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.

MESNEX (NDA-019884)

(MESNA)

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

Download Data

Expand all

12/17/2018 (SUPPL-16)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.3 Benzyl Alcohol Toxicity

(additions underlined)

Serious adverse reactions including fatal reactions and the “gasping syndrome” occurred in premature neonates and low-birth weight infants who received benzyl alcohol dosages of 99 to 234 mg/kg/day (blood levels of benzyl alcohol were 0.61 to 1.378 mmol/L). Symptoms associated with “gasping syndrome” and other potential adverse reactions include gradual neurological deterioration, seizures, intracranial hemorrhage, hematological abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Premature neonates and low-birth weight infants may be more likely to develop these reactions because they may be less able to metabolize benzyl alcohol. The minimum amount of benzyl alcohol at which toxicity may occur is not known. MESNEX injection contains 10.4 mg of the preservative benzyl alcohol. Avoid use of MESNEX injection in premature neonates and low-birth weight infants. MESNEX tablets do not contain benzyl alcohol.

8 Use in Specific Populations

8.1 Pregnancy

PLLR conversion)

Risk Summary

MESNEX is used in combination with ifosfamide or other cytotoxic agents. Ifosfamide can cause fetal harm when administered to a pregnant woman. Refer to the ifosfamide prescribing information for more information on use during pregnancy.

MESNEX injection contains the preservative benzyl alcohol. Because benzyl alcohol is rapidly metabolized by a pregnant woman, benzyl alcohol exposure in the fetus is unlikely.

The estimated background risk of major birth defects and miscarriage for the indicated populations are 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.

Data

Animal Data

MESNEX is used in combination with ifosfamide or other cytotoxic agents. Ifosfamide can cause fetal harm including embryo-fetal lethality. Refer to the ifosfamide prescribing information for more information on use during pregnancy.

In embryo-fetal development studies, oral administration of mesna to pregnant rats (500, 1000, 1500, and 2000 mg/kg) and rabbits (500 and 1000 mg/kg) during the period of organogenesis revealed no adverse developmental outcomes at doses approximately 10 times the maximum recommended total daily human equivalent dose based on body surface area.

8.2 Lactation

(PLLR conversion)

Risk Summary

MESNEX is used in combination with ifosfamide or other cytotoxic agents. Ifosfamide is excreted in breast milk. Refer to the ifosfamide prescribing information for more information on use during lactation. There are no data on the presence of mesna in human or animal milk, the effect on the breastfed child, or the effect on milk production.

MESNEX injection contains the preservative benzyl alcohol. Because benzyl alcohol is rapidly metabolized by a lactating woman, benzyl alcohol exposure in the breastfed infant is unlikely. However, adverse reactions have occurred in premature neonates and low birth weight infants who received intravenously administered benzyl alcohol-containing drugs.

Because of the potential for serious adverse reactions in a breastfed child, advise lactating women not to breastfeed during treatment and for 1 week after the last dose of MESNEX or ifosfamide.

8.3 Females and Males of Reproductive Potential

(PLLR conversion)

Pregnancy Testing

Verify the pregnancy status of females of reproductive potential prior to initiation of MESNEX in combination with ifosfamide.

Contraception

Females

Advise females of reproductive potential to use effective contraception during treatment with MESNEX in combination with ifosfamide and for 6 months after the last dose.

Males

Advise males with female partners of reproductive potential to use effective contraception during treatment with MESNEX in combination with ifosfamide and for 3 months after the last dose.

8.4 Pediatric Use

(subsection revised, additions underlined)

MESNEX injection contains the preservative benzyl alcohol which has been associated with serious adverse reactions and death administered intravenously to premature neonates and low birth weight infants. Avoid use of MESNEX injection in premature neonates and low-birth weight infants.

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

PATIENT COUNSELING INFORMATION

(additions underlined)

…

Benzyl Alcohol Toxicity

Advise patients that serious adverse reactions are associated with the benzyl alcohol found in MESNEX and other medications in premature neonates and low-birth weight infants.

Embryo-Fetal Toxicity

MESNEX is used in combination with ifosfamide. Ifosfamide or other cytotoxic agents can cause fetal harm when administered to a pregnant woman. Inform female patients of the risk to a fetus and potential loss of the pregnancy. Advise females to inform their healthcare provider if they are pregnant or become pregnant.

Contraception

Advise females of reproductive potential to use effective contraception during treatment with MESNEX in combination with ifosamide and for 6 months after the last dose.
Advise male patients with female partners of reproductive potential to use effective contraception during treatment with MESNEX in combination with ifosamide and for 3 months after the last dose.

Lactation

Advise lactating women not to breastfeed during treatment with MESNEX or ifosfamide and for 1 week after the last dose.

Patient Information

(additions, please refer to label for more information)

Other

(PLLR conversion)