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.

MARCAINE HYDROCHLORIDE (NDA-016964)

(BUPIVACAINE HYDROCHLORIDE)

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

Download Data

Expand all

08/21/2020 (SUPPL-82)

Approved Drug Label (PDF)

Boxed Warning

PLR conversion, newly created, with text taken from non-PLR warning section, with additions and/or revisions underlined:

WARNING: RISK OF CARDIAC ARREST WITH USE OF MARCAINE IN OBSTETRICAL ANESTHESIA

There have been reports of cardiac arrest with difficult resuscitation or death during use of MARCAINE for epidural anesthesia in obstetrical patients. In most cases, this has followed use of the 0.75% (7.5 mg/mL) concentration. Resuscitation has been difficult or impossible despite apparently adequate preparation and appropriate management. Cardiac arrest has occurred after convulsions resulting from systemic toxicity, presumably following unintentional intravascular injection. The 0.75% (7.5 mg/mL) concentration of MARCAINE is not recommended for obstetrical anesthesia and should be reserved for surgical procedures where a high degree of muscle relaxation and prolonged effect are necessary [see Warnings and Precautions (5.1)].

4 Contraindications

PLR conversion, additions and/or revisions underlined:

MARCAINE/ MARCAINE WITH EPINEPHRINE is contraindicated in:

obstetrical paracervical block anesthesia. Its use in this technique has resulted in fetal bradycardia and death.
intravenous regional anesthesia (Bier Block) [see Warnings and Precautions (5.7)].
patients with a known hypersensitivity to bupivacaine or to any local anesthetic agent of the amide-type or to other components of MARCAINE / MARCAINE WITH EPINEPHRINE.

5 Warnings and Precautions

PLR conversion; subsections created as follows (please refer to label for complete information):

5.1 Risk of Cardiac Arrest with Use of MARCAINE in Obstetrical Anesthesia

5.2 Dose-Related Toxicity

5.3 Methemoglobinemia

5.4 Antimicrobial Preservatives in Multiple-Dose Vials

5.5 Chondrolysis with Intra-Articular Infusion

5.6 Risk of Adverse Reactions Due to Drug Interactions with MARCAINE WITH EPINEPHRINE

5.7 Risk of Cardiac Arrest with Intravenous Regional Anesthesia Use (Bier Block)

5.8 Allergic-Type Reactions to Sulfites in MARCAINE WITH EPINEPHRINE

5.9 Risk of Systemic Toxicities with Unintended Intravascular or Intrathecal Injection

5.10 Risk of Toxicity in Patients with Hepatic Impairment

5.11 Risk of Use in Patients with Impaired Cardiovascular Function

5.12 Risk of Ischemic Injury or Necrosis in Body Areas with Limited Blood Supply

5.13 Risk of Cardiac Arrhythmias with Concomitant Use of Potent Inhalation Anesthetics

5.14 Risk of Adverse Reactions with Use in Head and Neck Area

5.15 Risk of Respiratory Arrest with Use in Ophthalmic Surgery

5.16 Risk of Inadvertent Trauma to Tongue, Lips, and Buccal Mucosa in Dental Applications

6 Adverse Reactions

PLR conversion; please refer to label for complete information

7 Drug Interactions

PLR conversion; subsections created as follows (please refer to label for complete information):

7.1 Local Anesthetics

7.2 Monoamine Oxidase Inhibitors and Tricyclic Antidepressants

7.3 Ergot-Type Oxytocic Drugs

7.4 Nonselective Beta-Adrenergic Antagonists

7.5 Drugs Associated with Methemoglobinemia

7.6 Potent Inhalation Anesthetics

7.7 Phenothiazines and Butyrophenones

8 Use in Specific Populations

8.1 Pregnancy

PLR conversion with extensive changes; please refer to label for complete information

8.2 Lactation

PLR conversion, as below:

Risk Summary

Lactation studies have not been conducted with bupivacaine. Bupivacaine has been reported to be excreted in human milk suggesting that the nursing infant could be theoretically exposed to a dose of the drug. MARCAINE / MARCAINE WITH EPINEPHRINE should be administered to lactating women only if clearly indicated. Studies assessing the effects of MARCAINE / MARCAINE WITH EPINEPHRINE in breastfed children have not been performed. Studies to assess the effect of MARCAINE / MARCAINE WITH EPINEPHRINE on milk production or excretion have not been performed. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for bupivacaine and any potential adverse effects on the breastfed child from bupivacaine or from the underlying maternal condition.

8.4 Pediatric Use

PLR conversion; additions and/or revisions underlined:

MARCAINE / MARCAINE WITH EPINEPHRINE is approved for use in adults. Administration of MARCAINE / MARCAINE WITH EPINEPHRINE in pediatric patients younger than 12 years is not recommended.

Continuous infusions of bupivacaine in pediatric patients have been reported to result in high systemic levels of bupivacaine and seizures; high plasma levels may also be associated with cardiovascular abnormalities.

8.5 Geriatric Use

PLR conversion; additions and/or revisions underlined:

Patients 65 years and over, particularly those with hypertension, may be at increased risk for developing hypotension while undergoing anesthesia with MARCAINE / MARCAINE WITH EPINEPHRINE.

In clinical studies of bupivacaine, elderly patients reached the maximal spread of analgesia and maximal motor blockade more rapidly than younger adult patients.

Differences in various pharmacokinetic parameters have been observed between elderly and younger adult patients [see Clinical Pharmacology (12.3)].

This product is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Elderly patients may require lower doses of MARCAINE / MARCAINE WITH EPINEPHRINE.

8.6 Hepatic Impairment

PLR conversion; additions and/or revisions underlined:

Amide-type local anesthetics, such as bupivacaine, are metabolized by the liver. Patients with severe hepatic impairment, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations, and potentially local anesthetic systemic toxicity. Therefore, consider reduced dosing and increased monitoring for local anesthetic systemic toxicity in patients with moderate to severe hepatic impairment treated with MARCAINE / MARCAINE WITH EPINEPHRINE, especially with repeat doses [see Warnings and Precautions (5.10)].

8.7 Renal Impairment

PLR conversion; as below:

Bupivacaine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with renal impairment. This should be considered when selecting the MARCAINE / MARCAINE WITH EPINEPHRINE dosage [see Use in Specific Populations (8.5)].

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

PATIENT COUSELING INFORMATION

PLR conversion, additions and/or revisions underlined:

Allergic-Type Reactions

Assess if the patient has had allergic-type reactions to amide-type local anesthetics or to other formulation ingredients, such as the antimicrobial preservative methylparaben contained in multiple-dose vials or sulfites in epinephrine-containing solutions [see Contraindications (4), Warnings and Precautions (5.8), Adverse Reactions (6)].

Temporary Loss of Sensation and Motor Activity After Caudal or Epidural Anesthesia

When appropriate, patients should be informed in advance that they may experience temporary loss of sensation and motor activity, usually in the lower half of the body, following proper administration of caudal or epidural anesthesia.

Instructions After Dental Injection of MARCAINE

Advise patients receiving dental injections of MARCAINE not to chew solid foods or to test the anesthetized area by biting or probing until anesthesia has worn off (up to 7 hours) [see Warnings and Precautions (5.16)].

Methemoglobinemia

Inform patients that use of local anesthetics may cause methemoglobinemia, a serious condition that must be treated promptly. Advise patients or caregivers to 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 [see Warnings and Precautions (5.3)].

Other

PLR conversion; please refer to label for complete information.

11/02/2018 (SUPPL-77)

Approved Drug Label (PDF)

5 Warnings and Precautions

WARNINGS

(additions underlined)

…

Methemoglobinemia: 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 CNS and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death.

Discontinue MARCAINE 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

Clinically Significant Drug Interactions

(additions underlined)

…

Patients who are administered local anesthetics are at increased risk of developing methemoglobinemia when concurrently exposed to 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)

Information for Patients

(additions underlined)

…