Fenfluramine

Fenfluramine is a prescription medication used for the treatment of seizures associated with Dravet syndrome or Lennox-Gastaut syndrome. 

• Fenfluramine is available under the following different brand names: Fintepla.

Common side effects of Fenfluramine include:

• Loss of appetite, 
• Vomiting, 
• Diarrhea, 
• Constipation, 
• Seizures that do not stop, 
• Weakness, 
• Tiredness, 
• Fever, 
• Infection, 
• Abnormal heart function tests, 
• Problems with balance, walking, or muscle movement, 
• Drooling, and
• Cold symptoms (stuffy nose, sneezing, sore throat)

Serious side effects of Fenfluramine include:

• Hives, 
• Difficulty breathing, 
• Swelling of the face, lips, tongue, or throat, 
• Mood or behavior changes, 
• Anxiety, 
• Panic attacks, 
• Trouble sleeping, 
• Impulsiveness, 
• Agitation, 
• Hostility, 
• Aggressions, 
• Restlessness, 
• Hyperactivity (mentally or physically), 
• Increased depression, 
• Thoughts of self-harm, 
• Chest pain, 
• Pounding heartbeats, 
• Fluttering in your chest, 
• Shortness of breath, 
• Blue-colored skin or lips, 
• Swelling in the lower legs, 
• Unusual tiredness, 
• Weakness, 
• Lightheadedness, 
• Loss of appetite, 
• Weight loss, 
• Worsening seizures, 
• Blurred vision, 
• Tunnel vision, 
• Eye pain or redness, 
• Seeing halos around lights, 
• Nausea, 
• Vomiting, 
• Severe headache, 
• Blurred vision, 
• Pounding in the neck or ears, 
• Nosebleed, 
• Fever, 
• Sweating, 
• Hallucinations, 
• Shivering, 
• Fast heart rate, 
• Muscle stiffness, 
• Twitching, 
• Slowed growth (in children)
• Loss of coordination, and
• Diarrhea

Rare side effects of Fenfluramine include:

• None 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Oral solution, Schedule IV

• 2.2 mg/mL

Seizures

Adult and pediatric dosage

• Without concomitant stiripentol
  • Initial dose: 0.1 mg/kg orally two times a day; not to exceed 26 mg/day.
  • May be increased weekly based on efficacy and tolerability.
  • On Day 7: May increase the dose up to 0.2 mg/kg orally two times a day (maximum of 26 mg/day)
  • On Day 14: May increase the dose up to 0.35 mg/kg orally two times a day (maximum of 26 mg/day)
  • Patients who require rapid titration may increase the dose every 4 days.
• With concomitant stiripentol and clobazam
  • Initial dose: 0.1 mg/kg orally two times a day; not to exceed 17 mg/day.
  • May be increased weekly based on efficacy and tolerability.
  • On Day 7: May increase the dose up to 0.15 mg/kg orally two times a day (maximum of 17 mg/day)
  • On Day 14: May increase the dose up to 0.2 mg/kg orally two times a day (maximum of 17 mg/day)

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Fenfluramine has severe interactions with the following drugs.
  • isocarboxazid
  • linezolid
  • phenelzine
  • selegiline transdermal
  • tranylcypromine
• Fenfluramine has serious interactions with at least 30 other drugs.
• Fenfluramine has moderate interactions with at least 242 other drugs.
• Fenfluramine has minor interactions with the following drugs:
  • desmopressin
  • eucalyptus
  • sage

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Hypersensitivity to fenfluramine or any of the excipients
• Concomitant use of, or within 14 days of, the administration of monoamine oxidase inhibitors (MAOIs)

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Fenfluramine?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Fenfluramine?”

Cautions

• May decrease appetite and weight; monitor weight regularly during treatment and modify dose if decreased weight observed; monitor growth regularly in children.
• May cause somnolence, sedation, and lethargy; other CNS depressants, including alcohol, could potentiate these effects; advise patients not to drive or operate machinery until they have gained sufficient experience on fenfluramine; somnolence effects may diminish with continued treatment.
• Antiepileptic drugs (AEDs) increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication; monitor for emergence or worsening of depression, suicidal thoughts or behavior, or any unusual changes in mood or behavior.
• As with most AEDs, withdraw gradually when discontinuing because of the risk of increased seizure frequency and status epilepticus; if withdrawal is needed owing to a serious adverse reaction, rapid discontinuation can be considered.
• Significantly increased blood pressure, including hypertensive crisis, reported; monitor blood pressure during treatment.
• Cardiac monitoring via echocardiogram can identify evidence of valvular heart disease and pulmonary arterial hypertension before a patient becomes symptomatic, aiding in the early detection of these conditions
• May cause mydriasis and can precipitate angle-closure glaucoma; discontinue therapy in patients with an acute decrease in visual acuity or ocular pain.
• VHD and PAH
  • Owing to the association between serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine, PAH, and VHD, cardiac monitoring is required before initiating treatment, during treatment, and after the completion of fenfluramine.
  • Echocardiograms should be repeated every 6 months, and once 3-6 months post-treatment with this drug
  • Consider benefits versus risks if the following signs are observed.
  • Valvular abnormality or new abnormality via ECHO
  • VHD as indicated by mild or greater aortic regurgitation or moderate or greater mitral regurgitation, with additional characteristics of VHD (. g, valve thickening, restrictive valve motion)
  • PAH as indicated by elevated right heart/pulmonary artery pressure (PASP above 35 mm Hg)
• Fintepla REMS program
  • Further information is available at http://www.FinteplaREMS.com or by telephone at 1-877-964-3649
• Prescribers
  • Must be certified by enrolling in the program.
  • Must counsel patients receiving fenfluramine regarding the risk of VHD and PAH, signs, and symptoms of VHD and PAH, cardiac monitoring via ECHO during treatment, and cardiac monitoring after treatment.
• Patients
  • Must enroll in the REMS program and comply with ongoing monitoring requirements.
• Pharmacies, wholesalers, and distributors
  • Must be certified by enrolling in the REMS program and must only dispense to patients who are authorized to receive treatment
  • Wholesalers and distributors must only distribute to certified pharmacies.
• Drug interaction overview
  • Stiripentol plus clobazam
    • Coadministration with stiripentol plus clobazam, with or without valproate, inhibits the metabolism of fenfluramine, thereby increasing fenfluramine plasma concentrations and decreasing its metabolite, norfenfluramine
    • Dose adjustment is required for patients taking stiripentol plus clobazam.
  • Strong CYP1A2 and CYP2B6 inducers
    • Coadministration with rifampin or strong CYP1A2 and CYP2B6 inducers decreases fenfluramine plasma levels and effects.
    • Consider increasing fenfluramine dosage when coadministered with rifampin or a strong CYP1A2 and CYP2B6 inducer; do not exceed the maximum daily dosage.
  • Serotonin receptor antagonists
    • Monitor appropriately when coadministered with cyproheptadine or potent 5-HT1A, 5-HT1D, 5-HT2A, or 5-HT2C serotonin receptor antagonists.
    • Cyproheptadine and potent 5-HT1A, 5-HT1D, 5-HT2A, and 5-HT2C serotonin receptor antagonists may decrease the efficacy of fenfluramine.
  • Serotonergic drugs
    • Coadministration with MAOIs is contraindicated.
    • Use with caution in patients taking medications that increase serotonin.
    • Coadministration with drugs (. g, SSRIs, SNRIs, TCAs) that increase serotonin may increase the risk of serotonin syndrome.

Pregnancy and Lactation

• There are no data on use in pregnant women; available data from epidemiologic studies with fenfluramine or dexfenfluramine are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes; this drug can cause decreased appetite and decreased weight; monitor for adequate weight gain during pregnancy
• Reproductive potential
  • In animal studies, oral administration of fenfluramine resulted in adverse reproductive effects
• Pregnancy exposure registry
  • Registry monitors pregnancy outcomes in females exposed to AEDs, such as fenfluramine during pregnancy.
  • Encourage females who are taking fenfluramine during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling the toll-free number 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org
• Lactation
  • There are no data on the presence of this drug or its metabolites in human milk, effects on the breastfed infant, or milk production; developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed infant from this drug or underlying maternal condition.