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.

EDARBYCLOR (NDA-202331)

(AZILSARTAN KAMEDOXOMIL; CHLORTHALIDONE)

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

Download Data

Expand all

03/09/2020 (SUPPL-16)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Fetal Toxicity

Additions and/or revisions underlined:
Azilsartan medoxomil

6 Adverse Reactions

6.2 Postmarketing Experience

Addition of ‘loss of consciousness’ to bulleted listing

8 Use in Specific Populations

8.1 Pregnancy

PLLR conversion; additions and/or revisions underlined:

Risk Summary

Edarbyclor can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death (see Clinical Considerations). Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents.

When pregnancy is detected, discontinue Edarbyclor as soon as possible.

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 2-4% and 15-20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryo/fetal risk

Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly.

Fetal/Neonatal adverse reactions

Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death.

Perform serial ultrasound examinations to assess the intra-amniotic environment. … Closely observe infants with histories of in utero exposure to Edarbyclor for hypotension, oliguria, and hyperkalemia. In neonates with a history of in utero exposure to Edarbyclor, if oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.

Chlorthalidone

Thiazides cross the placenta and use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice, thrombocytopenia, and possible other adverse reactions that have occurred in adults.

Data

Animal Data

Edarbyclor

The safety profiles of azilsartan medoxomil and chlorthalidone monotherapy have been individually established …

Azilsartan medoxomil

Reproductive Toxicology: In peri- and postnatal rat development studies, adverse effects on pup viability, delayed incisor eruption and dilatation of the renal pelvis along with hydronephrosis were seen when azilsartan medoxomil was administered to pregnant and nursing rats at 1.2 times the MRHD on a mg/m2 basis. Reproductive toxicity studies indicated that azilsartan medoxomil was not teratogenic when administered at oral doses up to 1000 mg azilsartan medoxomil/kg/day to pregnant rats (122 times the MRHD on a mg/m2 basis) or up to 50 mg azilsartan medoxomil/kg/day to pregnant rabbits (12 times the MRHD on a mg/m2 basis). M-II also was not teratogenic in rats or rabbits at doses up to 3000 mg M- II/kg/day. Azilsartan crossed the placenta and was found in the fetuses of pregnant rats and was excreted into the milk of lactating rats.

8.2 Lactation

PLLR conversion; additions and/or revisions underlined:

Risk Summary

There is limited information regarding the presence of azilsartan in human milk, the effects on the breastfed infant, or the effects on milk production. Azilsartan is present in rat milk. Thiazide-like diuretics like chlorthalidone are excreted in human milk. Because of the potential for adverse effects on the nursing infant, advise a nursing woman that breastfeeding is not recommended during treatment with Edarbyclor.

10/24/2016 (SUPPL-11)

4 Contraindications

Do not coadminister aliskiren-containing products with Edarbyclor in patients with diabetes. (addition underlined)

6 Adverse Reactions

6.2 Postmarketing Experience

The following adverse reactions have been identified during the postmarketing use of EDARBYCLOR…

Addition of the following:

Syncope
Loss of Consciousness