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.

VENOFER (NDA-021135)

(IRON SUCROSE)

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

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09/11/2020 (SUPPL-36)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

Risk Summary

… There are risks to the mother and fetus associated with untreated IDA in pregnancy as well as risks to the fetus associated with maternal severe hypersensitivity reactions (see Clinical Considerations) …

Clinical Considerations

Newly added information:

Fetal/Neonatal adverse reactions

Severe adverse reactions including circulatory failure (severe hypotension, shock including in the context of anaphylactic reaction) may occur in pregnant women with parenteral iron products (such as Venofer) which may cause fetal bradycardia, especially during the second and third trimester.

12/19/2018 (SUPPL-35)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; Additions and/or revisions are underlined)

Risk Summary

Published studies on intravenous iron sucrose treatment after the first trimester of pregnancy have not shown adverse maternal or fetal outcomes. Available reports of intravenous iron sucrose use in pregnant women during the first trimester are insufficient to assess the risk of major birth defects and miscarriage. Iron deficiency anemia during pregnancy should be treated because there are risks to the mother and fetus associated with untreated iron deficiency anemia (IDA) in pregnancy. Animal reproduction studies of iron sucrose administered to rats and rabbits during the period of organogenesis at elemental iron doses equivalent to the maximum recommended human dose based on body surface area revealed no evidence of harm to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. 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.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Iron deficiency anemia during pregnancy should be treated. Untreated IDA in pregnancy is associated with adverse maternal outcomes such as post-partum anemia. Adverse pregnancy outcomes associated with IDA include increased risk for preterm delivery and low birth weight.

Data

Human Data

Published data from randomized controlled studies and prospective observational studies on the use of Venofer in pregnant women have not reported an association of Venofer and adverse developmental outcomes. However, these studies did not include women exposed during the first trimester of pregnancy and were not designed to assess the risk of major birth defects. Maternal adverse events reported in these studies are similar to those reported during clinical trials in adult males and non-pregnant females.

Animal Data

Iron sucrose was administered intravenously to rats and rabbits during the period of organogenesis at elemental iron doses up to 13 mg/kg/day (0.25 times or equivalent to the maximum recommended human dose based on body surface area, respectively) and revealed no evidence of harm to the fetus.

8.2 Lactation

(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; Additions and/or revisions are underlined)

Risk Summary

Iron sucrose is present in human milk, and available published reports following exposure to 100-300 mg intravenous iron sucrose have not reported adverse reactions in breastfed infants.

There are no data on the effects on milk production. The developmental and health benefits of breastfeeding should be considered, along with the mother’s clinical need for Venofer and any potential adverse effects on the breastfed child from Venofer or from the underlying maternal condition.

Data

A published study showed no difference in iron concentration in the colostrum of 10 iron deficient breastfeeding women who were 2 to 3 days postpartum and received a single dose of 100 mg of intravenous iron sucrose compared to 5 breastfeeding women who received no iron. These results may underestimate the amount of iron in breastmilk following the standard dose of Venofer.

A published report of 78 breastfeeding women who received 300 mg of intravenous iron sucrose over 3 days (infant age not reported) did not report on the safety of iron sucrose in breastfed infants; however adverse reactions in breastfed infants were not reported.

Clinical Considerations

Monitor breastfed infants for gastrointestinal toxicity (constipation, diarrhea).

11/28/2017 (SUPPL-32)

Approved Drug Label (PDF)

6 Adverse Reactions

(Additions and/or revisions are underlined)

The following serious adverse reactions are described elsewhere in the labeling:

Hypersensitivity Reactions
Hypotension
Iron Overload

6.2 Adverse Reactions from Post-Marketing Experience

(Additions and/or revisions are underlined)

The following adverse reactions have been identified during post-approval use of Venofer…

Immune system disorders: anaphylactic-type reactions, angioedema
Psychiatric disorders: confusion
Nervous system disorders: convulsions, collapse, light-headedness, loss-of-consciousness
Cardiac disorders: bradycardia
Vascular disorders: shock
Respiratory, thoracic and mediastinal disorders: bronchospasm, dyspnea
Musculoskeletal and connective tissue disorders: back pain, swelling of the joints
Renal and urinary disorders: chromaturia
General disorders and administration site conditions: hyperhidrosis

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

17 PATIENT COUNSELING INFORMATION

(Additions and/or revisions are underlined)

Prior History of Reactions to Parenteral Iron Products

Question patients regarding any prior history of reactions to parenteral iron products.

Serious Hypersensitivity Reactions

Advise patients to report any symptoms of hypersensitivity that may develop during and following Venofer administration, such as rash, itching, dizziness, light-headedness, swelling, and breathing problems.