Drug Safety-related Labeling Changes (SrLC)

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INJECTAFER (NDA-203565)

(FERRIC CARBOXYMALTOSE)

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

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09/11/2020 (SUPPL-13)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

… 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 Injectafer) which may cause fetal bradycardia, especially during the second and third trimester.

8.2 Lactation

Additions and/or revisions underlined:

Clinical Considerations

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

02/19/2020 (SUPPL-9)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Symptomatic Hypophosphatemia

(new subsection added)

Symptomatic hypophosphatemia requiring clinical intervention has been reported in patients at risk of low serum phosphate in the postmarketing setting. These cases have occurred mostly after repeated exposure to Injectafer in patients with no reported history of renal impairment. Possible risk factors for hypophosphatemia include a history of gastrointestinal disorders associated with malabsorption of fat-soluble vitamins or phosphate, concurrent or prior use of medications that affect proximal renal tubular function, hyperparathyroidism, vitamin D deficiency and malnutrition.  In most cases, hypophosphatemia resolved within three months.

 

Monitor serum phosphate levels in patients at risk for low serum phosphate who require a repeat course of treatment.

6 Adverse Reactions

(additions underlined)

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling:

  • Hypophosphatemia

 

6.2 Post-marketing Experience

(subsection revised, addition underlined)

The following adverse reactions have been reported from the post-marketing spontaneous reports with Injectafer:

 

  • Cardiac disorders: Tachycardia

  • General disorders and administration site conditions: Chest discomfort, chills, pyrexia

  • Metabolism and nutrition disorders:  Hypophosphatemia

  • Musculoskeletal and connective tissue disorders:  Arthralgia, back pain, hypophosphatemic osteomalacia (rarely reported event)

  • Nervous system disorders: Syncope

  • Respiratory, thoracic and mediastinal disorders: Dyspnea

  • Skin and subcutaneous tissue disorders: Angioedema, erythema, pruritus, urticaria

01/26/2018 (SUPPL-5)

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 the use of ferric carboxymaltose in pregnant women have not reported an association with ferric carboxymaltose and adverse developmental outcomes. However, these studies cannot establish or exclude the absence of any drug-related risk during pregnancy because the studies were not designed to assess for the risk of major birth defects (see Data). There are risks to the mother and fetus associated with untreated iron deficiency anemia (IDA) in pregnancy.

In animal reproduction studies, administration of ferric carboxymaltose to rabbits during the period of organogenesis caused adverse developmental outcomes including fetal malformations and increased implantation loss at maternally toxic doses of approximately 12% to 23% of the human weekly dose of 750 mg (based on body surface area).

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

Untreated iron deficiency anemia (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, prospective observational studies and retrospective studies on the use of ferric carboxymaltose in pregnant women have not reported an association with ferric carboxymaltose and adverse developmental outcomes. However, these studies cannot establish or exclude the absence of any drug-related risk during pregnancy because of methodological limitations, including that the studies were not primarily designed to capture safety data nor 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

Administration of ferric carboxymaltose to rats as a one-hour intravenous infusion up to 30 mg/kg/day iron on gestation days 6 to 17 did not result in adverse embryonic or fetal findings… Adverse embryonic or fetal effects were observed in the presence of maternal toxicity.

8.2 Lactation

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

Risk Summary

The available published data on the use of ferric carboxymaltose in lactating women demonstrate that iron is present in breast milk. However, the data do not inform the full potential exposure of iron for the breastfed infant. Among the breastfed infants, there were no adverse events reported that were considered related to ferric carboxymaltose exposure through breastmilk. There is no information on the effects of ferric carboxymaltose on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Injectafer in addition to any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition.

 

Clinical Considerations

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

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

Patient Information

(Additions and/or revisions are underlined)

What is INJECTAFER?

INJECTAFER is a prescription iron replacement medicine used to treat iron deficiency anemia in adults who have:

  • intolerance to oral iron or who have not responded well to treatment with oral iron

  • non-dialysis dependent chronic kidney disease

It is not known if INJECTAFER is safe and effective for use in children.

Who should not receive INJECTAFER?

Do not receive INJECTAFER if you are allergic to ferric carboxymaltose or any of the ingredients in INJECTAFER. See the end of this leaflet for a complete list of ingredients in INJECTAFER.

Before receiving INJECTAFER, tell your healthcare provider about all of your medical conditions, including if you:

  • have had an allergic reaction to iron given into your vein

  • have high blood pressure

  • are pregnant or plan to become pregnant. It is not known if INJECTAFER will harm your unborn baby.

  • are breastfeeding or plan to breastfeed. INJECTAFER passes into your breast milk. It is unknown whether INJECTAFER would pose a risk to your baby. Talk to your healthcare provider about the best way to feed your baby during treatment with INJECTAFER.

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

How will I receive INJECTAFER?

INJECTAFER is given intravenously (into your vein) by your healthcare provider in 2 doses at least 7 days apart.

What are the possible side effects of INJECTAFER?

INJECTAFER may cause serious side effects, including:

  • Allergic (hypersensitivity) reactions. Serious life-threatening allergic reactions have happened in people who receive INJECTAFER. Other serious reactions including itching, hives, wheezing, and low blood pressure also have happened during treatment with INJECTAFER. Tell your healthcare provider if you have ever had any unusual or allergic reaction to any iron given by vein.

  • High blood pressure (hypertension). High blood pressure, sometimes with face flushing, dizziness, or nausea, has happened during treatment with INJECTAFER. Your healthcare provider will check your blood pressure and check for any signs and symptoms of high blood pressure after you receive INJECTAFER.

The most common side effects of INJECTAFER include:

  • nausea

  • flushing

  • dizziness

  • high blood pressure

  • low levels of phosphorous in your blood

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about INJECTAFER

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your pharmacist or healthcare provider for information about INJECTAFER that is written for health professionals.

What are the ingredients in INJECTAFER?

Active ingredient: ferric carboxymaltose

Inactive ingredients: water for injection. Sodium hydroxide and/or hydrochloric acid may have been added to adjust pH to 5.0-7.0.

Questions related to the drug data in these files should be directed to the Center for Drug Evaluation and Research, Division of Drug Information
druginfo@fda.hhs.gov.

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