Desferal

Desferal Dosage/Direction for Use

deferoxamine

Manufacturer:

Novartis

Distributor:

Zuellig
Full Prescribing Info
Dosage/Direction for Use
Treatment for chronic iron overload: The main aim of chelation therapy in iron overload in young patients is to maintain an iron balance and to prevent hemosiderosis, while in older patients a negative iron balance is desirable in order to reduce increased iron stores and prevent the toxic effects of iron.
Children and adults: Desferal therapy should be started after the first 10 to 20 blood transfusions or when there is evidence from clinical monitoring that chronic iron overload is present (e.g. serum ferritin >1,000 ng/mL). Growth retardation may result from iron overload or excessive Desferal doses. If chelation is begun in patients under 3 years of age, growth must be monitored carefully and the mean daily dose should not exceed 40 mg/kg (see Precautions).
The dosage and mode of administration may be individually determined and adapted during the course of therapy based on the severity of the patient's iron burden. The lowest effective dosage should be used. To assess the response to chelation therapy, 24-hour urinary iron excretion may initially be monitored daily and the response to increasing doses of Desferal established. Once the appropriate dosage has been established, urinary iron excretion rates may be assessed at intervals of a few weeks. Alternatively, the mean daily dose may be adjusted based on ferritin level in order to keep the therapeutic index below 0.025 (i.e. the mean daily dose (mg/kg) of Desferal divided by the serum ferritin level (micrograms/L) should be below 0.025. The therapeutic index is a valuable tool in protecting the patient from excess chelation, but it is not a substitute for careful clinical monitoring.
The average daily dose of Desferal 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 Desferal toxicity increases; it is important to monitor these patients particularly carefully and perhaps to consider lowering the total weekly dose. The doses specified here are the average daily doses. Since most patients use Desferal less than 7 days a week, the actual dose per infusion usually differs from the average daily dose; e.g. if an average daily dose of 40 mg/kg/day is required and the patient wears the pump 5 nights a week, each infusion should contain 56 mg/kg.
Regular chelation with Desferal has been shown to improve life expectancy in patients with thalassemia.
Slow subcutaneous infusion: Slow subcutaneous infusion using a portable, light-weight infusion pump over a period of 8 to 12 hours is regarded as effective and especially convenient for ambulant patients, but may also be given over a 24-hour period. Desferal should normally be used with the pump 5 to 7 times a week. Desferal is not formulated to support subcutaneous bolus injection.
Geriatrics: Clinical studies of Desferal did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently compared to younger subjects. 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 (see Precautions and Adverse Reactions).
Hepatic impairment: No studies have been performed in patients with hepatic impairment.
Intravenous infusion during blood transfusion: The availability of an intravenous line during blood transfusions makes it possible to administer an intravenous infusion, e.g. in patients who comply poorly with and/or do not tolerate subcutaneous infusions. The Desferal solution should not be put directly into the blood bag but may be added to the blood line by means of a "Y" adaptor located near the venous site of injection. The patient's pump should be used to administer Desferal as usual. Because of the limited amount of drug that can be administered by IV infusion during blood transfusion, the clinical benefit of this mode of administration is limited. Patients and nurses should be warned against accelerating the infusion, as an intravenous bolus of Desferal may lead to circulatory collapse (see Precautions).
Continuous intravenous infusion: Implanted intravenous systems can be used when intensive chelation is carried out.Continuous intravenous infusion is indicated in patients who are incapable of continuing subcutaneous infusions and in those who have cardiac problems secondary to iron overload. The dose of Desferal depends on the extent of the patient's iron overload. The 24-hour urinary iron excretion should be measured regularly where intensive chelation (i.v.) is required, and the dose adjusted accordingly. Care should be taken when flushing the line in order to avoid a sudden infusion of residual Desferal which may be present in the dead space of the line, as this may lead to circulatory collapse (see Precautions).
Intramuscular administration: Since subcutaneous infusions are more effective, intramuscular injections are given only when subcutaneous infusions are not feasible. Whichever route of administration is chosen, the individual maintenance dose to be selected will depend on the patient's iron excretion rate.
Concomitant use of vitamin C: Patients with iron overload usually develop vitamin C deficiencies, probably because iron oxidizes the vitamin. As an adjuvant to chelation therapy, vitamin C in doses up to 200 mg daily may be given in divided doses, starting after an initial month of regular treatment with Desferal (see Precautions). Vitamin C increases the availability of iron for chelation. In general, 50 mg suffices for children under 10 years of age and 100 mg for older children. Larger doses of vitamin C fail to produce any additional in the excretion of the iron complex.
Treatment for acute iron poisoning: Desferal is an adjunct to standard measures generally used in the treatment of acute iron poisoning.
Desferal treatment is indicated in any of the following situations: all symptomatic patients exhibiting more than transient minor symptoms (e.g., more than one episode of emesis or passage of one soft stool); patients with evidence of lethargy, significant abdominal pain, hypovolemia, or acidosis; patients with positive abdominal radiograph results demonstrating multiple radiopacities (the great majority of these patients will go on to develop symptomatic iron poisoning); any symptomatic patient with a serum iron level greater than 300 to 350 micrograms/dL regardless of total iron binding capacity (TIBC). It has also been suggested that a conservative approach without Desferal therapy or challenge should be considered when serum iron levels are in the 300 to 500 micrograms/dL range in asymptomatic patients, as well as in those with self-limited, non-bloody emesis or diarrhea without other symptoms.
Continuous intravenous administration of Desferal is the preferred route. The recommended infusion is 15 mg/kg per hour and should be reduced as soon as circumstances permit, usually after 4 to 6 hours, so that the total intravenous dose does not exceed the recommended 80 mg/kg in any 24-h period.
The following suggested criteria are believed to represent appropriate requirements for cessation of Desferal. Chelation therapy should be continued until the all of the following criteria are satisfied: The patient must be free of signs or symptoms of systemic iron poisoning (e.g. no acidosis, no worsening hepatotoxicity).
Ideally, a corrected serum iron level should be normal or low (i.e. below 100 micrograms/dL). Given that laboratories cannot measure serum iron concentrations accurately in the presence of Desferal, it is acceptable to discontinue Desferal when all other criteria are met if measured serum iron level is not elevated.
Repeat abdominal radiograph test should be obtained in patients who initially demonstrated multiple radiopacities to ensure they have disappeared before Desferal is discontinued because they serve as a marker for continued iron absorption.
If the patient initially developed vin-rosé colored urine with Desferal therapy, it seems reasonable that urine color should return to normal before halting Desferal (absence of vin-rosé urine is not sufficient by itself to warrant discontinuation of Desferal).
The effectiveness of treatment is dependent on an adequate output of urine in order to ensure that the iron complex ferrioxamine is excreted from the body. If oliguria or anuria develop, peritoneal dialysis, hemodialysis, or hemofiltration may become necessary.
Treatment for chronic aluminum overload in patients with end-stage renal failure: The iron and aluminum complexes of Desferal are dialyzable. Their elimination will be increased by dialysis in patients with renal failure.
Patients with evidence of symptoms or organ dysfunction due to aluminum overload should receive Desferal treatment. Even in asymptomatic patients, Desferal treatment should be considered if serum aluminum levels are consistently above 60 ng/mL and are associated with a positive Desferal infusion test (see as follows). This is particularly the case if bone biopsy findings present evidence of aluminum-related bone disease.
Desferal should be administered with a once-weekly 5 mg/kg dose (see Instructions for Use and Handling under Cautions for Usage and Precautions). For patients with post-DFO test serum aluminum levels up to 300 ng/mL Desferal should be given as a slow i.v. infusion during the last 60 minutes of a dialysis session. For patients with a post-DFO test serum aluminum level above 300 ng/mL Desferal should be administered by slow i.v. infusion 5 hours prior to the dialysis session. After completion of the first 3-month course of Desferal treatment, followed by a 4-week wash-out period, a Desferal infusion test should be performed. If two successive Desferal infusion tests performed at 1-month intervals yield serum aluminum levels less than 50 ng/mL above baseline, further Desferal treatment is not recommended.
In patients on continuous ambulatory peritoneal dialysis (CAPD) or continuous cyclic peritoneal dialysis (CCPD) Desferal should be given once weekly at a 5 mg/kg dose prior to the final exchange of the day. The intraperitoneal route is recommended in these patients, but Desferal can also be given i.m., by slow infusion i.v. or s.c..
Desferal test: This test is based on the principle that in normal subjects, Desferal does not raise iron and aluminum excretion above a certain limit.
1. Desferal test for iron overload in patients with normal kidney function: 500 mg Desferal should be injected intramuscularly. The urine should then be collected for a period of 6 hours and its iron content determined. An excretion of 1 to 1.5 mg of iron (18 to 27 micromol) during this 6-hour period is suggestive of an iron overload; values of more than 1.5 mg (27 micromol) can be regarded as pathological. The test yields reliable results only in cases where renal function is normal.
2. Desferal infusion test for aluminum overload in end-stage renal failure patients: A Desferal infusion test is recommended in patients with serum aluminum levels exceeding 60 ng/mL associated with serum ferritin levels above 100 ng/mL.
Just before starting a hemodialysis session, a blood sample is taken to determine the baseline serum aluminum level.
During the last 60 minutes of the hemodialysis session a 5 mg/kg dose (see Instructions for Use and Handling under Cautions for Usage and Precautions) is given as a slow intravenous infusion.
At the start of the next hemodialysis session (i.e. 44 hours after the aforementioned Desferal infusion) the second blood sample is taken to determine the serum aluminum level once more.
The Desferal test is considered positive if the increase in serum aluminum above the baseline level exceeds 150 ng/mL. A negative test, however, does not absolutely exclude the diagnosis of aluminum overload.
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