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.

VANDAZOLE (NDA-021806)

(METRONIDAZOLE)

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

Download Data

Expand all

02/11/2021 (SUPPL-8)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Carcinogenicity in Animals

(Additions and/or revisions underlined)

Metronidazole has been shown to be carcinogenic in mice and rats [see Nonclinical Toxicology (13.1)]. Unnecessary use of metronidazole should be avoided. Use of VANDAZOLE should be reserved for the treatment of bacterial vaginosis [see Indications and Usage (1)].

5.3 Interference with Laboratory Tests

(Additions and/or revisions underlined)

Metronidazole may interfere with certain types of determinations of serum chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT), lactate dehydrogenase (LDH), triglycerides, and glucose hexokinase. Values of zero may be observed. All of the assays in which interference has been reported involve enzymatic coupling of the assay to oxidation-reduction of nicotinamide-adenine dinucleotides (NAD + NADH).

Interference is due to the similarity in absorbance peaks of NADH (340 nm) and metronidazole (322 nm) at pH 7. Consider postponing chemistry laboratory tests until treatment with VANDAZOLE is completed.

8 Use in Specific Populations

8.1 Pregnancy

(Pregnancy and Lactation Rule (PLLR) conversion; Additions and/or revisions underlined)

Risk Summary

Available data on metronidazole use in pregnant women from published cohort studies, case-control studies, case series, meta analyses, and case reports over several decades have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, no adverse developmental effects were demonstrated when oral metronidazole was administered to mice at doses up to six times the recommended human dose (see Data).

The estimated 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.

Data

Human Data

Published case-control studies, cohort studies, meta analyses, case series, and case reports over several decades have not established a risk with metronidazole use in pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes. Many studies included first trimester exposures. One study showed an increased risk of cleft lip, with or without cleft palate, in infants exposed to metronidazole in-utero; however, these findings were not confirmed. Most studies did not show an increased risk for congenital anomalies or other adverse fetal outcomes following metronidazole exposure during pregnancy. Studies conducted to assess the risk of infant cancer following systemic metronidazole exposure during pregnancy did not show an increased risk; however, the ability of these studies to detect such a signal was limited.

Animal Data

Animal studies have shown that metronidazole crosses the placental barrier and enters the fetal circulation rapidly. Oral metronidazole reproductive toxicity studies have been performed in mice at doses up to six times the recommended human dose based on body surface area comparisons and have revealed no evidence of harm to the fetus. However, in a single small study where the drug was administered intraperitoneally, some intrauterine deaths were observed.

8.2 Lactation

(Pregnancy and Lactation Rule (PLLR) conversion; Additions and/or revisions underlined)

Risk Summary

There are no data on the presence of metronidazole in human milk following intravaginal administration. Metronidazole is present in human milk following oral metronidazole administration at concentrations similar to those found in plasma (see Data). The metronidazole vaginal gel achieves 2% of the mean maximum serum concentration of a 500 mg oral metronidazole dose [see Clinical Pharmacology (12.3)]. The published literature reports no adverse effects in infants exposed through breastmilk to maternal orally administered metronidazole. There are no data on the effects on milk production.

Animal studies have shown the potential for tumorigenicity after oral metronidazole was administered chronically to rats and mice [see Nonclinical Toxicology (13.1)]. The clinical relevance of these findings is unclear. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VANDAZOLE, and any potential adverse effects on the breastfed child from VANDAZOLE or from the underlying maternal condition.

Alternatively, a lactating patient may interrupt breastfeeding and choose to pump and discard breastmilk during treatment with VANDAZOLE and for 48 hours after the last dose and feed her infant previously stored human milk or formula.

Data

In a study of lactating women receiving oral metronidazole 600 mg (n=11) or 1200 mg (n=4) daily, mean maternal plasma concentrations were 5.0 and 12.5 mcg/mL, respectively, within 2 hours following administration; the milk: maternal plasma ratio was approximately 1.

8.4 Pediatric Use

(Additions and/or revisions underlined)

The safety and efficacy of VANDAZOLE in the treatment of bacterial vaginosis in post-menarchal females have been established on the extrapolation of clinical trial data from adult females.

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

17 PATIENT COUNSELING INFORMATION

(Additions and/or revisions underlined)

Advise the patient to read the FDA-approved patient labeling (Instructions for Use).

Fungal Vaginal Infections

Inform the patient that vaginal fungal infections can occur following use of VANDAZOLE and may require treatment with an antifungal drug [see Adverse Reactions (6.1)].

Lactation

A patient may choose to pump and discard breastmilk during treatment with VANDAZOLE and for 48 hours after last dose, and feed her infant previously stored human milk or formula [see Use in Specific Populations (8.2)].

Administration of Drug

Instruct the patient that VANDAZOLE (metronidazole gel, USP), 0.75% is supplied with 5 vaginal applicators. For once daily dosing, one applicator full should be used per dose.