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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.
AUVI-Q (NDA-201739)
(EPINEPHRINE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
04/30/2025 (SUPPL-30)
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 AUVI-Q is injected into the buttock, advise the patient to administer a second dose of AUVI-Q into the anterolateral aspect of the thigh and if symptoms worsen or persist, then go immediately to the nearest emergency room for further treatment of anaphylaxis. Additionally, injection into the buttock has been associated with Clostridial infections (gas gangrene). Cleansing with alcohol does not kill bacterial spores, and therefore, does not lower this 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 AUVI-Q 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)].
…
5.3 Risk Associated with Use of Epinephrine in Certain Coexisting Conditions
Section title revision
Additions and/or revisions underlined:
Some patients may be at greater risk for developing adverse reactions after epinephrine administration. Despite these concerns, the presence of these conditions is not a contraindication to epinephrine administration in an acute, life-threatening situation. Therefore, instruct patients with these conditions, and/or caregivers to the circumstances under which epinephrine should be used.
Administer epinephrine with caution to patients who have heart disease, including patients with cardiac arrhythmias, coronary artery disease, or hypertension. In such patients, or in patients who are on drugs that may sensitize the heart to arrhythmias, epinephrine may precipitate or aggravate angina pectoris as well as produce ventricular arrhythmias [see Drug Interactions (7) and Adverse Reactions (6)].
Epinephrine can temporarily exacerbate the underlying conditions 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.
6 Adverse Reactions
Additions and/or revisions underlined:
Addition of the following to the bulleted line listing:
The following clinically significant adverse reactions are described elsewhere in the labeling:
Injection-Related Complications [see Warnings and Precautions (5.1)]
Serious Infections at the Injection Site [see Warnings and Precautions (5.2)]
Risks Associated with Use of Epinephrine in Certain Coexisting Conditions [see Warnings and Precautions (5.3)]
- Allergic Reactions Associated with Sulfite [see Warnings and Precautions (5.4)]
Adverse Reactions from Postapproval Use of Epinephrine Products
The following adverse reactions have been identified during postapproval use of epinephrine. 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.
Cardiovascular: angina, arrhythmias (including fatal ventricular fibrillation), cerebral hemorrhage, hypertension, pallor, palpitations, tachyarrhythmia, tachycardia, vasoconstriction, ventricular ectopy, and stress cardiomyopathy
Gastrointestinal Disorders: nausea, vomiting
Infections: Clostridial infections (gas gangrene)
Metabolism and Nutrition Disorders: transient hyperglycemia, sweating
Neurological: disorientation, impaired memory, panic, psychomotor agitations, sleepiness, tingling, weakness, hypoesthesia, dizziness, tremor, headache
Psychiatric: anxiety, apprehensiveness, restlessness
Respiratory: respiratory difficulties
Skin and Subcutaneous Tissue Disorders: bruising, bleeding, discoloration, erythema, necrotizing fasciitis, myonecrosis
7 Drug Interactions
7.2 Drugs Potentiating Effects of Epinephrine
Additions and/or revisions underlined:
The effects of epinephrine may be potentiated by tricyclic antidepressants, monoamine oxidase inhibitors, levothyroxine sodium, and certain antihistamines, notably chlorpheniramine, tripelennamine, and diphenhydramine, and catechol-O-methyl transferase (COMT) inhibitors such as entacapone.
…
8 Use in Specific Populations
8.1 Pregnancy
Additions and/or revisions underlined:
Risk Summary
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. Epinephrine is first-line treatment of anaphylaxis and should not be delayed (see Clinical Considerations). In animal reproductive studies, epinephrine administered by the subcutaneous route to 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.
Clinical Considerations
Disease-associated maternal and embryo/fetal risk:
During pregnancy, anaphylaxis can be catastrophic and can lead to hypoxic-ischemic encephalopathy and permanent central nervous system damage or death in the mother and, more commonly, in the fetus or neonate. Treatment of anaphylaxis during pregnancy should not be delayed.
8.2 Lactation
Additions and/or revisions underlined:
Risk Summary
There is no information on the presence of epinephrine in human milk, the effects on 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 AUVI-Q for the emergency treatment of type I allergic reactions, including anaphylaxis have been established in pediatric patients who weigh 7.5 kg or greater. The use of AUVI-Q 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 AUVI-Q are fixed, use other forms of injectable epinephrine if doses lower than 0.1 mg are deemed necessary.
The safety and effectiveness of AUVI-Q have not been established in pediatric patients who weigh less than 7.5 kg.
8.5 Geriatric Use
Additions and/or revisions underlined:
Clinical studies of AUVI-Q for emergency treatment of type I allergic reactions, including anaphylaxis, were not conducted to determine whether they respond differently from younger patients. However, other reported clinical experience with use of epinephrine for 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 [see Overdosage (10)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or revisions underlined:
…
Administration and Training
- Instruct patients and/or caregivers in the appropriate use of AUVI-Q. AUVI-Q should be injected into the middle of the outer thigh (through clothing, if necessary). Each device is a single-dose injection.
- 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 to inspect the epinephrine solution visually through the viewing window periodically. AUVI-Q should be replaced if the epinephrine solution appears discolored, cloudy, or contains particles.
…
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, 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 (5.3)].
…
PATIENT INFORMATION
Additions and/or revisions underlined:
AUVI-Q® [Aw-Vee-Kyoo] (epinephrine injection)
For intramuscular or subcutaneous use
Read this Patient Information leaflet before you have to use AUVI-Q and each time you get a refill. There may be new information. You, your caregiver, or others who may be in a position to administer AUVI-Q should know how to use it before you have an allergic emergency. This information does nottake the place of talking with your healthcare provider about your medical condition or your treatment.
…
What is the most important information I should know about AUVI-Q?
…
3. Get medical care for further treatment of the allergic emergency if needed after using AUVI-Q.
Before you receive AUVI-Q, your healthcare provider should talk to you about when to get emergency help.
What is AUVI-Q?
- AUVI-Q is a prescription medicine used to treat life-threatening allergic reactions including anaphylaxis in adults and children who weigh 16.5 pounds (7.5 kilograms) or more who are at risk for or have a history of serious allergic reactions.
…
What should I tell my healthcare provider before using AUVI-Q?
…
have kidney problems.
…
How should I use AUVI-Q?
…
If a second dose of AUVI-Q is needed, it should be given starting 5 minutes after the first dose.
You should always carry 2 AUVI-Q devices with you.
If you need more than 2 doses of epinephrine for a single anaphylaxis episode, more doses must be given by a healthcare provider.
You may request a Trainer for AUVI-Q. Additional training resources are available at www.auvi-q.com.
Practice with the Trainer for AUVI-Q before an allergic emergency happens to familiarize yourself with the use of AUVI-Q in an allergic emergency.
The Trainer for AUVI-Q does not contain a needle or medicine and can be reused to practice your injection.
If you take too much AUVI-Q, call your healthcare provider or Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away.
…
How should I store AUVI-Q?
Store AUVI-Q at room temperature between 68° to 77°F (20° to 25°C).
Do not freeze. Do not expose to extreme heat or cold. For example, do not store in your vehicle’s glove box.
- Before using, examine contents in the viewing window. Solution should be clear. If the solution is discolored, cloudy or contains solid particles, replace the autoinjector.
…
09/28/2019 (SUPPL-15)
8 Use in Specific Populations
8.1 Pregnancy8.1 Pregnancy
(Pregnancy and Lactation Labeling Rule (PLLR) conversion)
Risk Summary
There are no adequate and well controlled studies of the acute effect of epinephrine in pregnant women. In animal reproductive studies, epinephrine administered by the subcutaneous route to 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/m^2 basis. Epinephrine is the first-line medication of choice for the treatment of anaphylaxis during pregnancy in humans. Epinephrine should be used for treatment of anaphylaxis during pregnancy in the same manner as it is used in non-pregnant patients.
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.
Clinical Considerations
Disease-associated maternal and embryo/fetal risk:
During pregnancy, anaphylaxis can be catastrophic and can lead to hypoxic-ischemic encephalopathy and permanent central nervous system damage or death in the mother and, more commonly, in the fetus or neonate. The prevalence of anaphylaxis occurring during pregnancy is reported to be approximately 3 cases per 100,000 deliveries.
Management of anaphylaxis during pregnancy is similar to management in the general population. Epinephrine is the first line-medication of choice for treatment of anaphylaxis; it should be used in the same manner in pregnant and non-pregnant patients. In conjunction with the administration of epinephrine, the patient should seek immediate medical or hospital care.
Data
Animal Data:
In an embryofetal development study with rabbits dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including gastroschisis and embryonic lethality) at doses approximately 40 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m2 basis at a maternal subcutaneous dose of 1.2 mg/kg/day for two to three days).
In an embryofetal development study with mice dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including embryonic lethality) at doses approximately 8 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m^2 basis at a maternal subcutaneous dose of 1 mg/kg/day for 10 days). These effects were not seen in mice at approximately 4 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m^2 basis at a subcutaneous maternal dose of 0.5 mg/kg/day for 10 days).
In an embryofetal development study with hamsters dosed during the period of organogenesis from gestation days 7 to 10, epinephrine was shown to be teratogenic at doses approximately 7 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m^2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day for 4 days).
(Pregnancy and Lactation Labeling Rule (PLLR) conversion)
Risk Summary
There is no information on the presence of epinephrine in human milk, the effects on breastfed infants, or the effects on milk production. Epinephrine is the first line-medication of choice for treatment of anaphylaxis; it should be used in the same manner in breastfeeding and non- breastfeeding patients.
11/17/2017 (SUPPL-8)
5 Warnings and Precautions
5.2 INJECTION-RELATED COMPLICATIONS(Additions and/or revisions are underlined)
- Hold leg firmly during injection. To minimize the risk of injection-related injury when administering AUVI-Q to young children or infants, instruct caregivers to hold the child’s leg firmly in place and limit movement prior to and during injection.
6 Adverse Reactions
(Additions and/or revisions are underlined)
…Rare cases of stress cardiomyopathy have been reported in patients treated with epinephrine…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION(Additions and/or revisions are underlined)
Administration and Training
…
Young children or infants may be uncooperative and kick or move during an injection. Instruct caregivers to hold the leg of young children or infants firmly in place and limit movement prior to and during injection.
(Additions and/or revisions are underlined)
What is AUVI-Q?
…It is not known if AUVI-Q is safe and effective in children who weigh less than 16.5 pounds (7.5 kg).
What are the possible side effects of AUVI-Q?
- If you inject a young child or infant with AUVI-Q, hold their leg firmly in place before and during the injection to prevent injuries. Ask your healthcare provider to show you how to properly hold the leg of a young child or infant during an injection.
11/17/2017 (SUPPL-9)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION(Additions and/or revisions are underlined)
…Instruct patients and/or caregivers that the needle will not be visible after the injection and they may not feel the injection when it occurs. Instruct patients that AUVI-Q includes a 2- second countdown after it is activated and then the voice instructions will indicate the injection is complete and to seek emergency medical attention. Instruct patients that AUVI-Q’s black base will lock up onto the device housing and the lights will blink red after the injection is complete. These post-use indicators help patients and/or caregivers know that AUVI-Q has been activated and an epinephrine injection administered.
05/18/2016 (SUPPL-4)
5 Warnings and Precautions
INJECTION-RELATED COMPLICATIONS- Do not inject into buttock. Additionally, injection into the buttock has been associated with Clostridial infections (gas gangrene). Cleansing with alcohol does not kill bacterial spores, and therefore, does not lower this risk.
- Hold leg firmly during injection. To minimize the risk of injection-related injury when administering Auvi-Q to young children, instruct caregivers to hold the child’s leg firmly in place and limit movement prior to and during injection.
- Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported at the injection site following epinephrine injection for anaphylaxis. Clostridium spores can be present on the skin and introduced into the deep tissue with subcutaneous or intramuscular injection. While cleansing with alcohol may reduce the presence of bacteria on the skin, alcohol cleansing does not kill Clostridium spores. To decrease the potential risk of a rare, but serious Clostridium infection, do not inject Auvi-Q into the buttock. Advise patients to seek medical care if they develop signs or symptoms of infection, such as persistent redness, warmth, swelling, or tenderness, at the epinephrine injection site.
6 Adverse Reactions
Adverse Reactions Associated with Intramuscular/Subcutaneous Use (for Anaphylaxis)- Due to lack of randomized, controlled clinical trials of epinephrine for the treatment of anaphylaxis, the true incidence of adverse reactions associated with the systemic use of epinephrine is difficult to determine. Adverse reactions reported in observational trials, case reports, and studies are listed below. Common adverse reactions to systemically administered epinephrine include anxiety; apprehensiveness; restlessness; tremor; weakness; dizziness; sweating; palpitations; pallor; nausea and vomiting; headache; and/or respiratory difficulties. These symptoms occur in some persons receiving therapeutic doses of epinephrine, but are more likely to occur in patients with hypertension or hyperthyroidism
- Injection of epinephrine into the buttock has resulted in cases of gas gangrene.
- Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported at the injection site following epinephrine injection in the thigh.