Fintepla

FINTEPLA is indicated for the treatment of seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) in patients 2 years of age and older.

• FINTEPLA is to be administered orally and may be taken with or without food. (
  
  
  2.2 Dosing Information

  FINTEPLA is to be administered orally and may be taken with or without food.

  Dravet Syndrome

  • The initial starting and maintenance dosage for patients with Dravet syndrome is 0.1 mg/kg twice daily, which can be increased weekly based on efficacy and tolerability. Table 1 provides the recommended titration schedule, if needed.
  • Patients with Dravet syndrome not on concomitant stiripentol who are tolerating FINTEPLA at 0.1 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 0.35 mg/kg twice daily (maximum daily dosage of 26 mg).
    
    Patients with Dravet syndrome taking concomitant stiripentol plus clobazam who are tolerating FINTEPLA at 0.1 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 0.2 mg/kg twice daily (maximum daily dosage of 17 mg)
    [see Drug Interactions (7.1)].

  Lennox-Gastaut Syndrome

  • The initial starting dosage for patients with Lennox-Gastaut syndrome is 0.1 mg/kg twice daily, which should be increased weekly based on tolerability. Table 1 provides the recommended titration schedule.
  • Patients with Lennox-Gastaut syndrome not on concomitant stiripentol who are tolerating FINTEPLA should be titrated to the recommended maintenance dosage of 0.35 mg/kg twice daily (maximum daily dosage of 26 mg).
  • Patients with Lennox-Gastaut syndrome taking concomitant stiripentol plus clobazam who are tolerating FINTEPLA should be titrated to the recommended maintenance dosage of 0.2 mg/kg twice daily (maximum daily dosage of 17 mg)
    [see Drug Interactions (7.1)].

  Table 1: FINTEPLA Recommended Titration ScheduleFor patients
  not on concomitant stiripentol in whom a more rapid titration is warranted, the dose may be increased every 4 days.

  	Without concomitant stiripentol		With concomitant stiripentol plus clobazam
  	Weight-based DosageTo calculate the dose volume: Weight (kg) × Weight-based dosage (mg/kg) ÷ 2.2 mg/mL = mL dose to be taken twice daily	Maximum Total Daily DosageFor maximum dosage with concomitant use of strong CYP1A2 or CYP2D6 inhibitors, in patients with severe renal impairment, or in patients with hepatic impairment see Dosage and Administration 2.3, 2.4, 2.5.	Weight-based Dosage	Maximum Total Daily Dosage
  Initial DosageFor patients with Dravet syndrome, dosage may be increased based on clinical response to the maximum recommended dosage, as needed.	0.1 mg/kg twice daily	26 mg	0.1 mg/kg twice daily	17 mg
  Day 7	0.2 mg/kg twice daily	26 mg	0.15 mg/kg twice daily	17 mg
  Day 14For patients with Lennox-Gastaut syndrome, dosage should be increased as tolerated to the recommended maintenance dosage (i.e., Day 14).	0.35 mg/kg twice daily	26 mg	0.2 mg/kg twice daily	17 mg
  )
  
• Dravet Syndrome
  
  
  • The initial starting and maintenance dosage is 0.1 mg/kg twice daily, which can be increased weekly based on efficacy and tolerability. (
    
    
    2.2 Dosing Information

    FINTEPLA is to be administered orally and may be taken with or without food.

    Dravet Syndrome

    • The initial starting and maintenance dosage for patients with Dravet syndrome is 0.1 mg/kg twice daily, which can be increased weekly based on efficacy and tolerability. Table 1 provides the recommended titration schedule, if needed.
    • Patients with Dravet syndrome not on concomitant stiripentol who are tolerating FINTEPLA at 0.1 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 0.35 mg/kg twice daily (maximum daily dosage of 26 mg).
      
      Patients with Dravet syndrome taking concomitant stiripentol plus clobazam who are tolerating FINTEPLA at 0.1 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 0.2 mg/kg twice daily (maximum daily dosage of 17 mg)
      [see Drug Interactions (7.1)].

    Lennox-Gastaut Syndrome

    • The initial starting dosage for patients with Lennox-Gastaut syndrome is 0.1 mg/kg twice daily, which should be increased weekly based on tolerability. Table 1 provides the recommended titration schedule.
    • Patients with Lennox-Gastaut syndrome not on concomitant stiripentol who are tolerating FINTEPLA should be titrated to the recommended maintenance dosage of 0.35 mg/kg twice daily (maximum daily dosage of 26 mg).
    • Patients with Lennox-Gastaut syndrome taking concomitant stiripentol plus clobazam who are tolerating FINTEPLA should be titrated to the recommended maintenance dosage of 0.2 mg/kg twice daily (maximum daily dosage of 17 mg)
      [see Drug Interactions (7.1)].

    Table 1: FINTEPLA Recommended Titration ScheduleFor patients
    not on concomitant stiripentol in whom a more rapid titration is warranted, the dose may be increased every 4 days.

    	Without concomitant stiripentol		With concomitant stiripentol plus clobazam
    	Weight-based DosageTo calculate the dose volume: Weight (kg) × Weight-based dosage (mg/kg) ÷ 2.2 mg/mL = mL dose to be taken twice daily	Maximum Total Daily DosageFor maximum dosage with concomitant use of strong CYP1A2 or CYP2D6 inhibitors, in patients with severe renal impairment, or in patients with hepatic impairment see Dosage and Administration 2.3, 2.4, 2.5.	Weight-based Dosage	Maximum Total Daily Dosage
    Initial DosageFor patients with Dravet syndrome, dosage may be increased based on clinical response to the maximum recommended dosage, as needed.	0.1 mg/kg twice daily	26 mg	0.1 mg/kg twice daily	17 mg
    Day 7	0.2 mg/kg twice daily	26 mg	0.15 mg/kg twice daily	17 mg
    Day 14For patients with Lennox-Gastaut syndrome, dosage should be increased as tolerated to the recommended maintenance dosage (i.e., Day 14).	0.35 mg/kg twice daily	26 mg	0.2 mg/kg twice daily	17 mg
    )
    
    
  • The maximum daily maintenance dosage of FINTEPLA is 0.35 mg/kg twice daily (maximum daily dosage of 26 mg). (
    
    
    2.2 Dosing Information

    FINTEPLA is to be administered orally and may be taken with or without food.

    Dravet Syndrome

    • The initial starting and maintenance dosage for patients with Dravet syndrome is 0.1 mg/kg twice daily, which can be increased weekly based on efficacy and tolerability. Table 1 provides the recommended titration schedule, if needed.
    • Patients with Dravet syndrome not on concomitant stiripentol who are tolerating FINTEPLA at 0.1 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 0.35 mg/kg twice daily (maximum daily dosage of 26 mg).
      
      Patients with Dravet syndrome taking concomitant stiripentol plus clobazam who are tolerating FINTEPLA at 0.1 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 0.2 mg/kg twice daily (maximum daily dosage of 17 mg)
      [see Drug Interactions (7.1)].

    Lennox-Gastaut Syndrome

    • The initial starting dosage for patients with Lennox-Gastaut syndrome is 0.1 mg/kg twice daily, which should be increased weekly based on tolerability. Table 1 provides the recommended titration schedule.
    • Patients with Lennox-Gastaut syndrome not on concomitant stiripentol who are tolerating FINTEPLA should be titrated to the recommended maintenance dosage of 0.35 mg/kg twice daily (maximum daily dosage of 26 mg).
    • Patients with Lennox-Gastaut syndrome taking concomitant stiripentol plus clobazam who are tolerating FINTEPLA should be titrated to the recommended maintenance dosage of 0.2 mg/kg twice daily (maximum daily dosage of 17 mg)
      [see Drug Interactions (7.1)].

    Table 1: FINTEPLA Recommended Titration ScheduleFor patients
    not on concomitant stiripentol in whom a more rapid titration is warranted, the dose may be increased every 4 days.

    	Without concomitant stiripentol		With concomitant stiripentol plus clobazam
    	Weight-based DosageTo calculate the dose volume: Weight (kg) × Weight-based dosage (mg/kg) ÷ 2.2 mg/mL = mL dose to be taken twice daily	Maximum Total Daily DosageFor maximum dosage with concomitant use of strong CYP1A2 or CYP2D6 inhibitors, in patients with severe renal impairment, or in patients with hepatic impairment see Dosage and Administration 2.3, 2.4, 2.5.	Weight-based Dosage	Maximum Total Daily Dosage
    Initial DosageFor patients with Dravet syndrome, dosage may be increased based on clinical response to the maximum recommended dosage, as needed.	0.1 mg/kg twice daily	26 mg	0.1 mg/kg twice daily	17 mg
    Day 7	0.2 mg/kg twice daily	26 mg	0.15 mg/kg twice daily	17 mg
    Day 14For patients with Lennox-Gastaut syndrome, dosage should be increased as tolerated to the recommended maintenance dosage (i.e., Day 14).	0.35 mg/kg twice daily	26 mg	0.2 mg/kg twice daily	17 mg
    )
    
    
• Lennox-Gastaut Syndrome
  
  
  • The initial starting dosage is 0.1 mg/kg twice daily, which should be
    
    
    increased weekly based on tolerability. (
    
    
    2.2 Dosing Information

    FINTEPLA is to be administered orally and may be taken with or without food.

    Dravet Syndrome

    • The initial starting and maintenance dosage for patients with Dravet syndrome is 0.1 mg/kg twice daily, which can be increased weekly based on efficacy and tolerability. Table 1 provides the recommended titration schedule, if needed.
    • Patients with Dravet syndrome not on concomitant stiripentol who are tolerating FINTEPLA at 0.1 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 0.35 mg/kg twice daily (maximum daily dosage of 26 mg).
      
      Patients with Dravet syndrome taking concomitant stiripentol plus clobazam who are tolerating FINTEPLA at 0.1 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 0.2 mg/kg twice daily (maximum daily dosage of 17 mg)
      [see Drug Interactions (7.1)].

    Lennox-Gastaut Syndrome

    • The initial starting dosage for patients with Lennox-Gastaut syndrome is 0.1 mg/kg twice daily, which should be increased weekly based on tolerability. Table 1 provides the recommended titration schedule.
    • Patients with Lennox-Gastaut syndrome not on concomitant stiripentol who are tolerating FINTEPLA should be titrated to the recommended maintenance dosage of 0.35 mg/kg twice daily (maximum daily dosage of 26 mg).
    • Patients with Lennox-Gastaut syndrome taking concomitant stiripentol plus clobazam who are tolerating FINTEPLA should be titrated to the recommended maintenance dosage of 0.2 mg/kg twice daily (maximum daily dosage of 17 mg)
      [see Drug Interactions (7.1)].

    Table 1: FINTEPLA Recommended Titration ScheduleFor patients
    not on concomitant stiripentol in whom a more rapid titration is warranted, the dose may be increased every 4 days.

    	Without concomitant stiripentol		With concomitant stiripentol plus clobazam
    	Weight-based DosageTo calculate the dose volume: Weight (kg) × Weight-based dosage (mg/kg) ÷ 2.2 mg/mL = mL dose to be taken twice daily	Maximum Total Daily DosageFor maximum dosage with concomitant use of strong CYP1A2 or CYP2D6 inhibitors, in patients with severe renal impairment, or in patients with hepatic impairment see Dosage and Administration 2.3, 2.4, 2.5.	Weight-based Dosage	Maximum Total Daily Dosage
    Initial DosageFor patients with Dravet syndrome, dosage may be increased based on clinical response to the maximum recommended dosage, as needed.	0.1 mg/kg twice daily	26 mg	0.1 mg/kg twice daily	17 mg
    Day 7	0.2 mg/kg twice daily	26 mg	0.15 mg/kg twice daily	17 mg
    Day 14For patients with Lennox-Gastaut syndrome, dosage should be increased as tolerated to the recommended maintenance dosage (i.e., Day 14).	0.35 mg/kg twice daily	26 mg	0.2 mg/kg twice daily	17 mg
    )
    
    
  • The recommended maintenance dosage of FINTEPLA is 0.35 mg/kg twice daily (maximum daily dosage of 26 mg). (
    
    
    2.2 Dosing Information

    FINTEPLA is to be administered orally and may be taken with or without food.

    Dravet Syndrome

    • The initial starting and maintenance dosage for patients with Dravet syndrome is 0.1 mg/kg twice daily, which can be increased weekly based on efficacy and tolerability. Table 1 provides the recommended titration schedule, if needed.
    • Patients with Dravet syndrome not on concomitant stiripentol who are tolerating FINTEPLA at 0.1 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 0.35 mg/kg twice daily (maximum daily dosage of 26 mg).
      
      Patients with Dravet syndrome taking concomitant stiripentol plus clobazam who are tolerating FINTEPLA at 0.1 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 0.2 mg/kg twice daily (maximum daily dosage of 17 mg)
      [see Drug Interactions (7.1)].

    Lennox-Gastaut Syndrome

    • The initial starting dosage for patients with Lennox-Gastaut syndrome is 0.1 mg/kg twice daily, which should be increased weekly based on tolerability. Table 1 provides the recommended titration schedule.
    • Patients with Lennox-Gastaut syndrome not on concomitant stiripentol who are tolerating FINTEPLA should be titrated to the recommended maintenance dosage of 0.35 mg/kg twice daily (maximum daily dosage of 26 mg).
    • Patients with Lennox-Gastaut syndrome taking concomitant stiripentol plus clobazam who are tolerating FINTEPLA should be titrated to the recommended maintenance dosage of 0.2 mg/kg twice daily (maximum daily dosage of 17 mg)
      [see Drug Interactions (7.1)].

    Table 1: FINTEPLA Recommended Titration ScheduleFor patients
    not on concomitant stiripentol in whom a more rapid titration is warranted, the dose may be increased every 4 days.

    	Without concomitant stiripentol		With concomitant stiripentol plus clobazam
    	Weight-based DosageTo calculate the dose volume: Weight (kg) × Weight-based dosage (mg/kg) ÷ 2.2 mg/mL = mL dose to be taken twice daily	Maximum Total Daily DosageFor maximum dosage with concomitant use of strong CYP1A2 or CYP2D6 inhibitors, in patients with severe renal impairment, or in patients with hepatic impairment see Dosage and Administration 2.3, 2.4, 2.5.	Weight-based Dosage	Maximum Total Daily Dosage
    Initial DosageFor patients with Dravet syndrome, dosage may be increased based on clinical response to the maximum recommended dosage, as needed.	0.1 mg/kg twice daily	26 mg	0.1 mg/kg twice daily	17 mg
    Day 7	0.2 mg/kg twice daily	26 mg	0.15 mg/kg twice daily	17 mg
    Day 14For patients with Lennox-Gastaut syndrome, dosage should be increased as tolerated to the recommended maintenance dosage (i.e., Day 14).	0.35 mg/kg twice daily	26 mg	0.2 mg/kg twice daily	17 mg
    )
    
    
• Dravet Syndrome and Lennox-Gastaut Syndrome
  
  
  • Dose adjustment is required in patients taking concomitant stiripentol plus clobazam: the maximum daily maintenance dosage of FINTEPLA is 0.2 mg/kg twice daily (maximum daily dosage of 17 mg). (
    
    
    2.2 Dosing Information

    FINTEPLA is to be administered orally and may be taken with or without food.

    Dravet Syndrome

    • The initial starting and maintenance dosage for patients with Dravet syndrome is 0.1 mg/kg twice daily, which can be increased weekly based on efficacy and tolerability. Table 1 provides the recommended titration schedule, if needed.
    • Patients with Dravet syndrome not on concomitant stiripentol who are tolerating FINTEPLA at 0.1 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 0.35 mg/kg twice daily (maximum daily dosage of 26 mg).
      
      Patients with Dravet syndrome taking concomitant stiripentol plus clobazam who are tolerating FINTEPLA at 0.1 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 0.2 mg/kg twice daily (maximum daily dosage of 17 mg)
      [see Drug Interactions (7.1)].

    Lennox-Gastaut Syndrome

    • The initial starting dosage for patients with Lennox-Gastaut syndrome is 0.1 mg/kg twice daily, which should be increased weekly based on tolerability. Table 1 provides the recommended titration schedule.
    • Patients with Lennox-Gastaut syndrome not on concomitant stiripentol who are tolerating FINTEPLA should be titrated to the recommended maintenance dosage of 0.35 mg/kg twice daily (maximum daily dosage of 26 mg).
    • Patients with Lennox-Gastaut syndrome taking concomitant stiripentol plus clobazam who are tolerating FINTEPLA should be titrated to the recommended maintenance dosage of 0.2 mg/kg twice daily (maximum daily dosage of 17 mg)
      [see Drug Interactions (7.1)].

    Table 1: FINTEPLA Recommended Titration ScheduleFor patients
    not on concomitant stiripentol in whom a more rapid titration is warranted, the dose may be increased every 4 days.

    	Without concomitant stiripentol		With concomitant stiripentol plus clobazam
    	Weight-based DosageTo calculate the dose volume: Weight (kg) × Weight-based dosage (mg/kg) ÷ 2.2 mg/mL = mL dose to be taken twice daily	Maximum Total Daily DosageFor maximum dosage with concomitant use of strong CYP1A2 or CYP2D6 inhibitors, in patients with severe renal impairment, or in patients with hepatic impairment see Dosage and Administration 2.3, 2.4, 2.5.	Weight-based Dosage	Maximum Total Daily Dosage
    Initial DosageFor patients with Dravet syndrome, dosage may be increased based on clinical response to the maximum recommended dosage, as needed.	0.1 mg/kg twice daily	26 mg	0.1 mg/kg twice daily	17 mg
    Day 7	0.2 mg/kg twice daily	26 mg	0.15 mg/kg twice daily	17 mg
    Day 14For patients with Lennox-Gastaut syndrome, dosage should be increased as tolerated to the recommended maintenance dosage (i.e., Day 14).	0.35 mg/kg twice daily	26 mg	0.2 mg/kg twice daily	17 mg
    ,
    
    
    2.3 Dosage Modifications for Patients with Concomitant Use of Strong CYP1A2 or CYP2D6 Inhibitors (DS and LGS)

    For patients with concomitant use of FINTEPLA with a strong CYP1A2 or CYP2D6 inhibitor, a maximum total daily dosage of 20 mg without concomitant stiripentol and 17 mg with concomitant stiripentol plus clobazam is recommended

    [see Drug Interactions (7.1)]

    .
    ,
    
    
    2.4 Dosage Modifications for Patients with Severe Renal Impairment (DS and LGS)

    For patients with severe renal impairment (estimated glomerular filtration rate (eGFR) 15 to 29 mL/min/1.73m²), a maximum total daily dosage of 20 mg without concomitant stiripentol and 17 mg with concomitant stiripentol plus clobazam is recommended

    [see Use in Specific Populations (8.6)]

    .
    ,
    
    
    7.1 Effect of Other Drugs on FINTEPLA

    Stiripentol Plus Clobazam

    Coadministration of FINTEPLA with stiripentol plus clobazam, with or without valproate, increases fenfluramine plasma concentrations

    [see Clinical Pharmacology (12.3)].

    If FINTEPLA is coadministered with stiripentol plus clobazam, the maximum daily dosage of FINTEPLA is 0.2 mg/kg twice daily (maximum daily dosage of 17 mg)

    [see Dosage and Administration (2.2)]

    .

    Strong CYP1A2, CYP2B6, or CYP3A Inducers

    Coadministration of FINTEPLA with strong CYP1A2, CYP2B6, or CYP3A inducers will decrease fenfluramine plasma concentrations, which may lower the efficacy of FINTEPLA

    [see Clinical Pharmacology (12.3)]

    .

    It is recommended to avoid coadministration of strong CYP1A2, CYP2B6 or CYP3A inducers. If coadministration of a strong CYP1A2, CYP2B6, or CYP3A inducer with FINTEPLA is necessary, monitor the patient for reduced efficacy and consider increasing the dosage of FINTEPLA as needed; however, do not exceed the maximum daily dosage of FINTEPLA

    [see Dosage and Administration (2.2)].

    If a strong CYP1A2, CYP2B6, or CYP3A inducer is discontinued during maintenance treatment with FINTEPLA, consider gradual reduction in the FINTEPLA dosage to the dose administered prior to initiating the inducer

    [see Warnings and Precautions (5.6)].

    Strong CYP1A2 or CYP2D6 Inhibitors

    Coadministration of FINTEPLA with strong CYP1A2 or CYP2D6 inhibitors will increase fenfluramine plasma concentrations

    [see Clinical Pharmacology (12.3)]

    . If FINTEPLA is coadministered with strong CYP1A2 or CYP2D6 inhibitors, the maximum daily dosage of FINTEPLA is 20 mg

    [see Dosage and Administration (2.3)].

    If a strong CYP1A2 or CYP2D6 inhibitor is discontinued during maintenance treatment with FINTEPLA, consider gradual increase in the FINTEPLA dosage to the dose recommended without CYP1A2 or CYP2D6 inhibitors; however, do not exceed the maximum daily dosage of FINTEPLA

    [see Dosage and Administration (2.2)].

    If FINTEPLA is coadministered with stiripentol and a strong CYP1A2 or CYP2D6 inhibitor, do not exceed the maximum daily dosage of FINTEPLA of 17 mg

    [see Dosage and Administration (2.3)].
    )
    
    
• Dosage adjustment is recommended in patients:
  
  
  • Taking strong CYP1A2 or CYP2D6 inhibitors (
    
    
    2.3 Dosage Modifications for Patients with Concomitant Use of Strong CYP1A2 or CYP2D6 Inhibitors (DS and LGS)

    For patients with concomitant use of FINTEPLA with a strong CYP1A2 or CYP2D6 inhibitor, a maximum total daily dosage of 20 mg without concomitant stiripentol and 17 mg with concomitant stiripentol plus clobazam is recommended

    [see Drug Interactions (7.1)]

    .
    ,
    
    
    7.1 Effect of Other Drugs on FINTEPLA

    Stiripentol Plus Clobazam

    Coadministration of FINTEPLA with stiripentol plus clobazam, with or without valproate, increases fenfluramine plasma concentrations

    [see Clinical Pharmacology (12.3)].

    If FINTEPLA is coadministered with stiripentol plus clobazam, the maximum daily dosage of FINTEPLA is 0.2 mg/kg twice daily (maximum daily dosage of 17 mg)

    [see Dosage and Administration (2.2)]

    .

    Strong CYP1A2, CYP2B6, or CYP3A Inducers

    Coadministration of FINTEPLA with strong CYP1A2, CYP2B6, or CYP3A inducers will decrease fenfluramine plasma concentrations, which may lower the efficacy of FINTEPLA

    [see Clinical Pharmacology (12.3)]

    .

    It is recommended to avoid coadministration of strong CYP1A2, CYP2B6 or CYP3A inducers. If coadministration of a strong CYP1A2, CYP2B6, or CYP3A inducer with FINTEPLA is necessary, monitor the patient for reduced efficacy and consider increasing the dosage of FINTEPLA as needed; however, do not exceed the maximum daily dosage of FINTEPLA

    [see Dosage and Administration (2.2)].

    If a strong CYP1A2, CYP2B6, or CYP3A inducer is discontinued during maintenance treatment with FINTEPLA, consider gradual reduction in the FINTEPLA dosage to the dose administered prior to initiating the inducer

    [see Warnings and Precautions (5.6)].

    Strong CYP1A2 or CYP2D6 Inhibitors

    Coadministration of FINTEPLA with strong CYP1A2 or CYP2D6 inhibitors will increase fenfluramine plasma concentrations

    [see Clinical Pharmacology (12.3)]

    . If FINTEPLA is coadministered with strong CYP1A2 or CYP2D6 inhibitors, the maximum daily dosage of FINTEPLA is 20 mg

    [see Dosage and Administration (2.3)].

    If a strong CYP1A2 or CYP2D6 inhibitor is discontinued during maintenance treatment with FINTEPLA, consider gradual increase in the FINTEPLA dosage to the dose recommended without CYP1A2 or CYP2D6 inhibitors; however, do not exceed the maximum daily dosage of FINTEPLA

    [see Dosage and Administration (2.2)].

    If FINTEPLA is coadministered with stiripentol and a strong CYP1A2 or CYP2D6 inhibitor, do not exceed the maximum daily dosage of FINTEPLA of 17 mg

    [see Dosage and Administration (2.3)].
    )
    
    
  • With severe renal impairment (
    
    
    2.4 Dosage Modifications for Patients with Severe Renal Impairment (DS and LGS)

    For patients with severe renal impairment (estimated glomerular filtration rate (eGFR) 15 to 29 mL/min/1.73m²), a maximum total daily dosage of 20 mg without concomitant stiripentol and 17 mg with concomitant stiripentol plus clobazam is recommended

    [see Use in Specific Populations (8.6)]

    .
    ,
    
    
    8.6 Renal Impairment

    In patients with estimated glomerular filtration rate (eGFR) 15 to 29 mL/min/1.73m², do not exceed the maximum daily dosage of FINTEPLA of 20 mg

    .

    In patients with eGFR 15 to 29 ml/min/1.73m²and concomitant stiripentol use, do not exceed the maximum daily dosage of FINTEPLA of 17 mg

    [see Dosage and Administration (2.4)and Clinical Pharmacology (12.3)].

    FINTEPLA has not been studied in patients with eGFR < 15 mL/min/1.73m².
    )
    
    
  • With mild, moderate, and severe hepatic impairment (
    
    
    2.5 Dosage Modifications for Patients with Mild, Moderate, and Severe Hepatic Impairment (DS and LGS)

    See Table 2for dosage adjustments and recommendations for patients with hepatic impairment

    [see Use in Specific Populations (8.7)]

    .

    Table 2: FINTEPLA Dosage Modifications and Recommendations for Patients with Hepatic Impairment

    Hepatic Impairment Classification	Without concomitant stiripentoltitrate as recommended [see Dosage and Administration (2.2)]	With concomitant stiripentol plus clobazam
    	Maximum total daily dosage	Maximum total daily dosage
    Mild (Child-Pugh A)	20 mg	13 mg
    Moderate (Child-Pugh B)	20 mg	Use not recommended
    Severe (Child-Pugh C)	17 mg	Use not recommended
    ,
    
    
    8.7 Hepatic Impairment

    Combined molar exposures of fenfluramine and norfenfluramine were increased in subjects with various degrees of hepatic impairment (Child-Pugh Class A, B, and C), necessitating a dosage adjustment in these patients

    [see Dosage and Administration (2.5)and Clinical Pharmacology (12.3)]

    .
    )
    
    

Oral solution: 2.2 mg/mL fenfluramine as a clear, colorless, cherry flavored liquid.

• Pregnancy: Based on animal data, may cause fetal harm (
  
  
  8.1 Pregnancy

  Pregnancy Exposure Registry

  There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as FINTEPLA, during pregnancy. Encourage women who are taking FINTEPLA during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling the toll-free number 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org.

  Risk Summary

  There are no data on FINTEPLA use in pregnant women. Available data from epidemiologic studies with fenfluramine or dexfenfluramine are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. FINTEPLA can cause decreased appetite and decreased weight

  [see Warnings and Precautions (5.3)];

  monitor for adequate weight gain during pregnancy. In animal studies, administration of fenfluramine throughout organogenesis (rat and rabbit) or throughout gestation and lactation (rat) resulted in adverse effects on development (fetal malformations, embryofetal and offspring mortality and growth impairment) in the presence of maternal toxicity at clinically relevant maternal plasma levels of fenfluramine and its major active metabolite

  (see Data)

  .

  All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

  Clinical Considerations

  Disease-associated Maternal and/or Embryofetal Risk

  Epilepsy, with or without exposure to antiepileptic drugs, has been associated with several adverse outcomes during pregnancy, including preeclampsia, preterm labor, antepartum and postpartum hemorrhage, placental abruption, poor fetal growth, prematurity, fetal death, and maternal mortality. The risk of maternal or fetal injury may be greatest for patients with untreated or poorly controlled convulsive seizures. Women with epilepsy who become pregnant should not abruptly discontinue antiepileptic drugs, including FINTEPLA, due to the risk of status epilepticus or severe seizures, which may be life-threatening

  [see Warnings and Precautions (5.6)].

  Data

  Animal Data

  Oral administration of fenfluramine (0, 4.5, 8.6, or 34.6 mg/kg/day) to pregnant rats during organogenesis resulted in decreased fetal body weights and marked increases in fetal malformations (external, visceral, and skeletal) at the highest dose tested, which was associated with maternal toxicity. At the no-effect dose (8.6 mg/kg/day) for adverse effects on embryofetal development in rats, maternal plasma exposures (AUC) of fenfluramine and norfenfluramine (the major metabolite) were approximately 2 and 5 times, respectively, those in humans at the maximum recommended human dose (MRHD) of 26 mg/day.

  Oral administration of fenfluramine (0, 4.3, 8.6, 13.0 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in increased embryofetal mortality at all doses and increases in fetal malformations (external and skeletal) at the highest dose tested, which was associated with maternal toxicity. A no-adverse-effect dose for adverse effects on embryofetal development in rabbits was not identified. At the lowest dose tested in rabbits (4.3 mg/kg/day), maternal plasma exposures of fenfluramine and norfenfluramine were lower than those in humans at the MRHD.

  Oral administration of fenfluramine (0, 4.3, 8.6, or 34.6 mg/kg/day) to female rats throughout gestation and lactation resulted in marked increases in stillborn pups and neonatal offspring deaths at the highest dose tested and delayed growth and reflex development during the pre- weaning period at all doses. Maternal body weight gain was decreased at all doses during pregnancy and at the two highest doses during lactation. A no-effect dose for adverse effects on pre- and postnatal development in rats was not determined. At the lowest dose tested in rats (4.3 mg/kg/day), maternal plasma exposures of fenfluramine and norfenfluramine were approximately 0.5 and 3 times, respectively, those in humans at the MRHD.
  )