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.

MARCAINE (NDA-018692)

(BUPIVACAINE HYDROCHLORIDE)

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

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09/28/2022 (SUPPL-24)

Approved Drug Label (PDF)

4 Contraindications

Additions and/or revisions underlined

MARCAINE SPINAL is contraindicated in:

intravenous regional anesthesia (Bier Block) [see Warnings and Precautions (5.8)].
patients with septicemia.
patients with severe hemorrhage, severe hypotension or shock, due to a reduced cardiac output.
patients with clinically significant arrhythmias, such as complete heartblock, due a reduced cardiac output.
patients with a known hypersensitivity to bupivacaine or to any local anesthetic agent of the amide-type or to other components of MARCAINE SPINAL.
patients with local infection at the site of proposed lumbar puncture.

5 Warnings and Precautions

The following subsections created to comply with Physician Labeling Rule (PLR); please refer to label for complete information

5.1 Use of Spinal Anesthetics During Uterine Contractions

5.2 Patients with Hypertension

5.3 Dose-Related Toxicity

5.4 Risk of Systemic Toxicities with Unintended Intravascular Injection

5.5 Methemoglobinemia

5.6 Risk of Cardiac Arrest with Use of Epidural Bupivacaine in Obstetrical Anesthes

5.7 Chondrolysis with Intra-Articular Infusion

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

5.9 Patients with Severe Disturbances of Cardiac Rhythm, Shock, or Heart Block

5.10 Risk of Toxicity in Patients with Hepatic Impairment

5.11 Risk of Use in Patients with Impaired Cardiovascular Function

7 Drug Interactions

The following subsections created to comply with Physician Labeling Rule (PLR); please refer to label for complete information

7.1 Local Anesthetics

7.2 Drugs Associated with Methemoglobinemia

8 Use in Specific Populations

8.1 Pregnancy

PLLR conversion, please refer to label

8.2 Lactation

PLLR conversion

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 SPINAL should be administered to lactating women only if clearly indicated. Studies assessing the effects of MARCAINE SPINAL in breastfed children have not been performed. Studies to assess the effect of MARCAINE SPINAL 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.

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

PATIENT COUNSELING INFORMATION

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 [see Contraindications (4), Adverse Reactions (6)].

…

11/02/2018 (SUPPL-20)

Approved Drug Label (PDF)

5 Warnings and Precautions

WARNINGS

(additions underlined)

…

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 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)

Information for Patients:

(additions underlined)

…

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.