Deferoxamine Mesylate
FDA Drug Information • Also known as: Deferoxamine, Deferoxamine Mesylate, Desferal
- Brand Names
- Deferoxamine, Deferoxamine Mesylate, Desferal
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
Description
11 DESCRIPTION Desferal, deferoxamine mesylate, is an iron-chelating agent, available in vials for injection via intramuscular, subcutaneous, and intravenous administration. Desferal is supplied as vials containing 500 mg of deferoxamine mesylate USP (corresponding to 426.82 mg 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 monomethanesul-fonate (salt), and its structural formula is: Deferoxamine mesylate USP is a white to almost white powder. It is freely soluble in water and slightly soluble in methanol. Its molecular weight is 656.79 g/mol. Deferoxamine mesylate structural formula
What Is Deferoxamine Mesylate Used For?
1 INDICATIONS AND USAGE DESFERAL is an iron-chelating agent indicated: 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 ( 1.3 ) Desferal 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 DESFERAL is indicated as an adjunct to standard measures for the treatment of acute iron intoxication. 1.2 Chronic Iron Overload DESFERAL is indicated for the treatment of transfusional iron overload in patients with chronic anemia. 1.3 Limitations of Use Desferal is not indicated for the treatment of primary hemochromatosis (since phlebotomy is the method of choice for removing excess iron in this disorder).
Dosage and Administration
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 Desferal 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 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 Desferal 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 Administration Use for all patients not in shock. The initial recommended dose of Desferal is 1,000 mg intramuscularly 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 Administration Administer Desferal intravenously 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 Desferal 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...
Side Effects (Adverse Reactions)
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 Desferal 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 Novartis Pharmaceuticals Corporation at 1-888-669-6682 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 Desferal 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, leucopenia) 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
Drug Interactions
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 Desferal bound gallium-67. Discontinue Desferal 48 hours prior to scintigraphy. ( 7.2 ) 7.1 Prochlorperazine Concurrent treatment with Desferal 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 Desferal-bound gallium-67. Discontinue Desferal 48 hours prior to scintigraphy.
Contraindications
4 CONTRAINDICATIONS Desferal 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 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no available data on Desferal 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 Desferal for the mother and possible risks to the fetus when prescribing Desferal 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...
Overdosage
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 Desferal in patients with acute iron intoxication and in patients with thalassemia. There is no specific antidote for Desferal overdose. In case of overdose, discontinue Desferal and provide symptomatic supportive care. Desferal is readily dialyzable.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Desferal is supplied in single-dose vials containing 500 mg of deferoxamine mesylate (corresponding to 426.82 mg of deferoxamine as free base) as a sterile, white to almost white lyophilized powder. Desferal is supplied in cartons of 4 vials (NDC 0078-0467-91). Storage and Handling Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F).
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.