Desferrioxamine Mesylate
A white to off-white, odourless or almost odourless, powder.
Freely soluble in water, very slightly soluble in alcohol: prac-
tically insoluble in ether: slightly soluble in methyl alcohol.
A 10% solution in water has a pH of 3.7 to 5.5 and a 1%
solution in water has a pH of 4.0 to 6.0. Store at 2Β° to 8Β° in
airtight containers. Protect from light.
The manufacturers report that desferrioxamine solutions are
Incompatible with heparin.
Adverse Effects and Treatment
Rapid intravenous injection of desferrioxamine may
cause flushing, urticaria, hypotension, and shock.
Local pain may occur with subcutaneous or intra-
muscular injections and pruritus, erythema, and
swelling have occurred after prolonged subcutane-
ous administration. Gastro-intestinal disorders, dys-
uria, fever, allergic skin rashes, tachycardia, cardiac
arrhythmias, convulsions, and leg cramps have been
reported. Visual disturbances, including retinal
changes, and hearing loss may occur and may be re-
versible if desferrioxamine is withdrawn. Cataract
formation has also been reported. Desferrioxamine
therapy may retard growth in very young children.
Reviews of the adverse effects of desferrioxamine.
Effects on the blood. A patient with end-stage renal dis-
ease developed reversible thrombocytopenia on 3 separate oc-
casions after intravenous infusion of desferrioxamine for
dialysis osteomalacia. Acute fatal aplastic anaemia occurred
in a 16-year-old girl with thalassaemia following intravenous
administration of high doses of desferrioxamine (80 mg per
kg body-weight daily) for 20 days.
Effects on the ear and eye. Lens opacities, retinal pig-
mentary changes and other retinal abnormalities, and ocular
disturbances including loss of colour vision, night blindness,
decreased visual acuity, and field defects have been reported
in patients receiving long-term or high-dose treatment with
desferrioxamine. In assessments of patients on long-term
therapy with desferrioxamine the incidence of symptomatic
and asymptomatic ocular changes has varied from 4% of 52
patients to 66% of 15 patients.
Sensorineural hearing impairment has also been report-
Ed . Tinnitus has been reported in a few patients.
Both ophthalmic and auditory abnormalities can improve
when desferrioxamine is withdrawn, although some-
times the effects may be irreversible or recovery may only
be partial .
Effects on growth rate. Growth retardation has been noted
in thalassaemic children undergoing desferrioxamine thera-
py. Growth retardation was related to dose and inversely
related to iron stores. Also retardation was greater in those
who started receiving desferrioxamine at the start of transfu-
sion therapy at approximately 9 months old than in those who
started desferrioxamine once iron accumulation was estab-
lished after about 3 years. A sharp increase in growth veloc-
ity was reported in 15 patients with low ferritin levels
following a 50% reduction in desferrioxamine dose.
Effects on the kidneys. A 14-yearΒ«ld boy with thalasse-
mia major and haemosiderosis developed acute renal insuffi-
ciency during intravenous infusion of desferrioxamine.
Acute decreases in renal function were reported in 3 patients
following infusions of desferrioxamine.- Two of these pa-
tients had received I80 mg per kg body-weight daily and il
was suggested that the nephrotoxicity could be related to
these high doses, although others reported also having seer
reductions in glomerular filtration rates following regular
doses.
Effects on the lungs. A pulmonary syndrome with tachyp-
noea ,hypoxaemia , reduced pulmonary function, and radio-
graphic evidence of diffuse interstitial pneumonia has been
reported in patients receiving high-dose intravenous therapy
with desferrioxamine. It has been suggested that a hyper-
sensitivity reaction was involved.
Fatal acute respiratory distress syndrome has occurred in 4
patients: in these cases desferrioxamine infusions had been
given for 65 to 92 hours. Pulmonary complications had not
been noted in patients given desferrioxamine for less than 24
hours This report did , however, generate subsequent corre-
spondence disagreeing with the view that prolonged use of
desferrioxamine was the cause of the toxicity. Alternative ex-
planations for the pulmonary injury included the administra-
tion of above maximum daily doses of desferrioxamine as
well as inadequate desferrioxamine therapy.
Eflects on the skin. Desferrioxamine may be used in the
management of porphyria cutanea tarda . Howev-
er. lesions resembling porphyria cutanea tarda developed in 3
patients during long-term treatment with desferrioxamine for
aluminium toxicity. The lesions worsened on exposure to sun
and resolved when desferrioxamine treatment was complet-
ed. It was also possible that the lesions were associated with
aluminium accumulation. Alopecia was noted in one patient
but an association with desferrioxamine therapy could not be
established.
Hypersensitivity. Individual cases of anaphylactoid reac-
tions to desferrioxamine have been reported. Rapid intrave-
nous desensitisation was successful in two patients. Effects
on the lungs have also been attributed to hypersensitivity (see
above).
Treatment of adverse effects. The adverse effects of des-
ferrioxamine generally respond to dosage reduction. In acute
overdosage desferrioxamine may be removed by haemodial-
ysis.
Isoniazid. 50 or 100 mg with pyridoxine. suppressed intoler-
able adverse effects of desferrioxamine in a patient with
Aizheimer's disease.' The adverse effects, anorexia and
weight loss, were attributed to a toxic metabolite of desferri-
oxamine generated by the plasma monoamine oxidase en-
zyme system and isoniazid reduced the formation of this
suspect metabolite.
Precautions
Desferrioxamine should be used with caution in pa-
tients with impaired renal function since the metal
complexes are excreted by the kidneys (in those
with severe renal impairment dialysis increases
elimination). Skeletal fetal anomalies have occurred
in animals. The desferrioxamine-iron complex ex-
creted by the kidneys may colour the urine reddish-
brown. Desferrioxamine may exacerbate alumini-
um-related encephalopathy and precipitate seizures.
Prophylactic treatment with antiepileptics such as
clonazepam has been suggested for patients judged
to be at risk. An increased susceptibility to infection,
particularly with Yersinia species, has been reported
in patients with iron overload treated with desferri-
oxamine. Severe fungal infections have also been re-
ported, predominantly in patients undergoing
dialysis. If infection is suspected, treatment with
desferrioxamine should be stopped and appropriate antimicrobial
treatment given.
The urinary excretion of iron should be regularly
monitored during treatment and periodic ophthal-
mological and audiological examinations are rec-
ommended for patients on long-term therapy.
Monitoring of cardiac function is also recommend-
ed for patients receiving combined treatment with
ascorbic acid (see also under Interactions, below).
Inappropriately high dosage in children with low
ferritin levels may retard growth, therefore regular
checks on height and weight are recommended for
children.
Aluminium encephalopathy. The precipitation of dialysis
dementia with some fatal outcomes has been associated
with desferrioxamine treatment for aluminium overload in di-
alysis patients. McCauley and Sorkin suggested that the
effects could be dose related, but Lillevang and Pedersen
reported exacerbation of aluminium encephalopathy following the
low dose of 0.5 g twice weekly. Sherrard and colleagues suggest-
ed that the onset of symptoms could be associated with high
concentrations of aluminium observed after desferrioxamine
administration. They recommended the use of low doses (for
example 10 mg per kg body-weight) given immediately be-
fore dialysis in affected patients in conjunction with
charcoal haemoperfusion to avoid high serum-aluminium
concentrations.
Infection susceptibility. Yercinia enterocolitica is one of
the most iron-dependent of all microbes, but unlike most oth-
er aerobic bacteria, it produces no detectable iron-binding
compounds, or siderophores. Exogenous siderophores , such
as desferrioxamine may enable Y. enterocolitica to overcome
this handicap and the apparent increased susceptibility to
yersiniosis in patients with severe iron overload may there-
fore be attributable at least in part to desferrioxamine
therapy rather than just the increased availability of iron.
Infections due to Y. enterocolitica have been reported in
patients receiving desferrioxamine for acute iron overdosage
or for chronic iron overload. Severe infection with Y.
pseudotuberculosis has also been reported in a thalassaemic
patient on long-term desferrioxamine therapy.
Treatment with desferrioxamine may also increase suscepti-
bility to mucormycosis . Infections have occurred both
in patients with iron overload disorders and in those who
do not have excessive iron stores.Of 26 cases of mu-
cormycosis in patients undergoing treatment with desferriox-
amine reviewed by Daly and colleagues 23 patients died: in
19 cases the diagnosis was only made at necropsy and only 9
patients received potentially effective treatment (surgery
and/or amphotericin). The organisms responsible were Rhiz-
opus species in 13 cases and Cunninghamella bertholletiae in
3. In another review of 24 cases of mucormycosis in patients
on dialysis , at least 21 were receiving desferrioxamine: in-
fection was fatal in 21 of the 24 patients.
In view of the serious nature of these infections it is
important that they should be recognised and treated promptly.
It has been suggested that a short course of a suitable
antibacterial could be given as prophylaxis to young children
from areas with a high incidence of yersiniosis (see Yersinia
Enteritis , who require treatment with desferrioxamine.
Pregnancy. Abnormalities in animals have been noted fol-
lowing the administration of desferrioxamine in pregnancy.
Thus the outcome following iron overdose during pregnancy
was studied in 66 patients reported to the Teratology Informa
tion Service in London of whom 35 received
desferrioxamine. Seven infants of the 66 pregnancies had
malformations (severe in only one) and all were associated
with maternal overdoses after the first trimester and
therefore could not be directly related to either iron or
desferrioxamine. It was concluded that treatment of iron
overdose with desferrioxamine should not be withheld solely
on the grounds of pregnancy.
Interactions
Desferrioxamine is usually administered parenteral-
ly and thus drug interactions due to chelation with
oral metal ions are not a problem.
Ascorbic acid. Ascorbic acid is often given in addition
to desferrioxamine to patients with iron overload to achieve
better iron excretion. However, early on in treatment when
there is excess tissue iron there is some evidence that
ascorbic acid may worsen the iron toxicity , particularly to
the heart. Thus ascorbic acid should not be given for the first
month after starting desferrioxamine treatment.
Diagnostic tests. Desferrioxamine could interfere with es-
timations of total iron-binding capacity. It may also
interfere with colorimetric iron assays.
Desferrioxamine may distort the results of gallium-67 imag-
ing studies.
Phenothiazines. Neurological symptoms including loss of
consciousness, occurred in 2 patients who received prochlo-
rperazine during desferrioxamine administration. Concomi-
tant use should be avoided.
Pharmacokinetics
Desferrioxamine mesylate is poorly absorbed from
the gastro-intestinal tract. Following parenteral ad-
ministration, desferrioxamine forms chelates with
metal ions and is also metabolised, primarily in the
plasma. The iron-desferrioxamine chelate is excret-
ed in the urine and bile. Desferrioxamine is ab-
sorbed during peritoneal dialysis if added to the
dialysis fluid.
Uses and Administration
Desferrioxamine is a chelator which has a high af-
finity for ferric iron. When given by injection it
forms a stable water-soluble iron-complex (ferriox-
amine) which is readily excreted in the urine and in
bile. Desferrioxamine appears to remove both free
iron and bound iron from haemosiderin and ferritin
but not from haemoglobin, transferrin, or cyto-
chromes. It is estimated that 100 mg of desferriox-
amine mesylate could bind about 8.5 mg of iron but
it is unlikely that such a figure could be achieved in
practice. Desferrioxamine also has an affinity for
other trivalent metal ions including aluminium and
theoretically 100 mg of the mesylate could bind
4.1 mg of aluminium.
Desferrioxamine increases the excretion of iron
from the body and is used in conditions associated
with chronic iron overload such as the iron storage
disorder haemochromatosis and haemosiderosis
and following repeated transfusions as in thalassae-
mia and in acute iron poisoning. It has been used as
eye drops in the management of ocular siderosis and
corneal rust stains. It is also used to reduce alumini-
um overload in patients with end-stage renal failure
on maintenance dialysis. Desferrioxamine is administered as
the mesylate and may be given by subcutaneous or intravenous
infusion. by intramuscular injection, orally, or intra-
peritoneally.
In the treatment of chronic iron overload the dos-
age and route of administration should be deter-
mined for each patient by monitoring urinary iron
excretion, with the aim of normalising serum-ferri-
tin concentrations. Continuous subcutaneous infu-
sions, preferably with the aid of a small portable
infusion pump, are particularly convenient for am-
bulant patients and are more effective than intramus-
cular injections. Continuous intravenous infusion
has been recommended for patients incapable of
continuing subcutaneous infusions or for those with
cardiac problems secondary to iron overload. An in-
itial daily dose of desferrioxamine mesylate 500 mg
may be given by subcutaneous infusion or intrave-
nous infusion, increasing until a plateau of iron ex-
cretion is reached. The usual effective dose range is
20 to 60 mg per kg body-weight daily. Subcutane-
ous infusions are administered 4 to 7 times a week
depending on the degree of iron overload and are
given over 8 to 12 hours, or over 24 hours in some
patients. When given by intramuscular injection the
initial dose has been 0.5 to I g daily as I or 2 injec-
tions, but again the maintenance dose is determined
by response. It has been suggested that in addition to
intramuscular treatment, up to 2 g of desferrioxam-
ine mesylate should be given by intravenous infu-
sion for each unit of blood transfused, at a rate not
more than 15 mg per kg body-weight per hour at the
time of each blood transfusion. Desferrioxamine
should be administered separately from the blood.
The co-administration of ascorbic acid supplements
can enhance the excretion of iron, but should not be
started until I month after starting desferrioxamine
treatment (to reduce the risk of toxicity, see under
Interactions, above). Ascorbic acid is given in doses
of 200 mg daily for adults or 100 mg daily for in-
fants; it should be administered separately from
food since it also enhances iron absorption.
Desferrioxamine has been used as a diagnostic test
for iron storage disease in patients with normal renal
function by injecting 0.5 g of the mesylate intramus-
cularly and estimating the excretion of iron in the
urine collected over the next 6 hours, an excretion of
more than I mg of iron by the patient under test is
suggestive of iron storage disease and more than
1.5 mg can be regarded as pathological.
In the treatment of acute iron poisoning the follow-
ing doses and routes are suggested. In the UK. des-
ferrioxamine mesylate 5 to lO g in 50 to 100 mL of
water may be given by mouth, or by stomach tube.
to chelate any iron left in the stomach and prevent
further absorption following gastric lavage. To elim-
inate iron already absorbed, desferrioxamine me-
sylate should be given intramuscularly or, if the
patient is hypotensive or in shock, intravenously by
slow infusion. The dose and route of parenteral ad-
ministration should be adjusted according to the se-
verity of the poisoning, preferably as indicated by
the serum-iron concentration and total iron binding
capacity, if available, although chelation therapy
should be started in patients with significant symp-
toms without waiting for the results of blood con-
centrations. In the UK the usual dose of
desferrioxamine mesylate is 2 g in adults or 1 g in
children by intramuscular injection. Alternatively it
may be given by slow intravenous infusion of up to
15 mg per kg body-weight per hour, reducing after 4
to 6 hours to provide a total dose not exceeding
80 mg per kg in 24 hours, although larger doses may
be tolerated. In the USA, a recommended procedure
is to give desferrioxamine mesylate I g initially by
intramuscular injection followed by 0.5 g every 4
hours for 2 doses. Subsequent doses of 0.5 g may be
administered every 4 to 12 hours to a maximum of
6 g in 24 hours. Alternatively, the same doses may
be given by slow intravenous infusion at a rate of not
more than 15 mg per kg per hour; but this route of
administration is only recommended for patients in
a state of cardiovascular collapse.
In the treatment of aluminium overload in patients
with end-stage renal failure, those undergoing main-
tenance haemodialysis or haemofiltration may be
given desferrioxamine mesylate 5 mg per kg once a
week by slow intravenous infusion during the last
hour of a dialysis. In patients on peritoneal dialysis
(CAPD or CCPD) desferrioxamine mesylate 5 mg
per kg may be given once a week, by slow intrave-
nous infusion, subcutaneously, intramuscularly, or
intraperitoneally (the recommended route) before
the final exchange of the day. For the diagnosis of
aluminium overload desferrioxamine mesylate 5 mg
per kg is administered by slow intravenous infusion
during the last hour of haemodialysis. An increase in
serum-aluminium concentration, above base-line of
more than 150 ng per mL (measured at the start of
the next dialysis session) suggests aluminium over-
load.
Eye drops containing desferrioxamine mesylate
10% have been administered for the treatment of oc-
ular siderosis and corneal rust stains.
Administration. In the absence of a suitable alternative to
desferrioxamine as a chelator in chronic iron overload syn-
dromes several attempts have been made to overcome compli-
ance problems encountered with standard parenteral
administration by developing oral, rectal or intranasal
regimens. Although most regimens produced an increase in
urinary iron excretion above base-line, the amount excreted
was generally considered to be insufficient to be clinically
useful, particularly in young children with low iron stores
However, these alternate routes of administration could be
useful as an adjunct in selected patients.
Greater success has been reported with daily intravenous
infusion of desferrioxamine 6 to 12 g over 12 hours or inter-
mittent intravenous infusions in addition to subcutaneous
administration7 in patients poorly compliant with convention-
al subcutaneous therapy. No major disturbances in vision or
hearing were encountered in 8 patients undergoing intensive
intravenous treatment for up to 24 months and established
iron-induced heart disease in 2 of these patients improved
during therapy. Administration by twice-daily subcutaneous
bolus injection has also been reported.
Intraperitoneal administration of desferrioxamine may be
used to reduce aluminium levels in patients receiving perito-
neal dialysis for chronic renal failure. Good results have also,
been reported in a patient with haemochromatosis compli-
cated by cirrhosis and cardiomyopathy, in whom a chronic
peritoneal dialysis catheter was used to control ascites and to
administer desferrioxamine.
Aluminium overload. Aluminium has been implicated in a
number of disorders including renal osteodystrophy, dialysis
dementia, and Alzheimer's disease . Patients with
chronic renal failure may be exposed to aluminium from the
use of aluminium-containing phosphate binders and from the
high concentrations of aluminium sometimes found in tap
water used to prepare dialysis fluids. Sources of aluminium in
other patients include aluminium-containing antacids, prepa-
rations for total parenteral nutrition, contaminated albumin
solutions, and environmental and industrial sources. Further
references to aluminium toxicity are included under Alumin-
ium .
In patients with chronic renal failure the major sources of alu-
minium can be substantially reduced by the use of alternative
phosphate binders (sec Renal Osteodystrophy) and by
reduction in the aluminium concentration of dialysis fluids by
reverse osmosis and deionisation. Desferrioxamine may also
be used (but see under Precautions, above, for a discussion of
aluminium toxicity being exacerbated by desferrioxamine).
Chang and Barre have demonstrated that desferrioxamine
greatly increased the removal of aluminium by adsorbent hae-
moperfusion or haemodialysis. In the treatment of dialysis
encephalopathy. desferrioxamine has been reported to have
beneficial effects by the mobilisation and removal of alumin-
ium when administered in doses of up to 6 g once a week via
the arterial line during the first 2 hours of haemodialysis. Of
11 patients with dialysis encephalopathy studied by Milne et
al. 5 were treated with deionised or reverse-osmosis water
alone and all died. The other 6 were treated similarly but were
also given desferrioxamine 6 to 10 g intravenously each week
at dialysis; 4 of these patients improved but 2 died of progres
sive dementia.
Although the total amount of aluminium removed with des-
ferrioxamine treatment during peritoneal dialysis may be
small compared with the amounts removed during haemodi-
alysis, substantial improvement in early aluminium encepha-
lopathy has been achieved in a-patient on continuous
ambulatory peritoneal dialysis by using intraperitoneal des-
ferrioxamine. In a study of 27 patients undergoing haemodi-
alysis but without clinical encephalopathy Altmann and
colleagues demonstrated impaired cerebral function associ-
ated with only mildly elevated plasma-aluminium concentra-
tions. Administration of desferrioxamine to 15 of these
patients for 3 months improved psychomotor performance.
Desferrioxamine has produced rapid clinical improvement in
patients with dialysis-related bone disease. Reduction in
the aluminium content of bone was reported in a study of 7
patients by Malluche and colleagues and in 9 patients by
McCarthy and colleagues. but not by Brown and colleagues
in a report of 2 patients. Measurement of plasma-aluminium
concentrations 24 and 44 hours after administration of desfer-
rioxamine 40 mg per kg body-weight has been used to diag-
nose aluminium-related osteodystrophy , but Malluche et
al. using a lower dose of desferrioxamine (28.5 mg per kg)
and measuring plasma aluminium 5 hours later, found similar
increases in patients both with and without bone-aluminium
accumulation.
Desferrioxamine therapy has also produced beneficial results
in dialysis patients with anaemia and has also been found
to reverse aluminium-induced resistance to erythropoie-
tin.
Prurigo nodularis in chronic aluminium overload has re-
sponded to desferrioxamine with resolution of itch and skin
lesions.
McLachlan and colleagues found that sustained low doses
of desferrioxamine could slow the progression of the demen-
tia of Alzheimer's disease in a study of 48 patients although
their results have been questioned.
Iron overload disease. Chronic iron overload can be
caused by inappropriately increased gastro-intestinal absorp-
tion, by grossly excessive oral intake over long periods, or by
parenteral administration of iron. for example from trans-
fused blood. Excess iron is stored in the form of ferritin and
haemosiderin. The term haemosiderosis is applied to the ac-
cumulation of haemosiderin in body tissues without associat-
ed tissue damage;- haemochromatosis refers to a chronic
disease state in which iron overload leads to tissue damage,
predominantly in the heart, liver, and pancreas . Primary or
hereditary haemochromatosis is caused by a genetic defect in
iron metabolism which results in excessive gastro-intestinal
absorption of iron. The treatment of choice for primary .
haemochromatosis is phlebotomy, but chelation therapy ,
may be needed in patients with anaemia, hypoproteinaemia.
or severe cardiac disease. Secondary or acquired haemo-
chromatosis is commonly associated with chronic anaemias ,
ip particular thalassaemia. in which excessive iron uptake due
to disordered erythropoiesis and excess iron from repeated
blood transfusions contribute to iron overload. In these pa-
tients the usual therapy is iron chelation with desferrioxamine
(see below).
THALASSAEMIA. Patients homozygous for beta-thalassaemia
have severe anaemia requiring regular blood transfu-
sions. As a consequence of this treatment iron overload devel-
ops and the excessive deposition of iron in the myocardium
usually results in these patients dying in their second or third
decade from arrhythmias or cardiac failure. Desferrioxamine
is used to retard the accumulation of iron. the greatest in-.
crease in iron excretion being seen in patients given the drug
by continuous subcutaneous infusion rather than intramuscu-
lar bolus. Better iron excretion may be achieved if patients are
given ascorbic acid 100 to 200 mg daily in addition to desfer-
lioxamine (but see Interactions, above).
Desferrioxamine has been shown lo improve survival in tha-
lassaemic children given regular systemic therapy, and
there has also been preliminary evidence that impaired organ
function might improve with intensive desferrioxamine ther-
apy. A reduction in liver-iron concentrations and an improve-
ment in liver function was reported in some patients with
transfusional iron overload treated with desferrioxamine 2 to
4 g by slow subcutaneous infusion over 12 hours on 6 nights
a week/ although Maurer and colleagues' observed improve-
ment in the degree of hepatic fibrosis in only 2 of 7 patients
given desferrioxamine up to 85 mg per kg body-weight daily
by subcutaneous injection after 3 to 5 years, despite reduc-
tions in iron concentrations. Bronspiegel-Weintrob and
colleagues' showed that beginning chelation therapy before
puberty could help to ensure normal sexual development in
patients with thalassaemia major. Studies indicating that des-
ferrioxamine treatment might preserve or possibly improve
cardiac function impaired by iron overload in thalassaemic
patients have been supported by a decrease in mortality .
from cardiac disease since the introduction of desferrioxam-.
inc in Italy, although this continues to be the main cause of
death in patients with thalassaemia . A recent study in pa-
tients with beta-thalassaemia demonstrated a markedly im-
proved prognosis for survival without cardiac disease in
patients who began chelation therapy with desferrioxamine
before iron loading was severe and in whom reduced serum-
ferritin concentrations were maintained over a long period.
Failure to prevent the accumulation of excess iron or to re-
move large stores of iron was associated with a poor progno-
sis at any age. Thus. it is considered advisable to begin
chelation therapy as early as possible (in practice usually at 2
to 3 years of age when iron overload becomes significant) to
try to prevent organ damage developing.
Iron poisoning. Despite the frequency of acute poisoning
with iron preparations, no universally accepted treatment pro-
tocol exists. It is often difficult to determine the amount of
iron ingested, and assessment of clinical symptoms can be
misleading since patients may exhibit mild symptoms despite
having ingested potentially toxic quantities of iron. Measure-
ment of serum iron concentration and total iron-bind-
ing capacity (TIBC) is useful in assessing the severity of
poisoning but may not be immediately available and may be
misleading. The desferrioxamine challenge test entails giving
desferrioxamine 50 mg per kg body-weight (to a maximum
dose of I g) intramuscularly: if free iron is present, ferriox-
amine will be excreted in the urine imparting a classic "vin
rose" colour. However, the results can be difficult to
interpret and a negative result does not rule out iron
toxicity.
The initial stage of treatment entails removal of unabsorbed
iron from the gastro-intestinal tract by induction of emesis
and/or gastric lavage, with whole-bowel irrigation as a treat-
ment option in patients suspected of ingesting modified-re-
lease preparations or those with radiographic evidence of
unabsorbed tablets remaining after gastric lavage. The addi-
tion of desferrioxamine to the lavage fluid is controversial
since there is little evidence of its efficacy and concern over
possible toxic effects of ferrioxamine. However, in the UK it
is common practice to leave 5 to 10 g of desferrioxamine in
the stomach after gastric lavage. Supportive care should be
given as appropriate and may be all that is required in mild
poisoning. Activated charcoal is not effective in iron poison-
ing.
Chelation therapy with desferrioxamine given intramuscular-
ly or intravenously is indicated in patients with impaired con-
sciousness, shock or hypotension; in those with other
symptoms of severe poisoning, for example leucocytosis; in
those in whom the scrum-iron concentration exceeds the
TIBC; in those with a positive desferrioxamine challenge test;
and those with a serum-iron concentration above 350 ng per
100 mL if TIBC estimations are unavailable. In severe toxic-
ity intravenous desferrioxamine is given immediately without
waiting for the results of serum-iron measurements. There is
no general agreement on the duration of chelation therapy;
among the suggested end-points are the disappearance of the
vin rose coloration of the urine, 24 hours after the disappear-
ance of coloration, and reduction of serum-iron concentra-
tions to less than 100 ng per 100 mL.
General references.
Malaria. Following the suggestion that iron-deficiency anae-
mia may offer some protection against infections (see Infec-
tions in the Precautions for Iron ), desferrioxamine
was tried in a few patients with malaria. Any antimalarial
effect of desferrioxamine was thought to be as a result of che-
lation of parasite-associated iron rather than reduction in
body-iron concentrations in the patient. Desferrioxamine giv-
en intravenously was reported to shorten the time to regain
consciousness in children with cerebral malaria receiving
standard therapy with intravenous quinine and oral pyrimeth-
amine-sulfadoxine. However, in a more recent study there
was no evidence of a beneficial effect on mortality when des-
ferrioxamine was added to an antimalarial treatment regimen
that included a loading dose of quinine.
Porphyria.
Desferrioxamine may be used to re-
duce serum-iron concentrations in porphyria cutanea tarda if
phlebotomy is contra-indicated. In a study of 25 patients with
porphyria cutanea tarda, subcutaneous infusion of desferri-
oxamine was found to be as effective as repeated phleboto-
mies in normalising porphyrin excretion and iron storage.
Desferrioxamine was also used successfully to treat haemodi-
alysis-related porphyria cutanea tarda in a 22-year-old man in
whom venesection therapy was contra-indicated because of
severe anaemia requiring multiple blood transfusion.2 Each
course of intravenous desferrioxamine therapy after the end
of 3 haemodialysis sessions was accompanied by a marked
decrease in plasma porphyrins, a sharp increase in haemat-
ocrit values, and a simultaneous improvement in skin lesions.