DOSAGE & ADMINISTRATION SECTION

Highlight: * Administer orally in divided doses (3 to 4 times daily). (2.1)

• 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 can be increased by 5 mg daily every 3 to 4 days. (2.1)
  • The maximum single dose is 20 mg. (2.1)
  • Dosage is not to exceed a maximum of 80 mg daily. (2.1)
• 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 can be increased by 2.5 mg daily every 3 to 4 days. (2.1)
  • The maximum single dose is 10 mg. (2.1)
  • Dosage is not to exceed a maximum of 40 mg daily. (2.1)
• 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, 2.2, 2.3, 2.4)
• 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)

2 DOSAGE AND ADMINISTRATION

2.1 Dosage Information

The recommended dosage regimen 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

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 (2.1), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].

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 (2.1), Use in Specific Populations (8.7), and Clinical Pharmacology (12.3)].

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 (2.1), Use in Specific Populations (8.8), and Clinical Pharmacology (12.5)].

2.5 Administration Instructions

FIRDAPSE can be taken without regard to food.

Preparation of a 1mg/mL Suspension (see the Instructions for Use for 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.

---

WARNINGS AND PRECAUTIONS SECTION

Highlight: * Seizures: FIRDAPSE can cause seizures. Consider discontinuation or dose-reduction of FIRDAPSE in patients who have a seizure while on treatment. (5.1)

• Hypersensitivity reactions: If a hypersensitivity reaction such as anaphylaxis occurs, FIRDAPSE should be discontinued and appropriate therapy initiated. (5.2)

5 WARNINGS AND PRECAUTIONS

5.1 Seizures

FIRDAPSE can cause seizures. Seizures have been observed in patients without a history of seizures taking FIRDAPSE at the recommended doses, at various times after initiation of treatment, at an incidence of approximately 2%. Many of the patients were taking medications or had comorbid medical conditions that may have lowered the seizure threshold [see Drug Interactions (7.1)]. Seizures may be dose-dependent. Consider discontinuation or dose-reduction of FIRDAPSE in patients who have a seizure while on treatment. FIRDAPSE is contraindicated in patients with a history of seizures.

5.2 Hypersensitivity

In clinical trials, hypersensitivity reactions and anaphylaxis associated with FIRDAPSE administration have not been reported. Anaphylaxis has been reported in patients taking another aminopyridine; therefore, it may occur with FIRDAPSE. If anaphylaxis occurs, administration of FIRDAPSE should be discontinued and appropriate therapy initiated.

---

INFORMATION FOR PATIENTS SECTION

17 PATIENT COUNSELING INFORMATION

Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Risk of Seizures

Inform patients that FIRDAPSE can cause seizures, and to notify their healthcare provider if they experience a seizure [see Warnings and Precautions (5.1)].

Hypersensitivity

Instruct patients to inform their healthcare provider if they have signs or symptoms of hypersensitivity, and to seek emergency help if symptoms of anaphylaxis occur [see Warnings and Precautions (5.2)].

FIRDAPSE Dosing

Instruct patients to take FIRDAPSE exactly as prescribed. Patients should carefully follow the dose escalation schedule provided by their healthcare provider to safely achieve the therapeutic dosage [see Dosage and Administration (2)]. Inform patients that the tablets may be divided in half at the score, if needed. Instruct patients not to take a double dose to make up for a missed dose. If they require a dosage in less than 5 mg increments, have difficulty swallowing tablets, or require feeding tubes, refer patients and/or caregivers to the Instructions for Use on how to prepare a 1 mg/mL suspension [see Dosage and Administration (2.5)]. If the patient requires treatment with the 1 mg/mL FIRDAPSE suspension, advise patients and/or caregivers that supplies required to prepare the suspension may be obtained at their local pharmacy.

Drug Interactions

Instruct patients to notify their healthcare provider prior to starting any new medication, including over-the-counter drugs [see Drug Interactions (7)].

Pregnancy

Instruct patients that if they are pregnant or plan to become pregnant while taking FIRDAPSE they should inform their healthcare provider. Advise patients that there is a pregnancy registry that monitors pregnancy outcomes in women exposed to FIRDAPSE during pregnancy and encourage them to enroll if they become pregnant while taking FIRDAPSE [see Use in Specific Populations (8.1)].

Storage

Advise patients to store FIRDAPSE at 68ºF to 77ºF (20ºC to 25ºC).

Instruct patients and/or caregivers who prepare the 1 mg/mL suspension of FIRDAPSE that it should be prepared daily and refrigerated between doses. The suspension can be stored under refrigeration for up to 24 hours. Instruct the patient and/or caregiver to discard any unused portion of the suspension after 24 hours.

---

HOW SUPPLIED SECTION

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

FIRDAPSE 10 mg tablets 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. Tablets can be divided in half at the score. FIRDAPSE is supplied as follows:

Child Resistant Blister Pack

• Blister pack containing 10 tablets NDC 69616-211-04
• Carton containing 12 blister packs (120 tablets total) NDC 69616-211-06

Bottles

• 60 tablets NDC 69616-211-08
• 240 tablets NDC 69616-211-03

16.2 Storage and Handling

Store FIRDAPSE tablets at 20°C to 25°C (68°F to 77°F) with excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP controlled room temperature]. See Dosage and Administration (2.5) for storage instructions for FIRDAPSE prepared suspension.

---