TABLE III.

Chelator Toxicity

Toxicity	Incidence	Management
Desferal (DFO)
Injection site reaction	Common	Make sure a small subcutaneous needle is used that is perpendicular to the skin and goes all the way through the dermis. Intra-dermal injection is a major cause of local reaction. Rotate the injection sites. Lower the DFO concentration. A small amount of hydrocortisone can be put into the DFO, but should be avoided.
Anaphylaxis	Rare	This is a rare serious reaction. If the patient has systemic allergic symptoms from DFO, we would discontinue the drug. Desensitization can be done. However, given the adherence issues with DFO, patients stop the DFO and then restart several days later and can have a serious reaction. We do not recommend desensitization.
Infection	Rare	Increased risk of infection with ferophilic organisms like Yersina Enterocolitca, V. Vulcanificus and Mucorales
Retinal / Auditory	Rare	Change in colour perception or visual impairment should prompt immediate stopping of DFO. May restart when symptoms resolve. DFP and DFX essentially do not have these complications (isolated cases) and are alternatives.
Deferiprone (DFP)
Gastrointestinal	33 % at first	Symptoms are usually mild and transient. Starting at a lower dose (40 mg/mg/day) and increasing over a period of weeks to months can help. Liquid formulation may be better tolerated. DFP is well tolerated and gastrointestinal symptoms usually resolve after month or two.
Transaminitis	7%	Transaminases can be 2 to 4 times normal levels from severe iron overload. There may be transient increase in the first few months of DFP treatment. If there is significant increase, hold the drug and restart at lower dose after return to baseline levels to see if elevations are truly due to DFP. Evidence of cholestasis suggests other pathology.
Neutropenia (ANC <1.5 × 109/l)	8%	Hold medication until recovery and re-challenge. Make sure patients know to stop DFP and seek medical attention for any fever/mouth sores.
Agranulocytosis (ANC <0.5 × 109/l)	1.5%	Most cases occur during first year on DFP. Make sure patients know to stop DFP if any significant fever or mouth sores and seek immediate medical attention and notify the emergency personal they are on a drug that causes agranulocytosis. They should be treated with parenteral antibiotics if febrile. GCSF may be helpful.
Arthropathy	3.9–40%	More likely at high LIC. Stop DFP and restart at lower dose. Treat with antiinflammatory agents.
Deferasirox (DFX)
Gastrointestinal	15%	Major toxicity of DFX. Starting at lower dose increasing slowing can help with nausea. LactAid can help some with lactose intolerance. Splitting the dose twice a day can also help. Some patients find taking the dose at night is helpful. The new formulation Jadenu, is much better tolerated and does not contain lactose. Significant gastrointestinal bleeding is rare but has occurred and the risk may be higher at low LIC levels. Patients should be warned to stop the drug and seek attention for several abdominal pain.
Renal	36%	33% will have a 30% increase in creatinine. Increase above the upper limit of normal is very rare, though we have seen renal failure and severe hypertension when the renal complication was unrecognised. The urine protein/creatine ratio must be followed carefully although this can be difficult in SCD because of SCD-related renal disease. Hold DFX and re-challenge at a 10 mg/kg lower dose per the specific recommendations in the DFX package insert. We monitor renal function and urine protein/creatinine at each transfusion visit.
Transaminitis	< 5%	Monitor liver function every three months. Liver toxicity is rare with DFX. Comments for DFP apply.

ANC, absolute neutrophil count; GCSF, granulocyte colony-stimulating factor; LIC, liver iron concentration, SCD, sickle cell disease.

The above toxicities are not exhaustive, see references