ferric carboxymaltose (Rx)

1-10%

Nausea (7.2%)

Hypertension (3.8%)

Flushing (3.6%)

Decreased blood phosphorus (2.1%)

Dizziness (2%)

Vomiting (1.7%)

Pruritus (1.5%)

Rash (1.5%)

Urticaria (1.5%)

Wheezing (1.5%)

Injection site discoloration (1.4%)

Headache (1.2%)

Increased alanine aminotransferase (1.1%)

Dysgeusia (1.1%)

Hypotension 1%)

<1%

Constipation (0.5%)

Serious anaphylactic/anaphylactoid reactions (0.1%)

Postmarketing Reports

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

Contraindications

Hypersensitivity

Cautions

Hypertension reported; transient elevations in systolic BP were observed and sometimes occurred with facial flushing, dizziness, or nausea; monitor patients for signs and symptoms of hypertension following the administration of the product

Laboratory assays may overestimate serum iron and transferrin bound iron in the 24 hr following administration

Hypophosphatemia

• Symptomatic hypophosphatemia requiring clinical intervention has been reported in patients at risk of low serum phosphate in 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

Serious hypersensitivity reactions

• Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported
• Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse
• Monitor for signs and symptoms of hypersensitivity during and after administration for at least 30 minutes and until clinically stable following completion of the infusion
• Only administer when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions

Pregnancy

Studies on use in pregnant women have not reported adverse developmental outcomes; however, these studies cannot establish or exclude absence of any drug-related risk during pregnancy because studies were not designed to assess for risk of major birth defects; there are risks to mother and fetus associated with untreated iron deficiency anemia (IDA) in pregnancy

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

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, which may cause fetal bradycardia, especially during second and third trimester

Lactation

Available published data on 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 breastfed infant; among breastfed infants, there were no adverse events reported that were considered related to ferric carboxymaltose exposure through breastmilk

There is no information on effects of ferric carboxymaltose on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy in addition to any potential adverse effects on breastfed child from drug or from underlying maternal condition; monitor breastfed infants for gastrointestinal toxicity

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Non-dextran, IV is a colloidal iron hydroxide in complex with carboxymaltose, a carbohydrate polymer that releases iron; replaces iron stores found in hemoglobin, myoglobin, and enzymes; works to transport oxygen via hemoglobin

RBC uptake of iron released from ferric carboxymaltose ranges between 61-99%; in patients with IDA, uptake was 91-99% at day 24; in patients with renal anemia, RBC update was 61-84% at day 24

Pharmacokinetics

Maximum Fe levels: 37-333 mcg/mL (15 min to 1.21 hr post dose)

Vd: 3 L

Half-life, terminal: 7-12 hr

Excretion: Negligible renal elimination

IV Preparation

Inspect parenteral drug products visually for the absence of particulate matter and discoloration prior to administration

Contains no preservatives

Each vial is intended for single-use only

Discard any unused drug remaining after injection

For IV infusion, dilute in up to 250 mL 0.9% NaCl; resulting concentration should be ≥2 mg/mL

IV Administration

IV push: May administer undiluted at rate of 100 mg/minute

IV infusion: Dilute dose in up to 250 mL 0.9% NaCl and infuse over at least 15 minutes

Storage

Store unopened vials at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)

Do not freeze