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.

CYANOKIT (NDA-022041)

(HYDROXOCOBALAMIN)

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

Download Data

Expand all

12/31/2018 (SUPPL-19)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Risk of Anaphylactic and Other Hypersensitivity Reactions replaces ALLERGIC REACTIONS

Newly added subsection:

5.3 Risk of Renal Injury

Cases of acute renal failure with acute tubular necrosis, renal impairment, and urine calcium oxalate crystals have been reported. In some situations, hemodialysis was required to achieve recovery. Regular monitoring of renal function, including but not limited to blood urea nitrogen (BUN) and serum creatinine, should be performed for 7 days following CYANOKIT therapy.

Additions and/or revisions underlined:

5.4 Risk of Increased Blood Pressure

… These elevations were generally transient and returned to baseline levels within 4 hours of dosing. Monitor blood pressure during treatment with CYANOKIT.

5.7 Use of Blood Cyanide Assay

While determination of blood cyanide concentration is not required for management of cyanide poisoning …

6 Adverse Reactions

Additions and/or revisions underlined:

Serious adverse reactions with hydroxocobalamin include … renal injury …

6.1 Clinical Studies Experience

Experience in Healthy Subjects

A double-blind, randomized, placebo-controlled, single-ascending-dose (2.5, 5, 7.5, and 10 g) study was conducted to assess the safety, tolerability, and pharmacokinetics of hydroxocobalamin in 136 healthy adult subjects. Because of the dark red color of hydroxocobalamin, the two most frequently occurring adverse reactions were chromaturia (red-colored urine) which was reported in all subjects receiving a 5 g dose or greater; and erythema (skin redness), which occurred in most subjects receiving a 5 g dose or greater. Adverse reactions reported in at least 5% of the 5 g dose group and corresponding rates in the 10 g and placebo groups are shown in Table 3.

Table 3 Incidence of Adverse Reactions Occurring in >5% of Subjects in 5 g Dose Group and Corresponding Incidence in 10 g Dose Group and Placebo Table moved to this subsection.

Newly added subsection:

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of CYANOKIT. Because adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency.

Cases of acute renal failure with acute tubular necrosis, renal impairment, and urine calcium oxalate crystals have been reported in patients treated with CYANOKIT.

7 Drug Interactions

Additions and/or revisions underlined:

Formal drug interaction studies have not been conducted with CYANOKIT.

Interference with Laboratory Tests

Because of its deep red color, hydroxocobalamin has been found to interfere with colorimetric determination of certain laboratory parameters (e.g., clinical chemistry, hematology, coagulation, and urine parameters). Be aware of this when reporting and interpreting laboratory results.

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

PATIENT COUNSELING INFORMATION

Newly added information:

Renal Function Monitoring

Advise patients that renal function will be monitored for 7 days following treatment with CYANOKIT or, in the event of renal impairment, until renal function returns to normal.

12/31/2018 (SUPPL-20)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

8.2 Lactation

PLLR conversion; extensive changes. Please refer to label for complete information.

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Pregnancy

Advise pregnant women that maternal cyanide poisoning results in fetal cyanide poisoning. Treatment for cyanide poisoning may be lifesaving for both the pregnant woman and fetus. Advise females of reproductive potential to notify their provider if they were pregnant during therapy with CYANOKIT.

Lactation

Advise women that breastfeeding is recommended during treatment with CYANOKIT.