DESFERAL^® (deferoxamine mesylate USP)

DESFERAL is indicated for the treatment of acute iron intoxication and of chronic iron overload due to transfusion-dependent anemias.

DESFERAL is not indicated for the treatment of primary hemochromatosis, since phlebotomy is the method of choice for removing excess iron in this disorder.

Important Safety Information

DESFERAL is contraindicated in patients with severe renal disease or anuria, since the drug and the iron chelate are excreted primarily by the kidney.

Ocular and auditory disturbances have been reported when DESFERAL was administered over prolonged periods of time, at high doses, or in patients with low ferritin levels. The ocular disturbances observed have been blurring of vision; cataracts after prolonged administration in chronic iron overload; decreased visual acuity including visual loss, visual defects, scotoma; impaired peripheral, color, and night vision; optic neuritis, cataracts, corneal opacities, and retinal pigmentary abnormalities. The auditory abnormalities reported have been tinnitus and hearing loss, including high frequency sensorineural hearing loss. In most cases, both ocular and auditory disturbances were reversible upon immediate cessation of treatment. In the geriatric population, postmarketing reports suggest a possible trend for an increased risk of eye disorders (specifically the occurrence of blindness, maculopathy, and scotoma), deafness and hearing loss.

Visual acuity tests, slit-lamp examinations, funduscopy and audiometry are recommended periodically in patients treated for prolonged periods of time. Toxicity is more likely to be reversed if symptoms or test abnormalities are detected early.

High doses of DESFERAL and concomitant low ferritin levels have also been associated with growth retardation. After reduction of DESFERAL dose, growth velocity may partially resume to pretreatment rates. Pediatric patients receiving DESFERAL should be monitored for body weight and growth every 3 months.

Adult respiratory distress syndrome, also reported in children, has been described following treatment with excessively high intravenous doses of DESFERAL in patients with acute iron intoxication or thalassemia.

Flushing of the skin, urticaria, hypotension, and shock have occurred in a few patients when DESFERAL was administered by rapid intravenous injection. THEREFORE, DESFERAL SHOULD BE GIVEN INTRAMUSCULARLY OR BY SLOW SUBCUTANEOUS OR INTRAVENOUS INFUSION.

Iron overload increases susceptibility of patients to Yersinia enterocolitica and Yersinia pseudotuberculosis infections. In some rare cases, treatment with DESFERAL has enhanced this susceptibility, resulting in generalized infections by providing this bacteria with a siderophore otherwise missing. In such cases, DESFERAL treatment should be discontinued until the infection is resolved.

In patients receiving DESFERAL, rare cases of mucormycosis, some with a fatal outcomes, have been reported. If any of the suspected signs or symptoms occur, DESFERAL should be discontinued, mycological tests carried out and appropriate treatment instituted immediately.

In patients with severe chronic iron overload, impairment of cardiac function has been reported following concomitant treatment with DESFERAL and high doses of vitamin C (more than 500 mg daily in adults). The cardiac dysfunction was reversible when vitamin C was discontinued. Precautions should be taken when vitamin C and DESFERAL are used concomitantly.

In patients with aluminum-related encephalopathy, high doses of DESFERAL may exacerbate neurological dysfunction (seizures), probably owing to an acute increase in circulating aluminum. DESFERAL may precipitate the onset of dialysis dementia. Treatment with DESFERAL in the presence of aluminum overload may result in decreased serum calcium and aggravation of hyperparathyroidism.

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 including arthralgia, fever, headache, myalgia, nausea, vomiting, abdominal pain, or asthma.

Hypersensitivity Reactions and Systemic Allergic Reactions: Generalized rash, urticaria, anaphylactic reaction with or without shock, angioedema.

Cardiovascular: Tachycardia, hypotension, shock.

Digestive: Abdominal discomfort, diarrhea, nausea, vomiting.

Hematologic: Blood dyscrasia (e.g., thrombocytopenia, leukopenia).

Musculoskeletal: Leg cramps. 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.

Nervous System: Neurological disturbances including dizziness, peripheral sensory, motor, or mixed neuropathy, paresthesias; exacerbation or precipitation of aluminum-related dialysis encephalopathy.

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.

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

Skin: Very rare generalized rash.

Urogenital: Dysuria, impaired renal function.