Deferoxamine Mesylate (Page 2 of 3)

Information for Patients

Patients experiencing dizziness or other nervous system disturbances, or impairment of vision or hearing, should refrain from driving or operating potentially hazardous machines (see ADVERSE REACTIONS).

Patients should be informed that occasionally their urine may show a reddish discoloration.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term carcinogenicity studies in animals have not been performed with deferoxamine mesylate.

Cytotoxicity may occur, since deferoxamine mesylate has been shown to inhibit DNA synthesis in vitro.

Delayed ossification in mice and skeletal anomalies in rabbits were observed after deferoxamine mesylate was administered in daily doses up to 4.5 times the maximum daily human dose. No adverse effects were observed in similar studies in rats.

There are no adequate and well-controlled studies in pregnant women. Deferoxamine mesylate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when deferoxamine mesylate is administered to a nursing woman.

Pediatric Use

Pediatric patients receiving deferoxamine mesylate should be monitored for body weight and growth every 3 months.

Safety and effectiveness in pediatric patients under the age of 3 years have not been established (see INDICATIONS AND USAGE, WARNINGS, PRECAUTIONS/Drug Interactions/Vitamin C, and ADVERSE REACTIONS).

Geriatric Use

Clinical Studies of deferoxamine mesylate did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from the younger subjects. Postmarketing reports suggest a possible trend for an increased risk of eye disorders in the geriatric population, specifically the occurrence of color blindness, maculopathy, and scotoma. However, it is unclear if these eye disorders were dose related. Although the number of reports was very small, certain elderly patients may be predisposed to eye disorders when taking deferoxamine mesylate. Postmarketing reports also suggest that there may be an increased risk of deafness and hearing loss in the geriatric population (see ADVERSE REACTIONS). In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Hepatic Impairment

No studies have been performed in patients with hepatic impairment.

ADVERSE REACTIONS

The following adverse reactions have been observed, but there are not enough data to support an estimate of their frequency.

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 with Yersinia and Mucormycosis have been reported in association with deferoxamine mesylate use (see PRECAUTIONS).

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) are common in chelated patients given doses above 60 mg/kg, especially those who begin iron chelation in the first three years of life. If doses are kept to 40 mg/kg or below, the risk may be reduced (see WARNINGS, PRECAUTIONS/Pediatric Use).

Nervous System: Neurological disturbances including dizziness, peripheral sensory, motor, or mixed neuropathy, paresthesias, seizures; exacerbation or precipitation of aluminum-related dialysis encephalopathy (see PRECAUTIONS/Information for Patients).

Special Senses: High-frequency sensorineural hearing loss and/or tinnitus are uncommon if dosage guidelines are not exceeded and if dose is reduced when ferritin levels decline. Visual disturbances are rare if dosage guidelines are not exceeded. These may include decreased acuity, blurred vision, loss of vision, dyschromatopsia, night blindness, visual field defects, scotoma, retinopathy (pigmentary degeneration), optic neuritis, and cataracts (see WARNINGS).

Respiratory: Acute respiratory distress syndrome (with dyspnea, cyanosis, and/or interstitial infiltrates) (see WARNINGS).

Skin: Very rare generalized rash.

Urogenital: Dysuria, acute renal failure, increased serum creatinine and renal tubular disorders (see CONTRAINDICATIONS and WARNINGS).

Postmarketing Reports

There are postmarketing reports of deferoxamine-associated renal dysfunction, including renal failure. Monitor patients for changes in renal function (e.g., increased serum creatinine).

OVERDOSAGE

Acute Toxicity

Intravenous LD50 s (mg/kg): mice, 287; rats, 329.

Signs and Symptoms

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, USP in patients with acute iron intoxication and in patients with thalassemia.

Treatment

There is no specific antidote. Deferoxamine mesylate should be discontinued and appropriate symptomatic measures undertaken.

Deferoxamine mesylate is readily dialyzable.

DOSAGE AND ADMINISTRATION

Acute Iron Intoxication

Intramuscular Administration

This route is preferred and should be used for ALL PATIENTS NOT IN SHOCK.

A dose of 1,000 mg should be administered initially. This may be followed by 500 mg every 4 hours for two doses. Depending upon the clinical response, subsequent doses of 500 mg may be administered every 4 to 12 hours. The total amount administered should not exceed 6,000 mg in 24 hours. For reconstitution instructions for intramuscular administration see Table 1.

Intravenous Administration

THIS ROUTE SHOULD BE USED ONLY FOR PATIENTS IN A STATE OF CARDIOVASCULAR COLLAPSE AND THEN ONLY BY SLOW INFUSION. THE RATE OF INFUSION SHOULD NOT EXCEED 15 MG/KG/HR FOR THE FIRST 1,000 MG ADMINISTERED. SUBSEQUENT IV DOSING, IF NEEDED, MUST BE AT A SLOWER RATE, NOT TO EXCEED 125 MG/HR.

For reconstitution instructions for intravenous administration see Table 2. The reconstituted solution is added to physiologic saline, (e.g., 0.9% sodium chloride, 0.45% sodium chloride), glucose in water, or Ringer’s lactate solution.

An initial dose of 1,000 mg should be administered at a rate NOT TO EXCEED 15 mg/kg/hr. This may be followed by 500 mg over 4 hours for two doses. Depending upon the clinical response, subsequent doses of 500 mg may be administered over 4 to 12 hours. The total amount administered should not exceed 6,000 mg in 24 hours.

As soon as the clinical condition of the patient permits, intravenous administration should be discontinued and the drug should be administered intramuscularly.

Chronic Iron Overload

Subcutaneous Administration

A daily dose of 1,000 to 2,000 mg (20 to 40 mg/kg/day) should be administered over 8 to 24 hours, utilizing a small portable pump capable of providing continuous mini-infusion. The duration of infusion must be individualized. In some patients, as much iron will be excreted after a short infusion of 8 to 12 hours as with the same dose given over 24 hours. For reconstitution instructions for subcutaneous administration see Table 3.

Intravenous Administration

The standard recommended method of Deferoxamine Mesylate for Injection, USP administration is via slow subcutaneous infusion over 8 to 12 hours. In patients with intravenous access, the daily dose of Deferoxamine Mesylate for Injection, USP can be administered intravenously. The standard dose is 20 to 40 mg/kg/day for children and 40 to 50 mg/kg/day over 8 to 12 hours in adults for 5 to 7 days per week. In children, average doses should not exceed 40 mg/kg/day until growth has ceased. In adults, average doses should not exceed 60 mg/kg/day. The intravenous infusion rate should not exceed 15 mg/kg/hour. For reconstitution instructions for intravenous administration see Table 2.

In patients who are poorly compliant, Deferoxamine Mesylate for Injection, USP may be administered prior to or following same day blood transfusion (for example 1 gram over 4 hours on the day of transfusion); however, the contribution of this mode of administration to iron balance is limited. Deferoxamine Mesylate for Injection, USP should not be administered concurrently with the blood transfusion as this can lead to errors in interpreting side effects such as rash, anaphylaxis and hypotension.

Intramuscular Administration

A daily dose of 500 to 1,000 mg may be administered intramuscularly. The total daily dose should not exceed 1,000 mg. For reconstitution instructions for intramuscular administration see Table 1.

Reconstitution and Preparation

Table 1: Preparation for Intramuscular Administration

RECONSTITUTE DEFEROXAMINE MESYLATE FOR INJECTION, USP WITHSTERILE WATER FOR INJECTION

Vial Size

Amount of Sterile Water for Injection Required for Reconstitution

Total Drug Content after Reconstitution

Final Concentration per mL after Reconstitution

500 mg

2 mL

500 mg/2.35 mL

213 mg/mL

2 grams

8 mL

2 grams/9.4 mL

213 mg/mL

Table 2: Preparation for Intravenous Administration

RECONSTITUTE DEFEROXAMINE MESYLATE FOR INJECTION, USP WITH STERILE WATER FOR INJECTION

Vial Size

Amount of Sterile Water for Injection Required for Reconstitution

Total Drug Content after Reconstitution

Final Concentration per mL after Reconstitution

500 mg

5 mL

500 mg/5.3 mL

95 mg/mL

2 grams

20 mL

2 grams/21.1 mL

95 mg/mL

Table 3: Preparation for Subcutaneous Administration

RECONSTITUTE DEFEROXAMINE MESYLATE FOR INJECTION, USP WITHSTERILE WATER FOR INJECTION

Vial Size

Amount of Sterile Water for Injection Required for Reconstitution

Total Drug Content after Reconstitution

Final Concentration per mL after Reconstitution

500 mg

5 mL

500 mg/5.3 mL

95 mg/mL

2 grams

20 mL

2 grams/21.1 mL

95 mg/mL

The reconstituted deferoxamine mesylate solution is an isotonic, clear and colorless to slightly-yellowish solution. The drug should be completely dissolved before the solution is withdrawn. Deferoxamine Mesylate for Injection, USP reconstituted with Sterile Water for Injection IS FOR SINGLE-DOSE ONLY. Discard unused portion.

The product should be used immediately after reconstitution (commencement of treatment within 3 hours) for microbiological safety. When reconstitution is carried out under validated aseptic conditions (in a sterile laminar flow hood using aseptic technique), the product may be stored at room temperature for a maximum period of 24 hours before use. Do not refrigerate reconstituted solution. Reconstituting Deferoxamine Mesylate for Injection, USP in solvents or under conditions other than indicated may result in precipitation. Turbid solutions should not be used.

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