From the SOC:
7 Assessment of Chelator Side Effects and
Toxicity
The primary signs of chelator toxicity are hearing loss, temporary
loss of sight, cataracts, renal dysfunction, growth failure,
and symptoms related to iron deficiency. Side effects from
deferoxamine toxicity include auditory and visual changes,
and may occur when total body iron is low but high doses of
deferoxamine are still being used. The table below indicates
toxicity-monitoring parameters. The following should be routinely
monitored.
7.1 Audiology
A baseline formal audiology exam should be given prior to starting
a chelator. Any history of hearing difficulty or tinnitus should
prompt a physical exam of the tympanic membranes and formal
audiology testing.
Inquire about hearing problems at each monthly visit. A screening
audiogram should be performed in clinic every six months. Refer
patients for formal audiogram assessment every 12 months, or
more often if a patient is unable to undergo a screening test in
clinic.
If there is new onset of hearing loss or tinnitus, the chelator should
be stopped and the audiogram repeated. The testing should be
confirmed within a month. The chelator can be restarted if the
hearing changes have improved. Reevaluation of iron status may
be necessary.
7.2 Ophthalmology
Inquire about decreased visual acuity at each visit—especially
changes in color perception. Changes in color vision are often the
first symptoms of over-chelation
An annual evaluation by an ophthalmologist should be performed
to rule out cataracts, decreased acuity, night blindness, and
decreased visual fields. Any vision change should be examined
with causes unrelated to iron in mind, as well. A reevaluation
of the chelation regimen should be done if any ophthalmologic
abnormalities are found.
7.3 Nephrology
Creatinine and BUN with the serum chemistry, urine protein/
creatinine, and microalbumin should be monitored monthly for
patients on deferasirox and every three months for patients on
deferoxamine.
7.4 Neutropenia
Neutropenia, or low neutrophil count, must be monitored weekly
with a CBC for patients on deferiprone.
7.5 Growth
Evaluate patients for evidence of growth delay. Routinely record
height and weight monthly and calculate annually growth
velocity. Measure sitting height every six months to assess truncal
shortening. Tibial and spinal radiographs should be evaluated for
evidence of metaphyseal cartilaginous dysplasia in younger patients
with evidence of growth delay.
7.6 Local and allergic reactions
Local reactions at the deferoxamine injection site that are
urticarial in nature will usually respond to increased dilution of
the deferoxamine by 25 to 30 percent. Hydrocortisone should be
used only in severe cases and under the direction of the consulting
hematologist. In some cases, treatment with antihistamines may be
helpful.
Severe, life-threatening allergic reactions may occur. Patients
who report systemic allergic symptoms should be observed and
possibly challenged in clinic. Desensitization protocols have
been used successfully on some patients. When desensitization
has been accomplished, it is critical that the patient does not
stop the medication, as it may necessitate reinstitution of the
entire desensitization process. With the availability of alternative
chelation drugs, changing chelators may be a better option than
desensitization.
7.7 Over-chelation
Persistent low serum ferritin levels (below 500 ng/mL) in the face
of regular chelation are not optimal due to the increased toxicity of
deferoxamine, particularly in children, and presumably deferasirox,
at low levels of total body iron. The chelation program should
be modified and the LIC evaluated. In select high-risk patients,
very low iron levels are maintained but consultation with experts
in iron chelation is required due to toxicity. Low levels of zinc,
copper, selenium, and ionized calcium can also be indicators of
deferoxamine toxicity.
Please see Table 7.7: Chelator Toxicity Monitoring of the SOC (available in our documents section) for the monitoring schedule.