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.

ANGIOMAX (NDA-020873)

(BIVALIRUDIN)

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

Download Data

Expand all

12/21/2018 (SUPPL-37)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Bleeding Events

(Additions and/or revisions are underlined)

Angiomax increases the risk of bleeding. An unexplained fall in blood pressure or hematocrit should lead to serious consideration of a hemorrhagic event and cessation of Angiomax administration. Monitor patients receiving Angiomax for signs and symptoms of bleeding. Monitor patients with disease states associated with an increased risk of bleeding more frequently for bleeding.

6 Adverse Reactions

6.1 Clinical Trials Experience

(Additions and/or revisions are underlined)

In the BAT trials, 79 of the 2161 (3.7%) patients undergoing PCI for treatment of unstable angina and randomized to Angiomax experienced major bleeding events which consisted of: intracranial bleeding, retroperitoneal bleeding and clinically overt bleeding with a decrease in hemoglobin greater than or equal to 3 g/dL or leading to a transfusion of >2 units of blood.

6.2 Immunogenicity

(Additions and/or revisions are underlined)

As with all peptides, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Angiomax in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

8 Use in Specific Populations

8.1 Pregnancy

(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; Additions and/or revisions are underlined)

Risk Summary

There are no data available on use of Angiomax in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Reproduction studies in rats and rabbits administered subcutaneously doses up to 1.6 times and 3.2 times the maximum recommended human dose (MRHD) of 15 mg/kg/day based on body surface area (BSA) during organogenesis, respectively, revealed no evidence of fetal harm.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and 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 2–4% and 15–20%, respectively.

Data

Animal Data

Reproductive studies have been performed in rats at subcutaneous doses up to 150 mg/kg/day, (1.6 times the maximum recommended human dose based on body surface area) and rabbits at subcutaneous doses up to 150 mg/kg/day (3.2 times the maximum recommended human dose based on body surface area). These studies revealed no harm to the fetus attributable to bivalirudin.

At 500 mg/kg/day (equivalent to 5.4 times the maximum recommended human dose based on body surface area) subcutaneously, litter sizes and live fetuses in rats were reduced. Fetal skeletal variations were also noted. Some of these changes could be attributed to maternal toxicity observed at high doses.

There is no study covering the peri-natal period because of the potential complications of drug- induced hemorrhage during delivery.

8.2 Lactation

(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; Additions and/or revisions are underlined)

Risk Summary

It is not known whether bivalirudin is present in human milk. No data are available on the effects on the breastfed child or on milk production.

Bivalirudin was administered to lactating rats in reproduction studies (see Data). The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Angiomax and any potential adverse effects on the breastfed child from Angiomax or from the underlying maternal condition.

Data

Animal Data

Reproduction studies conducted in lactating female rats dosed subcutaneously daily with bivalirudin at doses up to 150 mg/kg/day (1.6 times the maximum recommended human dose, based on body surface area) from day 2 through day 20 of lactation revealed no adverse developmental outcomes to the pups.

8.6 Renal Impairment

(Additions and/or revisions are underlined)

The disposition of Angiomax was studied in PTCA patients with mild, moderate and severe renal impairment. The clearance of Angiomax was reduced approximately 21% in patients with moderate and severe renal impairment and was reduced approximately 70% in dialysis-dependent patients. Reduce the infusion dose of Angiomax and monitor the anticoagulant status more frequently in patients with renal impairment creatinine clearance less than 30mL/min (by Cockcroft Gault equation).

03/21/2016 (SUPPL-36)

Approved Drug Label (PDF)

5 Warnings and Precautions

Acute Stent Thrombosis in Patients with STEMI undergoing PCI

Acute stent thrombosis (AST) (<4 hours) has been observed at a greater frequency in Angiomax treated patients (1.2%, 36/2889) compared to heparin treated patients (0.2%, 6/2911) with STEMI undergoing primary PCI. Among patients who experienced an AST, one fatality (0.03%) occurred in an Angiomax treated patient and one fatality (0.03%) in a heparin treated patient.
These patients have been managed by Target Vessel Revascularization (TVR). Patients should remain for at least 24 hours in a facility capable of managing ischemic complications and should be carefully monitored following primary PCI for signs and symptoms consistent with myocardial ischemia.

Laboratory Test Interference

Angiomax affects International Normalized Ratio (INR), therefore INR measurements made in patients who have been treated with Angiomax may not be useful for determining the appropriate dose of warfarin.

6 Adverse Reactions

Postmarketing Experience

Pulmonary hemorrhage; cardiac tamponade; and INR increased.