Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | 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.

KLOXXADO (NDA-212045)

(NALOXONE HYDROCHLORIDE)

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

Download Data

Expand all

08/25/2025 (SUPPL-5)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.3 Precipitation of Severe Opioid Withdrawal

Additions and/or revisions underlined:

The use of KLOXXADO in patients who are opioid-dependent may precipitate opioid withdrawal; the risk and severity of withdrawal increases as naloxone exposure increases. Opioid withdrawal is characterized by the following signs and symptoms: body aches, diarrhea, tachycardia, fever, runny nose, sneezing, piloerection, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure. In neonates, opioid withdrawal may be life-threatening if not recognized and properly treated and may include the following signs and symptoms: convulsion, excessive crying, and hyperactive reflexes. Monitor the patient for the development of the signs and symptoms of opioid withdrawal.

…

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to the rates in the clinical studies of another drug and may not reflect the rates observed in practice.
KLOXXADO nasal spray, 4 mg
No adverse events were reported in a pharmacokinetic study of 72 healthy adult volunteers exposed to one spray of 4 mg KLOXXADO nasal spray in one nostril.

KLOXXADO nasal spray, 8 mg

In two pharmacokinetic studies a total of 47 healthy adult volunteers were exposed to a single dose of KLOXXADO nasal spray 8 mg, one spray in one nostril. The following adverse reactions were reported in two subjects each: abdominal pain, asthenia, dizziness, headache, nasal discomfort, and presyncope. On local tissue assessments for nasal irritation, signs of nasal inflammation and nasal congestion were observed.

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

PATIENT INFORMATION

Additions and/or revisions underlined:

….

What is KLOXXADO nasal spray?

KLOXXADO nasal spray is a prescription medicine used in adults and children for the treatment of an opioid emergency such as an overdose or a possible opioid overdose with signs of breathing problems and severe sleepiness or not being able to respond.
KLOXXADO nasal spray is to be given right away and does not take the place of emergency medical care.
Get emergency medical help right away after giving the first dose of KLOXXADO nasal spray, even if the person wakes up.

KLOXXADO nasal spray is safe and effective in children for known or suspected opioid overdose.

…

How should I store KLOXXADO nasal spray?

Store KLOXXADO nasal spray at room temperature between 68ºF to 77ºF (20°C to 25°C).
Do not freeze. Do not expose to temperatures below 41°F (5°C) or above 104°F (40°C).
Keep KLOXXADO nasal spray in its box until ready to use. Protect from light.
Replace KLOXXADO nasal spray before the expiration date on the box.

Keep KLOXXADO nasal spray and all medicines out of the reach of children.

…

What are the ingredients in KLOXXADO nasal spray? Active ingredient: naloxone hydrochloride

Inactive ingredients: dehydrated alcohol (4 mg strength: 24.305% (w/w); 8 mg strength: 20% (w/w)), edetate disodium dihydrate, propylene glycol, and sodium hydroxide and hydrochloric acid as pH adjusters in purified water.

KLOXXADO nasal spray is not made with natural rubber latex.