Fintepla

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Fintepla 2.2 mg/mL oral solution 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each mL contains 2.2 mg of fenfluramine (as fenfluramine hydrochloride). 
 
Excipient(s) with known effect 
 
Glucose (maize): 0.627 mg/mL 
Sodium ethyl para-hydroxybenzoate (E 215): 0.23 mg/mL 
Sodium methyl para-hydroxybenzoate (E 219): 2.3 mg/mL 
Sulfur dioxide (E 220): 0.000009 mg/mL 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Oral solution.  
 
Clear, colourless, slightly viscous liquid, with a pH of 5. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Fintepla is indicated for the treatment of seizures associated with Dravet syndrome as an add-on 
therapy to other anti-epileptic medicines for patients 2 years of age and older. 
 
4.2 Posology and method of administration 
 
Fintepla should be initiated and supervised by physicians with experience in the treatment of epilepsy. 
 
Fintepla is prescribed and dispensed according to the Fintepla controlled access programme (see 
section 4.4).  
 
Posology 
 
Paediatric (children aged 2 years and older) and adult populations 
 
Patients who are not taking stiripentol 
The starting dose is 0.1 mg/kg twice daily (0.2 mg/kg/day). 
After 7 days, for patients who are tolerating fenfluramine, and require a further reduction of seizures, 
the dose can be increased to 0.2 mg/kg twice daily (0.4 mg/kg/day).  
After an additional 7 days, for patients who are tolerating fenfluramine, and require a further reduction 
of seizures, the dose can be increased to a maximum of 0.35 mg/kg twice daily (0.7 mg/kg/day), which 
is the recommended maintenance dose. 



3 

For patients requiring more rapid titration, the dose may be increased every 4 days. 
The maximum daily dose of 26 mg (13 mg twice daily i.e. 6.0 mL twice daily) should not be 
exceeded. 
The twice daily dose in mL can be determined as follows: 
 
Table 1: Dosing table in mL in patients not taking stiripentol 
 
Recommended 

titration 
schedule – 
without 

stiripentol 

Twice 
daily dose 
(mg/kg) 

Weight (kg) 

10 15 20 25 30 35 40 45 50 55 60 65 70 

Starting dose 0.1 0.5 
mL 

0.6 
mL 

0.8 
mL 

1.0 
mL 

1.3 
mL 

1.5 
mL 

1.7 
mL 

1.9 
mL 

2.1 
mL 

2.3 
mL 

2.5 
mL 

2.7 
mL 

2.9 
mL 

Day 7 0.2 0.8 
mL 

1.2 
mL 

1.6 
mL 

2.0 
mL 

2.4 
mL 

2.8 
mL 

3.2 
mL 

3.6 
mL 

4.0 
mL  

4.4 
mL  

4.8 
mL  

5.2 
mL  

5.6 
mL  

Day 14 0.35 1.6 
mL 

2.4 
mL 

3.2 
mL 

4.0 
mL  

4.8 
mL 

5.6 
mL  

6.0 
mL 

6.0 
mL 

6.0 
mL 

6.0 
mL 

6.0 
mL 

6.0 
mL 

6.0 
mL 

 
If the calculated dose is 3.0 mL or less, the green printed 3 mL syringe should be used. 
If the calculated dose is more than 3.0 mL, the purple printed 6 mL syringe should be used. 
The calculated dose should be rounded to the nearest graduated increment. 
 
Patients who are taking stiripentol 
The starting dose is 0.1 mg/kg twice daily (0.2 mg/kg/day). 
After 7 days, for patients who are tolerating fenfluramine, and require a further reduction of seizures, 
the dose can be increased to 0.2 mg/kg twice daily (0.4 mg/kg/day), which is the recommended 
maintenance dose. 
For patients requiring more rapid titration, the dose may be increased every 4 days. 
A total dose of 17 mg (8.6 mg twice daily i.e. 4.0 mL twice daily) should not be exceeded. 
The twice daily dose in mL can be determined as follows: 
 
Table 2: Dosing table in mL in patients receiving stiripentol 
 
Recommended 

titration 
schedule with 

stiripentol 

Twice 
daily dose 
(mg/kg) 

Weight (kg) 

10 15 20 25 30 35 40 45 50 55 60 65 70 

Starting dose 0.1 0.5 
mL 

0.6 
mL 

0.8 
mL 

1.0 
mL 

1.3 
mL 

1.5 
mL 

1.7 
mL 

1.9 
mL 

2.1 
mL 

2.3 
mL 

2.5 
mL 

2.7 
mL 

2.9 
mL 

Day 7 0.2 1.0 
mL 

1.5 
mL 

2.0 
mL 

2.5 
mL 

3.0 
mL 

3.6 
mL 

4.0 
mL  

4.0 
mL  

4.0 
mL  

4.0 
mL  

4.0 
mL  

4.0 
mL  

4.0 
mL  

 
If the calculated dose is 3.0 mL or less, the green printed 3 mL syringe should be used. 
If the calculated dose is more than 3.0 mL, the purple printed 6 mL syringe should be used. 
The calculated dose should be rounded to the nearest graduated increment. 
 
Discontinuation of treatment 
 
When discontinuing treatment, the dose should be decreased gradually. As with all anti-epileptic 
medicines, abrupt discontinuation should be avoided when possible to minimize the risk of increased 
seizure frequency and status epilepticus. 
 
Special populations 
 



4 

Patients with renal impairment 
There are no clinical data available in subjects with renal impairment.  
 
Patients with hepatic impairment 
There are no clinical data available in subjects with hepatic impairment.  
Administration to patients with moderate or severe liver impairment is not recommended. 
 
Elderly 
There are no data on the use of Fintepla in elderly patients. 
 
Paediatric population 
The safety and efficacy of Fintepla in children below 2 years of age has not yet been established. No 
data are available. 
 
Method of administration  
 
Fintepla is to be administered orally. 
Fintepla may be taken with or without food. 
Fintepla is compatible with commercially available gastric and nasogastric feeding tubes (see section 
6.6). 
Fintepla contains a very limited amount of digestible carbohydrates and is compatible with a ketogenic 
diet. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or any of the excipients listed in section 6.1. 
Aortic or mitral valvular heart disease. 
Pulmonary arterial hypertension. 
Within 14 days of the administration of monoamine oxidase inhibitors due to an increased risk of 
serotonin syndrome. 
 
4.4  Special warnings and precautions for use 
 
Aortic or mitral valvular heart disease and pulmonary arterial hypertension 
 
Because of reported cases of valvular heart disease that may have been caused by fenfluramine at 
higher doses used to treat adult obesity, cardiac monitoring must be performed using 
echocardiography. In the controlled clinical studies of fenfluramine for the treatment of Dravet 
syndrome, no valvular heart disease was observed. 
 
Prior to starting treatment, patients must undergo an echocardiogram to establish a baseline prior to 
initiating treatment (see section 4.3) and exclude any pre-existing valvular heart disease or pulmonary 
hypertension. 
 
Echocardiogram monitoring should be conducted every 6 months for the first 2 years and annually 
thereafter. If an echocardiogram indicates pathological valvular changes, a follow-up echocardiogram 
should be considered at an earlier timeframe to evaluate whether the abnormality is persistent. If 
pathological abnormalities on the echocardiogram are observed, it is recommended to evaluate the 
benefit versus risk of continuing fenfluramine treatment with the prescriber, caregiver, and 
cardiologist. 
 
If treatment is stopped because of aortic or mitral valvular heart disease, appropriate monitoring and 
follow-up should be provided in accordance with local guidelines for the treatment of aortic or mitral 
valvular heart disease. 
 



5 

With past use in higher doses to treat adult obesity, fenfluramine was reported to be associated with 
pulmonary arterial hypertension. Pulmonary arterial hypertension was not observed in the clinical 
programme, but because of the low incidence of this disease, the clinical trial experience with 
fenfluramine is inadequate to determine if fenfluramine increases the risk for pulmonary arterial 
hypertension in patients with Dravet syndrome. 
 
If echocardiogram findings are suggestive of pulmonary arterial hypertension, a repeat 
echocardiogram should be performed as soon as possible and within 3 months to confirm these 
findings.  If the echocardiogram finding is confirmed suggestive of an increased probability of 
pulmonary arterial hypertension defined as “intermediate probability” by the 2015 European Society 
of Cardiology (ESC) and the European Respiratory Society (ERS) Guidelines, it should lead to a 
benefit-risk evaluation of continuation of Fintepla by the prescriber, carer, and cardiologist. If the 
echocardiogram finding, after confirmation, suggests of a high probability of pulmonary arterial 
hypertension, as defined by the 2015 ESC and ERS Guidelines, it is recommended fenfluramine 
treatment should be stopped. 
 
Decreased appetite and weight loss 
 
Fenfluramine can cause decreased appetite and weight loss (see section 4.8). An additive effect on 
decreased appetite can occur when fenfluramine is combined with other anti-epileptic medicines, for 
example stiripentol. The decrease in weight appears to be dose related. Most subjects resumed weight 
gain over time while continuing treatment. The patient's weight should be monitored. A benefit risk 
evaluation should be undertaken prior to commencing treatment with fenfluramine in patients with a 
history of anorexia nervosa or bulimia nervosa. 
 
Fintepla controlled access programme 
 
A controlled access programme has been created to 1) prevent off-label use in weight management in 
obese patients and 2) confirm that prescribing physicians have been informed of the need for periodic 
cardiac monitoring in patients taking Fintepla.  
 
Somnolence 
 
Fenfluramine can cause somnolence. 
 
Other central nervous system depressants, including alcohol, could potentiate the somnolence effect of 
fenfluramine (see sections 4.5 and 4.7). 
 
Suicidal behaviour and ideation  
 
Suicidal behaviour and ideation have been reported in patients treated with anti-epileptic medicines in 
several indications. A meta-analysis of randomised placebo-controlled trials with anti-epileptic 
medicines that did not include fenfluramine has shown a small increased risk of suicidal behaviour and 
ideation. The mechanism of this risk is not known, and the available data do not exclude the 
possibility of an increased risk for fenfluramine. Patients and caregivers of patients should be advised 
to seek medical advice should any signs of suicidal behaviour and ideation emerge. 
 
Serotonin syndrome 
 
As with other serotonergic agents, serotonin syndrome, a potentially life-threatening condition, may 
occur with fenfluramine treatment, particularly with concomitant use of other serotonergic agents 
(including SSRIs, SNRIs, tricyclic antidepressants, or triptans); with agents that impair metabolism of 
serotonin such as MAOIs; or with antipsychotics that may affect the serotonergic neurotransmitter 
systems (see sections 4.3 and 4.5). 
 



6 

Serotonin syndrome symptoms may include mental status changes (eg, agitation, hallucinations, 
coma), autonomic instability (eg, tachycardia, labile blood pressure, hyperthermia), neuromuscular 
aberrations (eg, hyperreflexia, incoordination), and/or gastrointestinal symptoms (eg, nausea, 
vomiting, diarrhoea). 
 
If concomitant treatment with fenfluramine and other serotonergic agents that may affect the 
serotonergic systems is clinically warranted, careful observation of the patient is advised, particularly 
during treatment initiation and dose increases. 

 
Increased seizure frequency 
 
As with other anti-epileptic medicines, a clinically relevant increase in seizure frequency may occur 
during treatment with fenfluramine, which may require adjustment in the dose of fenfluramine and/or 
concomitant anti-epileptic medicines, or discontinuation of fenfluramine, should the benefit-risk be 
negative.  
 
Cyproheptadine  
 
Cyproheptadine is a potent serotonin receptor antagonist and may therefore decrease the efficacy of 
fenfluramine. If cyproheptadine is added to treatment with fenfluramine, patients should be monitored 
for worsening of seizures. If fenfluramine treatment is initiated in a patient taking cyproheptadine, 
fenfluramine’s efficacy may be reduced. 
 
Glaucoma 
 
Fenfluramine can cause mydriasis and can precipitate angle closure glaucoma. Discontinue therapy in 
patients with acute decreases in visual acuity. Consider discontinuation if there is ocular pain and 
another cause cannot be determined. 
 
Strong CYP1A2 or CYP2B6 inducers 
 
Co-administration with strong CYP1A2 inducers or CYP2B6 inducers may decrease fenfluramine 
plasma concentrations (see section 4.5). 
An increase in fenfluramine dosage should be considered when co-administered with a strong 
CYP1A2 or CYP2B6 inducer; the maximum daily dose should not be exceeded. 
 
Excipients 
 
This medicinal product contains sodium ethyl para-hydroxybenzoate (E 215) and sodium methyl para-
hydroxybenzoate (E 219) which may cause allergic reactions (possibly delayed).  
 
It also contains sulfur dioxide (E 220) which may rarely cause severe hypersensitivity reactions and 
bronchospasm. 
 
Patients with rare glucose-galactose malabsorption should not take this medicinal product. 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per the maximum daily dose of 
12 mL, that is to say essentially ‘sodium-free’. 
 
This medicinal product contains glucose which may be harmful to the teeth. 
 
4.5  Interaction with other medicinal products and other forms of interaction 
 
Pharmacodyamic interactions 
 



7 

Pharmacodynamic interactions with other central nervous system depressants increase the risk of 
aggravated central nervous system depression. Examples of such depressants are other serotonergic 
agents (including SSRIs, SNRIs, tricyclic antidepressants, or triptans); agents that impair metabolism 
of serotonin such as MAOIs; or antipsychotics that may affect the serotonergic neurotransmitter 
systems (see sections 4.3 and 4.4). 
 
Pharmacokinetic interactions 
 
Clinical studies 
 
Effect of steady state stiripentol plus clobazam and/or valproate on fenfluramine 
At steady state in the Phase 3 studies, the co-administration of 0.2 mg/kg twice daily (0.4 mg/kg/day), 
maximum 17 mg/day, fenfluramine with a standard anti-epileptic medicine regimen of stiripentol plus 
clobazam and/or valproate, resulted in a 130% increase in fenfluramine AUC0-24 and a 60% decrease 
in norfenfluramine AUC0-24, as compared to 0.35 mg/kg twice daily (0.7 mg/kg/day), maximum 
26 mg/day, fenfluramine without stiripentol (see section 4.2). 
 
Effect of steady state cannabidiol on fenfluramine 
Co-administration of a single 0.35 mg/kg dose of fenfluramine with repeated doses of cannabidiol 
increased the AUC0-INF of fenfluramine by 59% and the Cmax by 10%, and decreased the AUC0-INF of 
norfenfluramine by 22% and the Cmax by 33%, as compared to fenfluramine administered alone. 
Co-administration of a single 0.35 mg/kg dose of fenfluramine, with repeated doses of cannabidiol, 
did not affect the pharmacokinetics of cannabidiol, as compared to cannabidiol alone. No dose 
adjustment is necessary when fenfluramine is co-administered with cannabidiol. 
 
In vitro studies 
Co-administration with strong CYP1A2 inducers or CYP2B6 inducers may decrease fenfluramine 
plasma concentrations. 
 
Effect of fenfluramine on other medicinal products 
Co-administration of a single 0.7 mg/kg dose of fenfluramine, with a single dose of a stiripentol, 
clobazam, and valproic acid combination, did not affect the pharmacokinetics of stiripentol, nor the 
pharmacokinetics of clobazam or its Ndesmethyl-metabolite norclobazam, nor the pharmacokinetics 
of valproic acid, as compared to the stiripentol, clobazam, and valproic acid combination alone.  
 
Effect of fenfluramine on CYP2D6 substrates  
In vitro studies indicate that fenfluramine may inhibit CYP2D6. It has been reported that steady-state 
desipramine concentrations increase approximately 2-fold with concomitant administration of 
fenfluramine. Co-administration of fenfluramine with CYP2D6 substrates may increase their plasma 
concentrations. 
 
Effect of fenfluramine on CYP2B6 and CYP3A4 substrates  
In vitro studies indicate that fenfluramine may induce CYP2B6 and may induce intestinal CYP3A4. 
Co-administration of fenfluramine with CYP2B6 substrates or CYP3A4 substrates may decrease their 
plasma concentrations. 
 
Effect of fenfluramine on MATE1 substrates  
In vitro studies indicate that norfenfluramine (major and pharmacologically active metabolite) may 
inhibit MATE1 at clinically relevant concentrations. Co-administration of fenfluramine with MATE1 
substrates may increase their plasma concentrations. 
 
4.6  Fertility, pregnancy, and lactation 
 
Pregnancy 
 



8 

There are limited data (less than 300 pregnancy outcomes) from the use of fenfluramine in pregnant 
women. 
 
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity 
in the absence of paternal or maternal toxicity (see section 5.3). 
  
As a precautionary measure, it is preferable to avoid the use of Fintepla during pregnancy. 
 
Breast-feeding 
 
It is unknown whether fenfluramine/metabolites are excreted in human milk. 
Available pharmacokinetic data in animals have shown excretion of fenfluramine/metabolites in milk 
(see section 5.3). 
 
A risk to the suckling child cannot be excluded. 
 
A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from 
Fintepla therapy taking into account the benefit of breast-feeding for the child and the benefit of 
therapy for the woman. 
 
Fertility 
 
No effects of fenfluramine on human fertility up to clinical doses of 104 mg/day were noted. However, 
animal studies suggest that Fintepla may possibly affect female fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Fintepla has moderate influence on the ability to drive and use machines because it may cause 
somnolence and fatigue. Patients should be advised not to drive or operate machinery until they have 
gained sufficient experience to gauge whether it adversely affects their abilities (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most commonly reported adverse reactions are decreased appetite (44.2%), diarrhoea (30.8%), 
pyrexia (25.6%), fatigue (25.6%), upper respiratory tract infection (20.5%), lethargy (17.5%), 
somnolence (15.4%), and bronchitis (11.6%). 
 
Tabulated list of adverse reactions 
 
Adverse reactions reported with fenfluramine in placebo-controlled clinical studies are listed in the 
table below by System Organ Class and frequency. Frequencies are defined as very common (≥1/10) 
or common (≥1/100 to <1/10).  
 
Table 3: Adverse reactions  

MedDRA System Organ 
Class  

Very common  Common  

Infections and infestations  Bronchitis 
Upper respiratory tract 
infection 

Ear infection  
 

Metabolism and nutrition 
disorders  

Decreased appetite    

Psychiatric disorders    Abnormal behaviour  
Irritability 

Nervous system disorders  Lethargy   



9 

Somnolence  
Status epilepticus 
Tremor 

Gastrointestinal disorders  Constipation 
Diarrhoea  
Vomiting 

 

General disorders and 
administration site conditions  

Pyrexia  
Fatigue  

  

Investigations  Blood glucose decreased 
Echocardiogram abnormal 
(trace regurgitation) 
Weight decreased 

 

Injury, poisoning, and 
procedural complications 

Fall   

 
Description of selected adverse reactions 
 
Long-term safety 
Fenfluramine was used by 330 patients in an open-label trial for up to 3 years. The most commonly 
reported adverse reactions were decreased appetite (18.8%), echocardiogram abnormal (trace 
regurgitation) (8.2%), weight decreased (6.1%) and abnormal behaviour (5.2%). 
 
Decreased appetite and weight loss 
Fenfluramine can cause decreased appetite and weight loss. In the controlled trials of children and 
young adults with Dravet syndrome 34.4% of fenfluramine-treated patients had decreased appetite, 
compared to 8.3% of patients on placebo and approximately 18.9% of fenfluramine-treated patients 
had a decrease in weight ≥7% from their baseline weight, compared to 2.4% of patients on placebo. 
The decreases in appetite and weight appeared to be dose related. Most subjects resumed weight gain 
over time while continuing fenfluramine treatment. 
 
Status epilepticus 
In the phase 3 clinical trials the observed frequency of status epilepticus was 2.4% in the placebo 
group and 6.6% in the fenfluramine group. There were no discontinuations due to status epilepticus.  
 
Echocardiographic safety assessments of valvular regurgitation 
The possible occurrence of valvular heart disease was evaluated in the placebo-controlled and open-
label extension studies for up to 3 years duration.  
 
No patient developed any valvular heart disease in the double-blind studies or during the open-label 
extension study with treatment up to 3 years duration. Trace mitral valve regurgitation was reported 
17.9% of subjects in the 0.2 mg/kg/day group (n=7/39), 22.5% in the 0.7 mg/kg/day group (n= 9/40), 
20.9% in the 0.4 mg/kg/day group (n=9/43) and in 9.5% in the placebo group (n= 8/84). Mild mitral 
regurgitation was reported in 2.3% of the 0.4 mg/kg/day group (n=1/43). Trace aortic regurgitation 
was reported in 7.9% of the subjects in the 0.7 mg/kg/day group (n= 3/40). However, trace and mild 
mitral regurgitation, and trace aortic regurgitation are all non-pathologic findings as defined by the 
2015 ESC and ERS Guidelines. All of the incidences reported were transient.  
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


10 

Only limited data have been reported concerning clinical effects and management of overdose of 
fenfluramine. Agitation, drowsiness, confusion, flushing, tremor (or shivering), fever, sweating, 
abdominal pain, hyperventilation, and dilated non-reactive pupils were reported at much higher doses 
of fenfluramine than those included in the clinical trial program.  
 
Reportedly, the treatment of fenfluramine intoxication should include gastric lavage. Vital functions 
should be monitored closely, and supportive treatment administered in case of convulsions, 
arrhythmias, or respiratory difficulties. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: antiepileptics, other antiepileptics; ATC code: N03AX26 
 
Mechanism of action 
 
Fenfluramine is a serotonin releasing agent, and thereby stimulates multiple 5-HT receptor sub-types 
through the release of serotonin. Fenfluramine may reduce seizures by acting as an agonist at specific 
serotonin receptors in the brain, including the 5-HT1D, 5-HT2A, and 5-HT2C receptors, and also by 
acting on the sigma-1 receptor. The precise mode of action of fenfluramine in Dravet syndrome is not 
known. 
 
Clinical efficacy 
 
Children and young adults 
The effectiveness of fenfluramine in children and young adults with Dravet syndrome was evaluated 
in two randomised, multicentre, placebo-controlled studies. 
 
Study 1 (N=119) was a 3-arm, multicentre, randomised, double-blind, parallel group, 
placebo-controlled study consisting of a 6-week baseline period followed by a 2-week titration period 
and a 12-week maintenance period for a total of 14 weeks treatment. Eligible patients were 
randomised 1:1:1 to one of two doses of fenfluramine (0.7 mg/kg/day or 0.2 mg/kg/day, maximum 
26 mg/day) or placebo. The mean (standard deviation) age of patients enrolled in Study 1 was 
9.0 (4.7) years, with a range of 2 to 18 years. The majority of patients were ≥6 years of age (73.9%) 
and the minority <6 years (26.1%), male (53.8%), and white (82.4%). All enrolled patients were 
inadequately controlled on at least one anti-epileptic medicine, with or without vagal nerve stimulation 
and/or ketogenic diet. Patients were taking between one and five anti-epileptic medicines at study 
entry. The most frequently used concomitant anti-epileptic medicines (≥25% overall) were valproate 
(59.6%), clobazam (58.8%), and topiramate (25.2%). In Study 1, the median baseline convulsive 
seizure frequency per 28 days was 34.0, 17.5, and 21.2 in the placebo, fenfluramine 0.2 mg/kg/day, 
and fenfluramine 0.7 mg/kg/day groups, respectively.  
 
Study 2 (previously known as 1504) (N=87) was a 2-arm, multicentre, randomised, double-blind, 
parallel group, placebo-controlled study consisting of a 6-week baseline period followed by a 3-week 
titration period and a 12-week maintenance period for a total of 15 weeks treatment. Eligible patients 
were randomised 1:1 to fenfluramine 0.4 mg/kg/day (maximum 17 mg/day) or placebo added to their 
stable standard of care regimen of stiripentol (plus clobazam and/or valproate) and possibly other 
anti-epileptic medicines. The mean (standard deviation) age of patients enrolled in Study 2 was 
9.1 (4.80) years, with a range of 2 to 19 years. The majority of patients were ≥6 years of age (72.4%) 
and the minority <6 years (27.6%), male (57.5%) and, where reported, white (59.8%). All enrolled 
subjects were inadequately controlled on at least one anti-epileptic medicine, which included 
stiripentol, with or without vagal nerve stimulation and/or ketogenic diet. The median baseline 
convulsive seizure frequency per 28 days was 10.7 and 14.3 in the placebo and fenfluramine 
0.4 mg/kg/day groups, respectively.  



11 

 
Table 4: Study 1 and Study 2 (previously known as 1504): results of primary and selected 
secondary efficacy endpoints 

  Study 1 Study 2 
  Placebo Fenfluramine 

0.2 mg/kg/day 
Fenfluramine 
0.7 mg/kg/day 

Placebo + 
stiripentol 

Fenfluramine 
0.4 mg/kg/day 
+ stiripentol 

Convulsive 
Seizure 
Frequency 
 
Maintenance 
period 

N 
Baseline. 
Median (min, 
max) 

39 
34.0 
(3.3, 

147.3) 

39 
17.5 

(4.8, 623.5) 

40 
21.2 

(4.9, 127.0) 

44 
10.7 

(2.7, 162.7) 

43 
14.3 

(2.7, 213.3) 

N 
At end of 
maintenance 
period. 
Median (min, 
max) 

39 
25.7 
(3.6, 

204.7) 

39 
17.1 

(0.0, 194.3) 

40 
4.9 

(0, 105.5) 

44 
11.4 

(0.7, 169.3) 

42 
3.9 

(0.0, 518.0) 

Reduction in 
mean monthly 
baseline-
adjusted 
Convulsive 
Seizure 
Frequency 
compared to 
Placebo 

- 36.7% 
p=0.016 

67.3% 
p<0.001 

- 54.9 % 
p<0.001 

% reduction 
in convulsive 
seizures  
  
Maintenance 
period  

Number (%) of 
patients with 
≥50% 
reduction in 
monthly 
convulsive 
seizures - 
change 
from baseline  
Effect size1 

Relative Risk  

4 
(10.3%)  

17 (43.6%)  
ES=33.3%  
RR: 4.25 

29 (72.5%)  
ES=62.2%  
RR: 7.07 

4 (9.1%)  23 (54.8%)  
ES=45.7 
RR: 6.02 

 

Number (%) of 
patients with 
≥75% 
reduction in 
monthly 
convulsive 
seizures 
- change 
from baseline  
Effect size1  
Relative Risk 

2 (5.1%)  10 (25.6%)  
ES=20.5% 
RR: 5.00 

21 (52.5%)  
ES=47.4% 
RR: 10.24 

2 (4.5%)  17 (40.5%)  
ES=36.0%  
RR: 8.90 

 

Number (%) of 
patients with 
≥100% 
reduction in 
monthly 
convulsive 
seizures - 
change 
from baseline  
Effect size1  

0 (0%)  6 (15.4%)  
ES=15.4% 

 

6 (15.0%)  
ES=15.0% 

 

0 (0%)  2 (4.8%)  
ES=4.8% 

  



12 

  Study 1 Study 2 
  Placebo Fenfluramine 

0.2 mg/kg/day 
Fenfluramine 
0.7 mg/kg/day 

Placebo + 
stiripentol 

Fenfluramine 
0.4 mg/kg/day 
+ stiripentol 

Longest seizure-free interval 
(median) 
 
Titration + maintenance 
period 

9.5 days 
 

15.0 days 
p=0.035 

 

25.0 days 
p<0.001 

 

13.0 days 
 

22.0 days 
p=0.004 

 

1 Effect size (ES) (Risk difference) calculated as proportion of Active-Placebo; RR: Relative Risk  
 
Adults 
The Dravet syndrome population in Study 1 and Study 2 was predominantly paediatric patients, with 
only 7 adult patients who were 18-19 years old (3.4%), and therefore limited efficacy and safety data 
were obtained in the adult Dravet syndrome population. 
 
Open-label data 
 
Patients who participated in Study 1 and Study 2 could participate in an open-label extension study. 
The primary objective of the open-label study was long-term effectiveness and safety of fenfluramine 
at doses of 0.2 to 0.7 mg/kg/day, whereby the dose of fenfluramine could be titrated to optimize 
treatment. Data are reported for 330 patients who participated in the open-label study and received 
fenfluramine for up to 3 years (median treatment period: 631 days; range: 7-1086). A total of 23% of 
subjects discontinued study participation during the open-label extension treatment period, including 
15% due to lack of efficacy and 1% due to adverse events.  
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Fintepla in one or more subsets of the paediatric population in Dravet syndrome (see section 4.2 for 
information on paediatric use). 
  
5.2 Pharmacokinetic properties 
 
Pharmacokinetics 
 
The pharmacokinetics of fenfluramine and norfenfluramine were studied in healthy subjects and in 
paediatric patients with Dravet syndrome.  
 
Absorption 
 
For fenfluramine, the Cmax occurs ~3 h following a single oral dose in healthy volunteers and is 28.6 
ng/mL following a dose of 0.35 mg/kg and 59.3 ng/mL following a dose of 0.7 mg/kg fenfluramine. 
The AUCinf is 673 ng × h/mL and 1660 ng × h/mL following 0.35 mg/kg and 0.7 mg/kg, respectively. 
For norfenfluramine, the Cmax occurs ~12 h following a single oral dose in healthy volunteers and is 
11.7 ng/mL and 16.1 ng/mL following a dose of 0.354 mg/kg or 0.78 mg/kg, respectively. The AUCinf 
is 798 ng × h/mL and ~800 ng × h/mL following 0.35 mg/kg and 0.7 mg/kg, respectively. Cmax and 
AUCinf of fenfluramine appear dose proportional over the 0.35 to 0.7 mg/kg dose range in healthy 
volunteers. The Cmax and AUCinf of norfenfluramine are less than dose proportional over the 0.35 to 
0.7 mg/kg dose range in healthy volunteers. The AUCinf increase was 0.5-fold for the 0.7 mg/kg dose 
compared to the 0.35 mg/kg dose. The Cmax increase was 0.7-fold for the 0.7 mg/kg dose compared to 
the 0.35 mg/kg dose. 
 
In paediatric patients following fenfluramine dosing of 0.2 mg/kg/day, administered twice daily, 
steady state exposure (AUC0-24) is 371 ng*h/mL for fenfluramine and 222 ng*h/mL for 



13 

norfenfluramine. In paediatric patients following fenfluramine dosing of 0.7 mg/kg/day, administered 
twice daily with a maximum of 26 mg/day; steady state AUC0-24 is 1400 ng*h/mL for fenfluramine 
and 869 ng*h/mL for norfenfluramine following a dose of 0.7 mg/kg/day, administered twice daily. 
Cmax,ss was 68.6 ng/mL for fenfluramine and 37.8 ng/mL for norfenfluramine. When stiripentol is 
given concomitantly, the steady state AUC0-24 is 1030 ng*h/mL for fenfluramine and 139 ng*h/mL for 
norfenfluramine following a dose of 0.2 mg/kg/day, administered twice daily; the steady state AUC0-24 
is 3240 ng*h/mL for fenfluramine and 364 ng*h/mL for norfenfluramine following a dose of 
0.35 mg/kg/day, administered twice daily. 
 
The absolute bioavailability of fenfluramine is approximately 75-83%. There was no effect of food on 
the pharmacokinetics of fenfluramine or norfenfluramine. 
 
The plasma half-life of fenfluramine and norfenfluramine indicates that approximately 94% of 
steady-state would be reached in approximately 4 days for fenfluramine and 5 days for 
norfenfluramine (4 half-lives). In healthy subjects, the Cmax accumulation ratio is 3.7-fold for 
fenfluramine and 6.4-fold for norfenfluramine and the AUC0-24 accumulation ratio is 2.6-fold for 
fenfluramine and 3.7-fold for norfenfluramine.  
 
Distribution 
 
Fenfluramine is 50% bound to human plasma proteins in vitro and binding is independent of 
fenfluramine concentrations. The geometric mean (CV%) volume of distribution (Vz/F) of 
fenfluramine is 11.9 (16.5%) L/kg following oral administration of fenfluramine in healthy subjects.  
 
Biotransformation 
 
Over 75% of fenfluramine is metabolised to norfenfluramine prior to elimination, primarily by 
CYP1A2, CYP2B6, and CYP2D6. Norfenfluramine is then deaminated and oxidized to form inactive 
metabolites. The extent to which these inactive metabolites are present in plasma and urine is 
unknown. The involvement of enzymes other than CYPs (e.g. UGTs) in the metabolism of 
norfenfluramine is unknown, but literature data indicate that norfenfluramine may be glucuronidated 
to a significant extent. 
 
Transporters 
 
Fenfluramine and norfenfluramine were not in vitro substrates of P-glycoprotein, BCRP, OATP1B1, 
OATP1B3, OATP1A2, OATP2B1, OCT1, OAT1, OAT3, OCT2, MATE1 and MATE2-K. 
 
Elimination 
 
Most of an orally administered dose of fenfluramine (>90%) is excreted in the urine mainly as 
metabolite; less than 5% is found in faeces. The geometric mean (CV%) clearance (CL/F) of 
fenfluramine is 6.9 L/h (29%) and the half-life is 20 hours following oral administration of 
fenfluramine in healthy subjects. The elimination half-life of norfenfluramine is ~30 h. 
 
Special populations 
 
Genetic polymorphisms 
No impact of genotype in CYP1A2, CYP2B6, CYP2C19, CYP2D6, or CYP3A4 on fenfluramine or 
norfenfluramine PK was observed. 
 
Renal impairment 
Renal elimination is the predominant route of elimination of fenfluramine-related products, with more 
than 90% of the administered dose eliminated in the urine as parent or metabolites. There are no 
human clinical data on the effect of renal impairment on the PK of fenfluramine and norfenfluramine. 
 



14 

Hepatic impairment 
No studies on the effect of hepatic impairment on the PK of fenfluramine in adults or children were 
found. With hepatic metabolism of fenfluramine, plasma drug concentrations may be affected in 
patients with significant hepatic impairment. Subjects with moderate or severe hepatic impairment 
were excluded from the phase 3 clinical trials. 
 
Body weight 
Drug clearance and PK exposure of fenfluramine and norfenfluramine are consistent across a broad 
range of BMI (12.3 to 35 kg/m2). 
 
Gender 
The pharmacokinetics of fenfluramine and norfenfluramine were consistent between males and 
females. 
 
Race 
The evaluation was limited by the small sample size of non-white subjects that no conclusion on the 
effect of race on the pharmacokinetics can be made. The genetic polymorphs of the enzymes that 
metabolize fenfluramine are similar across races, only their frequency differs. Thus, although the mean 
exposure may differ slightly depending on race, the range of exposure would be expected to be 
similar. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity or genotoxicity. Knowledge of potential long-term toxicity 
including carcinogenic potential is however still limited. 
 
In a lactation study, rats were dosed orally with radiolabeled dexfenfluramine at 1.2 mg/kg, and 
samples of plasma and milk were collected over 24 hours following the dose. Both dexfenfluramine 
and nordexfenfluramine were found in milk at 2 hours after dosing and levels declined over 24 hours. 
No dexfenfluramine was found in the milk at 24 hours. Nordexfenfluramine was present in small 
amounts at 24 hours. The radioactivity milk:plasma ratio was 9 ± 2 at 2 hours and 5 ± 1 at 24 hours. 
Based on a bodyweight comparison, the human equivalent dose (0.2 mg/kg dexfenfluramine) is less 
than the maximum recommended human dose of Fintepla. 
 
Reproduction and development 
 
Fenfluramine and norfenfluramine crossed the placenta in pregnant rats and rabbits. Plasma exposures 
were higher in rat foetuses than in the dams, while plasma exposures in rabbits were comparable 
between does and foetuses; however the effects in human foetuses are unknown. 
 
In an embryofoetal development study in rats, decreased foetal body weight and increased incidences 
of external and skeletal malformations were observed at the high dose level in association with 
maternal toxicity. No foetal abnormalities were noted at exposures at least five-fold the plasma AUC 
in humans administered the maximum recommended therapeutic dose of Fintepla. 
 
No fenfluramine-related external, visceral or skeletal malformations or variations were determined in 
an embryofoetal development study in rabbits but increased post-implantation losses were evident at 
all doses secondarily to fenfluramine maternal toxicity (body weight loss and decreased food 
consumption). Additional clinical signs of dilated pupils and increased respiration rate and tremors 
were observed. Plasma exposures (AUC) in rabbits were below those in humans at the maximum 
recommended therapeutic dose of Fintepla. 
 
In a pre- and post-natal study in rats, maternal toxicity was associated with an increase in stillbirths at 
the high dose. No adverse effects on the F0 and F1 generations were confirmed at five-fold higher 



15 

plasma exposures (AUC) than in humans at the maximum recommended therapeutic dose of Fintepla. 
In the first generation of offspring, there were no effects on overall reproductive function.  
 
Fenfluramine did not affect the reproductive performance of male rats. In female rats, a reduction in 
the fertility index (defined by the proportion of matings that resulted in pregnancies) was observed at 
maternally toxic doses that correlated with less corpora lutea, significantly fewer implantation sites 
and a higher percentage of pre- and post-implantation losses. No effects on the fertility index were 
noticed at plasma exposures (AUC) approximately equivalent to those in humans at the maximum 
recommended therapeutic dose of Fintepla. 
  
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium ethyl para-hydroxybenzoate (E 215) 
Sodium methyl para-hydroxybenzoate (E 219)  
Sucralose (E 955) 
Hydroxyethylcellulose (E 1525) 
Monosodium phosphate (E 339) 
Disodium phosphate (E 339) 
Cherry flavouring powder: 

Acacia (E 414) 
Glucose (maize) 
Ethyl benzoate 
Natural flavouring preparations 
Natural flavouring substances 
Flavouring substances 
Maltodextrin (maize) 
Sulfur dioxide (E 220) 

Potassium citrate (E 332) 
Citric acid monohydrate (E 330) 
Water for injections 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
4 years. 
 
Shelf life after first opening 
 
This medicinal product should be used within 3 months of first opening the bottle. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. Do not refrigerate or freeze. 
 
6.5 Nature and contents of container  
 
Fintepla is presented in a white High Density Polyethylene (HDPE) bottle with a child-resistant, 
tamper-evident cap packaged in a carton, a Low Density Polyethylene (LDPE) press-in bottle adaptor, 
and Polypropylene (PP)/HDPE oral syringes. The oral syringe included in the pack should be used to 
administer the prescribed dose. 



16 

 
Presentations: 
 
Bottle containing 60 mL oral solution, a bottle adaptor, two 3 mL oral syringes with 0.1 mL 
graduations, and two 6 mL syringes with 0.2 mL graduations. 
Bottle containing 120 mL oral solution, a bottle adaptor, two 3 mL oral syringes with 0.1 mL 
graduations, and two 6 mL syringes with 0.2 mL graduations. 
Bottle containing 250 mL oral solution, a bottle adaptor, two 3 mL oral syringes with 0.1 mL 
graduations, and two 6 mL syringes with 0.2 mL graduations. 
Bottle containing 360 mL oral solution, a bottle adaptor, two 3 mL oral syringes with 0.1 mL 
graduations, and two 6 mL syringes with 0.2 mL graduations. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
Inserting the bottle adaptor: 
 
When the bottle is first opened the bottle adaptor must be pushed into the bottle. 
Wash and dry hands. 
Remove the bottle adaptor packaging. 
Place the bottle on a flat, firm surface. 
Open the bottle. 
Hold the bottle firmly. 
Align the bottle adaptor with the open top of the bottle. 
Push the bottle adaptor into the bottle using the palm of the hand. 
The bottle adaptor should be flush with the top of the bottle. 
The bottle adaptor should not be removed after each use. 
The bottle cap can be screwed onto the bottle with the bottle adaptor in place. 
 
Cleaning the syringe: 
 
Separate the plunger from the syringe to rinse each part. 
Rinse the oral syringe with clean water and allow it to air dry after each use.  
Rinse the inside of the syringe and the plunger. 
The syringe and plunger can be cleaned in a dishwasher. 
Clean water can be pulled into the syringe with the plunger and pushed out several times to clean the 
syringe. 
The syringe and plunger must be completely dry before the next use. 
 
Feeding tubes 
 
Fintepla oral solution is compatible with most enteral feeding tubes. 
To flush the feeding tube, fill the syringe used for dosing with water and flush the tube. Do this 3 
times.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Zogenix ROI Limited, 
Trinity House, 
Charleston Road, 
Ranelagh, 



17 

Dublin 6, 
D06 C8X4  
Ireland 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/20/1491/001 
EU/1/20/1491/002 
EU/1/20/1491/003 
EU/1/20/1491/004 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 
 
  

http://www.ema.europa.eu/


18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 
RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 



19 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Zogenix ROI Limited, 
Trinity House, 
Charleston Road, 
Ranelagh, 
Dublin 6, 
D06 C8X4,  
Ireland 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of 
Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 
and any subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder (MAH) shall submit the first PSUR for this product within 
6 months following authorisation.  
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk management plan (RMP) 

 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 
activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 
marketing authorisation and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
• Additional risk minimisation measures  

 
Prior to launch of Fintepla in each Member State (MS), the marketing authorisation holder (MAH) 
must agree about the content and format of the educational materials (EM) and the controlled access 



20 

programme (CAP) including communication media, distribution modalities and any other aspects of 
the programme, with the National Competent Authorities (NCA).  

The MAH shall ensure that, in each MS where Fintepla is marketed, a CAP is implemented to prevent 
off-label use for weight management in obese patients, since the benefit-risk ratio in this population is 
known to be negative.  

In addition, the CAP shall be implemented to confirm that prescribing physicians have been informed 
of the need for periodic cardiac monitoring in patients taking Fintepla due to the potential risk of 
valvular heart disease and pulmonary arterial hypertension.  

The MAH shall ensure that in each MS where Fintepla is marketed, all healthcare professionals who 
are expected to prescribe the product are aware of the CAP and are provided with the educational 
package consisting of: 

• Summary of product characteristics (SmPC) 

• HCP guide  

The educational material for healthcare professionals (HCP guide) shall address the following risks: 

• Valvular heart disease (VHD) 

• Pulmonary arterial hypertension (PAH) 

• Off-label use for weight management 

 

The HCP guide shall contain the following key messages:  

 Brief information about the historical background on fenfluramine and its market withdrawal 

due to the risks of VHD and PAH. 

 Emphasis that the currently approved indication has to be strictly adhered to and access is 

therefore controlled ensuring proper information of physicians before prescribing. 

 Informing physicians about the conditions of the Fintepla Controlled Access Programme (that 

are agreed on national level). 

 Instruction on detection, monitoring, and/or proper management of VHD and PAH associated 

with fenfluramine.  

 Advice to encourage patients/carers to enrol patients in the fenfluramine registry to collect 

long-term safety data. 

The educational material for patients and/or caregivers should address the following risks: 

• Valvular heart disease (VHD) 

• Pulmonary arterial hypertension (PAH) 

 

The patient/carer guide shall contain the following key messages: 

 Information about the importance of periodic cardiac monitoring (ECHOs) 



21 

 Education about the detection and proper management of VHD and PAH associated with 

fenfluramine.  

 Encouragement to participate in the fenfluramine registry to collect long-term safety data. 

 
• Obligation to conduct post-authorisation measures  
 
The MAH shall complete, within the stated timeframe, the below measures: 
 

Description Due date 
Fintepla Registry on long-term safety 
The MAH shall perform an observational registry to provide data on long-term 
safety of fenfluramine in routine practice, with a focus on characterising and 
quantifying the important potential risks VHD and PAH (primary objective), and 
growth retardation (secondary objective). In addition, data on the frequency of 
echocardiographic monitoring will contribute to assess the effectiveness of risk 
minimisation measures.  

Final report:  
October 2031 

  



22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



24 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
Outer carton  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Fintepla 2.2 mg/mL oral solution 
fenfluramine  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each mL contains 2.2 mg fenfluramine (as hydrochloride) 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: 
E 215, E 219 
Cherry flavouring (glucose, E 220) 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Oral solution 
 
Bottle of 60 mL, bottle adaptor, two 3 mL oral syringes, and two 6 mL oral syringes  
Bottle of 120 mL, bottle adaptor, two 3 mL oral syringes, and two 6 mL oral syringes 
Bottle of 250 mL, bottle adaptor, two 3 mL oral syringes, and two 6 mL oral syringes 
Bottle of 360 mL, bottle adaptor, two 3 mL oral syringes, and two 6 mL oral syringes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
Use within 3 months of first opening the bottle. 



25 

 
Date of first bottle opening: __ / __ / ____ 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not refrigerate or freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Zogenix ROI Limited 
Trinity House 
Charleston Road 
Ranelagh 
Dublin 6 
D06 C8X4 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/20/1491/001 60 mL oral solution 
EU/1/20/1491/002 120 mL oral solution 
EU/1/20/1491/003 250 mL oral solution 
EU/1/20/1491/004 360 mL oral solution 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Fintepla 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 



26 

SN  
NN 
 
  



27 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
Bottle  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Fintepla 2.2 mg/mL oral solution 
fenfluramine  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each mL contains 2.2 mg fenfluramine (as hydrochloride) 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: 
E 215, E 219 
Cherry flavouring (glucose, E 220) 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Oral solution 
 
Bottle of 60 mL, bottle adaptor, two 3 mL oral syringes, and two 6 mL oral syringes  
Bottle of 120 mL, bottle adaptor, two 3 mL oral syringes, and two 6 mL oral syringes 
Bottle of 250 mL, bottle adaptor, two 3 mL oral syringes, and two 6 mL oral syringes 
Bottle of 360 mL, bottle adaptor, two 3 mL oral syringes, and two 6 mL oral syringes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
Use within 3 months of first opening the bottle. 



28 

 
Date of first bottle opening: __ / __ / ____ 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not refrigerate or freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Zogenix ROI Limited 
Trinity House 
Charleston Road 
Ranelagh 
Dublin 6 
D06 C8X4 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/20/1491/001 60 mL oral solution 
EU/1/20/1491/002 120 mL oral solution 
EU/1/20/1491/003 250 mL oral solution 
EU/1/20/1491/004 360 mL oral solution 
 
 
13. BATCH NUMBER 
 
Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Fintepla 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
 



29 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



30 

Package leaflet: Information for the patient 
 

Fintepla 2.2 mg/mL oral solution 
fenfluramine 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you or your child may experience. See 
the end of section 4 for how to report side effects. 
 
Read all of this leaflet carefully before you or your child starts taking this medicine because it 

contains important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you or your child only. Do not pass it on to others. It may 

harm them, even if their signs of illness are the same as yours or your child’s. 
- If you or your child experience any side effects, talk to your doctor, pharmacist or nurse. This 

includes any possible side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Fintepla is and what it is used for 
2. What you need to know before you take Fintepla 
3. How to take Fintepla  
4. Possible side effects 
5. How to store Fintepla 
6. Contents of the pack and other information 
 
 
1. What Fintepla is and what it is used for 
 
Fintepla contains the active substance fenfluramine.  
 
Fintepla is used to treat seizures (fits) in patients aged 2 years and over who have a type of epilepsy 
called Dravet syndrome. It can help to reduce the number and severity of seizures. 
 
It is not completely known how Fintepla works. However, it is thought to work by increasing the 
activity in the brain of a natural substance called serotonin, and this may reduce seizures. 
 
 
2. What you need to know before you or your child takes Fintepla 
 
Do not take Fintepla if:  
• you or your child are allergic to fenfluramine or any of the other ingredients of this medicine 

(listed in section 6) 
• you or your child have a heart problem such as ‘valve disease’ or ‘pulmonary arterial 

hypertension’ (high pressure in the arteries of the lungs)  
• you or your child have taken medicines called monoamine oxidase inhibitors in the last 

2 weeks. 
 
Do not take Fintepla if any of the above apply to you. If you are not sure, talk to your doctor, 
pharmacist or nurse before taking Fintepla. 
 
Warnings and precautions  
Talk to your doctor, pharmacist or nurse before taking Fintepla if: 
• you or your child have glaucoma 
• you or your child have had thoughts about harming or killing yourself 



31 

• you or your child are taking a medicine called cyproheptadine, which is used to treat allergies or 
to improve appetite. 
 

If any of the above applies to you or your child (or you are not sure), talk to your doctor, pharmacist or 
nurse before taking Fintepla. 
 
Tests and checks 
Before you or your child start taking Fintepla your doctor must check the heart with an 
echocardiogram (ECHO). The doctor will check that the valves in the heart work properly and the 
pressure in the artery between the heart and lungs is not too high. Once you or your child has started 
taking Fintepla, you will have an echocardiogram check every 6 months for the first 2 years and then 
once a year. If Fintepla treatment is stopped, you or your child will need to have an echocardiogram 
6 months after the last dose. 
 
Your doctor should also check your weight before and during your treatment as Fintepla can cause you 
to lose weight. 
 
‘Serotonin syndrome’ 
Tell your doctor or pharmacist before taking Fintepla if you or your child are taking medicines which 
can increase the levels of serotonin in your brain. This is because taking these medicines and Fintepla 
can cause serotonin syndrome, which is a life-threatening condition. Medicines that can increase 
serotonin levels include: 
• ‘triptans’ (such as sumatriptan) – used for migraine 
• MAOI medicines – used for depression 
• SSRI or SNRI medicines – used for depression and anxiety. 
 
Look out for the signs of serotonin syndrome which include: 
• being agitated, seeing things which are not there (hallucinations) or passing out 
• heart and circulation problems such as fast heartbeat, blood pressure going up and down, high 

body temperature, sweating 
• twitching muscles and being uncoordinated 
• feeling or being sick and diarrhoea. 

 
Tell your doctor straight away if you notice any of the serious side effects above. 
 
Other medicines and Fintepla 
Tell your doctor or pharmacist if you or your child are taking, have recently taken, or might take any 
other medicines. This is because Fintepla can affect the way some other medicines work. Also, some 
other medicines can affect the way Fintepla works.  
 
Fintepla can make you or your child feel sleepy. You or your child may be even more sleepy if you 
take other medicines such as anti-depressants or alcohol at the same time as Fintepla. 
 
In particular, tell your doctor or pharmacist if you or your child are taking, have recently taken, or 
might take: 
• stiripentol, a medicine for epilepsy, as your dose of Fintepla may need to be reduced 
• ‘triptans’, MAOI, SNRI or SSRI medicines – see above under ‘Serotonin syndrome’ 
• carbamazepine, primidone, rifampicin, phenobarbital and other barbiturates, phenytoin, and 

efavirenz, as your dose of Fintepla may need to be increased. 
 
Also speak with your doctor or pharmacist if you or your child smoke as the dose of Fintepla may 
need to be increased. 
 



32 

Pregnancy and breast-feeding 
If you or your child are pregnant, think you or your child might be pregnant, or are planning to have a 
baby or are breast-feeding, ask your doctor for advice before taking this medicine.  
 
Driving and using machines 
Talk to your doctor about driving, using machines, or if you or your child undertake activities such as 
cycling or other sports, because you or your child may feel sleepy after taking this medicine. 
 
Fintepla contains sodium ethyl p-hydroxybenzoate (E 215) and sodium methyl p-
hydroxybenzoate (E 219)  
This may cause allergic reactions (possibly delayed). 
 
Fintepla contains sulfur dioxide (E 220)  
This may rarely cause hypersensitivity reactions and bronchospasm. 
 
Fintepla contains glucose 
This may be harmful to the teeth. 
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicinal product. 
 
Fintepla contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per 12 mL, that is to say essentially 
‘sodium-free’. 
 
 
3. How to take Fintepla 
 
Always take this medicine exactly as your doctor, pharmacist or nurse has told you. Check with them 
if you are not sure.  
 
How much to take 
• You will be told how many mL to take for each dose. 
• Take the medicine twice a day. 
• Your doctor will start you or your child on a low dose. This can then be gradually increased 

depending on how well the medicine works and how it affects you or your child. 
• The maximum amount you can take is 6 mL twice a day. 
• If you are taking stiripentol, the maximum amount you can take is 4 mL twice a day. 
• Do not take more than the prescribed dose as it may cause serious side effects. 
 
Taking this medicine 
• Take this medicine by mouth. 
• Take the medicine with food or between meals. 
• Fintepla oral solution is compatible with a ketogenic diet. 
• The medicine is a liquid. Use the oral syringes provided to measure your dose, as explained below. 
• Use the green 3 mL syringe for doses up to 3.0 mL. 
• Use the purple 6 mL syringe for doses between 3.2 mL and 6.0 mL. 
• Fintepla oral solution is compatible with most enteral feeding tubes. 
• To flush the feeding tube, fill the syringe used for dosing with water and flush the tube. Do this 3 

times.  
  



33 

3 mL syringe - green 6 mL syringe - purple 

 

 
 
 
  



34 

 
 

 

Write on the carton the date you first opened 
the bottle. 
You must attach the bottle adaptor the first 
time you open the bottle. The following 
instructions tell you how to attach the 
adaptor. 
Inserting the bottle adaptor: 
When the bottle is first opened the bottle 
adaptor must be pushed into the bottle. 
Wash and dry your hands. 
Remove the bottle adaptor from its 
packaging. 
Place the bottle on a flat, firm surface. 
Open the bottle. 
 

 

Hold the bottle firmly. 
Line up the bottle adapter with the open top 
of the bottle. 
Push the bottle adaptor into the bottle with 
your palm until the adaptor is flush with the 
top of the bottle. 
Leave in the bottle adaptor after using the 
medicine. 
Screw the bottle cap onto the bottle with the 
bottle adaptor left in. 

 

Taking the medicine: 
Before you measure out the dose, make sure 
the plunger is pushed all the way into the oral 
syringe. 
Hold the bottle of medicine firmly on a hard, 
flat surface. 
Push the tip of the oral syringe into the bottle 
adaptor until it cannot be pushed further. 
 

 

Hold the oral syringe and bottle together and 
turn upside down. 
Slowly pull the plunger to draw up the right 
dose. 
Hold the oral syringe and bottle together and 
then turn over. 
Holding the bottle firmly, gently pull the oral 
syringe out of the bottle adaptor. 



35 

 

 

Place the tip of the oral syringe against the 
inside of the patient’s cheek. 
Gently push the plunger until it is fully 
pressed. There will be a small volume left in 
the tip of the syringe. This is normal. 
Do not squirt the medicine into the back of 
the throat as this may cause choking. 

 

Place the cap back on the bottle and turn until 
it stops.  
Always leave the adaptor in place in the 
bottle. 

 

Cleaning the syringe: 
Rinse the oral syringe with clean water and 
allow it to air dry after each use.  
Rinse the inside of the syringe and the 
plunger. 
Clean water can be pulled into the syringe 
with the plunger and pushed out several 
times to clean the syringe. 
It is okay to separate the plunger from the 
syringe to rinse each part. 
It is safe to clean the syringe and plunger in a 
dishwasher. 
The syringe and plunger must be completely 
dry before the next use. 

 
If you or your child take more Fintepla than you or your child should 
Talk to a doctor or go to a hospital straight away. Take the medicine bottle with you. The following 
effects may happen: being agitated, sleepy or confused, being flushed or hot, shivering and sweating. 
 
If you or your child forget to take Fintepla 
• Take it as soon as you remember it. However, if it is nearly time to take the next dose, skip the 

missed dose.  
• Do not take a double dose to make up for a forgotten dose. 
 
If you or your child stop taking Fintepla 
Do not stop taking Fintepla without talking to your doctor. If your doctor decides to stop this 
medicine, the doctor will ask you or your child to slowly lower the amount taken each day. Slowly 
lowering the dose will reduce the risk of having a seizure and status epilepticus. 
Six months after the last dose of Fintepla, you or your child will need to have an echocardiogram . 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.  
 
 



36 

4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Very common: may affect more than 1 in 10 people 
• falling 
• diarrhoea  
• vomiting 
• weight loss 
• constipation 
• loss of appetite 
• high temperature 
• lower blood sugar  
• abnormal echocardiogram 
• feeling tired, sleepy or weak 
• chest infection and bronchitis 
• trembling of the hands, arms or legs 
• long-lasting seizures (status epilepticus) 
 
Common: may affect up to 1 in 10 people  
• irritability 
• ear infection  
• abnormal behaviour 
 
Tell your doctor, pharmacist or nurse if you notice any of the side effects listed above. 
 
Reporting of side effects 
If you experience any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 
side effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Fintepla 
 
• Keep this medicine out of the sight and reach of children. 
• Do not use this medicine after the expiry date which is stated on the carton and bottle label after 

EXP. The expiry date refers to the last day of that month. 
• Do not refrigerate or freeze. 
• Use within 3 months of first opening the bottle. 
• Wash the syringe after each use. 
• If you lose or damage a syringe, or cannot read the dose markings on a syringe, use another oral 

syringe provided in your pack, or speak to your pharmacist. 
• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how 

to throw away medicines you no longer use. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Fintepla contains  
The active substance is called fenfluramine. Each ml contains 2.2 mg of fenfluramine (as fenfluramine 
hydrochloride). 
The other ingredients are: 
• Sodium ethyl para-hydroxybenzoate (E 215) 
• Sodium methyl para-hydroxybenzoate (E 219)  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


37 

• Sucralose (E 955) 
• Hydroxyethylcellulose (E 1525) 
• Monosodium phosphate (E 339) 
• Disodium phosphate (E 339) 
• Cherry flavouring powder: 

o Acacia (E 414) 
o Glucose (maize) 
o Ethyl benzoate 
o Natural flavouring preparations 
o Natural flavouring substances 
o Flavouring substances 
o Maltodextrin (maize) 
o Sulphur dioxide (E 220) 

• Potassium citrate (E 332) 
• Citric acid monohydrate (E 330) 
• Water for injections 
 
What Fintepla looks like and contents of the pack 
• Fintepla oral solution is supplied as a clear, colourless, cherry-flavoured slightly viscous liquid. 
• The solution is available in a white bottle with a child-resistant, tamper-evident cap. 
• Each carton contains either: 

o Bottle containing 60 mL oral solution, a bottle adaptor, two 3 mL oral syringes with 
0.1 mL graduations, and two 6 mL syringes with 0.2 mL graduations. 

o Bottle containing 120 mL oral solution, a bottle adaptor, two 3 mL oral syringes with 
0.1 mL graduations, and two 6 mL syringes with 0.2 mL graduations. 

o Bottle containing 250 mL oral solution, a bottle adaptor, two 3 mL oral syringes with 
0.1 mL graduations, and two 6 mL syringes with 0.2 mL graduations. 

o Bottle containing 360 mL oral solution, a bottle adaptor, two 3 mL oral syringes with 
0.1 mL graduations, and two 6 mL syringes with 0.2 mL graduations. 

• Not all pack sizes may be marketed in your country. 
 
Marketing Authorisation Holder and Manufacturer 
Zogenix ROI Limited, 
Trinity House, 
Charleston Road, 
Ranelagh, 
Dublin 6, 
D06 C8X4,  
Ireland 
 
This leaflet was last revised in 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments. 


	1ANNEX ISUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET