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.

FIRMAGON (NDA-022201)

(DEGARELIX ACETATE)

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

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02/24/2020 (SUPPL-16)

Approved Drug Label (PDF)

4 Contraindications

(subsection revised, additions underlined)

FIRMAGON is contraindicated in patients with history of severe hypersensitivity to degarelix or to any of the product components.

5 Warnings and Precautions

5.1 Hypersensitivity Reactions

(additions underlined)

FIRMAGON is contraindicated in patients with history of severe hypersensitivity to degarelix or to any of the product components.

…

5.4 Embryo-Fetal Toxicity

(new subsection added)

Based on findings in animal studies, FIRMAGON can cause fetal harm and loss of pregnancy when administered to a pregnant woman. In animal developmental and reproductive toxicity studies in rats and rabbits, oral administration of degarelix during organogenesis caused embryo-fetal lethality and abortion as well as increased post-implantation loss and decreased the number of live fetuses in animals at doses less than the clinical loading dose based on body surface area. Advise pregnant patients and females of reproductive potential of the potential risk to the fetus.

6 Adverse Reactions

6.1 Clinical Trials Experience

(new subsection added, please refer to label for complete information)

6.2 Immunogenicity

(new subsection added, additions underlined)

As with all peptides, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.

Anti-Degarelix Antibodies

Anti-degarelix antibody development has been observed in 10% of patients after treatment with FIRMAGON for 1 year. There is no indication that the efficacy or safety of FIRMAGON treatment is affected by antibody formation.

6.3 Postmarketing Experience

(new subsection added, additions underlined)

The following adverse reactions have been identified during post-approval use of FIRMAGON. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Changes in bone density

Decreased bone density has been reported in the medical literature in men who have had orchiectomy or who have been treated with a GnRH agonist. It can be anticipated that long periods of medical castration in men will result in decreased bone density.

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion)

Risk Summary

The safety and efficacy of FIRMAGON have not been established in women.

Based on findings in animal studies and mechanism of action, FIRMAGON can cause fetal harm and loss of pregnancy when administered to a pregnant woman. There are no human data on the use of FIRMAGON in pregnant women to inform the drug-associated risk. In animal developmental and reproductive toxicity studies in rats and rabbits, oral administration of degarelix during organogenesis caused embryo-fetal lethality and abortion as well as increased post-implantation loss and decreased the number of live fetuses in animals at doses less than the clinical loading dose based on body surface area (see Data). Advise pregnant patients and females of reproductive potential of the potential risk to the fetus.

Data

Animal Data

When degarelix was given to rabbits during early organogenesis at doses of 0.002 mg/kg/day (about 0.02% of the clinical loading dose based on body surface area), there was an increase in early post-implantation loss. Degarelix given to rabbits during mid and late organogenesis at doses of 0.006 mg/kg/day (about 0.05% of the clinical loading dose based on body surface area) caused embryo/fetal lethality and abortion. When degarelix was given to female rats during early organogenesis, at doses of 0.0045 mg/kg/day (about 0.036% of the clinical loading dose based on body surface area), there was an increase in early post-implantation loss. When degarelix was given to female rats during mid and late organogenesis, at doses of 0.045 mg/kg/day (about 0.36% of the clinical loading dose based on body surface area), there was an increase in the number of minor skeletal abnormalities and variants.

8.2 Lactation

(PLLR conversion)

The safety and efficacy of FIRMAGON have not been established in females. There are no data on the presence of degarelix in human milk, the effects on the breastfed child, or the effects on milk production. Because many drugs are present in human milk and because of the potential for serious adverse reactions in a breastfed child from degarelix, a decision should be made whether to discontinue nursing or discontinue the drug taking into account the importance of the drug to the mother.

8.3 Females and Males of Reproductive Potential

(PLLR conversion)

Infertility

Based on findings in animals and mechanism of action, degarelix may impair fertility in males and females of reproductive potential.

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

PATIENT COUNSELING INFORMATION

(section revised, additions underlined)

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Hypersensitivity

Inform patients that if they have experienced severe hypersensitivity with degarelix or to any of the product components, FIRMAGON is contraindicated. Instruct patients to immediately report signs of a severe hypersensitivity reaction.
QT Interval Prolongation
Advise patients that androgen deprivation therapy treatment with FIRMAGON may prolong the QT interval. Inform patients of the signs and symptoms of QT prolongation. Advise patients to contact their healthcare provider immediately for signs or symptoms of QT prolongation.
Androgen Deprivation
Inform patients about adverese reactions related to androgen deprivation therapy with FIRMAGON, including hot flashes, flushing of the skin, increased weight, decreased sex drive, and difficulties with erectile function.
Injection Site Reactions
Inform patients that FIRMAGON may cause redness, swelling, and itching at the injection site. Advise patients that these adverse reactions are usually mild, self limiting, and decrease within three days.
Infertility
Inform patients that FIRMAGON may cause infertility.

PATIENT INFORMATION

(additions underlined)

…

Before receiving FIRMAGON, tell your healthcare provider about all your medical conditions, including if you:

…

are pregnant or plan to become pregnant. FIRMAGON can cause harm to your unborn baby and loss of pregnancy (miscarriage)

…