fintepla

Important safety information

Decreased Appetite and Decreased Weight: Advise patients that FINTEPLA can cause decreased appetite and decreased weight. ( 5.3 ) Somnolence, Sedation, and Lethargy: Monitor for somnolence and sedation. Advise patients not to drive or operate machinery until they have gained sufficient experience on FINTEPLA. ( 5.4 ) Suicidal Behavior and Ideation: Monitor patients for suicidal behavior and thoughts. ( 5.5 ) Withdrawal of Antiepileptic Drugs: FINTEPLA should be gradually withdrawn to minimize the risk of increased seizure frequency and status epilepticus. ( 5.6 ) Serotonin Syndrome: Advise patients that serotonin syndrome is a potentially life-threatening condition and may occur with FINTEPLA, particularly with concomitant administration of FINTEPLA with other serotonergic drugs. ( 5.7 ) Increase in Blood Pressure: Monitor blood pressure during treatment. ( 5.8 ) Glaucoma: Discontinue therapy in patients with acute decrease in visual acuity or ocular pain. ( 5.9 ) 5.1 Valvular Heart Disease and Pulmonary Arterial Hypertension FINTEPLA can cause valvular heart disease (VHD) and pulmonary arterial hypertension (PAH). There is a known 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. Although no patients receiving FINTEPLA developed valvular heart disease or pulmonary arterial hypertension in clinical trials for DS and LGS of up to 3 years in duration, cases of valvular heart disease and pulmonary arterial hypertension have been reported during use of FINTEPLA in the postmarketing setting [see Boxed Warning and Adverse Reactions (6.1) ] . Because of this risk, cardiac monitoring is required prior to starting treatment, during treatment, and after treatment with FINTEPLA concludes . Cardiac monitoring via echocardiogram can identify evidence of valvular heart disease and pulmonary arterial hypertension prior to a patient becoming symptomatic, aiding in early detection of these conditions. 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 3-6 months post-treatment with FINTEPLA. 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 ECHO: Valvular abnormality or new abnormality via echocardiogram. VHD as indicated by mild or greater aortic regurgitation or moderate or greater mitral regurgitation, with additional characteristics of VHD (e.g., valve thickening or restrictive valve motion). PAH as indicated by elevated right heart/pulmonary artery pressure (PASP > 35 mm Hg). FINTEPLA is available only through a restricted program under a REMS [see Warnings and Precautions (5.2) ]. 5.2 FINTEPLA REMS Program FINTEPLA is available only through a restricted distribution program called the FINTEPLA REMS program because of the risk of valvular heart disease and pulmonary arterial hypertension [see Warnings and Precautions (5.1) ]. Notable requirements of the FINTEPLA REMS Program include: Prescribers must be certified by enrolling in the FINTEPLA REMS program. 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 REMS program and comply with ongoing monitoring requirements [see Warnings and Precautions (5.1) ]. The pharmacy must be certified by enrolling in the REMS program 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. 5.3 Decreased Appetite and Decreased Weight FINTEPLA can cause decreases in appetite and weight. In placebo-controlled studies for DS (Study 1 and Study 2 combined), approximately 37% of patients treated with FINTEPLA reported, as an adverse reaction, decreased appetite and approximately 9% reported decreased weight, as compared to 8% and 1%, respectively, of patients on placebo . In the placebo- controlled study for LGS (Study 3), approximately 28% of patients treated with FINTEPLA reported, as an adverse reaction, decreased appetite and approximately 5% reported decreased weight, as compared to 15% and 2%, respectively, of patients on placebo [see Adverse Reactions (6.1) ] . By the end of the controlled studies, 19% (Studies 1 and 2 combined) of DS patients and 7% (Study 3) of LGS patients treated with FINTEPLA had a measured decrease in weight of 7% or greater from their baseline weight, compared to 2% (Study 1 and 2) and 0% (Study 3) of patients on placebo. This measured decrease in weight appeared to be dose-related. In the controlled studies for DS, 26% of patients on FINTEPLA 0.7 mg/kg/day (Study 1), 19% of patients on FINTEPLA 0.4 mg/kg/day in combination with stiripentol (Study 2), and 13% of patients taking FINTEPLA 0.2 mg/kg/day (Study 1) experienced at least a 7% decrease in weight from baseline. In the controlled study for LGS, 9% of patients on FINTEPLA 0.7 mg/kg/day (Study 3) and 6% of patients on FINTEPLA 0.2 mg/kg/day (Study 3) experienced at least a 7% decrease in weight from baseline. Approximately half of the patients with LGS and most patients with DS resumed the expected measured increases in weight during the open-label extension studies. Given the frequency of these adverse reactions, the growth of pediatric patients treated with FINTEPLA should be carefully monitored. Weight should be monitored regularly during treatment with FINTEPLA, and dose modifications should be considered if a decrease in weight is observed. 5.4 Somnolence, Sedation, and Lethargy FINTEPLA can cause somnolence, sedation, and lethargy. In controlled studies for DS (Study 1 and Study 2 combined), the incidence of somnolence, sedation, and lethargy was 25% in patients treated with FINTEPLA, compared with 11% of patients on placebo. In the controlled study for LGS (Study 3), the incidence of somnolence, sedation, and lethargy was 19% in patients treated with FINTEPLA, compared with 16% of patients on placebo. In general, these effects may diminish with continued treatment [see Adverse Reactions (6.1) ]. 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. 5.5 Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including FINTEPLA, increase the risk of suicidal thoughts or behavior 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 behavior, or any unusual changes in mood or behavior. Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs that did not include FINTEPLA showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029…