Deferoxamine mesylate

Dosage and Administration, Preparation (2.3) 3/2026

1 INDICATIONS AND USAGE Deferoxamine mesylate for injection is an iron-chelating agent indicated: Limitations of Use Deferoxamine mesylate for injection is not indicated for the treatment of primary hemochromatosis (since phlebotomy is the method of choice for removing excess iron in this disorder). As an adjunct to standard measures for the treatment of acute iron intoxication. ( 1.1 ) For the treatment of transfusional iron overload in patients with chronic anemia. ( 1.2 ) Limitations of Use Deferoxamine mesylate for injection is not indicated for the treatment of primary hemochromatosis (since phlebotomy is the method of choice for removing excess iron in this disorder). 1.1 Acute Iron Intoxication Deferoxamine mesylate for injection is indicated as an adjunct to standard measures for the treatment of acute iron intoxication. 1.2 Chronic Iron Overload Deferoxamine mesylate for injection is indicated for the treatment of transfusional iron overload in patients with chronic anemia. 1.3 Limitations of Use Deferoxamine mesylate for injection is not indicated for the treatment of primary hemochromatosis (since phlebotomy is the method of choice for removing excess iron in this disorder).

2 DOSAGE AND ADMINISTRATION The dosage (based on body weight in mg/kg/day), rates of administration, and mode of administration for both adults and pediatric patients are individually determined and adapted during the course of therapy based on the severity of the patient's iron overload. The minimum daily dose of deferoxamine mesylate is 20 mg/kg/day for both adults and pediatric patients. The maximum daily dose is 40 mg/kg/day for pediatric patients and 60 mg/kg/day for adults. Acute Iron Intoxication : ( 2.1 ) • Intramuscular Administration: Use for all patients not in shock. Initial dose is 1,000 mg. Depending upon the clinical response, subsequent doses of 500 mg may be administered every 4 hours to 12 hours. Maximum dose is 6,000 mg in 24 hours. • Intravenous Administration: Only for patients in a state of cardiovascular collapse. Initial dose is 1,000 mg at a rate not to exceed 15 mg/kg/hr. Depending upon the clinical response, subsequent doses of 500 mg may be administered every 4 hours to 12 hours at a rate of up to 125 mg/hr. Maximum dose is 6,000 mg in 24 hours. Chronic Iron Overload : ( 2.2 ) • Subcutaneous Infusion: Average daily dose is between 20 and 60 mg/kg. In patients with serum ferritin level below 2,000 ng/mL require about 25 mg/kg/day. Patients with serum ferritin level between 2,000 and 3,000 ng/mL require about 35 mg/kg/day. Patients with higher serum ferritin may require up to 55 mg/kg/day. • Intravenous Administration: 20 mg/kg/day to 40 mg/kg/day for pediatric patients and 40 mg/kg/day to 50 mg/kg/day over 8 hours to 12 hours in adults for 5 days to 7 days per week. In pediatric patients and adults, maximum dose should not exceed 40 mg/kg/day and 60 mg/kg/day, respectively. • Intramuscular Administration: 500 mg to maximum daily dose of 1,000 mg. See Full Prescribing Information for instructions on preparation of Deferoxamine mesylate for administration. ( 2.3 ) Vitamin C (up to 200 mg) increases availability of iron for chelation and may be given as an adjuvant to iron chelation therapy. ( 2.4 ) 2.1 Recommended Dosage for Treatment of Acute Iron Intoxication for Adults and Pediatric Patients Intramuscular (IM) Administration Use for all patients not in shock. The initial recommended dose of Deferoxamine Mesylate for injection is 1,000 mg intramuscularly (IM) once. If needed based on the clinical response, administer subsequent doses of 500 mg every 4 hours to 12 hours. The maximum recommended daily dose is 6,000 mg in 24 hours. Intravenous (IV) Administration Administer Deferoxamine Mesylate for injection intravenously (IV) to patients in a state of cardiovascular collapse and then only by slow infusion. As soon as the clinical condition of the patient permits, intravenous administration should be discontinued, and the drug should be administered intramuscularly. The initial recommended IV dose of Deferoxamine Mesylate for injection is 1,000 mg administered at an infusion rate of up to 15 mg/kg/hr. If needed based on the clinical response administer additional doses of 500 mg over 4 hours to 12 hours at a slower infusion rate of up to 125 mg/hr. The maximum recommended daily dose is 6,000 mg in 24 hours. 2.2 Recommended Dosage for Treatment of Chronic Iron Overload for Adults and Pediatric Patients Subcutaneous Infusion Administration The average daily dose of Deferoxamine Mesylate for injection is usually between 20 and 60 mg/kg. In general patients with serum ferritin level below 2,000 ng/mL require about 25 mg/kg/day. Patients with serum ferritin level between 2,000 and 3,000 ng/mL require about 35 mg/kg/day. Patients with higher serum ferritin may require up to 55 mg/kg/day. It is not advisable to regularly exceed an average daily dose of 50 mg/kg/day except when very intensive chelation is needed in patients who have completed growth. If ferritin levels fall below 1,000 ng/mL, the risk of Deferoxamine mesylate toxicity increases; it is important to monitor these patients particularly carefully …

3 DOSAGE FORMS AND STRENGTHS For injection: 500 mg of deferoxamine mesylate (corresponding to 426.82 mg of deferoxamine as free base) as a white to off-white lyophilized powder in single-dose fliptop vial for reconstitution. For injection: 2 g of deferoxamine mesylate (corresponding to 1707.28 mg of deferoxamine as free base) as a white to off-white lyophilized powder in single-dose fliptop vial for reconstitution. For injection: 500 mg of deferoxamine mesylate as a lyophilized powder in single-dose fliptop vial for reconstitution. ( 3 ) For injection: 2 g of deferoxamine mesylate as a lyophilized powder in single-dose fliptop vial for reconstitution. ( 3 )

4 CONTRAINDICATIONS Deferoxamine mesylate for injection is contraindicated in patients with: • A history of a hypersensitivity reaction to deferoxamine or any of its inactive ingredients [see Description ( 11 )] . Reactions have included anaphylaxis [see Warnings and Precautions ( 5.1 )] . • Severe renal disease or anuria since the drug and the iron chelate are excreted primarily by the kidney [see Warnings and Precautions ( 5.3 )] . • Known hypersensitivity to the active substance. ( 4 ) • Patients with severe renal disease or anuria. ( 4 )

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] • Auditory and Ocular Toxicity [see Warnings and Precautions ( 5.2 )] • Renal Toxicity [see Warnings and Precautions ( 5.3 )] • Respiratory Toxicity [see Warnings and Precautions ( 5.4 )] • Growth Suppression [see Warnings and Precautions ( 5.5 )] • Serious Infections [see Warnings and Precautions ( 5.6 )] • Cardiac Dysfunction with Concomitant Use of Vitamin C [see Warnings and Precautions ( 5.7 )] • Risks of Deferoxamine mesylate Treatment in Patients with Aluminum Overload [see Warnings and Precautions ( 5.8 )] • Effects on Ability to Drive and Use Machines [see Warnings and Precautions ( 5.9 )] Most common adverse reactions are injection reactions (local and systemic), hypersensitivity reactions, infections with Yersinia and Mucormycosis, cardiovascular, gastrointestinal, hematologic, hepatic, musculoskeletal, urogenital, nervous, respiratory, ocular and hearing. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Gland Pharma Limited at 866-770-7144 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience The following adverse reactions associated with the use of deferoxamine mesylate were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. At the Injection Site: Localized irritation, pain, burning, swelling, induration, infiltration, pruritus, erythema, wheal formation, eschar, crust, vesicles, local edema. Injection site reactions may be associated with systemic allergic reactions ([see Body as a Whole, below)] Hypersensitivity Reactions and Systemic Allergic Reactions: Generalized rash, urticaria, anaphylactic reaction with or without shock, angioedema Body as a Whole: Local injection site reactions may be accompanied by systemic reactions like arthralgia, fever, headache, myalgia, nausea, vomiting, abdominal pain, or asthma Infections: Yersinia, mucormycosis Cardiovascular: Tachycardia, hypotension, shock Digestive: Abdominal discomfort, diarrhea, nausea, vomiting Hematologic: Blood dyscrasia (thrombocytopenia, leukopenia) Hepatic: Increased transaminases, hepatic dysfunction Musculoskeletal: Muscle spasms. Growth retardation and bone changes (e.g., metaphyseal dysplasia) Nervous System: Neurological disturbances, including dizziness, peripheral sensory, motor, or mixed neuropathy, paresthesias, seizures; exacerbation or precipitation of aluminum-related dialysis encephalopathy Special Senses: High-frequency sensorineural hearing loss, tinnitus, visual disturbances including acuity, blurred vision, loss of vision, dyschromatopsia, night blindness, visual field defects, scotoma, retinopathy (pigmentary degeneration), optic neuritis, and cataracts Respiratory: Acute respiratory distress syndrome (with dyspnea, cyanosis, and/or interstitial infiltrates) Skin: Generalized rash Urogenital: Dysuria, acute renal failure, increased serum creatinine and renal tubular disorders

7 DRUG INTERACTIONS • Concurrent treatment with prochlorperazine may lead to temporary impairment of consciousness. ( 7.1 ) • Imaging results may be distorted due to rapid urinary excretion of deferoxamine mesylate bound gallium-67. Discontinue deferoxamine mesylate 48 hours prior to scintigraphy. ( 7.2 ) 7.1 Prochlorperazine Concurrent treatment with deferoxamine mesylate and prochlorperazine, a phenothiazine derivative, may lead to temporary impairment of consciousness. 7.2 Gallium-67 Imaging results may be distorted because of the rapid urinary excretion of deferoxamine mesylate-bound gallium-67. Discontinue deferoxamine mesylate 48 hours prior to scintigraphy.

8 USE IN SPECIFIC POPULATIONS Lactation:Advise not to breastfeed ( 8.2 ) Geriatric Use: Increased risk of ocular disorders ( 8.5 ) See 17 for PATIENT COUNSELING INFORMATION. 8.1 Pregnancy Risk Summary There are no available data on deferoxamine mesylate use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriages or adverse maternal or fetal outcomes. In animal reproduction studies subcutaneous administration of deferoxamine to pregnant animals (mice or rabbits) during organogenesis at doses approximately ≥0.2- (mice) and ≥0.7 (rabbits) times the maximum recommended human dose resulted in maternal toxicity and adverse developmental outcomes (see Data) . Advise pregnant women of the potential risk to a fetus. Consider the benefits and risks of deferoxamine mesylate for the mother and possible risks to the fetus when prescribing deferoxamine mesylate to a pregnant woman. The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. 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 miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal developmental study in mice, pregnant animals administered subcutaneous doses of deferoxamine at 180, and 540 mg/kg/day from gestation day 7 to gestation day 12 resulted in a dose dependent delay and irregularities of fetal skeletal maturation at doses ≥0.2 times the MRHD. At the highest dose of 540 mg/kg, in 1/23 fetuses had a unilateral lesion to the eye lens (approximately 0.5 times the MRHD). In the embryo-fetal developmental studies in rabbits, pregnant animals administered subcutaneous doses of deferoxamine either 200 mg/kg or 200, 300, and 540 mg/kg from gestation day 6 to gestation day 14 resulted in maternal toxicity and embryo-fetal developmental effects at 0.7 times the MRHD. Maternal toxicity included reduced fetal body weights and embryo-fetal effects included malformations of spina bifida, and increased incidence of abnormally ossified ribs and vertebrae. No maternal toxicity or embryo-fetal effects were observed in rats at deferoxamine doses tested (up to 0.9 times the MRHD). 8.2 Lactation There are no data on the presence of deferoxamine or its metabolite in either human or animal milk, the effects on the breastfed child, or the effects on milk production. It is not known whether deferoxamine is excreted in human milk. Because of the potential for serious adverse reactions in the breastfed child, advise patients not to breastfeed during treatment with deferoxamine mesylate, and for one week after the last dose. 8.3 Females and Males of Reproductive Potential Based on animal data, deferoxamine mesylate can cause malformations at doses less than the human dose [see Use in Specific Populations ( 8.1 )] . Contraception Females Deferoxamine mesylate can cause embryo-fetal harm when administered to pregnant women [see Use in Specific Populations ( 8.1 )] . Advise female patients of reproductive potential to use effective contraception during treatment with deferoxamine mesylate and for one month after the last dose. 8.4 Pediatric Use Safety and effectiveness in pediatric patients 3 years of age and older have been established for the treatment of acute iron intoxication and for the treatment of transfusional iron overload in patients with chronic anemia. Safety and effectiveness in pediatric patients under the age of 3 years have not been established. Iron mobilization with deferoxamine mesylate is relatively poor in patients under the age of 3 years with relatively little iron overload. Deferoxamine mesylate is not recommended for use. The drug should ordinarily not be given to these patients unless significant iron mobilization (e.g., 1 mg or more of iron per day) can be demonstrated. High doses of defer …

12.1 Mechanism of Action Deferoxamine mesylate chelates iron by forming a stable complex that prevents the iron from entering into further chemical reactions. It readily chelates iron from ferritin and hemosiderin but not readily from transferrin; it does not combine with the iron from cytochromes and hemoglobin. Deferoxamine mesylate does not cause any demonstrable increase in the excretion of electrolytes or trace metals. Theoretically, 100 parts by weight of deferoxamine mesylate is capable of binding approximately 8.5 parts by weight of ferric iron.

11 DESCRIPTION Deferoxamine mesylate for injection USP, is an iron-chelating agent, available in vials for injection via intramuscular, subcutaneous, and intravenous administration. Deferoxamine mesylate for injection USP, is supplied as vials containing 500 mg of deferoxamine mesylate USP (corresponding to 426.82 mg of deferoxamine as free base) and 2 g of deferoxamine mesylate USP (corresponding to 1.707 g of deferoxamine as free base) in sterile, lyophilized form. Deferoxamine mesylate is N -[5-[3-[(5-aminopentyl)hydroxycarbamoyl]propionamido]pentyl]-3-[[5-( N -hydroxyacetamido)pentyl]carbamoyl]propionohydroxamic acid monomethanesulfonate (salt), and its structural formula is: Deferoxamine mesylate, USP is a white crystalline powder. It is freely soluble in water and slightly soluble in methanol. Its molecular weight is 656.79 g/mol. deferoxamine-spl-structure

10 OVERDOSAGE Acute Toxicity Intravenous LD 50 s (mg/kg): mice, 287; rats, 329. Inadvertent administration of an overdose or inadvertent intravenous bolus administration/rapid intravenous infusion may be associated with hypotension, tachycardia and gastrointestinal disturbances; acute but transient loss of vision, aphasia, agitation, headache, nausea, pallor, CNS depression, including coma, bradycardia and acute renal failure have been reported. Acute respiratory distress syndrome has been reported following treatment with excessively high intravenous doses of deferoxamine mesylate for injection in patients with acute iron intoxication and in patients with thalassemia. There is no specific antidote for deferoxamine mesylate overdose. In case of overdose, discontinue deferoxamine mesylate and provide symptomatic supportive care. Deferoxamine mesylate is readily dialyzable.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Deferoxamine mesylate for injection USP, is supplied in single-dose vials containing 500 mg and 2 g of deferoxamine mesylate (corresponding to 426.82 mg and 1.707 g of deferoxamine as free base) as a sterile, white to off-white lyophilized powder. Deferoxamine mesylate for injection USP, is supplied in cartons as follows: 500 mg/vial Cartons of 4 vials NDC 60505-6236-6 2 g/vial Cartons of 4 vials NDC 60505-6237-6 Storage and Handling Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Each vial is for single dose only. Discard unused portion.