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.

GLUCAGEN (NDA-020918)

(GLUCAGON HYDROCHLORIDE)

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

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03/11/2021 (SUPPL-54)

Approved Drug Label (PDF)

4 Contraindications

Additions underlined

Pheochromocytoma because of the risk of substantial increase in blood pressure [see Warnings and Precautions (5.1)]
Insulinoma because of the risk of hypoglycemia [see Warnings and Precautions (5.2)]
Known hypersensitivity to glucagon or the excipients in GlucaGen. Allergic reactions have been reported with glucagon and include anaphylactic shock with breathing difficulties and hypotension [see Warnings and Precautions (5.3)]
Glucagonoma when used as a diagnostic aid because of risk of hypoglycemia [see Warnings and Precautions (5.8)]

5 Warnings and Precautions

5.1 Substantial Increase in Blood Pressure in Patients with Pheochromocytoma

Additions underlined

GlucaGen is contraindicated in patients with pheochromocytoma because GlucaGen may stimulate the release of catecholamines from the tumor [see Contraindications (4)]. If the patient develops a substantial increase in blood pressure and a previously undiagnosed pheochromocytoma is suspected, 5 to 10 mg of phentolamine mesylate, administered intravenously, has been shown to be effective in lowering blood pressure for the short time that control would be needed.

5.2 Hypoglycemia in Patients with Insulinoma

Additions underlined

In patients with insulinoma, administration of glucagon may produce an initial increase in blood glucose; however, GlucaGen administration may directly or indirectly (through an initial rise in blood glucose) stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia. GlucaGen is contraindicated in patients with insulinoma [see Contraindications (4)]. If a patient develops symptoms of hypoglycemia after a dose of GlucaGen, give glucose orally or intravenously.

5.3 Hypersensitivity and Allergic Reactions

Additions underlined

Allergic reactions have been reported with glucagon, these include generalized rash, and in some cases anaphylactic shock with breathing difficulties and hypotension. GlucaGen is contraindicated in patients with a prior hypersensitivity reaction [see Contraindications (4)].

5.4 Lack of Efficacy in Patients with Decreased Hepatic Glycogen

Additions underlined

GlucaGen is effective in treating hypoglycemia only if sufficient hepatic glycogen is present. Patients in states of starvation, with adrenal insufficiency or chronic hypoglycemia may not have adequate levels of hepatic glycogen for GlucaGen administration to be effective. Patients with these conditions should be treated with glucose

5.6 Hyperglycemia in Patients with Diabetes Mellitus when Used as a Diagnostic Aid

New subsection added

Treatment with GlucaGen in patients with diabetes mellitus may cause hyperglycemia. Monitor diabetic patients for changes in blood glucose levels during treatment and treat if indicated.

5.7 Blood Pressure and Heart Rate Increase in Patients with Cardiac Disease

Additions underlined

GlucaGen may increase myocardial oxygen demand, blood pressure, and pulse rate which may be life-threatening in patients with cardiac disease. Cardiac monitoring is recommended in patients with cardiac disease during use of GlucaGen as a diagnostic aid, and an increase in blood pressure and pulse rate may require therapy.

5.8 Hypoglycemia in Patients with Glucagonoma

New subsection added

Glucagon administered to patients with glucagonoma may cause secondary hypoglycemia. Test patients suspected of having glucagonoma for blood levels of glucagon prior to use as a diagnostic aid as GlucaGen is contraindicated in this setting [see Contraindications (4)].

6 Adverse Reactions

Section updated to conform with class labeling and current labeling practices; please refer to label for complete information.

7 Drug Interactions

Section updated to conform with class labeling and current labeling practices; please refer to Table 1 in label for complete information.

8 Use in Specific Populations

8.1 Pregnancy

PLLR conversion

Risk Summary

Available data from case reports and a small number of observational studies with glucagon use in pregnant women over decades of use have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Multiple small studies have demonstrated a lack of transfer of pancreatic glucagon across the human placental barrier during early gestation. In rat and rabbit reproduction studies, no embryofetal toxicity was observed with glucagon administered by injection during the period of organogenesis at doses representing up to 100 and 200 times the human dose, respectively, based on body surface area (mg/m2) (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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.

Data

Animal Data

In rats and rabbits given glucagon by injection at doses of 0.4, 2, and 10 mg/kg (up to 100 and 200 times the human dose based on mg/m2 for rats and rabbits, respectively) there was no evidence of increased malformations or embryofetal lethality.

8.2 Lactation

PLLR conversion

Risk Summary

There is no information available on the presence of glucagon in human or animal milk, the effects of glucagon on the breastfed child or the effects of glucagon on milk production.

However, glucagon is a peptide and would be expected to be broken down to its constituent amino acids in the infant's digestive tract and is therefore, unlikely to cause harm to an exposed infant.

8.4 Pediatric Use

Additions underlined

The safety and effectiveness of GlucaGen for the treatment of severe hypoglycemia in pediatric patients with diabetes have been established.

Safety and effectiveness for use as a diagnosic aid during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract in pediatric patients have not been established.

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

PATIENT COUNSELING INFORMATION

Section updated to conform with class labeling and current labeling practices.

Advise the patient to read the FDA-approved (Patient Information and Instructions for Use).

Recognition of Severe Hypoglycemia

Inform patient and family members or caregivers on how to recognize the signs and symptoms of severe hypoglycemia and the risks of prolonged hypoglycemia.

Administration

Review the Patient Information and Instructions for Use with the patient and family members or caregivers.

Serious Hypersensitivity

Inform patients that allergic reactions can occur with GlucaGen. Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions (5.3)].

PATIENT INFORMATION

Section updated to conform with class labeling and current labeling practices; please refer to label for complete information.

07/06/2018 (SUPPL-52)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.5 Necrolytic Migratory Erythema

(Newly Added Subsection)

Necrolytic migratory erythema (NME), a skin rash commonly associated with glucagonomas (glucagon-producing tumors) and characterized by scaly, pruritic erythematous plaques, bullae, and erosions, has been reported postmarketing following continuous glucagon infusion. NME lesions may affect the face, groin, perineum and legs or be more widespread. In the reported cases NME resolved with discontinuation of the glucagon, and treatment with corticosteroids was not effective. Should NME occur, consider whether the benefits of continuous glucagon infusion outweigh the risks.

6 Adverse Reactions

(Additions and/or revisions are underlined)

The following important adverse reactions are described below and elsewhere in the labeling:

Hypersensitivity and Allergic Reactions

Necrolytic Migratory Erythema

Necrolytic migratory erythema (NME) cases have been reported postmarketing in patients receiving continuous infusion of glucagon.