fenfluramine

Contraindicated in:

Hypersensitivity;
Concurrent use (or within 14 days) of MAO inhibitors;
End-stage renal disease;
Moderate or severe hepatic impairment (with concurrent stiripentol and clobazam therapy).

Use Cautiously in:

All patients (may ↑ risk of suicidal thoughts/behaviors);
Valvular heart disease;
Pulmonary arterial hypertension;
Hypertension;
Angle-closure glaucoma;
OB: Safety not established;
Lactation: Safety not established;
Pedi: Children <2 yr (safety and effectiveness not established);
Geri: Initial dosage ↓ recommended.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, tachycardia, VALVULAR HEART DISEASE

Derm: rash

EENT: drooling, angle-closure glaucoma, rhinitis

Endo: hyperprolactinemia

F and E: dehydration

GI: constipation, diarrhea, vomiting

GU: urinary incontinence

Metab: ↓appetite, weight loss

Neuro: ataxia, drowsiness, falls, headache, insomnia, irritability, SUICIDAL THOUGHTS/BEHAVIOR, tremor

Resp: PULMONARY ARTERIAL HYPERTENSION, upper respiratory tract infection

Misc: fatigue, fever, chills, SEROTONIN SYNDROME

Interactions ⬆ ⬇

Drug-drug:

Discontinue use of MAO inhibitors for 14 days before fenfluramine therapy; concurrent use contraindicated because of ↑ risk of serotonin syndrome.
↑risk of CNS depression with alcohol, antihistamines, other antidepressants, opioid analgesics, or sedative/hypnotics.
Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SSRIs, SNRIs, TCAs,bupropion, trazodone, mirtazapine, 5-HT3 receptor antagonists, dextromethorphan, linezolid, lithium, methylene blue, and triptans, ↑ risk of serotonin syndrome; use concurrently with caution.
Stiripentol and clobazam may ↑ levels of fenfluramine and ↓ levels of norfenfluramine; do not exceed fenfluramine dosage of 0.2 mg/kg twice daily.
Strong CYP1A2 inhibitors, including fluvoxamine, may ↑ levels and risk of toxicity.
Strong CYP2D6 inhibitors, including paroxetine, may ↑ levels and risk of toxicity.
Strong CYP1A2 inducers and strong CYP2B6 inducers, including rifampin, may ↓ levels and effectiveness; consider ↑ fenfluramine dosage.
Cyproheptadine and potent serotonin antagonists may ↓ effectiveness.

Drug-Natural Products:

↑risk of serotonin syndrome when used with St. John's wort.

Availability ⬆ ⬇

(Generic available)

Oral solution cherry flavor: 2.2 mg/mL

Route/Dosage ⬆ ⬇

Without Concurrent Stiripentol Therapy

PO (Adults and Children ≥2 yr): 0.1 mg/kg twice daily (max dosage = 26 mg/day); may ↑ to 0.2 mg/kg twice daily (max dosage = 26 mg/day) in 7 days and then ↑ to 0.35 mg/kg twice daily (max dosage = 26 mg/day) after another 7 days. If rapid titration is needed, may titrate dosage every 4 days. Concurrent use of strong CYP1A2 or CYP2D6 inhibitor: Not to exceed 20 mg/day.

Renal Impairment

PO (Adults and Children ≥2 yr): CCr 15–29 mL/min/1.73 m²: Not to exceed 20 mg/day.

Hepatic Impairment

PO (Adults and Children ≥2 yr): Mild or moderate hepatic impairment: Not to exceed 20 mg/day. Severe hepatic impairment: Not to exceed 17 mg/day.

With Concurrent Stiripentol and Clobazam Therapy

PO (Adults and Children ≥2 yr): 0.1 mg/kg twice daily (max dosage = 17 mg/day); may ↑ to 0.15 mg/kg twice daily (max dosage = 17 mg/day) in 7 days and then ↑ to 0.2 mg/kg twice daily (max dosage = 17 mg/day) after another 7 days. Concurrent use of strong CYP1A2 or CYP2D6 inhibitor: Dose should not exceed 17 mg/day.

Renal Impairment

PO (Adults and Children ≥2 yr): CCr 15–29 mL/min/1.73 m²: Not to exceed 17 mg/day.

Hepatic Impairment

PO (Adults and Children ≥2 yr): Mild hepatic impairment: Not to exceed 13 mg/day. Moderate or severe hepatic impairment: Use not recommended.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Mechanism for anticonvulsant effect unknown. Both fenfluramine and norfenfluramine are agonists of serotonin 5-HT₂ receptors and increase serotonin concentrations.

Therapeutic effects:

Reduction in frequency of seizures.

Classifications ⬆ ⬇

Therapeutic Classification: anticonvulsants

Pharmacokinetics ⬆ ⬇

Absorption: 68–74% absorbed following oral administration.

Distribution: Widely distributed to extravascular tissues.

Metabolism/Excretion: Primarily metabolized by the liver via CYP1A2, CYP2B6, and CYP2D6 isoenzymes to norfenfluramine (active metabolite); CYP2C9, CYP2C19, and CYP3A involved to a minor extent. Primarily excreted in urine (>90%) as fenfluramine, norfenfluramine, and other metabolites.

Half-Life: 20 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	4–5 hr	12 hr

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of fenfluramine. Advise patient to take as directed. Advise patient to read Medication Guide before starting and periodically during therapy in case of changes.
Advise patient or caregiver to use the oral dosing syringe provided by the pharmacy.
Advise patient against sudden discontinuation of drug due to potential for ↑ seizures or status epilepticus.
Inform the patient regarding their enrollment in the Fintepla REMS program. More information including the Patient Guide can be found at www.finteplarems.com, and side effects can be reported by calling 1-844-599-2273.
Counsel the patient on the risks of valvular heart disease and pulmonary arterial hypertension, including how to recognize and respond to signs and symptoms of these conditions, and the need for cardiac monitoring via echocardiogram at baseline (treatment initiation), every 6 mo during treatment, and 3–6 mo after treatment discontinuation. Advise the patient to seek treatment for an report signs and symptoms of valvular heart disease (chest pain; palpitations; fatigue; light-headedness or fainting; trouble breathing; swelling in the ankles, feet, or abdomen) and/or pulmonary arterial hypertension (blue or gray skin or lips, dizziness, fast HR).
Instruct patients and caregivers to monitor for emergence of suicidal thoughts and behaviors. Notify health care professional immediately if suicidal thoughts; new or worsening depression; anxiety; changes in behavior or mood; thoughts of suicide, dying, or hurting self; or acting on dangerous impulses occur. Instruct patient to carry wallet card and to call the National Suicide Prevention Lifeline at 1-800-273-8255 or visit www.988lifeline.org if they experience suicidal thoughts.
Advise patient to report signs and symptoms of serotonin syndrome (agitation, confusion, hallucinations, fast heartbeat, palpitations, lack of coordination, nausea, vomiting, diarrhea).
May cause dizziness and drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Recommend patient or caregiver report ↓ in visual acuity or eye pain.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications. Instruct patient to use caution when taking dextromethorphan or St. John's wort concurrently with this drug.
Rep: May cause fetal harm. Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Encourage women who are taking fenfluramine during pregnancy to enroll in the North American Antiepileptic Drug Pregnancy Registry by calling 1-888-233-2334 or by visiting www.aedpregnancyregistry.org. Monitor for adequate weight gain during pregnancy as ↓ appetite and weight can occur.

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Indications ⬇

Contraind./Precautions ⬆ ⬇