Fintepla

Fintepla should be initiated and supervised by physicians with experience in the treatment of epilepsy. 4). e. e. 35 mg/kg twice daily Not applicable *For patients not on concomitant stiripentol requiring more rapid titration, the dose may be increased every 4 days.

+For patients with Dravet syndrome, dosage may be increased based on clinical response to the maximum recommended dose, as needed. 2 mg/ml = ml dose to be taken twice daily Always round the calculated dose up or down to the nearest graduation mark, following standard rounding conventions.

2 ml. 1 ml. 2 ml. 2 ml. 1 ml graduation marks). 2 ml graduation marks). The table below must only be used as a check on the calculated dose volume. Table 2 does not replace the requirement to calculate the specific dose volume. 5-3 ml 4 ml (maximum dose) 65-86 kg 3-4 ml 6 ml (maximum dose) 6 ml (maximum dose) 3-4 ml (maximum dose) 4 ml (maximum dose) 86-130 kg 4-6 ml (maximum dose) 6 ml (maximum dose) 6 ml (maximum dose) 4 ml (maximum dose) 4 ml (maximum dose) *Without concomitant STP: The maximum dose 13 mg twice daily corresponds to 6 ml twice daily.

6 mg twice daily corresponds to 4 ml twice daily. Discontinuation of treatment When discontinuing treatment, the dose should be decreased gradually. Abrupt discontinuation should be avoided when possible to minimize the risk of increased seizure frequency and status epilepticus.

A final echocardiogram should be conducted 3-6 months after the last dose of treatment with fenfluramine. Special populations Renal impairment Generally, no dose adjustment is recommended when Fintepla is administered to patients with mild to severe renal impairment, however, a slower titration may be considered.

If adverse reactions are reported, a dose reduction may be needed. 2) Fintepla has not been studied in patients with end-stage renal disease. It is not known if fenfluramine or its active metabolite, norfenfluramine, is dialyzable. There are no specific clinical data on the use of Fintepla with stiripentol in patients with impaired renal function.

Fintepla is therefore not recommended for use in patients with impaired renal function treated with stiripentol. Hepatic impairment Generally, no dose adjustment is recommended when Fintepla is administered without concomitant stiripentol to patients with mild and moderate hepatic impairment (Child-Pugh Class A and B).

7%), and somnolence (15%). Tabulated list of adverse reactions Adverse reactions reported with fenfluramine in placebo-controlled clinical studies and from post- marketing surveillance are listed in the tables below by System Organ Class and frequency.

Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10) or not known (cannot be estimated from the available data).

Table 3:

Adverse reactions MedDRA System Organ Class Very common Common Not known Infections and infestations Bronchitis Metabolism and nutrition disorders Decreased appetite Psychiatric disorders Abnormal behaviour Aggression Agitation Insomnia Mood swings Irritability Nervous system disorders Somnolence Ataxia Hypotonia Lethargy Seizure Status epilepticus Tremor Serotonin syndrome Cardiac disorders Valvular heart disease Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension Gastrointestinal disorders Diarrhoea Constipation Salivary Hypersecretion Vomiting 11 Skin and subcutaneous tissue disorders Rash General disorders and administration site conditions Fatigue Investigations Weight decreased Blood glucose decreased Blood prolactin increased Description of selected adverse reactions Decreased appetite and weight loss Fenfluramine can cause decreased appetite and weight loss.

8% of patients on placebo. 1% 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. 1% in the combined fenfluramine group.

5% in the fenfluramine group. There were no discontinuations due to status epilepticus in the Dravet syndrome and the LGS phase 3 clinical trials. 6%). 5% of patients on placebo. 2%). 0% of patients on placebo. 6 days in the placebo group.

Echocardiographic safety assessments Valvular heart disease and pulmonary arterial hypertension were evaluated via echocardiography in the clinical studies for Dravet syndrome and Lennox-Gastaut syndrome. No patient developed valvular heart disease or pulmonary arterial hypertension in the completed clinical studies for both indications.

8). Therefore, echocardiographic monitoring must be performed. 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.

Once treatment is discontinued for any reasons, a final echocardiogram should be conducted 3-6 months after the last dose of treatment with fenfluramine. 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. 6 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.

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 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 ESC and ERS guidelines, it is recommended fenfluramine treatment should be stopped. 8). An additive effect on decreased appetite can occur when fenfluramine is combined with other anti-epileptic medicines, for example stiripentol.

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.