Drug Safety-related Labeling Changes (SrLC)

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Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

FIRDAPSE (NDA-208078)

(AMIFAMPRIDINE PHOSPHATE)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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05/30/2024 (SUPPL-12)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

Adults

…

In controlled and uncontrolled clinical trials (Study 1 and 2) in patients with LEMS [see Clinical Studies (14)], 63 patients were treated with FIRDAPSE, including 40 patients treated for more than 6 months, and 39 patients treated for more than 12 months. In an expanded access program, 139 patients with LEMS were treated with FIRDAPSE, including 102 patients treated for more than 6 months, 77 patients treated for more than 12 months, and 53 patients treated for more than 18 months. In the expanded access program, patients were treated with FIRDAPSE with up to 100 mg daily in divided doses.

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

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.

05/15/2023 (SUPPL-9)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.4 Hepatic Impairment

(Additions and/or revisions underlined)

In patients with any degree of hepatic impairment, FIRDAPSE should be initiated at the lowest recommended initial daily dosage, and patients should be monitored for adverse reactions [see Dosage and Administration (2.3)]. Consider dosage modification or discontinuation of FIRDAPSE for patients with hepatic impairment as needed based on clinical effect and tolerability.

09/29/2022 (SUPPL-8)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined

…

Pediatrics

Safety of FIRDAPSE was evaluated in pediatric patients in an expanded access program, where 21 pediatric patients received FIRDAPSE for at least 1 year. Adverse reactions reported in pediatric patients were similar to those seen in adult patients, with the exception of clinically significant weight loss in two pediatric patients at doses of 60 mg per day and higher.

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined

Safety and effectiveness of FIRDAPSE for the treatment of LEMS have been established in pediatric patients 6 years of age and older. Use of FIRDAPSE for this indication is supported by evidence from adequate and well-controlled studies of FIRDAPSE in adults with LEMS, pharmacokinetic data in adult patients, pharmacokinetic modeling and simulation to identify the dosing regimen in pediatric patients, and safety data from pediatric patients aged 6 years and older [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14)].

Safety and effectiveness in pediatric patients below the age of 6 years have not been established.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined

…

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.

…

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.

MEDICATION GUIDE

Additions and/or revisions underlined

…

What is FIRDAPSE?

FIRDAPSE is a prescription medicine used to treat Lambert-Eaton myasthenic syndrome (LEMS) in people 6 years of age and older.

It is not known if FIRDAPSE is safe or effective in children less than 6 years of age.

…

How should I take FIRDAPSE?

If your dose is less than 5mg, you have trouble swallowing tablets, or a feeding tube is needed, see the detailed Instructions for Use on how to take and prepare a suspension of FIRDAPSE.
Take FIRDAPSE exactly as your doctor tells you to take it.
Do not change your dose of FIRDAPSE.
Do not stop taking FIRDAPSE without first talking to your doctor.
FIRDAPSE tablets are scored and can be split if less than a full tablet is need for you to get the right dose.
…
How should I store FIRDAPSE?

Store FIRDAPSE tablets at room temperature between 68ºF to 77ºF (20ºC to 25ºC).
Safely throw away FIRDAPSE tablets that are out of date or no longer needed.
Store FIRDAPSE prepared oral suspension in the refrigerator between 36°F to 46°F (2°C to 8°C) between doses for up to 24 hours.
Safely throw away unused FIRDAPSE oral suspension after 24 hours.
Keep FIRDAPSE and all medicines out of the reach of children.
…

03/01/2021 (SUPPL-7)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Hypersensitivity

Additions and/or revisions underlined:

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.

6 Adverse Reactions

6.1 Clinical Trials Experience

Table 1. Adverse Reactions in greater than or equal to 5% of LEMS Patients Newly Treated with

FIRDAPSE in Study 1

Comment referring to ‘Elevated liver enzymes’ is newly added under the table:

** Includes elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and gamma-glutamyl transferase (GGT)

8 Use in Specific Populations

8.1 Pregnancy

Newly added information:

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.

Newly added subtitle:

8.5 Geriatric Use

Clinical studies of FIRDAPSE did not include sufficient numbers of subjects aged 65 and over (19 of 63 patients in Studies 1 and 2) to determine whether they respond differently from younger subjects …

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

Additions and/or revisions underlined:

PATIENT COUNSELING INFORMATION

Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide) …

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)].

MEDICATION GUIDE

Before you take FIRDAPSE, tell your doctor about all of your medical conditions.

including if you:

Newly added information:

There is a registry for women who become pregnant during treatment with FIRDAPSE. The purpose of this registry is to collect information about your health and your baby’s health. Contact the registry as soon as you learn that you are pregnant, or ask your healthcare provider to contact for you by calling 855-212-5856 (toll free), contacting the Fax number 877-867-1874 (toll free), emailing the Pregnancy Coordinating Center at firdapsepregnancyregistry@ubc.com, or visiting the study website www.firdapsepregnancystudy.com.