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.

COUMADIN (NDA-009218)

(WARFARIN SODIUM)

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

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08/14/2017 (SUPPL-118)

Approved Drug Label (PDF)

8 Use in Specific Populations

Additions and/or revisions underlined

8.5 Geriatric Use

… COUMADIN is contraindicated in any unsupervised patient with senility. Conduct more frequent monitoring for bleeding with administration of COUMADIN to elderly patients in any situation …

8.7 Hepatic Impairment

… impaired synthesis of clotting factors and decreased metabolism of warfarin. Conduct more frequent monitoring for bleeding when using COUMADIN in these patients.

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

PATIENT COUNSELING INFORMATION

Instructions for Patients

Advise patient to:

Addition of the following:

Immediately contact their physician when experiencing pain and discoloration of the skin (a purple bruise like rash) mostly on areas of the body with a high fat content, such as breasts, thighs, buttocks, hips and abdomen.
Immediately contact their physician when experiencing any unusual symptom or pain since COUMADIN may cause small cholesterol or athero emboli. On feet it may appear as a sudden cool, painful, purple discoloration of toe(s) or forefoot.
Immediately contact their physician when taking COUMADIN after any heparin formulation therapy and experiencing bloody or black stools or appearence of bruises, or bleeding.
To tell all of their healthcare professionals and dentists that they are taking COUMADIN. This should be done before they have any surgery or dental procedure.
Pregnancy and Nursing
Additions and/or revisions underlined
Advise patients to:

Notify their physician if they are pregnant or planning to become pregnant or considering breast feeding.
Avoid COUMADIN during pregnancy except in pregnant women with mechanical heart valves, who are at risk of thromboembolism. Use effective measures to avoid pregnancy while taking COUMADIN. This is very important because their unborn baby could be seriously harmed if they take COUMADIN while they are pregnant.

05/22/2017 (SUPPL-117)

Approved Drug Label (PDF)

5 Warnings and Precautions

Addition of the following:

5.4 Acute Kidney Injury

In patients with altered glomerular integrity or with a history of kidney disease, acute kidney injury may occur with COUMADIN, possibly in relation to episodes of excessive anticoagulation and hematuria. More frequent monitoring of anticoagulation is advised in patients with compromised renal function.

6 Adverse Reactions

Additions and/or revisions underlined:

The following serious adverse reactions to COUMADIN are discussed in greater detail in other sections of the labeling:

Tissue Necrosis
Acute Kidney Injury
Limb Ischemia, Necrosis, and Gangrene in Patients with HIT and HITTS
Other Clinical Settings with Increased Risks

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

Risk Summary

… risks of COUMADIN and possible risks to the fetus when prescribing COUMADIN to a pregnant woman.

Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population …

8.6 Renal Impairment

Additions and/or revisions underlined:

… No dosage adjustment is necessary for patients with renal impairment. Instruct patients with renal impairment taking warfarin to monitor their INR more frequently.

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

MEDICATION GUIDE

Additions and/or revisions underlined:

What are the possible side effects of COUMADIN?

COUMADIN may cause serious side effects, including:

Death of skin tissue (skin necrosis or gangrene) … Call your healthcare provider right away if you have pain, color, or temperature change to any area of your body. You may need medical care right away to prevent death or loss (amputation) of your affected body part.
Kidney problems. Kidney injury may happen in people who take COUMADIN. Tell your healthcare provider right away if develop blood in your urine. Your healthcare provider may do tests more often during treatment with COUMADIN to check for bleeding if you already have kidney problems.

General information about the safe and effective use of COUMADIN.

09/08/2016 (SUPPL-116)

Approved Drug Label (PDF)

5 Warnings and Precautions

Calciphylaxis

Fatal and serious calciphylaxis or calcium uremic arteriolopathy has been reported in patients with and without end-stage renal disease. When calciphylaxis is diagnosed in these patients, discontinue COUMADIN and treat calciphylaxis as appropriate. Consider alternative anticoagulation therapy.

6 Adverse Reactions

The following serious adverse reactions to COUMADIN are discussed in greater detail in other sections of the labeling:

Calciphylaxis (added)

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

Patient Counseling Information (Extensively revised; see below)

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Instructions for Patients

Advise patients to:
- Strictly adhere to the prescribed dosage schedule
- If the prescribed dose of COUMADIN is missed, take the dose as soon as possible on the same day but do not take a double dose of COUMADIN the next day to make up for missed doses
- Obtain prothrombin time tests and make regular visits to their physician or clinic to monitor therapy.
- Be aware that if therapy with COUMADIN is discontinued, the anticoagulant effects of COUMADIN may persist for about 2 to 5 day.
- Avoid any activity or sport that may result in traumatic injury. And to tell their physician if they fall often as this may increase their risk for complications.
- Eat a normal, balanced diet to maintain a consistent intake of vitamin K. Avoid drastic changes in dietary habits, such as eating large amounts of leafy, green vegetables.
- Contact their physician to report any serious illness, such as severe diarrhea, infection, or fever.
- Carry identification stating that they are taking COUMADIN.

Bleeding Risks

Advise patients to:

Notify their physician immediately if any unusual bleeding or symptoms occur. Signs and symptoms of bleeding include: pain, swelling or discomfort, prolonged bleeding from cuts, increased menstrual flow or vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or dark brown urine, red or tar black stools, headache, dizziness, or weakness.

Concomitant Medications and Botanicals (Herbals)

Advise patients to:
- Not take or discontinue any other drug, including salicylates (e.g., aspirin and topical analgesics), other over-the-counter drugs, and botanical (herbal) products except on advice of your physician.

Pregnancy and Nursing

Advise patients to:
- Contact their doctor,
- immediately if they think they are pregnant,
- to discuss pregnancy planning,
- if they are considering breastfeeding.