ferric carboxymaltose (Rx)

>10%

Pediatric patients

• Hypophosphatemia (13%)

1-10%

Adults

• Nausea (1-7.2%)
• Injection site reactions (3-4%)
• Hypertension (1-4%
• Flushing (0.3-4%)
• Erythema (0.3-3%)
• Dizziness (1-2.1%)
• Hyperphosphatemia (1-2.1%)
• Vomiting (0.2-2%
• Injection site extravasation (0.2-2%)
• Injection site discoloration (<1.4%)
• Headache (1-1.3%)
• Hepatic enzyme increased (1.2%)
• Rash (1-1.2%)
• Dysgeusia (1-1.2%)
• Hypotension (<1%)

Pediatric patients

• Injection site reactions (8%)
• Rash (8%)
• Headache (5%)
• Vomiting (5%)
• Nasopharyngitis (3%)
• Flushing (3%)
• Gastrointestinal infections (3%)
• Liver function test increased (3%)
• Platelet count decreased (3%)
• White blood cell count decreased (3%)

<1%

Adults

• Constipation (0.5%)

Postmarketing Reports

Adults

• 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
• Pregnancy: Fetal bradycardia

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

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

Data are insufficient to assess risk of major birth defects and miscarriage

Animal data

• Administration of ferric carboxymaltose to rabbits during organogenesis caused adverse developmental outcomes including malformations and increased implantation loss at maternally toxic doses of ~12-23% of the human weekly dose of 750 mg (based on body surface area)

Clinical considerations

• There are risks to mother and fetus associated with untreated IDA in pregnancy
• Untreated IDA in pregnancy is associated with adverse maternal outcomes such as postpartum 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, which may cause fetal bradycardia, especially during second and third trimester

Lactation

Available published data on use in lactating females demonstrate that iron is present in breast milk

Adverse reactions like constipation and diarrhea reported in the breastfed infants but not considered related to drug exposure

There is no information on effects on milk production

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

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

Absorption

Peak plasma concentration: 37-333 mcg/mL

Peak plasma time: 0.25-1.21 hr

Distribution

Vd: 3 L

Elimination

Half-life: 7-12 hr

Renal elimination of iron was negligible

IV Compatibilities

0.9% NaCl

IV Preparation

Visually inspect vials for particulate matter and discoloration before 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 2-4 mg/mL

IV Administration

IV infusion: Infuse over at least 15 minutes

IV push

• 750-mg dose: Infuse over ~100 mg/min
• 1000-mg dose: Infuse over 15 mg/min
• Discard any unused portion

Extravasation

• Avoid extravasation since brown discoloration of site may be long lasting
• Monitor for extravasation; if extravasation occurs, discontinue administration at that site

Storage

Unopened vials

• Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
• Do not freeze

Diluted solutions

• Store at room temperature for 72 hr
• Do not dilute to concentration less than 2 mg iron/mL to maintain physical and chemical stability