severe renal dysfunction
• Hepatic conditions
• Avoid abrupt cessation of drug
• Use cautiously in valvular heart disease
• Use cautiously in pulmonary hypertension
• Use cautiously in hypertensives
• Use cautiously in alcoholics
• Use cautiously in suicidal patients
• Use cautiously in patients using CNS depressants
Dosing :
Dosage form and strength: oral solution 2.2 mg per ml.
Start with 0.1 mg/kg orally twice a day; maximum dose = 26 mg/day.
Dose may be adjusted based on its effects.
On day 7: dose can be raised to 0.2 mg/kg PO twice a day; maximal dose = 26 mg/day.
On Day 14: dose can be raised to 0.35 mg/kg PO twice a day; maximal dose = 26 mg/day.
Dose can be raised every 4 days in patients who require rapid titration.
With stripentol and clobazam:
Start with 0.1 mg/kg orally twice a day; maximum dose = 17 mg/day.
Dose may be titrated based of efficacy and tolerability.
On Day 7: dose can be raised to 0.15 mg/kg PO twice a day; maximum dose = 17 mg/day.
On Day 14: dose can be raised to 0.2 mg/kg PO twice a day; maximum dose = 17 mg/day.
Growth should be monitored for children and adolescents.
Weight should be monitored frequently while taking this drug. If any weight loss is noticed, dose should be adjusted.
Echocardiogram should be done 6 monthly during treatment and 3 to 6 months after the last dose.
Do not discontinue the drug suddenly. Gradually taper down the dose to avoid increased risk of seizures and status epilepticus.
Adverse Effect :
Weight loss, increased salivation, hypertension, mild aortic or mitral regurgitation, status epilepticus, abnormality on echocardiogram, sedation, upper respiratory tract infection, loss of balance, vomiting, constipation, hypoglycemia, irritability, bronchitis, rash, rhinitis, dehydration, loss of appetite, high prolactin levels in blood, enteritis, tremor, hypotonia, contusion, headache, dry skin, laryngitis, UTI, croup, viral infections, fatigue, tachycardia, insomnia, chills, and urinary incontinence, fever.
Interaction :
Co-administration with CYP1A2/CYP2B6 inducers may lower the plasma concentration of fenfluramine.
Lactation :
caution while breastfeeding due to lack of availability of data
Hepatic Dose :
Avoid use in hepatic impairment.
Pregnanacy :
No data available regarding safety during pregnancy.