Dejex Special Precautions

The decision to remove accumulated iron should be individualized based on anticipated clinical benefit and risk of chelation therapy (see Recommended dose under Dosage & Administration).
Caution should be used in elderly patients due to a higher frequency of adverse reactions.
Renal impairment: Non-progressive rises in serum creatinine have been noted, usually within the normal range. Cases of acute renal failure have been reported. There have been rare cases of acute renal failure requiring dialysis.
It is recommended that serum creatinine and/or creatinine clearance be assessed in duplicate before initiating therapy and monitored monthly thereafter.
Patients with pre-existing renal conditions, or patients who are receiving medicinal products that may depress renal function may be more at risk of complications and weekly monitoring of serum creatinine and/or creatinine clearance is recommended in the first month after initiation or modification of therapy, and monthly thereafter. Caution should be used in patients with creatinine clearance between 40 - 60 mL/min, particularly in cases where there are additional risk factors that may impair renal function such as concomitant medications, dehydration, or severe infections.
Renal tubulopathy has been reported. Most of these patients were children and adolescents with beta-thalassemia and serum ferritin levels < 1,500 mcg/L.
Tests for proteinuria should be performed monthly.
Care should be taken to maintain adequate hydration in patients who develop diarrhea or vomiting.
For adult patients, the daily dose may be reduced by 10 mg/kg if a non-progressive rise in serum creatinine by > 33% above the average of the pre-treatment measurements is seen at two consecutive visits and cannot be attributed to other causes.
For pediatric patients, the dose may be reduced by 10 mg/kg if serum creatinine levels rise above the age-appropriate upper limit of normal at two consecutive visits.
If there is a progressive increase in serum creatinine beyond the upper limit of normal, treatment should be interrupted. Re-initiation is depending on the individual clinical circumstances.
Hepatic impairment: Deferasirox is not recommended in patients with severe hepatic impairment (Child - Pugh class C).
Most reports of hepatic failure involved patients with significant co-morbidities including liver cirrhosis and multi-organ failure; fatal outcomes were reported in some of these patients.
It is recommended that serum transaminases, bilirubin and alkaline phosphatase be monitored before the initiation of treatment, every 2 weeks during the first month and monthly thereafter. If there is a persistent and progressive increase in serum transaminase levels that cannot be attributed to other causes, treatment should be interrupted. Once the cause of the abnormalities has been clarified or after return to normal levels, cautious re-initiation of treatment at a lower dose followed by gradual dose escalation may be considered.
Blood disorders: There have been reports of cytopenia in patients treated with deferasirox. Most of these patients had pre-existing hematologic disorders that are frequently associated with bone marrow failure. The relationship of these episodes to treatment with deferasirox is uncertain. Blood counts should be monitored regularly. Dose interruption of treatment with deferasirox should be considered in patients who develop unexplained cytopenia.
Gastrointestinal disorders: Gastrointestinal irritation may occur during treatment. Upper gastrointestinal ulceration and hemorrhage have been reported. There have been rare reports of fatal GI hemorrhages, especially in elderly patients who had advanced hematologic malignancies and/or low platelet counts.
Physicians and patients should remain alert for signs and symptoms of GI ulceration and hemorrhage during deferasirox therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected There have been reports of ulcers complicated with gastrointestinal perforation (including fatal outcome).
Caution should be exercised in patients who are taking deferasirox in combination with drugs that have known ulcerogenic potential, such as NSAIDs, corticosteroids, or oral bisphosphonates, in patients receiving anticoagulant (see Interactions) and in patients with platelet counts < 50 x 10⁹/L.
Hypersensitivity reactions: Rare cases of serious hypersensitivity reactions (such as anaphylaxis and angioedema) have been reported, the onset of the reaction occurring in the most of cases within the first month of treatment. If reactions are severe, deferasirox should be discontinued and appropriate medical intervention instituted.
Skin disorders: Cases of Stevens-Johnson syndrome (SJS) have been reported. If SJS is suspected deferasirox should be discontinued immediately and should not be re-introduced.
Rare cases of erythema multiforme have been reported during deferasirox treatment.
Skin rashes may appear during deferasirox treatment. For rashes of mild to moderate severity, may be continued without dose adjustment, since the rash often resolves spontaneously. For more severe rash, where interruption of treatment may be necessary, may be re-introduced after resolution of the rash, at a lower dose followed by gradual dose escalation.
Vision and hearing: Auditory (decreased hearing) and ocular (lens opacities) disturbances have been reported. Auditory and ophthalmic testing is recommended before the start of deferasirox treatment and at regular intervals thereafter (every 12 months). If disturbances are noted, dose reduction or interruption may be considered.
Other considerations: As with other iron chelator treatment, the risk of toxicity of deferasirox may be increased when inappropriately high doses are given in patients with a low iron burden or with serum ferritin levels that are only slightly elevated.
Deferasirox must not be combined with other iron chelator therapies as the safety of such combinations has not been established.
The tablets contain lactose. This medicine is not recommended for patients with rare hereditary problems of galactose intolerance, of severe lactase deficiency or of glucose-galactose malabsorption.
Driving and using machines: No studies on the effects of deferasirox on the ability to drive and use machines have been performed. Patients experiencing the uncommon adverse effect of dizziness should exercise caution when driving or operating machinery.
Use in Children: Deferasirox has not been associated with growth retardation in children followed for up to 5 years in clinical trials. However, as a general precautionary measure, body weight and longitudinal growth in pediatric patients can be monitored at regular interval (every 12 months).