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.

D.H.E. 45 (NDA-005929)

(DIHYDROERGOTAMINE MESYLATE)

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

Download Data

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05/09/2022 (SUPPL-45)

Approved Drug Label (PDF)

5 Warnings and Precautions

Precautions

Newly added information:

Pregnancy

Risk Summary

Available data from published literature indicate an increased risk of preterm delivery with D.H.E. 45 use during pregnancy. Avoid use of D.H.E. 45 during pregnancy (see WARNINGS). Data collected over decades have shown no increased risk of major birth defects or miscarriage with the use of dihydroergotamine mesylate during pregnancy.

In animal reproduction studies, adverse effects on development were observed following intranasal administration of dihydroergotamine mesylate during pregnancy (decreased fetal body weight and/or skeletal ossification) in rats and rabbits or during pregnancy and lactation in rats (decreased body weight and impaired reproductive function in the offspring) at doses that were not associated with maternal toxicity (see Data).

The estimated rate of major birth defects (2.2% to 2.9%) and miscarriage (17%) among deliveries to women with migraine are similar to rates reported in women without migraine. 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 miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

Intranasal administration of dihydroergotamine mesylate to pregnant rats throughout the period of organogenesis resulted in decreased fetal body weight and/or skeletal ossification at doses of 0.16 mg/day and greater. A no-effect level for adverse effects on embryofetal development was not identified in rats. Intranasal administration of dihydroergotamine mesylate to pregnant rabbits throughout organogenesis resulted in decreased skeletal ossification at 3.6 mg/day. The no-effect dose for adverse effects on embryofetal development in rabbits was 1.2 mg/day.

Intranasal administration of dihydroergotamine mesylate to female rats throughout pregnancy and lactation resulted in decreased body weight and impaired reproductive function (decreased mating indices) in the offspring at doses of 0.16 mg/day or greater. A no-effect dose for adverse effects on pre- and postnatal development in rats was not established. Effects on offspring development occurred at doses below those that produced evidence of maternal toxicity in these studies.

Dihydroergotamine-induced intrauterine growth retardation has been attributed to reduced uteroplacental blood flow resulting from prolonged vasoconstriction of the uterine vessels and/or increased myometrial tone.

Nursing Mothers

Risk Summary

There are no data on the presence of dihydroergotamine in human milk; however, ergotamine, a related drug, is present in human milk. There are reports of vomiting, diarrhea, weak pulse, and unstable blood pressure in breastfed infants exposed to ergotamine. D.H.E. 45 may reduce milk supply because it may decrease prolactin levels.

Warnings

Newly added information:

Medication Overuse Headache

Overuse of acute migraine drugs (e.g., ergotamines, triptans, opioids, or a combination of these drugs for 10 or more days per month) may lead to exacerbation of headache (i.e., medication overuse headache). Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Detoxification of patients including withdrawal of the overused drugs and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary.

Preterm Labor

Based on the mechanism of action of dihydroergotamine and findings from the published literature, D.H.E. 45 may cause preterm labor. Avoid use of D.H.E. 45 during pregnancy (see PRECAUTIONS).

Impairment of Fertility

Intranasal administration of dihydroergotamine to rats at doses up to 1.6 mg/day was not associated with adverse effects on fertility.

6 Adverse Reactions

Newly added information:

To report SUSPECTED ADVERSE REACTIONS, contact Bausch Health US, LLC at 1- 800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Because of the potential for reduced milk supply and serious adverse events in the breastfed infant, including diarrhea, vomiting, weak pulse, and unstable blood pressure, advise patients not to breastfeed during treatment with D.H.E. 45 and for 3 days after the last dose. Breast milk supply during this time should be pumped and discarded.

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

Patient Information

Newly added information:

D.H.E. 45 may cause preterm labor. D.H.E. 45 should be avoided during pregnancy. Talk to your healthcare provider right away if you are pregnant or want to become pregnant.

Are you breastfeeding?
- D.H.E. 45 may reduce breast milk supply and pass into your breast milk. D.H.E. 45 may be harmful to your baby. Do not breastfeed your baby while taking D.H.E. 45 and for 3 days after you use D.H.E. 45. Talk with your healthcare provider about the best way to feed your baby if you take D.H.E. 45.