Download mg/kg/day

A. Bazrafshan, MD
Felloweshipe of Pediatric Hematology-Oncology
Shiraz University of Medical Science
Shiraz – Iran
e-mail: [email protected]
1-Deferiprone (L1)
2- Deferasirox/ ICL670
Deferiprone is an orally absorbed iron
chelator that began clinical trials in the UK in
the 1980.
It was first licensed for use in thalassaemia
in India, followed by the European Union
and other countries outside the US and
Canada, in the late 1990
FDA approval is in 2011
Standard management of iron overload
Desferrioxamine (DFO)
1980
Deferiprone (DFP)
1999
Deferiprone approved by EMEA
Deferasirox (DFX)
2005
Deferasirox approved by FDA
2006
Deferasirox approved by EMEA
1960
1970
1980
FDA, Food and Drug Administration, USA
EMEA,
European Medicines Agency
1990
2000
2010
Please refer to prescribing information in your country of practice.
Deferasirox Summary of Product Characteristics.
Deferiprone Summary of Product Characteristics.
Deferoxamine Summary of Product Characteristics.
The daily dose of deferiprone that has been
evaluated most thoroughly is 75 mg/kg/day,
given in three doses.
the drug is licensed for doses up to
100mg/kg/day but formal safety studies of
this dose are limited.
High dose monotherapy with deferiprone has
not yet been prospectively evaluated for
safety and effectiveness for patients with
abnormal heart function
Three molecules of deferiprone are required
to bind one iron atom, and the efficiency of
iron binding decreases with falling
concentrations of iron or of chelator.
The drug is rapidly metabolised and inactivated
in the liver by glucuronidation.
about 6% of the drug binds iron before it is
excreted or metabolised (6% efficiency )iron
excretion is almost exclusively in the urine.
Property
Usual dose
(mg/kg/day)
Route
Half-life
Excretion
Main
adverse
effects
in prescribing
information
DFO
Deferiprone
Deferasirox
25–60
75–100
20–40
Sc, iv
(8–12 hours,
5 days/week)
Oral
3 times daily
Oral
Once daily
20–30 minutes
3–4 hours
8–16 hours
Urinary, fecal
Urinary
Fecal
Local reactions,
ophthalmologic,
auditory, growth
retardation, allergic
Gastrointestinal
disturbances,
agranulocytosis/
neutropenia, arthralgia,
elevated liver enzymes
Gastrointestinal
disturbances, rash, mild
non-progressive
creatinine increase,
elevated liver enzymes,
ophthalmologic, auditory
8
the safety and efficacy of this drug has not
been formally evaluated in children under 5
years of age.
Deferiprone is teratogenic in animals and
must never be given to patients attempting
to conceive.
Deferiprone should not be used in pregnant
women.
The effect of vitamin C on iron excretion
with deferiprone is not clear and is thus not
recommended.
1) The most severe adverse effect:
Agranulocytosis < 500
2) Arthralgia & arthritis
3) Liver fibrosis?
4) Nausea, vomiting, urine discoloration
5) Zinc deficiency
Oral preparations containing polyvalent cations
(e.g., aluminum containing antacids, and zinc)
allow at least a 4-hour interval
ANC should be monitored every week or more
frequently if there are signs of infection
if severe neutropenia or agranulocytosis
develop, the drug should be stopped and not
reintroduced, and the use of GM ,CSF should
be considered in the case of agranulocytosis.
Avoid concomitant use with drugs associated
with neutropenia
Variable fluctuation in liver enzymes has been
reported. About a quarter of patients show
ALT fluctuation of twice the normal upper
Limit.
The frequency of arthropathy varies greatly
between studies, from as low as 4.5% at one
Year to 15% after four years
It is not yet clear whether these differences
reflect environmental or genetic differences,
or differences in iron overload between
populations at the start of treatment
Symptoms range from mild non-progressive
arthropathy, typically in the knees,
controllable with non-steroidal
antiinflammatory drugs to (more rarely)
severe erosive arthropathy that may progress
even after treatment is stopped.
As a result of the various unwanted effects,
20-30% of patients are unable to sustain
long-term treatment with deferiprone
Thank you for your attention