FINTEPLA SIDE EFFECTS
- Generic Name: fenfluramineoral solution
- Brand Name: Fintepla
- Drug Class: Anticonvulsants, Other
SIDE EFFECTS
The following clinically significant adverse reactions are described elsewhere in labeling:
- Valvular Heart Disease
- Pulmonary Arterial Hypertension
- Decreased Appetite and Decreased Weight
- Somnolence, Sedation, and Lethargy
- Suicidal Behavior and Ideation
- Withdrawal of Antiepileptic Drugs
- Serotonin Syndrome
- Increase in Blood Pressure
- Glaucoma
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In controlled and uncontrolled trials in patients with Dravet syndrome, 341 patients were treated with FINTEPLA, including 312 patients treated for more than 6 months, 284 patients treated for more than 1 year, and 138 patients treated for more than 2 years.
In placebo-controlled trials of patients with Dravet syndrome, 122 patients were treated with FINTEPLA. The duration of treatment in these trials was 16 weeks (Study 1) or 17 weeks (Study 2). In Study 1 and Study 2, the mean age was 9 years (range 2 to 19 years) and approximately 46% of patients were female and 74% were White. All patients were receiving at least one other AED.
In Study 1 and Study 2, the rates of discontinuation as a result of any adverse reaction were 13%, 0%, and 7% for patients treated with FINTEPLA 0.7 mg/kg/day, 0.2 mg/kg/day, and 0.4 mg/kg/day in combination with stiripentol, respectively, compared to 6% for patients on placebo. The most frequent adverse reaction leading to discontinuation in the patients treated with any dose of FINTEPLA was somnolence (n=3, 3%).
The most common adverse reactions that occurred in patients treated with FINTEPLA (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.
Table 1 lists the adverse reactions that were reported in 5% or more of patients treated with FINTEPLA and at a rate greater than those on placebo during the titration and maintenance phases of Study 1 and Study 2.
Table 1: Adverse Reactions in 5% or More of Patients Treated with FINTEPLA and Greater Than Placebo in Placebo-Controlled Trials
| FINTEPLA Dose Group | Combined Placebo Group(2) | |||
| Study 1 | Study 2 | |||
| 0.2 mg/kg/day | 0.7 mg/kg/day | 0.4 mg/kg/day(1) | ||
| N=39 % |
N=40 % |
N=43 % |
N=84 % |
|
| Decreased appetite | 23 | 38 | 49 | 8 |
| Somnolence, sedation, lethargy | 26 | 25 | 23 | 11 |
| Abnormal echocardiogram(3) | 18 | 23 | 9 | 6 |
| Diarrhea | 31 | 15 | 23 | 6 |
| Constipation | 3 | 10 | 7 | 0 |
| Fatigue, malaise, asthenia | 15 | 10 | 30 | 5 |
| Ataxia, balance disorder, gait disturbance | 10 | 10 | 7 | 1 |
| Abnormal behavior | 0 | 8 | 9 | 0 |
| Blood pressure increased | 13 | 8 | 0 | 5 |
| Drooling, salivary hypersecretion | 13 | 8 | 2 | 0 |
| Hypotonia | 0 | 8 | 0 | 0 |
| Rash | 8 | 8 | 5 | 4 |
| Blood prolactin increased | 0 | 5 | 0 | 0 |
| Chills | 0 | 5 | 2 | 0 |
| Decreased activity | 0 | 5 | 0 | 1 |
| Dehydration | 0 | 5 | 0 | 0 |
| Insomnia | 0 | 5 | 5 | 2 |
| Pyrexia | 15 | 5 | 21 | 14 |
| Stereotypy | 0 | 5 | 0 | 0 |
| Upper respiratory tract infection | 21 | 5 | 7 | 10 |
| Vomiting | 10 | 5 | 5 | 8 |
| Weight decreased | 13 | 5 | 7 | 1 |
| Croup | 5 | 3 | 0 | 1 |
| Ear infection | 8 | 3 | 9 | 5 |
| Gastroenteritis | 8 | 3 | 2 | 0 |
| Increased heart rate | 5 | 3 | 0 | 2 |
| Irritability | 0 | 3 | 9 | 2 |
| Rhinitis | 8 | 3 | 7 | 2 |
| Tremor | 3 | 3 | 9 | 0 |
| Urinary incontinence | 5 | 3 | 0 | 0 |
| Decreased blood glucose | 0 | 0 | 9 | 1 |
| Bronchitis | 3 | 0 | 9 | 1 |
| Contusion | 5 | 0 | 0 | 0 |
| Eczema | 0 | 0 | 5 | 0 |
| Enuresis | 5 | 0 | 0 | 0 |
| Fall | 10 | 0 | 0 | 4 |
| Headache | 8 | 0 | 0 | 2 |
| Laryngitis | 0 | 0 | 5 | 0 |
| Negativism | 5 | 0 | 0 | 0 |
| Status epilepticus | 3 | 0 | 12 | 2 |
| Urinary tract infection | 5 | 0 | 5 | 0 |
| Viral infection | 0 | 0 | 5 | 1 |
| (1) 0.4 mg/kg/day was not an intermediate dose. Patients on the 0.4 mg/kg/day dose were also taking concomitant stiripentol plus clobazam, which increases exposure of FINTEPLA. (2) Patients in placebo groups from Studies 1 and 2 were pooled. (3) Consisted of trace and mild mitral regurgitation, and trace aortic regurgitation, which are considered physiologic. |
||||
Echocardiographic Safety Assessments Of Valvular Heart Disease And Pulmonary Arterial Hypertension
Valvular heart disease and pulmonary arterial hypertension were evaluated in the placebocontrolled and open-label extension studies via echocardiography for up to 3 years in duration.
No patient developed echocardiographic findings consistent with either valvular heart disease or pulmonary arterial hypertension in the placebo-controlled studies or during the open-label extension study of up to 3 years in duration. In Study 1 and Study 2, 16% of patients taking FINTEPLA compared to 6% of patients taking placebo were reported to have trace mitral regurgitation, and 3% of patients taking FINTEPLA and no patients taking placebo were found to have trace aortic regurgitation. During the open-label extension study, trace mitral regurgitation and trace aortic regurgitation were reported in 14% and 0.4%, respectively, of patients taking FINTEPLA. Trace and mild mitral regurgitation, and trace aortic regurgitation are considered physiologic in the absence of structural valve abnormalities.
SRC: NLM .