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.

PLIAGLIS (NDA-021717)

(LIDOCAINE; TETRACAINE)

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

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12/11/2018 (SUPPL-10)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

8.2 Lactation

PLLR conversion; extensive changes. Please refer to label for complete information.

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

PATIENT COUSELING INFORMATION

Addition of the following:

Advise breastfeeding women not to apply PLIAGLIS directly to the nipple and areola to avoid direct infant exposure.

11/02/2018 (SUPPL-11)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Methemoglobinemia

(subsection revised)

Cases of methemoglobinemia have been reported in association with local anesthetic use. Although all patients are at risk for methemoglobinemia, patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition. If local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended.

Signs of methemoglobinemia may occur immediately or may be delayed some hours after exposure, and are characterized by a cyanotic skin discoloration and/or abnormal coloration of the blood. Methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious central nervous system and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death. Discontinue PLIAGLIS and any other oxidizing agents. Depending on the severity of the signs and symptoms, patients may respond to supportive care, i.e., oxygen therapy, hydration. A more severe clinical presentation may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.

7 Drug Interactions

7.3 Drugs That May Cause Methemoglobinemia When Used with PLIAGLIS

(additions underlined)

Patients who are administered local anesthetics are at increased risk of developing methemoglobinemia when concurrently exposed to the following drugs, which could include other local anesthetics:

Examples of Drugs Associated with Methemoglobinemia:

(please refer to label to view examples)

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

PATIENT COUNSELING INFORMATION

(additions underlined)

Prior to treatment, advise patient of the following:

Inform patients that use of local anesthetics may cause methemoglobinemia, a serious condition that must be treated promptly. Advise patients or caregivers to stop use and seek immediate medical attention if they or someone in their care experience the following signs or symptoms: pale, gray, or blue colored skin (cyanosis); headache; rapid heart rate; shortness of breath; lightheadedness; or fatigue.

...

11/21/2017 (SUPPL-9)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.3 Methemoglobinemia

(Additions and/or revisions are underlined)

Several local anesthetics, including lidocaine and tetracaine, have been associated with methemoglobinemia (metHB), particularly in conjunction with methemoglobin-inducing agents. Based on the literature, patients with glucose-6-phosphate dehydrogenase deficiency or congenital or idiopathic methemoglobinemia are more susceptible to drug-induced methemoglobinemia. Use of PLIAGLIS in patients with a history of congenital or idiopathic methemoglobinemia is not advised.

Initial signs and symptoms of methemoglobinemia (which may be delayed for up to several hours following exposure) are characterized by a slate grey cyanosis seen in, e.g., buccal mucous membranes, lips and nail beds. In severe cases, symptoms may include central cyanosis, headache, lethargy, dizziness, fatigue, syncope, dyspnea, CNS depression, seizures, dysrythmia and shock. Methemoglobinemia should be considered if central cyanosis unresponsive to oxygen therapy occurs, especially if metHb-inducing agents have been used. Calculated oxygen saturation and pulse oximetry are inaccurate in the identification of methemoglobinemia. Confirm diagnosis by measuring methemoglobin level with co-oximetry. Normally, metHb levels are <1%, and cyanosis may not be evident until a level of at least 10% is present.

Treat clinically significant symptoms of methemoglobinemia with a standard clinical regimen such as intravenous infusion of methylene blue at a dosage of 1 mg/kg given over a 5 to 30-minute period. Refer to methylene blue dosing information for more detailed instructions on how to manage methemoglobinemia using that product.

5.4 Anaphylactic Reactions

(Newly revised subsection title; additions and/or revisions are underlined)

Allergic or anaphylactic reactions have been associated with lidocaine and tetracaine and may occur with other components of PLIAGLIS. They are characterized by urticaria, angioedema, bronchospasm, and shock. If an allergic reaction occurs, seek emergency help immediately.

6 Adverse Reactions

(Additions and/or revisions are underlined)

The following adverse reactions are described elsewhere in the labeling:

Overexposure
Risks of Secondary Exposure in Children and Pets
Methemoglobinemia
Anaphylactic Reactions
Eye Irritation

7 Drug Interactions

7.4 Drugs That May Cause Methemoglobinemia When Used with PLIAGLIS

(Newly added subsection)

Tetracaine may cause methemoglobinemia, particularly in conjunction with methemoglobin- inducing agents such as sulfonamides, acetaminophen, acetanilide, aniline dyes, benzocaine, chloroquine, dapsone, naphthalene, nitrates and nitrites, nitrofurantoin, nitroglycerin, nitroprusside, pamaquine, p- aminosalicylic acid, phenacetin, phenobarbital, phenytoin, primaquine, and quinine. Monitor patients carefully for signs of methemoglobinemia if PLIAGLIS is used in the setting of these drugs.

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

17 PATIENT COUNSELING INFORMATION

(Additions and/or revisions are underlined)

Advise patients to inform the healthcare provider if they experience skin irritation or a burning sensation because the product will need to be immediately removed.

Advise patients of the signs and symptoms of hypersensitivity reactions and to seek immediate medical attention should they occur.

Advise patients that PLIAGIS may lead to diminished or blocked sensation in the treated skin and to avoid inadvertent trauma through rubbing, scratching, or exposure to heat or cold before complete sensation occurs.