FINTEPLA Safety Profile

For a complete list of the adverse events reported in Study 1 and Study 2, please see the full Prescribing Information

FINTEPLA safety profile. List of adverse reactions that occurred in patients participating in Study 1 or Study 2

aThe 0.4 mg/kg/day was not an intermediate dose. Patients on the 0.4 mg/kg/day dose were also taking concomitant stiripentol (with clobazam and/or valproate), which increases exposure of FINTEPLA.

bConsisted of trace and mild mitral regurgitation, and trace aortic regurgitation, which are considered physiologic.

cThe most frequent adverse reaction leading to discontinuation in the patients treated with any dose of FINTEPLA was somnolence (n=3, 3%).

  • Most patients resumed the expected measured increases in weight by the end of the open-label extension study
    • Growth and weight of pediatric patients should be carefully monitored during treatment with FINTEPLA and dose modifications
      should be considered if a decrease in weight is observed
  • Somnolence, sedation, and lethargy may diminish with continued treatment
    • Other central nervous system depressants, including alcohol, could potentiate these effects of FINTEPLA
    • Monitor patients for somnolence and sedation and advise them not to drive or operate machinery

FINTEPLA Risk Evaluation and Mitigation Strategy (REMS) and Cardiovascular Monitoring

Because of the association between serotonergic drugs with 5‑HT2B receptor agonist activity, including fenfluramine (the active ingredient in FINTEPLA), and valvular heart disease and pulmonary arterial hypertension:

Degree of valve regurgitation as measured by echocardiogram

  • FINTEPLA is available only through a restricted distribution program called the FINTEPLA REMS Program
  • Echocardiography must be performed prior to starting treatment, during treatment, and after treatment with FINTEPLA concludes. In clinical trials of FINTEPLA for the treatment of Dravet syndrome, no cases of valvular heart disease or pulmonary hypertension have been reported

For more information about the FINTEPLA REMS, or to access FDA-mandated REMS forms, please call 1-877-964-3649 or visit FinteplaREMS.com.

Monitoring

Prescribers must assess the patient’s cardiovascular status and the appropriateness of treatment via echocardiography at baseline, every 6 months during treatment, and if FINTEPLA is discontinued, once 3 to 6 months after the last dose.

Echocardiogram monitoring schedule. Initial echocardiogram at baseline, repeat every 6 months, final echocardiogram 3 to 6 months after treatment discontinuation

The prescriber must consider the benefits versus the risks of initiating or continuing treatment with FINTEPLA if any of the following signs are observed via echocardiography:

Grade of blood regurgitation (backflow) at valve measured by echocardiogram. Trace aortic valve and mild mitral valve regurgitation measured by echocardiogram
  • Trace and mild mitral regurgitation and trace aortic regurgitation are considered physiologic in the absence of structural valve abnormalities
  • If a patient’s echocardiogram shows signs of valvular heart disease, pulmonary arterial hypertension, or other cardiac abnormalities, the prescriber must complete and submit a Cardiovascular Adverse Event Reporting Form

In clinical trials of up to 3 years in duration, no patient receiving FINTEPLA developed valvular heart disease or pulmonary arterial hypertension.

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INDICATIONS AND USAGE

FINTEPLA is indicated for the treatment of seizures associated with Dravet syndrome in patients 2 years of age and older.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: VALVULAR HEART DISEASE and PULMONARY ARTERIAL HYPERTENSION

  • There is an association between serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine (the active ingredient in FINTEPLA), and valvular heart disease and pulmonary arterial hypertension.
  • Echocardiogram assessments are required before, during, and after treatment with FINTEPLA.
  • FINTEPLA is available only through a restricted program called the FINTEPLA REMS.

CONTRAINDICATIONS

FINTEPLA is contraindicated in patients with hypersensitivity to fenfluramine or any of the excipients in FINTEPLA and with concomitant use of, or within 14 days of, the administration of monoamine oxidase inhibitors because of an increased risk of serotonin syndrome.

WARNINGS AND PRECAUTIONS

Valvular Heart Disease and Pulmonary Arterial Hypertension (see Boxed Warning): Because of the association between serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine (the active ingredient in FINTEPLA), and valvular heart disease and pulmonary arterial hypertension, cardiac monitoring via echocardiogram is required prior to starting treatment, during treatment, and after treatment with FINTEPLA concludes. Cardiac monitoring via echocardiogram can aid in early detection of this condition. In clinical trials of up to 3 years in duration, no patient receiving FINTEPLA developed valvular heart disease or pulmonary arterial hypertension.

Monitoring: Prior to starting treatment, patients must undergo an echocardiogram to evaluate for valvular heart disease and pulmonary arterial hypertension. Echocardiograms should be repeated every 6 months, and once at 3-6 months post treatment with FINTEPLA.

If valvular heart disease or pulmonary arterial hypertension is observed on an echocardiogram, the prescriber must consider the benefits versus the risks of initiating or continuing treatment with FINTEPLA.

FINTEPLA REMS Program (see Boxed Warning): FINTEPLA is available only through a restricted distribution program called the FINTEPLA Risk Evaluation and Mitigation Strategy (REMS) Program. Prescribers must be certified by enrolling in the FINTEPLA REMS. Prescribers must counsel patients receiving FINTEPLA about the risk of valvular heart disease and pulmonary arterial hypertension, how to recognize signs and symptoms of valvular heart disease and pulmonary arterial hypertension, the need for baseline (pretreatment) and periodic cardiac monitoring via echocardiogram during FINTEPLA treatment, and cardiac monitoring after FINTEPLA treatment. Patients must enroll in the FINTEPLA REMS and comply with ongoing monitoring requirements. The pharmacy must be certified by enrolling in the FINTEPLA REMS and must only dispense to patients who are authorized to receive FINTEPLA. Wholesalers and distributors must only distribute to certified pharmacies. Further information is available at www.FinteplaREMS.com or by telephone at 1-877-964-3649.

Decreased Appetite and Decreased Weight: FINTEPLA can cause decreases in appetite and weight. Decreases in weight appear to be dose related. Most patients resumed the expected measured increases in weight by the end of the open-label extension study. Weight should be monitored regularly during treatment with FINTEPLA and dose modifications should be considered if a decrease in weight is observed.

Somnolence, Sedation, and Lethargy: FINTEPLA can cause somnolence, sedation, and lethargy. Other central nervous system (CNS) depressants, including alcohol, could potentiate these effects of FINTEPLA. Prescribers should monitor patients for somnolence and sedation and should advise patients not to drive or operate machinery until they have gained sufficient experience on FINTEPLA to gauge whether it adversely affects their ability to drive or operate machinery.

Suicidal Behavior and Ideation: Antiepileptic drugs (AEDs) increase the risk of suicidal thoughts or behaviors in patients taking these drugs for any indication. Patients treated with an AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behaviors, or any unusual changes in mood or behavior.

Anyone considering prescribing FINTEPLA or any other AED must balance the risk of suicidal thoughts or behaviors with the risks of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behaviors. Should suicidal thoughts and behaviors emerge during treatment, consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

Withdrawal of Antiepileptic Drugs: As with most AEDs, FINTEPLA should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus. If withdrawal is needed because of a serious adverse reaction, rapid discontinuation can be considered.

Serotonin Syndrome: Serotonin syndrome, a potentially life-threatening condition, may occur with FINTEPLA, particularly during concomitant administration of FINTEPLA with other serotonergic drugs, including, but not limited to, selective serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), bupropion, triptans, dietary supplements (eg, St. John’s Wort, tryptophan), drugs that impair metabolism of serotonin (including monoamine oxidase inhibitors [MAOIs], which are contraindicated with FINTEPLA), dextromethorphan, lithium, tramadol, and antipsychotics with serotonergic agonist activity. Patients should be monitored for the emergence of signs and symptoms of serotonin syndrome, which include mental status changes (eg, agitation, hallucinations, coma), autonomic instability (eg, tachycardia, labile blood pressure, hyperthermia), neuromuscular signs (eg, hyperreflexia, incoordination), and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea). If serotonin syndrome is suspected, treatment with FINTEPLA should be stopped immediately and symptomatic treatment should be started.

Increase in Blood Pressure: FINTEPLA can cause an increase in blood pressure. Significant elevation in blood pressure, including hypertensive crisis, has been reported rarely in adult patients treated with fenfluramine, including patients without a history of hypertension. Monitor blood pressure in patients treated with FINTEPLA. In clinical trials of up to 3 years in duration, no patient receiving FINTEPLA developed hypertensive crisis.

Glaucoma: Fenfluramine can cause mydriasis and can precipitate angle closure glaucoma. Consider discontinuing treatment with FINTEPLA in patients with acute decreases in visual acuity or ocular pain.

ADVERSE REACTIONS

The most common adverse reactions (incidence at least 10% and greater than placebo) were decreased appetite; somnolence, sedation, lethargy; diarrhea; constipation; abnormal echocardiogram; fatigue, malaise, asthenia; ataxia, balance disorder, gait disturbance; blood pressure increased; drooling, salivary hypersecretion; pyrexia; upper respiratory tract infection; vomiting; decreased weight; fall; status epilepticus.

DRUG INTERACTIONS

Strong CYP1A2 and CYP2B6 Inducers: Coadministration with rifampin or a strong CYP1A2 and CYP2B6 inducer will decrease fenfluramine plasma concentrations. Consider an increase in FINTEPLA dosage when coadministered with rifampin or a strong CYP1A2 and CYP2B6 inducer.

USE IN SPECIFIC POPULATIONS

Administration to patients with moderate or severe renal impairment or to patients with hepatic impairment is not recommended.

Please see full Prescribing Information, including Boxed Warning, for additional important information on FINTEPLA.