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.

AVANDIA (NDA-021071)

(ROSIGLITAZONE MALEATE)

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

Download Data

Expand all

02/05/2019 (SUPPL-52)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion)

Risk Summary

Limited data with AVANDIA in pregnant women are not sufficient to determine a drug- associated risk for major birth defects or miscarriage. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations).

In animal reproduction studies, no adverse developmental effects were observed when rosiglitazone was administered to pregnant rats and rabbits during organogenesis at exposures up to 4 times the maximum recommended human dose (MRHD) of 8 mg daily (see Data).

The estimated background risk of major birth defects is 6% to 10% in women with pre- gestational diabetes with a HbA1c >7 and has been reported to be as high as 20% to 25% in women with a HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. 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.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk: Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity.

Data

Animal Data: Rosiglitazone administered during early pregnancy, organogenesis, and through lactation did not cause adverse effects in offspring of pregnant rats and rabbits at doses of

0.2 mg/kg and 15 mg/kg, respectively. These no-effect doses provide exposure of approximately 4 times the MRHD based on AUC. Higher exposures to rosiglitazone during organogenesis were associated with fetal death and growth retardation in rats and rabbits, and neonatal death (during lactation) and placental pathology in rats in the absence of maternal toxicity (exposures approximately 20 and 75 times MRHD based on AUC, respectively).

8.2 Lactation

(PLLR conversion)

Risk Summary

There are no data on the presence of rosiglitazone in human milk, the effects on the breastfed infant, or the effects on milk production. Rosiglitazone is present in rat milk; however, due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk (see Data). The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for AVANDIA and any potential adverse effects on the breastfed infant from AVANDIA or the underlying maternal condition.

Data

Rosiglitazone was detected in the milk of lactating rats, with peak milk concentrations of approximately 33% that of maternal plasma concentrations occurring 1 hour post dose.

8.3 Females and Males of Reproductive Potential

(PLLR conversion)

Discuss the potential for unintended pregnancy with premenopausal women as therapy with AVANDIA, like other thiazolidinediones, may result in ovulation in some anovulatory women.

09/19/2016 (SUPPL-51)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Cardiac Failure

Heart Failure in Observational Studies of Elderly Diabetic Patients Comparing AVANDIA with Pioglitazone

In this section all mentions of comparing Avandia to pioglitazone have been replaced with comparing Avandia with pioglitazone.

5.2 Major Adverse Cardiovascular Events

Mortality in Observational Studies of AVANDIA Compared with Pioglitazone

In this section all mentions of comparing Avandia to pioglitazone have been replaced with comparing Avandia with pioglitazone.

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

Medication Guide

What should I tell my doctor before taking AVANDIA?

Tell your doctor about all of the medicines you take including prescription and over the-counter medicines, vitamins, or herbal supplements.