Desferal

This medication may cause blurred vision and may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly.

Tell your doctor about all other medicines you use, especially prochlorperazine (Compazine, Compro) or a vitamin C supplement.

There may be other drugs that can interact with deferoxamine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Desferal is a prescription medication used to treat acute iron intoxication and chronic iron overload due to transfusion-dependent anemias. It removes excess iron in the body. If you have too much iron in the body, it can damage various organs and tissues.

Desferal belongs to a group of drugs called chelating agents. Desferal works by combining with iron in the blood. The combination of iron and Desferal is then removed from the body by the kidneys.

This medication is available in an injectable form to be given directly into a vein (IV) or a muscle (IM) or injected under the skin (subcutaneously) by a healthcare professional.

Common side effects of Desferal include redness or flushing of the skin, difficulty breathing, fast heartbeat, and injection site reactions.

Desferal can also cause blurred vision and dizziness. Do not drive or operate heavy machinery until you know how Desferal affects you.

• Novartis Pharmaceuticals Corporation

Serious side effects have been reported with Desferal. See the “Desferal Precautions” section.

Common side effects of Deferal include the following:

• bluish fingernails, lips, or skin
• blurred vision or other problems with vision
• convulsions (seizures)
• difficulty with breathing or fast breathing
• fast heartbeat
• hearing problems
• redness or flushing of the skin

This is not a complete list of Desferal side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Aluminum overload or
• Dialysis treatment or
• Encephalopathy (brain disease), aluminum-related—May increase risk for more serious side effects.

• Anuria (not able to form urine) or
• Kidney disease, severe—Should not be used in patients with these conditions.

• Hyperparathyroidism (overactive parathyroid) or
• Kidney problems or
• Seizures, history of—Use with caution. May make these conditions worse.

• Infection (e.g., bacteria, fungus)—May decrease your body's ability to fight infection.

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For injection dosage form:
  • For acute iron toxicity:
    • Adults, teenagers, and children 3 years of age and older—At first, 1000 milligrams (mg) per day injected into a muscle or vein. Your doctor may increase your dose by 500 mg every 4 hours for two doses. However, the total dose is usually not more than 6000 mg in 24 hours.
    • Children younger than 3 years of age—Use and dose must be determined by your doctor.
  • For chronic iron toxicity:
    • Adults, teenagers, and children 3 years of age and older—Dose is based on body weight and must be determined by your doctor. The dose is usually 1000 to 2000 milligrams (mg) (20 to 40 mg per kg of body weight) per day, injected under the skin, over a period of 8 to 24 hours.
    • Children younger than 3 years of age—Use and dose must be determined by your doctor.

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 Desferal use (see PRECAUTIONS).

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) 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 PATIENT INFORMATION).

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).

Read the entire FDA prescribing information for Desferal (Deferoxamine)

You should not use this medication if you are allergic to deferoxamine, if you have severe kidney disease, or if you are unable to urinate.

To make sure you can safely use deferoxamine, tell your doctor if you have any of these other conditions:

• kidney disease (or if you are on dialysis);

• heart disease;

• liver disease;

• vision or hearing problems;

• asthma or other breathing disorder;

• low levels of calcium in your blood (hypocalcemia); or

• a parathyroid disorder.

If you need to have any type of x-ray or CT scan using a dye that is injected into a vein, you may need to temporarily stop using deferoxamine. Be sure the doctor knows ahead of time that you are using this medication.

FDA pregnancy category C. It is not known whether deferoxamine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether deferoxamine passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Long-term use of deferoxamine can slow a child's growth. Tell your doctor if the child using this medication is not growing or gaining weight properly.

• Chelates iron by binding ferric ions to the 3 hydroxamic groups of the molecule and forming a stable complex, ferrioxamine, that prevents iron from entering into further chemical reactions.118 b

• A hexadentate ligand with high binding affinity for iron in a 1:1 ratio.198

• Theoretically, 1 g of deferoxamine mesylate is capable of sequestering 85 mg of iron (as the ferric ion);118 b however, the rate of complex formation appears to be pH dependent (most rapid at acid pH).b

• Main effect is probably on loosely bound stored iron; in vitro studies have shown that deferoxamine removes iron from ferritin, hemosiderin, and, to a lesser extent, transferrin, but not from cytochromes or hemoglobin.b

• Also chelates aluminum104 105 106 107 108 109 and increases its excretion by the kidneys106 and/or removal by dialysis.104 105 106 107 108 109

In the U.S.

• Desferal

Available Dosage Forms:

• Powder for Solution

Therapeutic Class: Heavy Metal Chelator

Deferoxamine injection is used to remove excess iron from the body in anemia or thalassemia patients who have many blood transfusions. It is also used with other medicines to treat acute iron poisoning, especially in small children.

Deferoxamine combines with iron in the blood. The combination of iron and deferoxamine is then removed from the body by the kidneys. If you have too much iron in the body, it can damage various organs and tissues.

This medicine is to be administered only by or under the immediate supervision of your doctor.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

• Bluish fingernails, lips, or skin
• blurred vision or other problems with vision
• convulsions (seizures)
• difficulty with breathing or fast breathing
• fast heartbeat
• hearing problems
• redness or flushing of the skin

• Diarrhea
• difficult urination
• fever
• leg cramps
• nausea
• stomach and muscle cramps
• stomach discomfort
• unusual bleeding or bruising
• vomiting

• Agitation
• coma
• confusion
• cough
• decreased urine output
• depression
• difficulty with swallowing
• dizziness
• headache
• hives
• hostility
• irritability
• itching
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• lethargy
• muscle twitching
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rapid weight gain
• shortness of breath
• skin rash
• stupor
• swelling of the face, ankles, or hands
• tightness in the chest
• unusual tiredness or weakness
• wheezing

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Known hypersensitivity to the active substance.

Desferal is contraindicated in patients with severe renal disease or anuria, since the drug and the iron chelate are excreted primarily by the kidney. (See WARNINGS).

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 Desferal use (see PRECAUTIONS).

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) 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).

Acute Iron Intoxication

Intramuscular Administration

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

A dose of 1000 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 4-12 hours. The total amount administered should not exceed 6000 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 1000 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 1000 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 4-12 hours. The total amount administered should not exceed 6000 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 1000-2000 mg (20-40 mg/kg/day) should be administered over 8-24 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 8-12 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 Desferal administration is via slow subcutaneous infusion over 8 – 12 hours. In patients with intravenous access, the daily dose of Desferal can be administered intravenously. The standard dose is 20 – 40 mg/kg/day for children and 40 – 50 mg/kg/day over 8 – 12 hours in adults for 5 – 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, Desferal 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. Desferal 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 500-1000 mg may be administered intramuscularly. The total daily dose should not exceed 1000 mg. For reconstitution instructions for intramuscular administration see Table 1.

Reconstitution and Preparation

Table 1: Preparation for Intramuscular Administration      

Table 2: Preparation for Intravenous Administrations

Table 3: Preparation for Subcutaneous Administration      

The reconstituted Desferal solution is an isotonic, clear and colorless to slightly- yellowish solution. The drug should be completely dissolved before the solution is withdrawn. Desferal reconstituted with Sterile Water for Injection IS FOR SINGLE USE 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 Desferal in solvents or under conditions other than indicated may result in precipitation. Turbid solutions should not be used.