Deferasirox Dispersible Tablets Instructions

Please read the instructions for dispersible tablets carefully.

[drug name]

Generic name: Deferasirox dispersible tablets

Product name: Enrig

English name: Deferasirox Dispersible Tablets

Chinese Pinyin: Dilaluosi Fensanpian

【Ingredients】

The active ingredient of this product is deferasirox.

Chemical name: 4-[3,5-bis(2-hydroxyphenyl)-1H-[1,2,4]-triazol-1-yl]benzoic acid

Molecular formula: C21H15N3O4

Molecular weight: 373.4

[Character] 125mg: white to slightly yellow tablets, about 12 mm in diameter;

        [Indications] It is used to treat chronic iron overload in beta-thalassemia patients older than 2 years old due to frequent blood transfusions (monthly administration of concentrated red blood cells ≥7ml/kg). For iron overload caused by other transfusion-dependent diseases, the safety and effectiveness data of this product in Chinese patients are limited, and it is recommended to take it as directed by the doctor.

【Specification】125mg

【Usage and Dosage】

Initial and maintenance treatment should be implemented by physicians experienced in treating chronic iron overload caused by blood transfusions. Individualized iron-depleting treatment decisions should be made based on the expected clinical benefits and risks of treatment with this product, while taking into account the patient's life expectancy and comorbidities. In patients requiring iron chelation therapy, it is recommended to initiate therapy with proven iron overload, for example after a transfusion of approximately 100 mL/kg of packed red blood cells (approximately 20 International Units for a patient weighing 40 kg) or when serum ferritin persists >1000ug/L.

The goals of iron chelation therapy are to remove iron introduced by transfusion and, if necessary, to reduce the existing iron load.

Starting dose

The recommended starting daily dose of this product is 20mg/kg

For patients who receive monthly transfusions of more than 14 mL/kg of packed red blood cells (i.e., approximately more than 4 international units/month in adults) and who need to reduce iron overload, a starting dose of 30 mg/kg/day may be considered.

For patients who receive monthly transfusions of less than 7 mL/kg of packed red blood cells (ie, approximately less than 2 international units/month for adults) and who need to maintain iron balance in the body, a starting dose of 10 mg/kg/day may be considered.

Patients who have already responded well to deferoxamine treatment may consider an initial dose of desferrioxamine equivalent to half the deferoxamine dose (e.g., a patient receiving deferoxamine 40 mg/kg/day 5 days per week, or equivalent, may start at 20 mg/kg if switched to desferrioxamine).

Dosage adjustment

Due to any of the following reasons or toxicity, it may be necessary to adjust the dose of this product, interrupt or terminate treatment.

Based on serum ferritin

After starting initial treatment, it is recommended to monitor serum ferritin every month and adjust the dose of this product every 3 to 6 months if necessary based on serum ferritin trends. Dose adjustments should be made step by step from 5 mg/kg to 10 mg/kg and must be individualized based on the patient's efficacy and treatment goals (maintaining or reducing body iron load). If the daily dose of 30 mg/kg cannot control the patient's condition well (for example, serum ferritin is persistently higher than 2500ug/L and does not show a downward trend over time), a dose of up to 40 mg/kg can be considered. Doses exceeding 40 mg/kg are not recommended because there is limited experience in using doses above this level.

For patients whose serum ferritin level has reached the target level (usually 500ug~1000ug/L), a gradual dose reduction by 5-10mg/kg should be considered to maintain the serum ferritin level within the target range.

If serum ferritin continues to be lower than 500pg/L, suspension of treatment with this product should be considered. Urinary iron excretion is not a suitable indicator for monitoring treatment. As with other iron-depleting therapies, the toxicity of this product may be increased when patients with low iron loads or only mildly elevated serum ferritin are treated with inappropriately high doses of this product.

Based on serum creatinine

For adults, if the serum creatinine level is found to be >33% higher than the average measured value before treatment on two consecutive visits, the daily dose of this product is reduced by 10 mg/kg. For pediatric patients, if the serum creatinine level is found to be higher than the upper limit of normal for the corresponding age on two consecutive visits, the dose is reduced by 10 mg/kg.

Coadministration with uridine diphosphate glucuronosyltransferase (UGT) inducer or cholestyramine

Concomitant use of UGT inducers or cholestyramine can reduce the exposure (AUC) of deferasirox. Avoid coadministration of deferasirox with cholestyramine or strong UGT inducers (such as rifampicin, phenytoin, phenobarbital, ritonavir).

If the above drugs must be used together, consider increasing the initial dose of deferasirox to 30 mg/kg, and monitor serum ferritin and end-of-life reactions to further adjust the dose.

Prepare

This product should be taken on an empty stomach at least 30 minutes before a meal, once a day preferably at the same time every day. Tablets should not be chewed or swallowed whole. This product should not be taken together with aluminum-containing antacids. The dosage (mg/kg) needs to be calculated and rounded to the nearest whole tablet.

Completely dissolve the tablets in water, apple juice or orange juice (100-200ml) by stirring until a uniform suspension is obtained and then drink it. The remaining medicine must be added with a small amount of water, apple juice or orange juice and mixed well before taking. Not recommended for dissolution in carbonated drinks or milk as it can cause foaming and slow dispersion.

Special dosage recommendations

There are no studies on the use of this product in patients with renal impairment. Use with caution.

patients with liver damage

This product has been studied in subjects with hepatic impairment. For patients with moderate hepatic impairment (Child-Pugh B), the initial dosage should be reduced by approximately 50%. This product should not be used in patients with severe hepatic impairment (Child-Pugh C). Before starting treatment, liver function tests should be performed in all patients every two weeks for the first month of treatment and then monthly.

【Taboo】

1. People who are known to be allergic to the active ingredients or any excipients

2. It should not be used in combination with other iron chelation treatments because the safety of such combined use has not been established.

3. It is prohibited to be used in patients with creatinine clearance <40mL/min or serum creatinine >2 times the upper limit of normal for the corresponding age.

4. Patients with poor general condition, high-risk myelodysplastic syndrome (MDS) or advanced malignant tumors.

5. Patients with myelodysplastic syndrome (MDS) whose platelet count is <50×109/L.

[Geriatric Use] Clinical studies of deferasirox included 431 patients aged ≥65 years. Most of the above patients had myelodysplastic syndrome (MDS) (n=393). In these studies, elderly patients experienced adverse reactions more frequently than younger patients. Elderly patients should be closely monitored for early symptoms or signs of adverse reactions that may require dose adjustment. Elderly patients are at increased risk for deferasirox toxicity due to reduced hepatic, renal, and cardiac function and a greater frequency of comorbidities or other medications. 

[Drug Overdose] Cases of drug overdose (taking 2-3 times the prescribed amount for several weeks) have been reported. One case report reported that an overdose resulted in subclinical hepatitis, which resolved after discontinuation of the drug, with no long-term effects. Thalassemia patients with iron overload can tolerate a single dose of 80 mg/kg with only mild nausea and diarrhea. A single dose of 40 mg/kg was well tolerated by healthy volunteers.

Signs of acute overdose include nausea, vomiting, headache, and diarrhea. Treatment of overdose includes induction of vomiting, gastric lavage, and symptomatic treatment. 

[Storage] Moisture-proof, sealed and stored below 30℃, out of reach of children.