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.

ARGATROBAN IN SODIUM CHLORIDE (NDA-022434)

(ARGATROBAN)

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

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06/18/2018 (SUPPL-11)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Use in Hepatic Impairment

Additions and/or revisions underlined:

When administering argatroban to patients with hepatic impairment, start with a lower dose and carefully titrate until the desired level of anticoagulation is achieved. Achievement of steady-state aPTT levels may take longer and require more argatroban dose adjustments in patients with hepatic impairment compared to patients with normal hepatic function … Avoid the use of high doses of argatroban in patients undergoing PCI who have clinically significant hepatic disease …

6 Adverse Reactions

Addition of the following:

The following serious adverse reactions are described elsewhere in the labeling:

Risk of Hemorrhage

6.1 Clinical Trials Experience

Adverse Events in Patients with HIT …

8 Use in Specific Populations

8.1 Pregnancy

PLLR conversion; addition of the following:

Risk Summary

Limited data from published literature and postmarketing reports do not suggest an association between argatroban and adverse fetal developmental outcomes. There are risks to the mother associated with untreated thrombosis in pregnancy and risk of hemorrhage in the mother and fetus associated with the use of anticoagulations. In animal reproductive studies, there was no evidence of adverse developmental outcomes with intravenous administration of argatroban during organogenesis in rats and rabbits at doses up to 0.3-and 0.2-times, respectively, the maximum recommended human dose (MHRD).

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

Pregnancy confers an increased risk for thromboembolism that is higher for women with underlying thromboembolic disease and certain high risk pregnancy conditions. Published data describe that women with a previous history of venous thrombosis are at high risk for recurrence during pregnancy.

Fetal/Neonatal Adverse Reactions

Use of anticoagulants, including argatroban, may increase the risk of bleeding in the fetus and neonate. Monitor neonates for bleeding.

Labor or Delivery

All patients receiving anticoagulants, including pregnant women, are at risk for bleeding. Pregnant women receiving argatroban should be carefully monitored for evidence of excessive bleeding or unexpected changes in coagulation parameters.

Data

Animal Data

Developmental studies performed in rats (during gestation Days 7 to 17) with argatroban at intravenous doses up to 27 mg/kg/day (0.3 times the maximum recommended human dose, based on body surface area) and in rabbits (during gestation Days 6 to 18) at intravenous doses up to 10.8 mg/kg/day … have revealed no evidence of harm to the fetus.

8.2 Lactation

PLLR conversion; additions and/or revisions underlined:

Risk Summary

There are no data on the presence of argatroban in human milk, or its effects on milk production. Argatroban is present in rat milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Argatroban and any potential adverse effects on the breastfed infant from Argatroban or from the underlying maternal condition.

Data

Argatroban is detected in rat milk.

8.4 Pediatric Use

Extensively changed; please refer to label for complete information.