Firdapse

FIRDAPSE^® is indicated for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in adults and pediatric patients 6 years of age and older.

• Administer orally in divided doses (3 to 5 times daily). (
  2.1 Dosage Information

  The recommended oral dosage of FIRDAPSE for adults and pediatric patients 6 years of age and older is included in Table 1. For pediatric patients, the recommended dosing regimen is dependent on body weight. Dosage should be increased every 3 to 4 days based on clinical response and tolerability. Titration increments should not exceed those shown in Table 1.

  Table 1: Recommended Oral Dosage for the Treatment of LEMS in Adults and Pediatric Patients 6 Years of Age and Older

  * See Dosage and Administration for a method to achieve these doses
  Age and Body Weight	Initial Daily Dosage *	Titration Regimen	Maximum Single Dose	Maximum Total Daily Maintenance Dosage
  Adults (any weight) Pediatric patients weighing 45 kg or more	15 mg to 30 mg daily, in 3 to 5 divided doses	Increase total daily dosage by 5 mg every 3 or 4 days	20 mg	100 mg Given in divided doses
  Pediatric patients weighing less than 45 kg	5 mg to 15 mg daily, in 3 to 5 divided doses	Increase total daily dosage by 2.5 mg every 3 or 4 days	10 mg	50 mg Given in divided doses

  Missed Dose

  If a dose is missed, patients should not take double or extra doses.
  )
• The recommended starting dosage for adults (any weight) and pediatric patients weighing 45 kg or more is 15 mg to 30 mg daily, in divided doses. (
  2.1 Dosage Information

  The recommended oral dosage of FIRDAPSE for adults and pediatric patients 6 years of age and older is included in Table 1. For pediatric patients, the recommended dosing regimen is dependent on body weight. Dosage should be increased every 3 to 4 days based on clinical response and tolerability. Titration increments should not exceed those shown in Table 1.

  Table 1: Recommended Oral Dosage for the Treatment of LEMS in Adults and Pediatric Patients 6 Years of Age and Older

  * See Dosage and Administration for a method to achieve these doses
  Age and Body Weight	Initial Daily Dosage *	Titration Regimen	Maximum Single Dose	Maximum Total Daily Maintenance Dosage
  Adults (any weight) Pediatric patients weighing 45 kg or more	15 mg to 30 mg daily, in 3 to 5 divided doses	Increase total daily dosage by 5 mg every 3 or 4 days	20 mg	100 mg Given in divided doses
  Pediatric patients weighing less than 45 kg	5 mg to 15 mg daily, in 3 to 5 divided doses	Increase total daily dosage by 2.5 mg every 3 or 4 days	10 mg	50 mg Given in divided doses

  Missed Dose

  If a dose is missed, patients should not take double or extra doses.
  )
  • Dosage can be increased by 5 mg daily every 3 to 4 days. (
    2.1 Dosage Information

    The recommended oral dosage of FIRDAPSE for adults and pediatric patients 6 years of age and older is included in Table 1. For pediatric patients, the recommended dosing regimen is dependent on body weight. Dosage should be increased every 3 to 4 days based on clinical response and tolerability. Titration increments should not exceed those shown in Table 1.

    Table 1: Recommended Oral Dosage for the Treatment of LEMS in Adults and Pediatric Patients 6 Years of Age and Older

    * See Dosage and Administration for a method to achieve these doses
    Age and Body Weight	Initial Daily Dosage *	Titration Regimen	Maximum Single Dose	Maximum Total Daily Maintenance Dosage
    Adults (any weight) Pediatric patients weighing 45 kg or more	15 mg to 30 mg daily, in 3 to 5 divided doses	Increase total daily dosage by 5 mg every 3 or 4 days	20 mg	100 mg Given in divided doses
    Pediatric patients weighing less than 45 kg	5 mg to 15 mg daily, in 3 to 5 divided doses	Increase total daily dosage by 2.5 mg every 3 or 4 days	10 mg	50 mg Given in divided doses

    Missed Dose

    If a dose is missed, patients should not take double or extra doses.
    )
  • The maximum single dose is 20 mg. (
    2.1 Dosage Information

    The recommended oral dosage of FIRDAPSE for adults and pediatric patients 6 years of age and older is included in Table 1. For pediatric patients, the recommended dosing regimen is dependent on body weight. Dosage should be increased every 3 to 4 days based on clinical response and tolerability. Titration increments should not exceed those shown in Table 1.

    Table 1: Recommended Oral Dosage for the Treatment of LEMS in Adults and Pediatric Patients 6 Years of Age and Older

    * See Dosage and Administration for a method to achieve these doses
    Age and Body Weight	Initial Daily Dosage *	Titration Regimen	Maximum Single Dose	Maximum Total Daily Maintenance Dosage
    Adults (any weight) Pediatric patients weighing 45 kg or more	15 mg to 30 mg daily, in 3 to 5 divided doses	Increase total daily dosage by 5 mg every 3 or 4 days	20 mg	100 mg Given in divided doses
    Pediatric patients weighing less than 45 kg	5 mg to 15 mg daily, in 3 to 5 divided doses	Increase total daily dosage by 2.5 mg every 3 or 4 days	10 mg	50 mg Given in divided doses

    Missed Dose

    If a dose is missed, patients should not take double or extra doses.
    )
  • Dosage is not to exceed a maximum of 100 mg daily. (
    2.1 Dosage Information

    The recommended oral dosage of FIRDAPSE for adults and pediatric patients 6 years of age and older is included in Table 1. For pediatric patients, the recommended dosing regimen is dependent on body weight. Dosage should be increased every 3 to 4 days based on clinical response and tolerability. Titration increments should not exceed those shown in Table 1.

    Table 1: Recommended Oral Dosage for the Treatment of LEMS in Adults and Pediatric Patients 6 Years of Age and Older

    * See Dosage and Administration for a method to achieve these doses
    Age and Body Weight	Initial Daily Dosage *	Titration Regimen	Maximum Single Dose	Maximum Total Daily Maintenance Dosage
    Adults (any weight) Pediatric patients weighing 45 kg or more	15 mg to 30 mg daily, in 3 to 5 divided doses	Increase total daily dosage by 5 mg every 3 or 4 days	20 mg	100 mg Given in divided doses
    Pediatric patients weighing less than 45 kg	5 mg to 15 mg daily, in 3 to 5 divided doses	Increase total daily dosage by 2.5 mg every 3 or 4 days	10 mg	50 mg Given in divided doses

    Missed Dose

    If a dose is missed, patients should not take double or extra doses.
    )
• The recommended starting dosage for pediatric patients weighing less than 45 kg is 5 mg to 15 mg daily, in divided doses. (
  2.1 Dosage Information

  The recommended oral dosage of FIRDAPSE for adults and pediatric patients 6 years of age and older is included in Table 1. For pediatric patients, the recommended dosing regimen is dependent on body weight. Dosage should be increased every 3 to 4 days based on clinical response and tolerability. Titration increments should not exceed those shown in Table 1.

  Table 1: Recommended Oral Dosage for the Treatment of LEMS in Adults and Pediatric Patients 6 Years of Age and Older

  * See Dosage and Administration for a method to achieve these doses
  Age and Body Weight	Initial Daily Dosage *	Titration Regimen	Maximum Single Dose	Maximum Total Daily Maintenance Dosage
  Adults (any weight) Pediatric patients weighing 45 kg or more	15 mg to 30 mg daily, in 3 to 5 divided doses	Increase total daily dosage by 5 mg every 3 or 4 days	20 mg	100 mg Given in divided doses
  Pediatric patients weighing less than 45 kg	5 mg to 15 mg daily, in 3 to 5 divided doses	Increase total daily dosage by 2.5 mg every 3 or 4 days	10 mg	50 mg Given in divided doses

  Missed Dose

  If a dose is missed, patients should not take double or extra doses.
  )
  • Dosage can be increased by 2.5 mg daily every 3 to 4 days. (
    2.1 Dosage Information

    The recommended oral dosage of FIRDAPSE for adults and pediatric patients 6 years of age and older is included in Table 1. For pediatric patients, the recommended dosing regimen is dependent on body weight. Dosage should be increased every 3 to 4 days based on clinical response and tolerability. Titration increments should not exceed those shown in Table 1.

    Table 1: Recommended Oral Dosage for the Treatment of LEMS in Adults and Pediatric Patients 6 Years of Age and Older

    * See Dosage and Administration for a method to achieve these doses
    Age and Body Weight	Initial Daily Dosage *	Titration Regimen	Maximum Single Dose	Maximum Total Daily Maintenance Dosage
    Adults (any weight) Pediatric patients weighing 45 kg or more	15 mg to 30 mg daily, in 3 to 5 divided doses	Increase total daily dosage by 5 mg every 3 or 4 days	20 mg	100 mg Given in divided doses
    Pediatric patients weighing less than 45 kg	5 mg to 15 mg daily, in 3 to 5 divided doses	Increase total daily dosage by 2.5 mg every 3 or 4 days	10 mg	50 mg Given in divided doses

    Missed Dose

    If a dose is missed, patients should not take double or extra doses.
    )
  • The maximum single dose is 10 mg. (
    2.1 Dosage Information

    The recommended oral dosage of FIRDAPSE for adults and pediatric patients 6 years of age and older is included in Table 1. For pediatric patients, the recommended dosing regimen is dependent on body weight. Dosage should be increased every 3 to 4 days based on clinical response and tolerability. Titration increments should not exceed those shown in Table 1.

    Table 1: Recommended Oral Dosage for the Treatment of LEMS in Adults and Pediatric Patients 6 Years of Age and Older

    * See Dosage and Administration for a method to achieve these doses
    Age and Body Weight	Initial Daily Dosage *	Titration Regimen	Maximum Single Dose	Maximum Total Daily Maintenance Dosage
    Adults (any weight) Pediatric patients weighing 45 kg or more	15 mg to 30 mg daily, in 3 to 5 divided doses	Increase total daily dosage by 5 mg every 3 or 4 days	20 mg	100 mg Given in divided doses
    Pediatric patients weighing less than 45 kg	5 mg to 15 mg daily, in 3 to 5 divided doses	Increase total daily dosage by 2.5 mg every 3 or 4 days	10 mg	50 mg Given in divided doses

    Missed Dose

    If a dose is missed, patients should not take double or extra doses.
    )
  • Dosage is not to exceed a maximum of 50 mg daily. (
    2.1 Dosage Information

    The recommended oral dosage of FIRDAPSE for adults and pediatric patients 6 years of age and older is included in Table 1. For pediatric patients, the recommended dosing regimen is dependent on body weight. Dosage should be increased every 3 to 4 days based on clinical response and tolerability. Titration increments should not exceed those shown in Table 1.

    Table 1: Recommended Oral Dosage for the Treatment of LEMS in Adults and Pediatric Patients 6 Years of Age and Older

    * See Dosage and Administration for a method to achieve these doses
    Age and Body Weight	Initial Daily Dosage *	Titration Regimen	Maximum Single Dose	Maximum Total Daily Maintenance Dosage
    Adults (any weight) Pediatric patients weighing 45 kg or more	15 mg to 30 mg daily, in 3 to 5 divided doses	Increase total daily dosage by 5 mg every 3 or 4 days	20 mg	100 mg Given in divided doses
    Pediatric patients weighing less than 45 kg	5 mg to 15 mg daily, in 3 to 5 divided doses	Increase total daily dosage by 2.5 mg every 3 or 4 days	10 mg	50 mg Given in divided doses

    Missed Dose

    If a dose is missed, patients should not take double or extra doses.
    )
• The recommended starting dosage for adult and pediatric patients with renal impairment, hepatic impairment, and in known N-acetyltransferase 2 (NAT2) poor metabolizers is the lowest recommended initial daily dosage (
  2.1 Dosage Information

  The recommended oral dosage of FIRDAPSE for adults and pediatric patients 6 years of age and older is included in Table 1. For pediatric patients, the recommended dosing regimen is dependent on body weight. Dosage should be increased every 3 to 4 days based on clinical response and tolerability. Titration increments should not exceed those shown in Table 1.

  Table 1: Recommended Oral Dosage for the Treatment of LEMS in Adults and Pediatric Patients 6 Years of Age and Older

  * See Dosage and Administration for a method to achieve these doses
  Age and Body Weight	Initial Daily Dosage *	Titration Regimen	Maximum Single Dose	Maximum Total Daily Maintenance Dosage
  Adults (any weight) Pediatric patients weighing 45 kg or more	15 mg to 30 mg daily, in 3 to 5 divided doses	Increase total daily dosage by 5 mg every 3 or 4 days	20 mg	100 mg Given in divided doses
  Pediatric patients weighing less than 45 kg	5 mg to 15 mg daily, in 3 to 5 divided doses	Increase total daily dosage by 2.5 mg every 3 or 4 days	10 mg	50 mg Given in divided doses

  Missed Dose

  If a dose is missed, patients should not take double or extra doses.
  ,
  2.2 Patients with Renal Impairment

  The recommended starting dosage of FIRDAPSE in patients with renal impairment [creatinine clearance (CLcr) 15 to 90 mL/min] is the lowest recommended initial daily dosage (i.e., 15 mg daily for pediatric patients weighing 45 kg or more and for adults, and 5 mg daily for pediatric patients weighing less than 45 kg) taken orally in divided doses. No dosage recommendation for FIRDAPSE can be made for patients with end-stage renal disease

  [see Dosage and Administration , Use in Specific Populations , and Clinical Pharmacology ].
  ,
  2.3 Patients with Hepatic Impairment

  The recommended starting dosage of FIRDAPSE in patients with any degree of hepatic impairment is the lowest recommended initial daily dosage (i.e., 15 mg daily for pediatric patients weighing 45 kg or more and for adults, and 5 mg daily for pediatric patients weighting less than 45 kg) taken orally in divided doses

  [see Dosage and Administration , Use in Specific Populations , and Clinical Pharmacology ].
  ,
  2.4 Known N-acetyltransferase 2 (NAT2) Poor Metabolizers

  The recommended starting dosage of FIRDAPSE in known N-acetyltransferase 2 (NAT2) poor metabolizers is the lowest recommended initial daily dosage (i.e., 15 mg daily for pediatric patients weighing 45 kg or more and for adults, and 5 mg daily for pediatric patients weighing less than 45 kg) taken orally in divided doses

  [see Dosage and Administration , Use in Specific Populations , and Clinical Pharmacology ].
  )
• For patients with a dosage adjustment of less than 5 mg increments, or who have difficulty swallowing, or require feeding tube, a l mg/mL suspension can be prepared. (
  2.5 Administration Instructions

  FIRDAPSE can be taken without regard to food.

  Preparation of a 1mg/mL Suspension

  (see the Instructions for Usefor full instructions on how to prepare the 1mg/mL suspension)

  When patients require a dosage in less than 5 mg increments, have difficulty swallowing tablets, or require feeding tubes, a 1 mg/mL suspension can be prepared (e.g., by placing the required number of tablets in a 50 to 100 mL container, adding 10 mL of sterile water for each tablet, waiting for 5 minutes, and shaking well for 30 seconds).

  Crushing the tablets prior to making the suspension is not necessary. After preparation of the suspension, an oral syringe can be used to draw up and administer the correct dose by mouth or by feeding tube.

  Storage of 1mg/mL Prepared Suspension

  Refrigerate the suspension between doses and shake well before drawing up each dose. The suspension can be stored under refrigeration [between 2°C and 8°C (36°F and 46°F)] for up to 24 hours. Discard any unused portion of the suspension after 24 hours.
  )

FIRDAPSE tablets contain 10 mg amifampridine and are white to off-white, round, and functionally scored. Each tablet is debossed on the non-scored side with “CATALYST” and on the scored side with “211” above the score and “10” below the score.

• 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 FIRDAPSE during pregnancy. Physicians are encouraged to enroll pregnant patients, or pregnant women may register themselves in the registry by calling 855- 212-5856 (toll-free), using the Fax number 877-867-1874 (toll-free), by contacting the Pregnancy Coordinating Center at firdapsepregnancyregistry@ubc.com, or by visiting the study website www.firdapsepregnancystudy.com.

  Risk Summary

  There are no data on the developmental risk associated with the use of FIRDAPSE in pregnant women. In animal studies, administration of amifampridine phosphate to rats during pregnancy and lactation resulted in developmental toxicity (increase in stillbirths and pup deaths, reduced pup weight, and delayed sexual development) at doses associated with maternal plasma drug levels lower than therapeutic drug levels (see Animal Data). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

  Data

  Animal Data

  Oral administration of amifampridine phosphate (0, 7.5, 22.5, or 75 mg/kg/day) to female rats prior to and during mating and continuing throughout organogenesis produced no adverse effects on embryofetal development. The highest dose tested is approximately 4 times the maximum recommended human dose (MRHD) of amifampridine (100 mg/day) on a body surface area (mg/m²) basis. Oral administration of amifampridine phosphate (0, 9, 30, or 57 mg/kg/day) to pregnant rabbits throughout organogenesis produced no adverse effects on embryofetal development. The highest dose tested is approximately 6 times the MRHD of amifampridine on a body surface area (mg/m²) basis.

  Oral administration of amifampridine phosphate (0, 7.5, 22.5, or 75 mg/kg/day) to female rats throughout pregnancy and lactation resulted in an increase in stillbirths and pup deaths, reduced pup weight, and delayed sexual development in female pups at the mid and high doses tested. The no-effect dose (7.5 mg/kg/day amifampridine phosphate) for adverse developmental effects is associated with a plasma amifampridine exposure (AUC) less than that in humans at the MRHD of amifampridine.
  )