Drug Safety-related Labeling Changes (SrLC)
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Guide
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.
ADRENACLICK (NDA-020800)
(EPINEPHRINE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
03/19/2026 (SUPPL-54)
5 Warnings and Precautions
5.1 Injection-Related Complications
Additions and/or revisions underlined:
…
Do not inject into buttock
Injection into the buttock may not provide effective treatment of anaphylaxis. If Epinephrine Injection is injected into the buttock, advise the patient to administer a second dose of Epinephrine Injection into the anterolateral aspect of the thigh if symptoms worsen or persist, and then go immediately to the nearest emergency room for further treatment of anaphylaxis. Additionally, injection into the buttock has been associated with the development of Clostridial infections (gas gangrene). Cleansing with alcohol does not kill bacterial spores, and therefore, does not lower the risk.
Do not inject into digits, hands or feet
Since epinephrine is a strong vasoconstrictor, accidental injection into the digits, hands or feet may result in loss of blood flow to the affected area and may not provide effective treatment of anaphylaxis. Advise the patient to administer a second dose of Epinephrine Injection into the anterolateral aspect of the thigh if experiencing anaphylaxis, and then go immediately to the nearest emergency room and inform the healthcare provider in the emergency room of the location of the accidental injection. Treatment of such inadvertent administration should consist of vasodilation, in addition to further appropriate treatment of anaphylaxis [see Adverse Reactions (6)].
Hold leg firmly during injection
To minimize the risk of injection related injury when administering Epinephrine Injection to young children or infants, instruct caregivers to hold the child’s leg firmly in place and limit movement prior to and during injection.
5.3 Risks Associated with Use of Epinephrine in Certain Coexisting Conditions
Additions and/or revisions underlined:
…
Epinephrine can temporarily exacerbate the underlying condition or increase symptoms in patients with the following: hyperthyroidism, Parkinson’s disease, diabetes, renal impairment.
Administer epinephrine with caution in patients with these conditions, including elderly patients and pregnant women.
8 Use in Specific Populations
8.1 Pregnancy
Additions and/or revisions underlined:
Prolonged experience with epinephrine use in pregnant women over several decades, based on published literature, have not identified a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with anaphylaxis, and treatment with epinephrine should not be delayed (see Clinical Considerations). In animal reproduction studies, epinephrine administered by the subcutaneous route to pregnant rabbits, mice, and hamsters, during the period of organogenesis was teratogenic at doses 7 times and higher than the maximum recommended human intramuscular and subcutaneous dose on a mg/m2 basis (see Data).
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
…
8.2 Lactation
Addition and/or revisions underlined:
Risk Summary
There is no information on the presence of epinephrine in human milk, the effects on the breastfed infants, or the effects on milk production. However, due to its poor oral bioavailability and short half-life, transfer of epinephrine into breastmilk is expected to be low. Treatment of anaphylaxis in breastfeeding patients should not be delayed.
8.4 Pediatric Use
Additions and/or revisions underlined:
The safety and effectiveness of Epinephrine Injection for the emergency treatment of type I allergic reactions, including anaphylaxis have been established in pediatric patients who weigh 15 kg or greater. The use of Epinephrine Injection for this indication is supported by clinical experience. Clinical experience with the use of epinephrine suggests that the adverse reactions seen in pediatric patients are similar in nature and extent to those both expected and reported in adults. Since the doses of epinephrine delivered from Epinephrine Injection are fixed, use other forms of injectable epinephrine if doses lower than 0.15 mg are deemed necessary.
The safety and effectiveness of Epinephrine Injection have not been established in pediatric patients who weigh less than 15 kg.
8.5 Geriatric Use
Additions and/or revisions underlined:
Clinical studies of Epinephrine Injection for emergency treatment of type I allergic reactions, including anaphylaxis, were not conducted in geriatric patients aged 65 and over to determine whether they respond differently from younger adult patients. However, other reported clinical experience with use of epinephrine for the treatment of anaphylaxis has identified that geriatric patients may be particularly sensitive to the effects of epinephrine. Therefore, these patients may be at greater risk for developing adverse reactions after epinephrine administration
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or revisions underlined:
…
Administration
Each Epinephrine Injection contains a single dose of epinephrine for single use.
Instruct patients and/or caregivers to inspect the epinephrine solution visually through the viewing window periodically. Epinephrine Injection should be replaced if the epinephrine solution appears discolored, cloudy, or contains particles.
Instruct patients and/or caregivers on proper intramuscular or subcutaneous injection technique using the Epinephrine Injection Trainer. A Trainer device is not provided with epinephrine injection. Patients and/or caregivers may obtain a Trainer device at www.epinephrineautoinject.com. Instructions for use of the Trainer device are provided on the Trainer label. Instruct patients and/or caregivers to use the Trainer to familiarize themselves with the use of epinephrine injection in an allergic emergency. The Trainer device may be used multiple times.
For additional video instructions on the use of epinephrine injection, go to www.epinephrineautoinject.com.
Instruct caregivers to hold the leg of young children or infants firmly in place and limit movement prior to and during injection. [see Warnings and Precautions (5.2)].
Instruct patients and/or caregivers in the appropriate use of Epinephrine Injection. Epinephrine Injection should be injected into the middle of the outer thigh (through clothing if necessary).
Instruct patients and/or caregivers when a second dose of Epinephrine Injection is needed. Administer a new Epinephrine Injection into the middle of the outer thigh starting 5 minutes after the first dose.
Advise patients and/or caregivers when to seek emergency medical care for close monitoring of the type I allergic emergency and in the event that further treatment is required.
Instruct patients and/or caregivers in the appropriate use of Epinephrine Injection. Epinephrine Injection should be injected into the middle of the outer thigh (through clothing if necessary).
Instruct patients and/or caregivers when a second dose of Epinephrine Injection is needed. Administer a new Epinephrine Injection into the middle of the outer thigh starting 5 minutes after the first dose.
Advise patients and/or caregivers when to seek emergency medical care for close monitoring of the type I allergic emergency and in the event that further treatment is required.
Injection-Related Complications
Advise patients to seek immediate medical care in the case of accidental injection into the digits, hands or feet because such an accidental injection to these areas may cause loss of blood flow to the affected area [see Warnings and Precautions (5.1)].
…
Risks Associated with Certain Coexisting Conditions
Advise patients with coexisting conditions (cardiac arrhythmia and ischemia, coronary artery disease, hypertension, pulmonary edema, hyperthyroidism, renal impairment, Parkinson's disease, diabetes), for increased risks that may be associated with use of epinephrine [see Warnings and Precautions (5.5)].
Storage and Handling
Epinephrine Injection is light sensitive and should be stored in the individual carrier tube provided to protect it from light. The individual carrier tube is not waterproof. Instruct patients that Epinephrine Injection must be properly disposed of once the blue end caps have been removed or after use [see How Supplied/Storage and Handling (16)].
PATIENT INFORMATION
Extensive additions and/or revisions, please refer to label for complete information.
Other
Updates throughout the labeling to be consistence with the current labeling for epinephrine products.