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.

AMERGE (NDA-020763)

(NARATRIPTAN HYDROCHLORIDE)

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

Download Data

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11/29/2016 (SUPPL-11)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion)

Risk Summary

There are no adequate data on the developmental risk associated with use of AMERGE in pregnant women. Data from a prospective pregnancy exposure registry and epidemiological studies of pregnant women have documented outcomes in women exposed to naratriptan during pregnancy; however, due to small sample sizes, no definitive conclusions can be drawn regarding the risk of birth defects following exposure to naratriptan. In animal studies, naratriptan produced developmental toxicity (including embryolethality and fetal abnormalities) when administered to pregnant rats and rabbits. The lowest doses producing evidence of developmental toxicity in animals were associated with plasma exposures 2.5(rabbit) to 11 (rat) times that in humans at the maximum recommended daily dose (MRDD).

In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The reported rate of major birth defects among deliveries to women with migraine ranged from 2.2% to 2.9% and of miscarriage was 17%, which were similar to rates reported in women without migraine.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Several studies have suggested that women with migraine may be at increased risk of preeclampsia during pregnancy.

Data

Human Data: The numbers of exposed pregnancy outcomes accumulated during the Sumatriptan/Naratriptan/Treximet (sumatriptan and naproxen sodium) Pregnancy Registry, a population-based international prospective study that collected data from October 1997 to September 2012, and smaller observational studies, were insufficient to define a level of risk for naratriptan in pregnant women. The Registry documented outcomes of 57 infants and fetuses exposed to naratriptan during pregnancy (52 exposed during the first trimester and 5 exposed during the second trimester). The occurrence of major birth defects (excluding fetal deaths and induced abortions without reported defects and all spontaneous pregnancy losses) during first- trimester exposure to naratriptan was 2.2% (1/46 [95% CI: 0.1% to 13.0%]) and during any trimester of exposure was 2.0% (1/51 [95% CI: 0.1% to 11.8%]). Seven infants were exposed to both naratriptan and sumatriptan in utero, and one of these infants with first-trimester exposure was born with a major birth defect (ventricular septal defect). The sample size in this study had 80% power to detect at least a 3.8- to 4.6-fold increase in the rate of major malformations.

In a study using data from the Swedish Medical Birth Register, women who used triptans or ergots during pregnancy were compared with women who did not. Of the 22 births with first- trimester exposure to naratriptan, one infant was born with a malformation (congenital deformity of the hand).

Animal Data:…the incidence of fetal variations (major blood vessel variations, supernumerary ribs, incomplete skeletal ossification) was increased at the mid and high doses, and embryonic death was increased at all doses...

8.2 Lactation

(PLLR conversion)

Risk Summary

There are no data on the presence of naratriptan in human milk, the effects of naratriptan on the breastfed infant, or the effects of naratriptan on milk production. Naratriptan is present in rat milk.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for AMERGE and any potential adverse effects on the breastfed infant from naratriptan or from the underlying maternal condition.

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

17 PATIENT COUNSELING INFORMATION

(additions and/or revisions are underlined)

Pregnancy

Advise patients to notify their healthcare provider if they become pregnant during treatment or intend to become pregnant.

Lactation

Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed.

What is AMERGE?

… It is not known if AMERGE is safe and effective in children younger than 18 years of age.

What should I tell my healthcare provider before taking AMERGE?

Before you take AMERGE, tell your healthcare provider about all of your medical conditions, including if you:

Are pregnant or plan to become pregnant

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins …